Publication date: Available online 22 May 2018
Source:Revista Española de Medicina Nuclear e Imagen Molecular
Author(s): C. Riola-Parada, J.L. Carreras-Delgado, V. Pérez-Dueñas, M. Garcerant-Tafur, L. García-Cañamaque
ObjetivoEvaluar la utilidad de la PET/RM con 18F-colina simultánea en la sospecha de recurrencia del carcinoma de próstata y relacionar su tasa de detección de enfermedad con variables analíticas y anatomopatológicas.Material y métodosEstudio retrospectivo de 27 pacientes con carcinoma de próstata que recibieron terapia local como tratamiento primario, a quienes se les realizó una PET/RM con 18F-colina por sospecha de recurrencia (elevación mantenida de los niveles de PSA). Los hallazgos patológicos de la PET/RM con 18F-colina fueron validados mediante el análisis anatomopatológico, otras pruebas de imagen o por la respuesta bioquímica al tratamiento oncológico.ResultadosLa PET/RM con 18F-colina detectó enfermedad en 15 de los 27 pacientes (tasa de detección del 55,56%); 4 (15%) presentaron recurrencia exclusivamente local, 5 (18%) metástasis ganglionares y 7 (26%) metástasis óseas. El PSA medio (PSAmed) a la realización del estudio fue de 2,94ng/mL (rango 0,18-10ng/mL). Los pacientes con PET/RM positiva presentaron un PSAmed de 3,70ng/mL (rango 0,24-10ng/mL), mayor que los pacientes con PET/RM negativa, PSAmed de 1,97ng/mL (rango 0,18-4,38ng/mL), aunque sin diferencias estadísticamente significativas. La puntuación Gleason al diagnóstico de los pacientes con estudio positivo fue de 7,33 (rango 6-9), y la de los pacientes con estudio negativo fue de 7 (rango 6-9), sin diferencias estadísticamente significativas.ConclusiónLa tasa de detección de la PET/RM con 18F-colina fue considerable pese a los valores relativamente bajos de PSA en nuestra muestra. La influencia de la puntuación Gleason y del nivel de PSA en la tasa de detección de la PET/RM con 18F-colina no fue estadísticamente significativa.ObjectiveTo evaluate the usefulness of simultaneous 18F-choline PET/MRI in the suspicion of prostate cancer recurrence and to relate 18F-choline PET/MRI detection rate with analytical and pathological variables.Material and methods27 patients with prostate cancer who received local therapy as primary treatment underwent a 18F-choline PET/MRI due to suspicion of recurrence (persistently rising serum PSA level). 18F-choline PET/MRI findings were validated by anatomopathological analysis, other imaging tests or by biochemical response to oncological treatment.Results18F-choline PET/MRI detected disease in 15 of 27 patients (detection rate 55.56%). 4 (15%) presented exclusively local recurrence, 5 (18%) lymph node metastases and 7 (26%) bone metastases. Mean PSA (PSAmed) at study time was 2.94ng/mL (range 0.18-10ng/mL). PSAmed in patients with positive PET/MRI was 3.70ng/mL (range 0.24-10ng/mL), higher than in patients with negative PET/MRI, PSAmed 1.97ng/mL (range 0.18-4.38ng/mL), although without statistically significant differences. Gleason score at diagnosis in patients with a positive study was 7.33 (range 6-9) and in patients with a negative study was 7 (range 6-9), without statistically significant differences.Conclusion18F-choline PET/MRI detection rate was considerable despite the relatively low PSA values in our sample. The influence of Gleason score and PSA level on 18F-choline PET/MRI detection rate was not statistically significant.
https://ift.tt/2GEcLJT
Δευτέρα 21 Μαΐου 2018
PET/RM con 18F-colina en la sospecha de recurrencia del carcinoma de próstata
Impact of genetic influence on serum total- and free 25-hydroxyvitamin-D in humans
Publication date: Available online 21 May 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Balázs Szili, Boglárka Szabó, Péter Horváth, Bence Bakos, Györgyi Kirschner, János P. Kósa, Erzsébet Toldy, Zsuzsanna Putz, Péter Lakatos, Ádám Tabák, István Takács
Serum 25-hydroxyvitamin D /25OHD/ levels in humans are determined primarily by environmental factors such as UV-B radiation and diet, including vitamin D intake. Although some genetic determinants of 25OHD levels have been shown, the magnitude of this association has not yet been clarified. The present study evaluates the genetic contribution to total- /t-25OHD/ and free-25OHD /f-25OHD/ in a representative sample of the Hungarian population (n = 462). The study was performed at the end of winter to minimize the effect of sunlight, which is a major determinant of serum vitamin D levels. Single nucleotide polymorphisms (SNPs) of five genes playing major roles in vitamin D metabolism were investigated (NADSYN1, DHCR7, GC, CYP2R1 and CYP24A1). The selected SNPs account for 13.1% of the variance of t-25OHD levels. More than half of the genetic effect on t-25OHD levels was explained by two polymorphisms (rs7935125 in NADSYN1 and rs2762941 in CYP24A1), which had not previously been investigated with respect to vitamin D metabolism. No SNPs exhibited association with f-25OHD levels. Unexpectedly, SNPs that showed univariate associations with vitamin D binding protein (DBP) levels were not associated with f-25OHD levels questioning the biological significance of these polymorphisms.The present study shows that t-25OHD levels are significantly influenced by genetic factors, however, the clinical significance of this observation remains to be defined, as variation in f-25OHD levels are marginally explained by genetic effects.
https://ift.tt/2s3oyw0
Vocal Cord Lateralization in Bilateral Abductor Paralysis by Extra-Endo Laryngeal Suture Technique: A Case Series
Abstract
Bilateral Abductor vocal cord paralysis is certainly amongst the most emergent situation an otorhinolaryngologist come across during his/her practice. The treatment of this condition has undergone prominent shift from a blind life-saving "Tracheostomy" to more exquisite and promising laryngeal function preserving surgeries. The objective of the study is to throw light on our experience of a novel method of lateralization of vocal cord in six patients. The procedure was found to be reliable as well as associated with numerous advantages including shorter operating time and lesser intra operative manipulation on larynx. The method is less irritant (knot on outer aspect of larynx), adjustable (knot can be tightened and loosened accordingly) and reversible (knot can be removed if patient recovers). Additional benefits of the practice are smooth learning curve and economic in nature. The procedure has also been modified from quadruple prick to triple prick technique by us. This development further led to decreased operative time as well as lowered risk of trauma to larynx.
https://ift.tt/2GDzjuk
Vocal Cord Lateralization in Bilateral Abductor Paralysis by Extra-Endo Laryngeal Suture Technique: A Case Series
Abstract
Bilateral Abductor vocal cord paralysis is certainly amongst the most emergent situation an otorhinolaryngologist come across during his/her practice. The treatment of this condition has undergone prominent shift from a blind life-saving "Tracheostomy" to more exquisite and promising laryngeal function preserving surgeries. The objective of the study is to throw light on our experience of a novel method of lateralization of vocal cord in six patients. The procedure was found to be reliable as well as associated with numerous advantages including shorter operating time and lesser intra operative manipulation on larynx. The method is less irritant (knot on outer aspect of larynx), adjustable (knot can be tightened and loosened accordingly) and reversible (knot can be removed if patient recovers). Additional benefits of the practice are smooth learning curve and economic in nature. The procedure has also been modified from quadruple prick to triple prick technique by us. This development further led to decreased operative time as well as lowered risk of trauma to larynx.
https://ift.tt/2GDzjuk
Basic red 2 and methyl violet adsorption by date pits: adsorbent characterization, optimization by RSM and CCD, equilibrium and kinetic studies
Abstract
The potential of raw date pits as a natural, widely available and low-cost agricultural waste has been studied in order to adsorb cationic dyes from an aqueous solution. Date pits were characterized by FTIR, SEM, BET, and XRD analysis. To optimize removal of two industrial dyes, basic red 2 (BR2) and methyl violet (MV), from aqueous solution using date pits, response surface methodology (RSM) is employed. Tests were carried out as per central composite design (CCD) with four input parameters namely contact time, temperature, initial concentration of adsorbate, and pH. Second-order polynomial model better fits experimental data for BR2 and MV and optimum values were then determined. In the optimum conditions, kinetic study was conducted and the pseudo-second-order model was found the best fitted model compared to pseudo-first-order model. Moreover, it was shown that intraparticle diffusion was not the sole controlling step and could be associated with other transfer resistance. On other hand, equilibrium isotherms were obtained for BR2 and MV and their maximum adsorption capacities were 92 and 136 mg g−1 respectively. Two-parameter isotherm models like Langmuir, Temkin, Freundlich, Dubinin–Radushkevich, and Halsay were investigated to fit equilibrium data. Three error functions of residual root mean square error, chi-square statistic, and average relative error were used to comfort us in the selected models, which were actually Dubinin–Radushkevich and Langmuir for BR2 and Frendlich, Temkin, and Halsay for MV.
https://ift.tt/2KI06bg
Microparticle Release from Cell Lines and Its Anti-influenza Activity
Viral Immunology, Ahead of Print.
https://ift.tt/2IH3hzh
Renoprotective effect of the isoflavonoid biochanin A against cisplatin induced acute kidney injury in mice: Effect on inflammatory burden and p53 apoptosis
Publication date: August 2018
Source:International Immunopharmacology, Volume 61
Author(s): Faiha A. Suliman, Dina M. Khodeer, Afaf Ibrahiem, Eman T. Mehanna, Mohamed K. El-Kherbetawy, Hala M.F. Mohammad, Sawsan A. Zaitone, Yasser M. Moustafa
Cisplatin is a potent widely-used chemotherapeutics; however, its clinical use is associated with nephrotoxicity. Renoprotective approaches are being discovered to halt the tubular cell death due to inflammatory and apoptotic burdens. In the present study, the renoprotective effects of different doses of biochanin A (10, 20 or 40 mg/kg) in mice treated with a single injection of cisplatin (10 mg/kg) were reported. Cisplatin administration resulted in marked increases in serum creatinine and blood urea nitrogen. Further, renal homogenates showed increased level of inflammatory cytokines and upregulation of the expression of p53 up-regulated modulator of apoptosis (PUMA), p53 and caspase 3 but downregulation in Nrf2 expression. Furthermore, cisplatin group showed marked necrosis and degenerated tubular lining epithelial cells with frequently detected apoptotic bodies. Mice treated with biochanin A (10, 20 or 40 mg/kg) for 14 days prior to cisplatin abrogated cisplatin-mediated damage. Furthermore, the elevated serum creatinine and urea levels were lessened by some doses of biochanin A, indicating protection against renal injury. Similarly, the changes in apoptosis and inflammatory markers have ameliorated to significant levels (P < 0.05). The results suggest biochanin A as a nephroprotective agent against cisplatin toxicity. Overall, this nephroprotective effect of biochanin A involved anti-inflammatory and antiapoptotic activities.
https://ift.tt/2s2cqLU
Inhibition of acetaminophen-induced hepatotoxicity in mice by exogenous thymosinβ4 treatment
Publication date: August 2018
Source:International Immunopharmacology, Volume 61
Author(s): Lei Wang, Xiankui Li, Cai Chen
ObjectiveTo study the effects of exogenous thymosinβ4 (Tβ4) treatment in acetaminophen (APAP)-induced hepatotoxicity.MethodsLiver injury was induced in mice by a single intraperitoneal injection of APAP (500 mg/kg). Exogenous Tβ4 was intraperitoneally administrated at 0 h, 2 h and 4 h after APAP injection. Chloroquine (CQ) (60 mg/kg) was intraperitoneally injected 2 h before APAP administration to inhibit autophagy. Six hours after APAP injection liver injury was evaluated by histological examinations, biochemical measurements and enzyme linked immunosorbent assay (ELISAs). Western blots were performed to detect proteins expression.ResultsSerum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were significantly increased 6 h after APAP administration, but were significantly reduced by co-administration of Tβ4. Histological examinations demonstrated that Tβ4 reduced necrosis and inflammation induced by APAP. Immunofluorescence showed that Tβ4 suppressed APAP-induced translocation of high mobility group box-1 protein (HMGB1) from the nucleus to cytosol and intercellular space. Hepatic glutathione (GSH) depletion, malondialdehyde (MDA) formation and decreased superoxide dismutase (SOD) activities induced by APAP were all attenuated by Tβ4. APAP-induced increases in hepatic nuclear factor-κB (NF-κB) p65 protein expression and inflammatory cytokines production including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were reduced by Tβ4 treatment. Increased LC3 and p62 proteins in the liver tissues of APAP-treated mice were decreased by Tβ4 treatment, which indicated the enhancement of autophagy flux by Tβ4. Furthermore, inhibiting autophagy by CQ abrogated the protective effects of Tβ4 against APAP hepatotoxicity.ConclusionExogenous Tβ4 treatment exerts protective effects against APAP-induced hepatotoxicity in mice. The underneath molecular mechanisms may involve autophagy enhancement and inhibition of oxidative stress by Tβ4.
https://ift.tt/2IzqkAh
Rethinking the prescription of biotin for dermatologic conditions
Dermatologic Therapy, EarlyView.
https://ift.tt/2IAzpZA
pH responsive label-assisted click chemistry triggered sensitivity amplification for ultrasensitive electrochemical detection of carbohydrate antigen 24-2
Publication date: 15 September 2018
Source:Biosensors and Bioelectronics, Volume 115
Author(s): Yun Zheng, Lihua Zhao, Zhanfang Ma
Sensitivity amplification strategy by implementing click chemistry in the construction of biosensing interface can efficiently improve the performance of immunosensor. Herein, we developed a sandwich-type amperometric immunosensor for ultrasensitive detection of carbohydrate antigen 24-2 (CA 242) based on pH responsive label-assisted click chemistry triggered sensitivity amplification strategy. The sensitivity of amperometric immunosensor relies on the current response differences (ΔI) caused by per unit concentration target analyte. The pH responsive Cu2+-loaded polydopamine (CuPDA) particles conjugated with detection antibodies were employed as labels, which can release Cu(II) ions by regulating pH. In the presence of ascorbic acid (reductant), Cu(II) ions were reduced to Cu(I) ions. Azide-functionalized double-stranded DNA (dsDNA) as signal enhancer was immobilized on the substrate through Cu+-catalyzed azide/alkyne cycloaddition reaction. With the help of the click reaction, the ΔI caused by target was elevated prominently, resulting in sensitivity amplification of the immunosensor. Under optimal condition, the proposed immunosensor exhibited excellent performance with linear range from 0.0001 to 100 U mL−1 and ultralow detection limit of 20.74 μU mL−1. This work successfully combines click chemistry with pH-responsive labels in sandwich-type amperometric immunosensor, providing a promising sensitivity amplification strategy to construct immunosensing platform for analysis of other tumor marker.
https://ift.tt/2GExUDV
CCTα Commands Phospholipid Homeostasis from the Nucleus
Publication date: 21 May 2018
Source:Developmental Cell, Volume 45, Issue 4
Author(s): Rosemary Cornell, Bruno Antonny
Enzyme control by their products facilitates cellular homeostasis, but for phospholipids, feedback mechanisms also arise from changes in membrane physical properties. In this issue of Developmental Cell, Haider et al. (2018) show that in many actively growing cells, an enzyme of phosphatidylcholine synthesis senses lipid packing in the nuclear membrane.
Teaser
Enzyme control by their products facilitates cellular homeostasis, but for phospholipids, feedback mechanisms also arise from changes in membrane physical properties. In this issue of Developmental Cell, Haider et al. (2018) show that in many actively growing cells, an enzyme of phosphatidylcholine synthesis senses lipid packing in the nuclear membrane.https://ift.tt/2rYS8DP
The Incredible Shrinking Spindle
Publication date: 21 May 2018
Source:Developmental Cell, Volume 45, Issue 4
Author(s): Christopher Brownlee, Rebecca Heald
As cell size decreases during the reductive divisions of early development, intracellular structures must shrink to fit. In this issue of Developmental Cell, Lacroix et al. (2018) identify a conserved mechanism of spindle scaling in nematode and sea urchin embryos whereby spindle microtubule polymerization rates decrease as development proceeds.
Teaser
As cell size decreases during the reductive divisions of early development, intracellular structures must shrink to fit. In this issue of Developmental Cell, Lacroix et al. (2018) identify a conserved mechanism of spindle scaling in nematode and sea urchin embryos whereby spindle microtubule polymerization rates decrease as development proceeds.https://ift.tt/2ID5KL4
Circuit Wiring: Neurite Speed Dating versus Stable Synaptic Matchmaking
Publication date: 21 May 2018
Source:Developmental Cell, Volume 45, Issue 4
Author(s): Heike Blockus, Franck Polleux
Understanding the mechanisms establishing the complex but precise pattern of connectivity characterizing neural circuits remains an immense challenge. In a recent issue of Neuron, Mao and colleagues (2018) provide new insights by showing that the activation kinetics of EphB2, a transmembrane receptor tyrosine kinase, control whether dendritic filopodia makes a synapse with candidate axons.
Teaser
Understanding the mechanisms establishing the complex but precise pattern of connectivity characterizing neural circuits remains an immense challenge. In a recent issue of Neuron, Mao and colleagues (2018) provide new insights by showing that the activation kinetics of EphB2, a transmembrane receptor tyrosine kinase, control whether dendritic filopodia makes a synapse with candidate axons.https://ift.tt/2rZ6tAf
Pulmonary Neuroendocrine Cells: Sensors and Sentinels of the Lung
Publication date: 21 May 2018
Source:Developmental Cell, Volume 45, Issue 4
Author(s): Yoshihiko Kobayashi, Purushothama Rao Tata
Organisms have developed cellular "antennas" to sense, interpret, and integrate environmental stimuli. In a recent issue of Science, Sui et al. (2018) demonstrate that discrete clusters of pulmonary neuroendocrine cells in the lung can sense airborne allergens and relay signals to stimulate immune cells and induce tissue/organ-wide responses.
Teaser
Organisms have developed cellular "antennas" to sense, interpret, and integrate environmental stimuli. In a recent issue of Science, Sui et al. (2018) demonstrate that discrete clusters of pulmonary neuroendocrine cells in the lung can sense airborne allergens and relay signals to stimulate immune cells and induce tissue/organ-wide responses.https://ift.tt/2KJVCB2
Misshapen Connects Food, Mechanosensing, and Intestinal Growth
Publication date: 21 May 2018
Source:Developmental Cell, Volume 45, Issue 4
Author(s): Jin Jiang
Adult tissues such as intestinal epithelium can rapidly adapt their growth in response to environmental stimuli. In this issue of Developmental Cell, Li et al. (2018) demonstrate that gut epithelium stretching caused by food ingestion drives Drosophila intestinal growth via Hippo pathway regulation.
Teaser
Adult tissues such as intestinal epithelium can rapidly adapt their growth in response to environmental stimuli. In this issue of Developmental Cell, Li et al. (2018) demonstrate that gut epithelium stretching caused by food ingestion drives Drosophila intestinal growth via Hippo pathway regulation.https://ift.tt/2ID12gp
Plasma Membrane Localization of Apoptotic Caspases for Non-apoptotic Functions
Publication date: 21 May 2018
Source:Developmental Cell, Volume 45, Issue 4
Author(s): Alla Amcheslavsky, Shiuan Wang, Caitlin E. Fogarty, Jillian L. Lindblad, Yun Fan, Andreas Bergmann
Caspases are best characterized for their function in apoptosis. However, they also have non-apoptotic functions such as apoptosis-induced proliferation (AiP), where caspases release mitogens for compensatory proliferation independently of their apoptotic role. Here, we report that the unconventional myosin, Myo1D, which is known for its involvement in left/right development, is an important mediator of AiP in Drosophila. Mechanistically, Myo1D translocates the initiator caspase Dronc to the basal side of the plasma membrane of epithelial cells where Dronc promotes the activation of the NADPH-oxidase Duox for reactive oxygen species generation and AiP in a non-apoptotic manner. We propose that the basal side of the plasma membrane constitutes a non-apoptotic compartment for caspases. Finally, Myo1D promotes tumor growth and invasiveness of the neoplastic scrib RasV12 model. Together, we identified a new function of Myo1D for AiP and tumorigenesis, and reveal a mechanism by which cells sequester apoptotic caspases in a non-apoptotic compartment at the plasma membrane.
Graphical abstract
Teaser
Amcheslavsky et al. provide a mechanism by which cells activate caspases without the detrimental consequences of apoptosis. In Drosophila, the unconventional myosin Myo1D localizes the initiator caspase Dronc to the basal side of the plasma membrane of epithelial cells. Here, Dronc can fulfill non-apoptotic functions such as apoptosis-induced proliferation.https://ift.tt/2rXp53s
Microtubule Dynamics Scale with Cell Size to Set Spindle Length and Assembly Timing
Publication date: 21 May 2018
Source:Developmental Cell, Volume 45, Issue 4
Author(s): Benjamin Lacroix, Gaëlle Letort, Laras Pitayu, Jérémy Sallé, Marine Stefanutti, Gilliane Maton, Anne-Marie Ladouceur, Julie C. Canman, Paul S. Maddox, Amy S. Maddox, Nicolas Minc, François Nédélec, Julien Dumont
Successive cell divisions during embryonic cleavage create increasingly smaller cells, so intracellular structures must adapt accordingly. Mitotic spindle size correlates with cell size, but the mechanisms for this scaling remain unclear. Using live cell imaging, we analyzed spindle scaling during embryo cleavage in the nematode Caenorhabditis elegans and sea urchin Paracentrotus lividus. We reveal a common scaling mechanism, where the growth rate of spindle microtubules scales with cell volume, which explains spindle shortening. Spindle assembly timing is, however, constant throughout successive divisions. Analyses in silico suggest that controlling the microtubule growth rate is sufficient to scale spindle length and maintain a constant assembly timing. We tested our in silico predictions to demonstrate that modulating cell volume or microtubule growth rate in vivo induces a proportional spindle size change. Our results suggest that scalability of the microtubule growth rate when cell size varies adapts spindle length to cell volume.
Graphical abstract
Teaser
During early embryonic development, the mitotic spindle scales with decreasing cell size across successive reductive divisions. Lacroix et al. uncover, using in vivo and in silico analyses, a common scaling mechanism whereby spindle microtubule growth rate is coupled to cell volume for size scaling while maintaining constant spindle assembly timing.https://ift.tt/2ICSZ3e
Tild-CRISPR Allows for Efficient and Precise Gene Knockin in Mouse and Human Cells
Publication date: 21 May 2018
Source:Developmental Cell, Volume 45, Issue 4
Author(s): Xuan Yao, Meiling Zhang, Xing Wang, Wenqin Ying, Xinde Hu, Pengfei Dai, Feilong Meng, Linyu Shi, Yun Sun, Ning Yao, Wanxia Zhong, Yun Li, Keliang Wu, Weiping Li, Zi-jiang Chen, Hui Yang
The targeting efficiency of knockin sequences via homologous recombination (HR) is generally low. Here we describe a method we call Tild-CRISPR (targeted integration with linearized dsDNA-CRISPR), a targeting strategy in which a PCR-amplified or precisely enzyme-cut transgene donor with 800-bp homology arms is injected with Cas9 mRNA and single guide RNA into mouse zygotes. Compared with existing targeting strategies, this method achieved much higher knockin efficiency in mouse embryos, as well as brain tissue. Importantly, the Tild-CRISPR method also yielded up to 12-fold higher knockin efficiency than HR-based methods in human embryos, making it suitable for studying gene functions in vivo and developing potential gene therapies.
Graphical abstract
Teaser
Yao et al. describe Tild-CRISPR, a targeting strategy using PCR-amplified or precisely enzyme-cut transgene donor sequence. Tild-CRISPR yields robust knockin efficiency in mouse and human embryos, as well as mouse brain in vivo, suitable for studying gene functions in vivo and developing potential gene therapies.https://ift.tt/2s0bWql
Myonuclear Positioning and Aneurysms Are LINC’d by Ariadne
Publication date: 21 May 2018
Source:Developmental Cell, Volume 45, Issue 4
Author(s): Mridula Balakrishnan, Mary K. Baylies
https://ift.tt/2KITVUl
Role of Ligands of Receptor for Advanced Glycation End Products (RAGE) in Peripheral Artery Disease
Rejuvenation Research, Ahead of Print.
https://ift.tt/2IH5tak
Frequency of mitochondrial m.1555A > G mutation in Syrian patients with non-syndromic hearing impairment
Mitochondrial maternally inherited hearing impairment (HI) appears to be increasing in frequency. The incidence of mitochondrial defects causing HI is estimated to be between 6 and 33% of all hearing deficienc...
https://ift.tt/2x3nPAQ
Harnessing Digital Media to Promote Health and Research.
https://ift.tt/2rXvBaf
Use of GLP-1 RAs in Cardiovascular Disease Prevention: A Practical Guide.
https://ift.tt/2IFRCkt
Cardiovascular Risk Prediction Functions Underestimate Risk in HIV Infection.
https://ift.tt/2rWsnUM
Challenges of Cardiovascular Disease Risk Evaluation in People Living With HIV Infection.
https://ift.tt/2KJVh19
Prevalence and Predictors of Cholesterol Screening, Awareness, and Statin Treatment Among US Adults With Familial Hypercholesterolemia or Other Forms of Severe Dyslipidemia (1999-2014).
https://ift.tt/2rUghLN
Randomized Comparisons of Double-Dose Clopidogrel or Adjunctive Cilostazol Versus Standard Dual Antiplatelet in Patients With High Posttreatment Platelet Reactivity: Results of the CREATIVE Trial.
https://ift.tt/2KJVbXl
Transplant-Free Survival and Interventions at 6 Years in the SVR Trial.
https://ift.tt/2rZUpOZ
Surgical Palliation for Hypoplastic Left Heart Syndrome: For Now, Just Keep Doing What You Do Best.
https://ift.tt/2IFRp0F
Nicotinamide Riboside Preserves Cardiac Function in a Mouse Model of Dilated Cardiomyopathy.
https://ift.tt/2s1tLW3
Raising NAD in Heart Failure: Time to Translate?.
https://ift.tt/2IFRi5f
Use of Intracardiac Echocardiography in Interventional Cardiology: Working With the Anatomy Rather Than Fighting It.
https://ift.tt/2rWsBeC
Association of Urinary Nitrate With Lower Prevalence of Hypertension and Stroke and With Reduced Risk of Cardiovascular Mortality.
https://ift.tt/2KKxMFg
Letter by Spartalis et al Regarding Article, "Left Ventricular Assist Device Malfunctions: It Is More Than Just the Pump".
https://ift.tt/2rXqZBa
Response by Kormos to Letter Regarding Article, "Left Ventricular Assist Device Malfunctions: It Is More Than Just the Pump".
https://ift.tt/2KKvXs0
Letter by Madias Regarding Article, "Early Outcomes of Repair of Left Ventricular Apical Aneurysms in Patients With Hypertrophic Cardiomyopathy".
https://ift.tt/2s5lIYv
Response by Nguyen et al to Letter Regarding Article, "Early Outcomes of Repair of Left Ventricular Apical Aneurysms in Patients with Hypertrophic Cardiomyopathy".
https://ift.tt/2IAOWVi
Letter by Rodriguez-Granillo et al Regarding Article, "Acute Myocardial Infarction: Changes in Patient Characteristics, Management, and 6-Month Outcomes Over a Period of 20 Years in the FAST-MI Program (French Registry of Acute ST-Elevation or Non-ST-Elevation Myocardial Infarction) 1995 to 2015".
https://ift.tt/2s5lArZ
Response by Puymirat et al to Letter Regarding Article, "Acute Myocardial Infarction Changes in Patient Characteristics, Management, and 6-Month Outcomes Over a Period of 20 Years in the FAST-MI Program (French Registry of Acute ST Elevation or Non-ST-Elevation Myocardial Infarction) 1995 to 2015".
https://ift.tt/2KHy4ga
Letter by Cattaneo and von Kugelgen Regarding Article, "International Expert Consensus on Switching Platelet P2Y12 Receptor-Inhibiting Therapies".
https://ift.tt/2rYOkCm
Response by Angiolillo et al to Letter Regarding Article, "International Expert Consensus Document on Switching Platelet P2Y12 Receptor Inhibiting Therapies".
https://ift.tt/2IAOAxW
Reuse of organobentonites with a carbon dioxide responsive solvent
Abstract
Synthesized organobentonite (SOB), montmorillonite (MMT), and commercial organobentonite (COB) were used as adsorbents for paraffin oil, a model pollutant in land-based oil spills and oil pipeline rupture. The characterization of clays was carried out with scanning electron microscopy (SEM), thermogravimetric analysis (TG), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). After adsorption, oil was separated from adsorbents with a carbon dioxide responsive solvent N,N-dimethylcyclohexylamine (DMCHA), and DMCHA was subsequently separated from paraffin oil upon CO2 bubbling instead of distillation with high energy cost. The adsorption capacity of oil to SOB, MMT, and COB was 0.686, 1.124, and 1.239 g/g, respectively. It was found that the adsorption capacity and rinsed amount of the adsorbents depended on the d-spacing, which is related to surfactant content. Electrical conductivity and pH measurements suggested that the separation process occurred via two steps. Firstly, during the initial 35 min, carbonate ions coexisted with bicarbonate ions. Then, only bicarbonate ions existed after the introduction of CO2 gas for 120 min. Thus, organobentonites were feasible for hydrocarbon adsorption and could be simply reused by an amine-based responsive solvent. This work provided a cost-effective and sustainable method of recycling of organobentonites and the responsive solvent, which can be used to deal with leaked oil and oil spills.
https://ift.tt/2IBq4R5
Glutathione system in animal model of solid tumors: From regulation to therapeutic target
Publication date: Available online 21 May 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Claudia Rita Corso, Alexandra Acco
Glutathione (GSH) is one of the most important defenses against oxidative stress through the fine-tuned regulation of redox homeostasis. Glutathione is also involved in many metabolic processes and is important for the regulation of cell survival, proliferation, and death. Furthermore, GSH and the enzymes that are involved in its biosynthesis, catabolism, and detoxification (e.g., disulfide-oxidized glutathione, glutathione S-transferase, glutathione peroxidase, glutathione reductase, and γ-glutamyltranspetidase) play an important role in several diseases, including cancer. In cancer cells, these enzymes protect the tumor microenvironment against oxidative stress and cell death and are important for tumor growth and development. Thus, the GSH system is an important tool for investigating new pharmacological approaches for cancer treatment. Several preclinical models of solid tumors are available for this purpose. This review summarizes and discusses the regulation and dysregulation of GSH and its related enzymes in different models of solid tumors, and potential treatments that target the GSH system.
https://ift.tt/2wZFrNQ
Cross-linked electrospun cartilage acellular matrix/poly(caprolactone-co-lactide-co-glycolide) nanofiber as an antiadhesive barrier
Publication date: Available online 21 May 2018
Source:Acta Biomaterialia
Author(s): Jin Woo Lee, Joon Yeong Park, Seung Hun Park, Min Ju Kim, Bo Ram Song, Hee-Woong Yun, Tae Woong Kang, Hak Soo Choi, Young Jick Kim, Byoung Hyun Min, Moon Suk Kim
In this work, we chose cartilage acellular matrix (CAM) as a promising antiadhesive material because CAM effectively inhibits the formation of blood vessels, and we used electrospinning to prepare antiadhesive barriers. Additionally, we synthesized N-hydroxysuccinimide (NHS)-poly(caprolactone-co-lactide-co-glycolide)-NHS (MP) copolymers (to tune degradation) as a cross-linking agent for CAM. This is the first report on the development of electrospun cross-linked (Cx) CAM/MP (CA/P) nanofiber (NF) (Cx-CA/P-NF) with a tunable degradation period as an antiadhesive barrier. Compared with the CA/P-NF before cross-linking, the electrospun Cx-CA/P-NF after cross-linking showed different biodegradation. Cx-CA/P-NF significantly inhibited the in vitro attachment and proliferation of human umbilical vein endothelial cells (HUVECs), as confirmed by an MTT assay and scanning electron microscopy images. Cx-CA/P-NFs implanted between a surgically damaged peritoneal wall and cecum gradually degraded in 7 days; this process was monitored by NIR imaging. The in vivo evaluation of the anti–tissue adhesive effect of Cx-CA/P-NFs revealed little adhesion, few blood vessels, and negligible inflammation at 7 days determined by hematoxylin and eosin staining. ED1 staining of Cx-CA/P-NFs showed infiltration of few macrophages because of the inflammatory response to the Cx-CA/P-NF as compared with an untreated injury model. Additionally, Cx-CA/P-NFs significantly suppressed the formation of blood vessels between the peritoneal wall and cecum, according to CD31 staining. Overall, Cx-CA/P-NFs yielded little adhesion, infiltration by macrophages, or formation of blood vessels in a postoperative antiadhesion assay. Thus, it is reasonable to conclude that the Cx-CA/P-NF designed herein successfully works as an antiadhesive barrier with a tunable degradation period.Statement of SignificanceThe cartilage acellular matrix (CAM) can inhibit the formation of fibrous tissue bridges and blood vessels between the tissue at an injured site and the surrounding healthy tissues. However, CAM has not been rigorously investigated as an antiadhesive barrier. In this manuscript, the cross-linked CAM nanofiber (Cx-CA/P-NF) designed herein successfully works as an antiadhesive barrier. Cx-CA/P-NFs yielded little adhesion, infiltration by macrophages, or formation of blood vessels in a postoperative antiadhesion assay. Moreover, we demonstrated the suitable properties of Cx-CA/P-NF such as easy cross-linking by maintaining the antiadhesive properties, controllable biodegradation, and in vivo antiadhesive effect of Cx-CA/P-NF.
Graphical abstract
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Bubble-generating polymersomes loaded with both indocyanine green and doxorubicin for effective chemotherapy combined with photothermal therapy
Publication date: Available online 21 May 2018
Source:Acta Biomaterialia
Author(s): Dunwan Zhu, Fan Fan, Chenlu Huang, Zhiming Zhang, Yu Qin, Li Lu, Hai Wang, Xu Jin, Hanxue Zhao, Hu Yang, Chao Zhang, Jun Yang, Zhipeng Liu, Hongfan Sun, Xigang Leng, Deling Kong, Linhua Zhang
The combination of chemotherapy and photothermaltherapy (PTT) via stimuli-responsive nanovesicles has great potential in tumor treatment. In the present study, bubble-generating polymersomes, which can generate bubbles in response to low pH or hyperthermia, were fabricated to simultaneously encapsulate chemotherapeutic drug and photosensitizing agent for the synergistic chemo-photothermal tumor therapy. Photosensitizer indocyanine green (ICG) was encapsulated into the bilayer of polymersomes formed by amphiphilic triblock copolymer PCL8000-PEG8000-PCL8000 through thin film re-hydration method, while chemotherapeutic doxorubicin (DOX) was loaded into the hydrophilic lumen using a transmembrane ammonium bicarbonate gradient loading procedure. Under acidic condition or laser irradiation, the ammonium bicarbonate (NH4HCO3) encapsulated in the bubble-generating DOX-ICG-co-delivery polymersomes (BG-DIPS) would decompose to produce CO2 bubbles, resulting in destruction of vesicle structure and rapid drug release. In vitro drug release study confirmed that acidic environment and NIR laser irradiation could accelerate DOX release from the BG-DIPS. Cellular uptake study indicated that laser-induced hyperthermia highly enhanced endocytosis of BG-DIPS into 4T1-Luc cancer cells. In vitro cytotoxicity study demonstrated that BG-DIPS exhibited much higher cytotoxicity than free drugs under laser irradiation. In vivo biodistribution study indicated that BG-DIPS could accumulate in the tumor region, prolong drug retention, and increase photothermal conversion efficiency. Furthermore, in vivo antitumor study showed that BG-DIPS with laser irradiation efficiently inhibited 4T1-Luc tumor growth with reduced systemic toxicity. Hence, the formulated bubble-generating polymersomes system was a superior multifunctional nanocarrier for stimuli-response controlled drug delivery and combination chemo-photothermal tumor therapy.Statement of SignificanceThe combination of chemotherapy and photothermaltherapy via stimuli-responsive nanovesicles has great potential in tumor treatment. Herein, bubble-generating polymersomes, which can generate bubbles in response to low pH or hyperthermia, were fabricated to simultaneously encapsulate chemotherapeutic drug (DOX) and photosensitizing agent (ICG) for the synergistic chemo-photothermal tumor therapy. The results in vitro and in vivo demonstrated that bubble-generating DOX-ICG-co-delivery polymersomes (BG-DIPS) would accelerate DOX release from the BG-DIPS and accumulate in the tumor region, prolong drug retention, and increase photothermal conversion efficiency. BG-DIPS with laser irradiation could efficiently inhibited 4T1-Luc tumor growth with reduced systemic toxicity. Hence, the formulated bubble-generating polymersomes system was a superior multifunctional nanocarrier for stimuli-response controlled drug delivery and combination chemo-photothermal tumor therapy.
Graphical abstract
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Targeted and controlled drug delivery by multifunctional mesoporous silica nanoparticles with internal fluorescent conjugates and external polydopamine and graphene oxide layers
Publication date: Available online 21 May 2018
Source:Acta Biomaterialia
Author(s): Anh-Vy Tran, KyuHwan Shim, Thu-Thao Vo Thi, Jeong-Keun Kook, Seong Soo A. An, Sang-Wha Lee
This study demonstrated the targeted delivery and controlled release of cisplatin drug molecules from doubly decorated mesoporous silica nanoparticles (MSNs), which were internally grafted with fluorescent conjugates and externally coated with polydopamine (PDA) and graphene oxide (GO) layers. The brush-like internal conjugates conferred fluorescent functionality and high capacity of cisplatin loading into MSNs, as well as contributing to a sustained release of the cisplatin through a porous channel with the assistance of external PDA layer. A consolidated double-layer formed by electrostatic interactions between the GO nanosheet and the PDA layer induced more controlled release kinetics which was well predicted by Higuchi model. In addition, Our MSNs exhibited stimuli (pH, NIR irradiation)-responsive controlled release as a potential chemo-photothermal agent against cancer cells. In a cell test, multifunctional MSNs showed a low toxicity itself, but gave a high cytotoxicity against human epithelial neuroblastoma cells (SH-SY5Y) after loading cisplatin. Notably, GO-wrapped MSNs exhibited very effective drug delivery because GO wrapping enhanced their dispensability in aqueous solution, photothermal heating effect, and efficient endocytosis into cells. Furthermore, monoclonal antibody (anti-human epidermal growth factor receptor)-conjugated MSNs showed a higher specificity, which resulted in more enhanced anticancer effects in vitro. The current study demonstrated a reliable synthesis of multifunctional MSNs, endowed with fluorescent imaging, stimuli-responsive controlled release, higher specificity, and efficient cytotoxicity toward cancer cells.Statement of SignificanceThe current study demonstrated the reliable synthesis of multifunctional mesoporous silica nanoparticles (MSNs) with internal fluorescent conjugates and external polydopamine and graphene oxide (GO) layers. The combination of internal conjugates and external coating layers produced an effective pore closure effect, leading to controlled and sustained release of small drug molecules. Notably, GO wrapping improved the dispensability and cellular uptake of the MSNs, as well as enhanced drug-controlled release. Our multifunctional MSNs revealed very efficient drug delivery effects against human epithelial neuroblastoma cells by demonstrating several strengths: i) fluorescent imaging, ii) sustained and controlled release of small drug molecules, iii) efficient cellular uptake, cytotoxicity and specificity, and v) stimuli (pH, NIR irradiation)-responsive controlled release as a potential chemo-photothermal agent.
Graphical abstract
https://ift.tt/2IGVqSg
Tackling bioactive glass excessive in vitro bioreactivity: Preconditioning approaches for cell culture tests
Publication date: Available online 21 May 2018
Source:Acta Biomaterialia
Author(s): Francesca E. Ciraldo, Elena Boccardi, Virginia Melli, Fabian Westhauser, Aldo R. Boccaccini
Bioactive glasses (BGs) are being increasingly considered for biomedical applications in bone and soft tissue replacement approaches thanks to their ability to form strong bonding with tissues. However, due to their high reactivity once in contact with water-based solutions BGs rapidly exchange ions with the surrounding environment leading in most cases to an undesired increase of the pH under static in vitro conditions (due to alkaline ion "burst release"), making difficult or even impossible to perform cell culture studies. Several pre-conditioning treatments have been therefore proposed in laboratories worldwide to limit this problem. This paper presents an overview of the different strategies that have been put forward to pre-treat BG samples to tackle the pH raise issue in order to enable cell biology studies. The paper also discusses the relevant criteria that determine the selection of the optimal pre-treatment depending on the BG composition and morphology (e.g. particles, scaffolds).Statement of SignificanceBioactive glasses (BGs), since their discovery in 1971 by L.L Hench, have been widely used for bone replacement and repair, and, more recently, they are becoming highly attractive for bone and soft tissue engineering applications. BGs have in fact the ability to form a strong bond with both hard and soft tissues once in contact with biological fluid. The enhanced interaction of BGs with the biological environment is based on their significant surface bioreactivity. This surface effect of BGs is, on the other hand, problematic for cell biology studies by standard (static) cell culture methods: an excessive bioreactivity leads in most cases to a rapid and dramatic increase of the pH of the surrounding medium, which results in cell death and makes cell culture tests on BG samples impossible. The BG research community has been aware of this for many years and numerous pre-treatments have been proposed by different groups worldwide to limit this problem. For the first time, we have reviewed in this paper the variety of surface preconditioning treatments that have been put forward over the years, we provide a summary of such pre-treatments used in laboratory practice, discussing and offering criteria that can be used for the determination of the optimal pre-treatment depending on BG composition and morphology of the sample tested (bulk, particulate, scaffolds). The information and discussion provided in this review should support best research practice when testing bioactive glasses in cell culture.
Graphical abstract
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NK Cells Mediate a Crucial Graft-versus-Leukemia Effect in Haploidentical-HSCT to Cure High-Risk Acute leukemia
Publication date: Available online 21 May 2018
Source:Trends in Immunology
Author(s): Franco Locatelli, Daniela Pende, Michela Falco, Mariella Della Chiesa, Alessandro Moretta, Lorenzo Moretta
Natural killer (NK) cells are involved in innate defenses against viruses and tumors. Their function is finely tuned by activating and inhibitory receptors. Among the latter, killer immunoglobulin-like receptors and CD94/NKG2A recognize human leukocyte antigen (HLA) Class I molecules, allowing NK cells to discriminate between normal and aberrant cells, as well as to recognize allogeneic cells, because of their ability to sense HLA polymorphisms. This latter phenomenon plays a key role in HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for high-risk acute leukemia patients transplanted from an NK-alloreactive donor. Different haplo-HSCT settings have been developed, either T depleted or T replete – the latter requiring graft-versus-host disease prophylaxis. A novel graft manipulation, based on depletion of αβ T cells and B cells, allows infusion of fully mature, including alloreactive, NK cells. The excellent patient clinical outcome underscores the importance of these innate cells in cancer therapy.
https://ift.tt/2IABDbj
Green certification, e-commerce, and low-carbon economy for international tourist hotels
Abstract
Increasing population and over-consumption are placing unprecedented demands on agriculture and natural resources. The Earth is suffering from global warning and environmental destruction while our agricultural systems are concurrently degrading land, water, biodiversity, and climate on a global scale. For a sustainable future, green certification, e-commerce, and environment education can boost low-carbon economy with decreasing carbon emissions, but very few researches address them for the hotel industry. This research studies the performance impact of e-commerce, international hotel chain, local hotel chain, and green certification for carbon emission reductions of international tourist hotels of Taiwan. It reveals that, after a sufficiently long time, there is an improvement in the environmental and economic performance of the green-certified hotel group. In addition, it reveals that, as recommended by the operation policy, the international hotel chain group together with e-commerce has better performance than local hotel chain. It is also discussed how to sustain the continuing improvement in low-carbon performance of the hotel industry.
https://ift.tt/2s3EIWp
Where did Roman masons get their material from? A preliminary DRIFTS/PCA investigation on mortar aggregates from X Regio buildings in the Veneto area (NE Italy) and their potential sources
Abstract
In this work, preliminary results are presented of an ongoing investigation aiming to identify the possible material sources employed by ancient Romans in their building activity in the X Regio, the European region corresponding to present north-eastern Italy and Istria (Croatia and Slovenia). The 63–420 μm fraction of the aggregate component recovered from eleven mortar fragments of buildings located in the Veneto area (in or close to Lio Piccolo, Vicenza, and Padua) is studied by diffuse reflection infrared Fourier transform spectroscopy and compared through principal component analysis to samples collected from local potential sources of raw materials. In this regard, the investigated samples from Lio Piccolo present a distinctive complexity, being this site located within the Venice lagoon, an area that has since been undergoing dramatic changes both due to natural and anthropic causes. The Vicenza and Padua sites were considered for comparison sake because they are or were located close to two rivers, the Bacchiglione and the Brenta, that in ancient times flowed into the Venice lagoon. As expected, from the exploratory investigation reported here, no firm conclusions can be obtained for the mortar samples collected in Lio Piccolo, whereas the likely provenance of the aggregate component of the samples from Vicenza and Padova from the Bacchiglione and the Brenta riverbeds, respectively, is confirmed.
https://ift.tt/2kd8HaL
Ameloblastoma with adenoid features: A series of eight cases
Publication date: Available online 21 May 2018
Source:Acta Histochemica
Author(s): Daniela Adorno-Farias, Vinícius Rio Verde Melo Muniz, Amanda Pinheiro Soares, Patrícia Ramos Cury, Rosângela Góes Rabelo, Ricardo Fernández-Ramires, Roberto Almeida de Azevedo, Jean Nunes dos Santos
BackgroundAmeloblastoma with adenoid features are characterized by the presence of duct-like structures formed from the parenchyma of the tumor. This study was conducted to report a series of eight ameloblastomas with adenoid features, highlighting their clinicopathological and immunohistochemical aspects.Material and MethodsOut of 71 cases of ameloblastomas, this study classified 8 cases as ameloblastomas with adenoid features. Clinicopathological data and immunohistochemistry for CK7, CK14, CK19, IMP3, p53 and Ki-67 were evaluated.ResultsFrom those cases of ameloblastoma exhibiting adenoid features, there were 4 women and 4 men, with mean age of 39 years. Most cases affected the mandible and all presented radiographically as a radiolucency. The predominant histopathological features were pseudoducts, squamous metaplasia, nuclear hyperchromatism, clear cells, whorled aspect of epithelial structures, cribriform growth pattern, proliferation of spindle cells and extracellular eosinophilic material. Immunohistochemical analysis showed high expression for CK14 (n = 6) and CK19 (n = 3) and all cases (n = 8) were negative for p53, IMP3 and CK7. In addition, all samples (n = 8) showed low expression for Ki-67.ConclusionsThe similarities between the histopathological and immunohistochemical features of eight cases described in the present study and those described in previous studies support the possibility that these lesions are adenoid ameloblastomas. In addition, the immunohistochemical results of CK14, CK19, p53 and Ki-67 did not differ from those of conventional ameloblastomas.
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Selection of inactivation medium for fungal spores in clinical wastes by supercritical carbon dioxide
Abstract
The present study aimed to select the best medium for inactivation of Aspergillus fumigatus, Aspergillus spp. in section Nigri, A. niger, A. terreus var. terreus, A. tubingensis, Penicillium waksmanii, P. simplicissimum, and Aspergillus sp. strain no. 145 spores in clinical wastes by using supercritical carbon dioxide (SC-CO2). There were three types of solutions used including normal saline, seawater, distilled water, and physiological saline with 1% of methanol; each solution was tested at 5, 10, and 20 mL of the water contents. The experiments were conducted at the optimum operating parameters of supercritical carbon dioxide (30 MPa, 75 °C, 90 min). The results showed that the inactivation rate was more effective in distilled water with the presence of 1% methanol (6 log reductions). Meanwhile, the seawater decreases inactivation rate more than normal saline (4.5 vs. 5.1 log reduction). On the other hand, the experiments performed with different volumes of distilled water (5, 10, and 20 mL) indicated that A. niger spores were completely inactivated with 10 mL of distilled water. The inactivation rate of fungal spores decreased from 6 to 4.5 log as the amount of distilled water increased from 10 to 20 mL. The analysis for the spore morphology of A. fumigatus and Aspergillus spp. in section Nigri using scanning electron microscopy (SEM) has revealed the role of temperature and pressure in the SC-CO2 in the destruction of the cell walls of the spores. It can be concluded that the distilled water represent the best medium for inactivation of fungal spores in the clinical solid wastes by SC-CO2.
https://ift.tt/2x6IdkK
Electrocortical reactivity to negative and positive facial expressions in individuals with a family history of major depression
Publication date: Available online 21 May 2018
Source:Biological Psychology
Author(s): Anna J. Watters, Anthony W.F. Harris, Leanne M. Williams
Facial expressions signaling threat and mood-congruent loss have been used to probe abnormal neural reactivity in major depressive disorder (MDD) and may be implicated in genetic vulnerability to MDD. This study investigated electro-cortical reactivity to facial expressions 101 unaffected, adult first degree relatives of probands with MDD and non-relative controls (n = 101). We investigated event-related potentials (ERPs) to five facial expressions of basic emotion: fear, anger, disgust, sadness and happiness under both subliminal (masked) and conscious (unmasked) presentation conditions, and the source localization of group differences. In the conscious condition, controls showed a distinctly positive-going shift in responsive to negative versus happy faces, reflected in a greater positivity for the VPP frontally and the P300 parietally, and less negativity for the N200. By contrast, relatives showed less differentiation of emotions, reflected in less VPP and P300 positivity, particularly for anger and disgust, and which produced an enhanced N200 for sadness. These group differences were consistently source localized to the anterior cingulate cortex. The findings contribute new evidence for neural disruptions underlying the differentiation of salient emotions in familial risk for depression. These disruptions occur in the appraisal (∼200 ms post-stimulus) through to the context evaluation (∼300 ms+ post-stimulus) phases of of emotion processing, consistent with theories that risk for depression involves biased or attenuated processing of emotion.
https://ift.tt/2Lj9ZgE
Acute effects of caffeine on threat-selective attention: Moderation by anxiety and EEG theta/beta ratio
Publication date: Available online 21 May 2018
Source:Biological Psychology
Author(s): Dana van Son, Rik Schalbroeck, Angelos Angelidis, Nic van der Wee, Willem van der Does, Peter Putman
BackgroundSpontaneous EEG theta/beta ratio (TBR) probably marks prefrontal cortical (PFC) executive control, and its regulation of attentional threat-bias. Caffeine at moderate doses may strengthen executive control through increased PFC catecholamine action, dependent on basal PFC function.GoalTo test if caffeine affects threat-bias, moderated by baseline frontal TBR and trait-anxiety.MethodsA pictorial emotional Stroop task was used to assess threat-bias in forty female participants in a cross-over, double-blind study after placebo and 200 mg caffeine.ResultsAt baseline and after placebo, comparable relations were observed for negative pictures: high TBR was related to low threat-bias in low trait-anxious people. Caffeine had opposite effects on threat-bias in low trait-anxious people with low and high TBR.ConclusionsThis further supports TBR as a marker of executive control and highlights the importance of taking baseline executive function into consideration when studying effects of caffeineon executive functions.
https://ift.tt/2IB6NuZ
A retrospective cohort study: do patients with graves’ disease need to be euthyroid prior to surgery?
The 2016 American Thyroid Association guidelines indicate that patients with Graves' disease who undergo a thyroidectomy should be rendered euthyroid through the use of antithyroid drugs (ATD) prior to surgery...
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Characteristics of laryngopharyngeal reflux in patients with chronic otitis media
To summarize the characteristics of laryngopharyngeal reflux (LPR) in patients with chronic otitis media.
https://ift.tt/2KLyFO2
Association of ibuprofen use with post-tonsillectomy bleeding in older children
Evaluate post-tonsillectomy outcomes in children discharged with ibuprofen versus those without.
https://ift.tt/2IXo312
Trace and macro elements in the femoral bone as indicators of long-term environmental exposure to toxic metals in European brown bear ( Ursus arctos ) from Croatia
Abstract
We explored the long-term accumulation of aluminium, strontium, cadmium and lead in the compact and trabecular bone of the femoral epiphysis, metaphysis and diaphysis in 41 brown bears (Ursus arctos) from Croatia. Also, we assessed their influence on macro and trace elements (sodium, magnesium, phosphorus, potassium, calcium, manganese, iron, cobalt, copper, zinc and barium) in bears' bone. There were no sex differences in element levels in general, while age was associated with bone length and levels of all elements, except for cadmium. Elements had different levels depending on the part of the bone sampled. More pronounced differences were observed between the compact and trabecular regions, with higher levels of majority of elements found in compact bone. Moderate to high associations (Spearman coefficient, rS = 0.59–0.97) were confirmed between calcium and potassium, magnesium, phosphorus, manganese, cobalt, zinc, strontium and lead. Lead levels in the bone were below those known to cause adverse health effects, but in 4 of 41 animals they exceeded baseline levels for domestic animals. The femoral bone of the brown bear reflected the accumulative nature of lead and strontium well, as it did the impairment of bone-forming essential element levels associated with these two elements. However, the distribution pattern of elements along the bone was not uniform, so additional care should be taken when choosing on the part of the bone sampled.
https://ift.tt/2rXAC2D
Cadmium phytoextraction potential of king grass ( Pennisetum sinese Roxb.) and responses of rhizosphere bacterial communities to a cadmium pollution gradient
Abstract
Screening for tolerant and high biomass producing plants is important for phytoextraction efforts in remediating agricultural soils contaminated by heavy metals. We carried out a greenhouse experiment involving a soil cadmium (Cd) concentration gradient (0.1, 0.5, 1, 2, 4, and 8 mg kg−1) to assess growth and phytoextraction capacity of king grass (Pennisetum sinese Roxb.) in soils contaminated by Cd and to explore changes in diversity and structure of rhizosphere soil bacterial communities in response to long-term Cd pollution. A significant positive relationship was observed between Cd concentrations in P. sinese stems, leaves, and roots and soil Cd concentration. The highest Cd concentrations in shoots and roots were 28.87 and 34.01 mg kg−1, respectively, at 8 mg kg−1of soil Cd supply. Total extraction amounts of Cd in P. sinese were 0.22–1.86 mg plant−1 corresponding to treatment with 0.5–8 mg kg−1 Cd. Most of the Cd was stored in shoots, and the largest accumulation was 1.56 mg plant−1 with 54.02 g dry shoot weight. After phytoextraction, changes in rhizobacterial community composition were found with different levels of Cd application, whereas there were no clear trends in diversity and richness. Results of this study show the feasibility of P. sinese in accumulating Cd and provide support for its application in remediation of soil moderately contaminated by Cd.
https://ift.tt/2KKkloC
Dermatofibrosarcoma Protuberans: A Retrospective Study of Clinicopathological Features and Related Akt/mTOR, STAT3, ERK, Cyclin D1, and PD-L1 Expression
In dermatofibrosarcoma protuberans, fibrosarcomatous subtype and inadequate surgical margin portend aggressive behavior. Complex factors of frequent local recurrence, larger tumor size, deeper invasion, fibrosarcomatous or myxoid subtype, and cyclin D1 high expression appear to predict worse outcome. Patients with dermatofibrosarcoma protuberans exhibiting any risk factor should be followed up comprehensively.
https://ift.tt/2IBGzNd
“Survey of Wellbeing of Young Children (SWYC)”: how does it fit for screening developmental delay in Brazilian children aged 4 to 58 months?
Publication date: July 2018
Source:Research in Developmental Disabilities, Volume 78
Author(s): R.S. Moreira, L.C. Magalhães, C.M. Siqueira, C.R.L. Alves
ObjectiveTo replicate the original normative study of the SWYC's Milestones Questionnaires for children in Brazil. Our goals were to compare the performance of Brazilian and North American children using this screening tool and to verify the reliability and validity of the Brazilian version.Study design and settingCross-sectional study with children aged 1–65 months and their guardians, recruited in southern Brazil. Parents were interviewed using the Developmental Milestones questionnaire, which contains 10 questions about cognitive, motor, social, and language abilities. Item response theory was used to examine item validity.ResultsWe interviewed 415 parents. SWYC provided the most information on the children's development between 10 and 30 months. The performance of Brazilian and North American children was quite similar when children are younger than 36 months old. Above 36 months, North American children performed almost all items earlier than Brazilians. Convergent validity was 0.73 and internal consistency 0.97.ConclusionThe Brazilian version of the Developmental Milestones questionnaire presented acceptable measurement qualities that support the SWYĆs potential as a developmental screening tool. As we found important differences between North American and Brazilian children in achieving the milestones, especially among the oldest children, additional normative studies are needed.
https://ift.tt/2IGwfzh
The influence of early intervention, informal support and the family environment on trajectories of competence for fathers raising children with developmental disabilities
Publication date: Available online 21 May 2018
Source:Research in Developmental Disabilities
Author(s): Morgan K. Crossman, Susan L. Parish, Penny Hauser-Cram, Dolores Acevedo Garcia, Marji Erickson Warfield
BackgroundScant research disentangles the relationship between parenting competence, early intervention (EI) services, the family environment and informal support among fathers of children with developmental disabilities.Aims(1) To determine the trajectory of parental competence for fathers of children with DD from age 3 to age 15. (2) Controlling for child and family characteristics, determine the main effects of the family environment, informal support, and EI services on paternal competence when their child with a developmental disability was age 3. (3) To determine whether there were lasting effects of the family environment, informal support, and the EI service system on differences in paternal competence over time.MethodsThis study used multilevel modeling to analyze longitudinal data from 93 American fathers from the Early Intervention Collaborative Study.ResultsThere was no significant change over time in paternal competence after controlling for various covariates. Fathers who initially reported low levels of competence when their child was three reported continuously lower competence over time. Family relationships, positive supports, and perceived helpfulness of home visits were significant predictors of paternal competence at age three.ConclusionImplications for programs and policy include developing and adopting rigorous ways to measure and carefully monitor service provision, including assessments of paternal competence, family relationships and informal supports at the start of early intervention, and fostering continuous collaborations between providers, researchers and clinicians to address challenges in data collection.
https://ift.tt/2LiZ5rl
Lysosomal Protein Lamtor1 Controls Innate Immune Responses via Nuclear Translocation of Transcription Factor EB [INNATE IMMUNITY AND INFLAMMATION]
Amino acid metabolism plays important roles in innate immune cells, including macrophages. Recently, we reported that a lysosomal adaptor protein, Lamtor1, which serves as the scaffold for amino acid–activated mechanistic target of rapamycin complex 1 (mTORC1), is critical for the polarization of M2 macrophages. However, little is known about how Lamtor1 affects the inflammatory responses that are triggered by the stimuli for TLRs. In this article, we show that Lamtor1 controls innate immune responses by regulating the phosphorylation and nuclear translocation of transcription factor EB (TFEB), which has been known as the master regulator for lysosome and autophagosome biogenesis. Furthermore, we show that nuclear translocation of TFEB occurs in alveolar macrophages of myeloid-specific Lamtor1 conditional knockout mice and that these mice are hypersensitive to intratracheal administration of LPS and bleomycin. Our observation clarified that the amino acid–sensing pathway consisting of Lamtor1, mTORC1, and TFEB is involved in the regulation of innate immune responses.
https://ift.tt/2IxjPhc
The Respiratory Environment Diverts the Development of Antiviral Memory CD8 T Cells [INFECTIOUS DISEASE AND HOST RESPONSE]
Our understanding of memory CD8+ T cells has been largely derived from acute, systemic infection models. However, memory CD8+ T cells generated from mucosal infection exhibit unique properties and, following respiratory infection, are not maintained in the lung long term. To better understand how infection route modifies memory differentiation, we compared murine CD8+ T cell responses to a vesicular stomatitis virus (VSV) challenge generated intranasally (i.n.) or i.v. The i.n. infection resulted in greater peak expansion of VSV-specific CD8+ T cells. However, this numerical advantage was rapidly lost during the contraction phase of the immune response, resulting in memory CD8+ T cell numerical deficiencies when compared with i.v. infection. Interestingly, the antiviral CD8+ T cells generated in response to i.n. VSV exhibited a biased and sustained proportion of early effector cells (CD127loKLRG1lo) akin to the developmental program favored after i.n. influenza infection, suggesting that respiratory infection broadly favors an incomplete memory differentiation program. Correspondingly, i.n. VSV infection resulted in lower CD122 expression and eomesodermin levels by VSV-specific CD8+ T cells, further indicative of an inferior transition to bona fide memory. These results may be due to distinct (CD103+CD11b+) dendritic cell subsets in the i.n. versus i.v. T cell priming environments, which express molecules that regulate T cell signaling and the balance between tolerance and immunity. Therefore, we propose that distinct immunization routes modulate both the quality and quantity of antiviral effector and memory CD8+ T cells in response to an identical pathogen and should be considered in CD8+ T cell–based vaccine design.
https://ift.tt/2kgh31o
Farnesyltransferase Inhibition Exacerbates Eosinophilic Inflammation and Airway Hyperreactivity in Mice with Experimental Asthma: The Complex Roles of Ras GTPase and Farnesylpyrophosphate in Type 2 Allergic Inflammation [MUCOSAL IMMUNOLOGY]
Ras, a small GTPase protein, is thought to mediate Th2-dependent eosinophilic inflammation in asthma. Ras requires cell membrane association for its biological activity, and this requires the posttranslational modification of Ras with an isoprenyl group by farnesyltransferase (FTase) or geranylgeranyltransferase (GGTase). We hypothesized that inhibition of FTase using FTase inhibitor (FTI)–277 would attenuate allergic asthma by depleting membrane-associated Ras. We used the OVA mouse model of allergic inflammation and human airway epithelial (HBE1) cells to determine the role of FTase in inflammatory cell recruitment. BALB/c mice were first sensitized then exposed to 1% OVA aerosol or filtered air, and half were injected daily with FTI-277 (20 mg/kg per day). Treatment of mice with FTI-277 had no significant effect on lung membrane–anchored Ras, Ras protein levels, or Ras GTPase activity. In OVA-exposed mice, FTI-277 treatment increased eosinophilic inflammation, goblet cell hyperplasia, and airway hyperreactivity. Human bronchial epithelial (HBE1) cells were pretreated with 5, 10, or 20 μM FTI-277 prior to and during 12 h IL-13 (20 ng/ml) stimulation. In HBE1 cells, FTase inhibition with FTI-277 had no significant effect on IL-13–induced STAT6 phosphorylation, eotaxin-3 peptide secretion, or Ras translocation. However, addition of exogenous FPP unexpectedly augmented IL-13–induced STAT6 phosphorylation and eotaxin-3 secretion from HBE1 cells without affecting Ras translocation. Pharmacological inhibition of FTase exacerbates allergic asthma, suggesting a protective role for FTase or possibly Ras farnesylation. FPP synergistically augments epithelial eotaxin-3 secretion, indicating a novel Ras-independent farnesylation mechanism or direct FPP effect that promotes epithelial eotaxin-3 production in allergic asthma.
https://ift.tt/2IDW4o1
Deletion of Inflammasome Components Is Not Sufficient To Prevent Fatal Inflammation in Models of Familial Hemophagocytic Lymphohistiocytosis [INNATE IMMUNITY AND INFLAMMATION]
Hemophagocytic lymphohistiocytosis (HLH) is a severe inflammatory condition that occurs in patients with genetic defects of cytotoxicity (familial HLH [FHL]) or secondary to other immunological disorders such as juvenile idiopathic arthritis. HLH is characterized by elevated levels of serum IL-18 and other cytokines. Moreover, a novel clinical entity has been recently identified in which constitutive NLRC4 inflammasome activation leads to severe HLH. Altogether, these clinical observations suggest that inflammasome activation is a central event in the development of all HLH forms and that inflammasome blockade could alleviate inflammation in FHL patients. To formally address this question, we invalidated genes encoding for Caspase-1 or the inflammasome adapter ASC in perforin-deficient mice that were subsequently infected with lymphocytic or mouse choriomeningitis virus as models of FHL. These deletions nearly abrogated IL-18 production occurring during HLH in all models. However, they did not reduce serum IFN- levels at the peak of the inflammatory reaction nor did they modulate inflammatory parameters at mid and late stages or fatal outcome. These data show that inflammasome blockade is not sufficient to prevent cytokine storm and lethality in mouse models of FHL and suggest that different pathophysiological mechanisms underlie HLH in genetic defects of cytotoxicity and genetic forms of inflammasome activation.
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Links between Immunologic Memory and Metabolic Cycling [BRIEF REVIEWS]
Treatments for metabolic diseases, such as diet and therapeutics, often provide short-term therapy for metabolic stressors, but relapse is common. Repeated bouts of exposure to, and relief from, metabolic stimuli results in a phenomenon we call "metabolic cycling." Recent human and rodent data suggest metabolic cycling promotes an exaggerated response and ultimately worsened metabolic health. This is particularly evident with cycling of body weight and hypertension. The innate and adaptive immune systems have a profound impact on development of metabolic disease, and current data suggest that immunologic memory may partially explain this association, especially in the context of metabolic cycling. In this Brief Review, we highlight recent work in this field and discuss potential immunologic mechanisms for worsened disease prognosis in individuals who experience metabolic cycling.
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Hu Antigen R Regulates Antiviral Innate Immune Responses through the Stabilization of mRNA for Polo-like Kinase 2 [INNATE IMMUNITY AND INFLAMMATION]
Retinoic acid–inducible gene I (RIG-I)–like receptors (RLRs), RIG-I, and melanoma differentiation-associated gene 5 (MDA5) play a critical role in inducing antiviral innate immune responses by activating IFN regulatory factor 3 (IRF3) and NF-B, which regulates the transcription of type I IFN and inflammatory cytokines. Antiviral innate immune responses are also regulated by posttranscriptional and translational mechanisms. In this study, we identified an RNA-binding protein HuR as a regulator for RLR signaling. Overexpression of HuR, but not of other Hu members, increased IFN-β promoter activity. HuR-deficient macrophage cells exhibited decreased Ifnb1 expression after RLR stimulation, whereas they showed normal induction after stimulation with bacterial LPS or immunostimulatory DNA. Moreover, HuR-deficient cells displayed impaired nuclear translocation of IRF3 after RLR stimulation. In HuR-deficient cells, the mRNA expression of Polo-like kinase (PLK) 2 was markedly reduced. We found that HuR bound to the 3' untranslated region of Plk2 mRNA and increased its stabilization. PLK2-deficient cells also showed reduced IRF3 nuclear translocation and Ifnb mRNA expression during RLR signaling. Together, these findings suggest that HuR bolsters RLR-mediated IRF3 nuclear translocation by controlling the stability of Plk2 mRNA.
https://ift.tt/2kggWTw
Cutting Edge: Identification of Marginal Reticular Cells as Phagocytes of Apoptotic B Cells in Germinal Centers [CUTTING EDGE]
Germinal centers (GCs) in secondary lymphoid organs generate large numbers of apoptotic B cells that must be eliminated by phagocytes to prevent the development of autoimmune diseases. Although tingible body macrophages engulf apoptotic GC B cells, whether stromal cells are also involved in this process is unclear. In this study, we identified marginal reticular cells (MRCs) as novel nonprofessional phagocytes for the clearance of apoptotic GC B cells in the spleen. We used CD19eGFP (CD19creZ/EG) mice, which express enhanced GFP (eGFP) under the control of CD19cre expression, to track B cells in the GCs after immunization with NP-chicken globulin plus aluminum salt. We demonstrated that the MRC population, as determined by expression of podoplanin or Rankl, specifically showed an eGFP signal in the cytoplasm after immunization. These results suggest that MRCs contribute to the clearance of apoptotic B cells in GCs.
https://ift.tt/2IzUHXo
Vasoactive Intestinal Peptide Ameliorates Acute Myocarditis and Atherosclerosis by Regulating Inflammatory and Autoimmune Responses [AUTOIMMUNITY]
Vasoactive intestinal peptide (VIP) is a neuropeptide that exerts various vascular and cardioprotective functions and regulates immune function and inflammatory response at multiple levels. However, its role in inflammatory cardiovascular disorders is largely unknown. Myocarditis and atherosclerosis are two inflammatory and autoimmune cardiovascular diseases that cause important adverse circulatory events. In this study, we investigate the therapeutic effects of VIP in various well-established preclinical models of experimental autoimmune myocarditis and atherosclerosis. Intraperitoneal injection of VIP during the effector phase of experimental autoimmune myocarditis in susceptible BALB/c mice significantly reduced its prevalence, ameliorated signs of heart hypertrophy and injury, attenuated myocardial inflammatory infiltration, and avoided subsequent profibrotic cardiac remodeling. This effect was accompanied by a reduction of Th17-driven cardiomyogenic responses in peripheral lymphoid organs and in the levels of myocardial autoantibodies. In contrast, acute and chronic atherosclerosis was induced in apolipoprotein E–deficient mice fed a hyperlipidemic diet and subjected to partial carotid ligation. Systemic VIP treatment reduced the number and size of atherosclerotic plaques in carotid, aorta, and sinus in hypercholesterolemic mice. VIP reduced Th1-driven inflammatory responses and increased regulatory T cells in atherosclerotic arteries and their draining lymph nodes. VIP also regulated cholesterol efflux in macrophages and reduced the formation of foam cells and their presence in atherosclerotic plaques. Finally, VIP inhibited proliferation and migration of smooth muscle cells and neointima formation in a mouse model of complete carotid ligation. These findings encourage further studies aimed to assess whether VIP can be used as a pharmaceutical agent to treat heart inflammation and atherosclerosis.
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NKp46 Calibrates Tumoricidal Potential of Type 1 Innate Lymphocytes by Regulating TRAIL Expression [INNATE IMMUNITY AND INFLAMMATION]
NK cells are a subset of group 1 innate lymphocytes that recognize and eliminate virus-infected and transformed cells. During the course of their development, NK cells acquire a repertoire of activating and inhibitory receptors, which ultimately define their reactivity against target cells. The array of receptors and their specificity during early developmental stages will control and imprint functional properties of NK cells, a process known as "NK cell education." Innate lymphoid cells (ILCs) are a diverse group of lymphocytes, which, like NK cells, do not rely on somatically rearranged Ag receptors for recognition. Among ILC subsets, ILC1s are most like NK cells functionally. Prototypic ILC1s reside in the liver, and a large part of their function is attributed to the expression of TRAIL, a TNF superfamily member with a well-documented antitumor activity. In this article, we show that TRAIL expression on mouse ILC1s is controlled by an activating receptor NKp46, which has been previously shown to control NK cell education. In the absence of NKp46, ILC1s fail to express normal levels of TRAIL on the surface, which results in diminished cytotoxicity toward TRAIL receptor-positive targets. To our knowledge, these findings provide the first evidence of a role of NKp46 in ILC1s that calibrates their antitumor response.
https://ift.tt/2s2HXgL
PD-L1/B7-H1 Inhibits Viral Clearance by Macrophages in HSV-1-Infected Corneas [IMMUNE REGULATION]
Immune privilege helps protect the cornea from damaging inflammation but can also impair pathogen clearance from this mucosal surface. Programmed death-ligand 1 (PD-L1 or B7-H1) contributes to corneal immune privilege by inhibiting the function of a variety of immune cells. We asked whether programmed death-1 (PD-1)/PD-L1 interaction regulates HSV-1 clearance from infected corneas. We show that PD-L1 is constitutively expressed in the corneal epithelium and is upregulated upon HSV-1 corneal infection, with peak expression on CD45+ cells NK cells, dendritic cells, neutrophils, and macrophages and CD45– corneal epithelial cells at 4 d postinfection (dpi). As early as 1 dpi, HSV-1–infected corneas of B7-H1–/– mice as compared with wild-type mice showed increased chemokine expression and this correlated with increased migration of inflammatory cells into the viral lesions and decreased HSV-1 corneal titers. Local PD-L1 blockade caused a similar increase in viral clearance, suggesting a local effect of PD-1/PD-L1 in the cornea. The enhanced HSV-1 clearance at 2 dpi resulting from PD-1/PD-L1 blockade is mediated primarily by a monocyte/macrophage population. Studies in bone marrow chimeras demonstrated enhanced viral clearance when PD-L1 was absent only from nonhematopoietic cells. We conclude that PD-L1 expression on corneal cells negatively impacts the ability of the innate immune system to clear HSV-1 from infected corneas.
https://ift.tt/2IzATDe
The TLR4 Agonist Monophosphoryl Lipid A Drives Broad Resistance to Infection via Dynamic Reprogramming of Macrophage Metabolism [INNATE IMMUNITY AND INFLAMMATION]
Monophosphoryl lipid A (MPLA) is a clinically used TLR4 agonist that has been found to drive nonspecific resistance to infection for up to 2 wk. However, the molecular mechanisms conferring protection are not well understood. In this study, we found that MPLA prompts resistance to infection, in part, by inducing a sustained and dynamic metabolic program in macrophages that supports improved pathogen clearance. Mice treated with MPLA had enhanced resistance to infection with Staphylococcus aureus and Candida albicans that was associated with augmented microbial clearance and organ protection. Tissue macrophages, which exhibited augmented phagocytosis and respiratory burst after MPLA treatment, were required for the beneficial effects of MPLA. Further analysis of the macrophage phenotype revealed that early TLR4-driven aerobic glycolysis was later coupled with mitochondrial biogenesis, enhanced malate shuttling, and increased mitochondrial ATP production. This metabolic program was initiated by overlapping and redundant contributions of MyD88- and TRIF-dependent signaling pathways as well as downstream mTOR activation. Blockade of mTOR signaling inhibited the development of the metabolic and functional macrophage phenotype and ablated MPLA-induced resistance to infection in vivo. Our findings reveal that MPLA drives macrophage metabolic reprogramming that evolves over a period of days to support a macrophage phenotype highly effective at mediating microbe clearance and that this results in nonspecific resistance to infection.
https://ift.tt/2rYeXqc
Identification of a Transcriptionally Forward {alpha} Gene and Two {upsilon} Genes within the Pigeon (Columba livia) IgH Gene Locus [IMMUNOGENETICS]
Compared with mammals, the bird Ig genetic system relies on gene conversion to create an Ab repertoire, with inversion of the IgA-encoding gene and very few cases of Ig subclass diversification. Although gene conversion has been studied intensively, class-switch recombination, a mechanism by which the IgH C region is exchanged, has rarely been investigated in birds. In this study, based on the published genome of pigeon (Columba livia) and high-throughput transcriptome sequencing of immune-related tissues, we identified a transcriptionally forward α gene and found that the pigeon IgH gene locus is arranged as μ-α-1-2. In this article, we show that both DNA deletion and inversion may result from IgA and IgY class switching, and similar junction patterns were observed for both types of class-switch recombination. We also identified two subclasses of genes in pigeon, which share low sequence identity. Phylogenetic analysis suggests that divergence of the two pigeon genes occurred during the early stage of bird evolution. The data obtained in this study provide new insight into class-switch recombination and Ig gene evolution in birds.
https://ift.tt/2GChax9
Synthesis of Human Neutrophil Extracellular Traps Contributes to Angiopoietin-Mediated In Vitro Proinflammatory and Proangiogenic Activities [INNATE IMMUNITY AND INFLAMMATION]
Neutrophil extracellular traps (NETs) are composed of nuclear DNA in a web-like structure extruded from neutrophils in response to either bacterial infection or inflammation. We previously reported the expression of angiopoietin Tie2 receptor on human neutrophils and the capacity of both angiopoietins (Ang1 and Ang2) to induce proinflammatory activities, such as synthesis and release of platelet-activating factor, upregulation of β2 integrin complex (CD11/CD18), and neutrophil chemotaxis. In contrast, only Ang1 but not Ang2 is capable of promoting translational and transcriptional activities in neutrophils. In this article, we addressed whether Ang1 and/or Ang2 could modulate the release of NETs and if they contribute to angiopoietin-mediated proinflammatory activities. We observed that Ang1 and Ang2, alone or combined (10 nM, 3 h), increase NET synthesis and release by 2.5-fold as compared with PBS-treated neutrophils. The release of NETs is Tie2 dependent and requires downstream intracellular participation of PI3K, p38, and p42/44 MAPK pathways; reactive oxygen species production; intracellular calcium store depletion; and protein arginine deiminase 4 activation. These isolated NETs induced neutrophil and endothelial cell activation, leading to neutrophil adhesion onto human extracellular matrix and HUVEC and in vitro formation of capillary-like tubes by endothelial cells. Our study reports the capacity of Ang1 and Ang2 to promote the release of NETs and that these NETs contribute to angiopoietin-mediated in vitro proinflammatory and proangiogenic activities.
https://ift.tt/2s3oQmN
Cyclooxygenase-1 and -2 Play Contrasting Roles in Listeria-Stimulated Immunity [IMMUNOTHERAPY AND VACCINES]
Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) activity and are commonly used for pain relief and fever reduction. NSAIDs are used following childhood vaccinations and cancer immunotherapies; however, how NSAIDs influence the development of immunity following these therapies is unknown. We hypothesized that NSAIDs would modulate the development of an immune response to Listeria monocytogenes–based immunotherapy. Treatment of mice with the nonspecific COX inhibitor indomethacin impaired the generation of cell-mediated immunity. This phenotype was due to inhibition of the inducible COX-2 enzyme, as treatment with the COX-2–selective inhibitor celecoxib similarly inhibited the development of immunity. In contrast, loss of COX-1 activity improved immunity to L. monocytogenes. Impairments in immunity were independent of bacterial burden, dendritic cell costimulation, or innate immune cell infiltrate. Instead, we observed that PGE2 production following L. monocytogenes is critical for the formation of an Ag-specific CD8+ T cell response. Use of the alternative analgesic acetaminophen did not impair immunity. Taken together, our results suggest that COX-2 is necessary for optimal CD8+ T cell responses to L. monocytogenes, whereas COX-1 is detrimental. Use of pharmacotherapies that spare COX-2 activity and the production of PGE2 like acetaminophen will be critical for the generation of optimal antitumor responses using L. monocytogenes.
https://ift.tt/2kf70ty
Mapping Interaction Sites on Human Chemokine Receptors by Deep Mutational Scanning [MOLECULAR AND STRUCTURAL IMMUNOLOGY]
Chemokine receptors CXCR4 and CCR5 regulate WBC trafficking and are engaged by the HIV-1 envelope glycoprotein gp120 during infection. We combine a selection of human CXCR4 and CCR5 libraries comprising nearly all of ~7000 single amino acid substitutions with deep sequencing to define sequence-activity landscapes for surface expression and ligand interactions. After consideration of sequence constraints for surface expression, known interaction sites with HIV-1–blocking Abs were appropriately identified as conserved residues following library sorting for Ab binding, validating the use of deep mutational scanning to map functional interaction sites in G protein–coupled receptors. Chemokine CXCL12 was found to interact with residues extending asymmetrically into the CXCR4 ligand-binding cavity, similar to the binding surface of CXCR4 recognized by an antagonistic viral chemokine previously observed crystallographically. CXCR4 mutations distal from the chemokine binding site were identified that enhance chemokine recognition. This included disruptive mutations in the G protein–coupling site that diminished calcium mobilization, as well as conservative mutations to a membrane-exposed site (CXCR4 residues H792.45 and W1614.50) that increased ligand binding without loss of signaling. Compared with CXCR4–CXCL12 interactions, CCR5 residues conserved for gp120 (HIV-1 BaL strain) interactions map to a more expansive surface, mimicking how the cognate chemokine CCL5 makes contacts across the entire CCR5 binding cavity. Acidic substitutions in the CCR5 N terminus and extracellular loops enhanced gp120 binding. This study demonstrates how comprehensive mutational scanning can define functional interaction sites on receptors, and novel mutations that enhance receptor activities can be found simultaneously.
https://ift.tt/2s7IBK3
Nasopharyngeal Exposure to Streptococcus pneumoniae Induces Extended Age-Dependent Protection against Pulmonary Infection Mediated by Antibodies and CD138+ Cells [INFECTIOUS DISEASE AND HOST RESPONSE]
Streptococcus pneumoniae commonly resides asymptomatically in the nasopharyngeal (NP) cavity of healthy individuals but can cause life-threatening pulmonary and systemic infections, particularly in the elderly. NP colonization results in a robust immune response that protects against invasive infections. However, the duration, mechanism, and cellular component of such responses are poorly understood. In this study, we found that repeated NP exposure of mice to S. pneumoniae TIGR4 strain results in pneumococcal-specific Ab responses that protect against lethal lung challenge. Abs were necessary and sufficient for protection because Ab-deficient μMT mice did not develop postexposure protection, only becoming resistant to lung infection after transfer of immune sera from NP-exposed mice. T cells contributed to immunity at the time of NP exposure, but neither CD4+ nor CD8+ T cells were required. The protective activity was detectable 20 wk after exposure and was maintained in irradiated mice, suggesting involvement of long-lived Ab-secreting cells (ASC), which are radioresistant and secrete Abs for extended periods of time in the absence of T cells or persistent Ag. CD138+ bone marrow cells, likely corresponding to long-lived ASC, were sufficient to confer protection. NP exposure of aged mice failed to protect against subsequent lung infection despite eliciting a robust Ab response. Furthermore, transfer of CD138+ bone marrow cells or sera from NP-exposed old mice failed to protect naive young mice. These findings suggest that NP exposure elicits extended protection against pneumococcal lung infection by generating long-lived CD138+ ASC and that the protective efficacy of these responses declines with age.
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Development of Dengue Virus Serotype-Specific NS1 Capture Assays for the Rapid and Highly Sensitive Identification of the Infecting Serotype in Human Sera [NOVEL IMMUNOLOGICAL METHODS]
Dengue fever can be caused by one of four distinct dengue virus (DENV) serotypes that cocirculate in many parts of the world. Point of care serotype-specific nonstructural protein-1 (NS1) capture assays for the rapid serotyping of DENV in human sera would greatly support epidemiological surveillance and potentially also prognosis in individual patients. To ensure both serotype specificity and broad coverage of variants within serotypes, we have applied an innovative approach for the generation and selection of serotype-specific anti-NS1 mAbs. To elicit mAbs against conformational epitopes, NMRI mice were immunized with living HEK 293 transfectants expressing the native target Ags in multiple display on the cell surface. For each serotype, three different NS1 sequence variants were sequentially used for immunization of mice, hybridoma selection, and capture assay development, respectively. Selection of optimal combinations of capturing and detecting mAbs yielded highly sensitive and specific NS1 serotyping ELISAs (st-ELISAs) for the four serotypes. st-ELISA testing of 41 dengue patient sera showed a 100% concordance with the serotype determined by serotype-specific reverse transcriptase real-time quantitative PCR. The respective NS1 variants could be detected for ~10 d after the onset of illness. Ab-dependent enhancement of DENV infections may be associated with a specific range of pre-existing anti-DENV serological Ab titers. Testing of patient sera with the developed st-ELISAs will not only be useful for epidemiological studies and surveillance, but it may also help to develop and validate assays that can distinguish protective versus enhancing Ab responses for risk assessment for the development of severe dengue disease in individual patients.
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Alteration in apoptotic rate of testicular cells and sperms following administration of Bisphenol A (BPA) in Wistar albino rats
Abstract
The aim of the study was to evaluate the effect of Bisphenol A [BPA] widely used as a plasticizer in the formation of polycarbonate plastics and epoxy resins, exposure causing alteration in apoptosis rate, and protective effect of Vitamin E when supplemented with BPA orally. Adult male Wistar albino rats aged 3 months were randomly divided into seven groups: control (olive oil treated) BPA-treated (dose 5, 50,100 μg/100gmBW) and Vitamin E intervention group (dose 5, 50, 100 μg/100gmBW BPA+ Vitamin E dose 4 mg/100gmBW). Animals were sacrificed 3 months later, and blood and tissue samples were collected. Apoptotic changes were analyzed in epididymal spermatozoa and testis tissue by binding of annexin V apoptotic biomarker. A significant decline in the weight of testis, testosterone level, and sperm count was observed. Histopathological and apoptotic changes were observed in testis tissue. In epididymal sperms, the early apoptotic cells were observed by staining of annexin V-conjugated FITC and PI green fluorescence in spermatozoa head which indicated the damage of membrane and late apoptotic cells. These changes reduced significantly in Vitamin E-treated groups though were not found to be comparable to control animals. All these changes were attributed to disrupted spermatogenesis that would interfere with sperm formation. Thus, the study infers that BPA affects the apoptosis process in the testis and epididymal sperm that would interfere with its function and contribute to infertility, whereas Vitamin E-supplemented dose has a protective effect towards these changes, indicating its role in improving male fertility.
https://ift.tt/2rWWnzK
Feasibility study of cadmium adsorption by palm oil fuel ash (POFA)-based low-cost hollow fibre zeolitic membrane
Abstract
Palm oil fuel ash (POFA) is an agricultural waste which was employed in this study to produce novel adsorptive ceramic hollow fibre membranes. The membranes were fabricated using phase inversion-based extrusion technique and sintered at 1150 °C. The membranes were then evaluated on their ability to adsorb cadmium (Cd(II)). These membranes were characterised using (nitrogen) N2 adsorption-desorption analysis, field emission scanning electron microscopy-energy-dispersive X-ray spectroscopy (FESEM-EDX) mapping, X-ray fluorescence (XRF), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) analyses while adsorptivity activity was examined by batch adsorption studies. The adsorption test results show that the quantity of hollow fibre used and water pH level significantly affected the adsorption performance with the 3-fibre membrane yielding 96.4% Cd(II) removal in 30 min equilibrium time at pH 7. These results are comparable to those reported by other studies, and hence demonstrate a promising alternative of low-cost hollow fibre adsorbent membrane.
Graphical abstract
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Symbiotic characteristics of Bradyrhizobium diazoefficiens USDA 110 mutants associated with shrubby sophora (Sophora flavescens) and soybean (Glycine max)
Publication date: September 2018
Source:Microbiological Research, Volume 214
Author(s): Yuan Hui Liu, En Tao Wang, Yin Shan Jiao, Chang Fu Tian, Lei Wang, Zi Jian Wang, Jia Jing Guan, Raghvendra Pratap Singh, Wen Xin Chen, Wen Feng Chen
Site-specific insertion plasmid pVO155 was used to knockout the genes involved in the alternation of host range of strain Bradyrhizobium diazoefficiens USDA 110 from its original determinate-nodule-forming host soybean (Glycine max), to promiscuous and indeterminate-nodule-forming shrubby legume sophora (Sophora flavescens). Symbiotic phenotypes of these mutants inoculated to these two legumes, were compared to those infected by wild-type strain USDA 110. Six genes of the total fourteen Tn5 transposon mutated genes were broken using the pVO155 plasmid. Both Tn5 and pVO155-inserted mutants could nodulate S. flavescens with different morphologies of low-efficient indeterminate nodules. One to several rod or irregular bacteroids, containing different contents of poly-β-hydroxybutyrate or polyphosphate were found within the symbiosomes in nodulated cells of S. flavescens infected by the pVO155-inserted mutants. Moreover, none of bacteroids were observed in the pseudonodules of S. flavescens, infected by wild-type strain USDA 110. These mutants had the nodulation ability with soybean but the symbiotic efficiency reduced to diverse extents. These findings enlighten the complicated interactions between rhizobia and legumes, i. e., mutation of genes involved in metabolic pathways, transporters, chemotaxis and mobility could alter the rhizobial entry and development of the bacteroid inside the nodules of a new host legume.
https://ift.tt/2rYerIM
t-GRASP, a targeted GRASP for assessing neuronal connectivity
Publication date: Available online 21 May 2018
Source:Journal of Neuroscience Methods
Author(s): Harold K. Shearin, Casey D. Quinn, Robert D. Mackin, Ian S. Macdonald, R. Steven Stowers
BackgroundUnderstanding how behaviors are generated by neural circuits requires knowledge of the synaptic connections between the composite neurons. Methods for mapping synaptic connections, such as electron microscopy and paired recordings, are labor intensive and alternative methods are thus desirable.New MethodDevelopment of a targeted GFP Reconstitution Across Synaptic Partners(GRASP) method, t-GRASP, for assessing neural connectivity is described.ResultsNumerous different pre-synaptic and post-synaptic/dendritic proteins were tested for enhancing the specificity of GRASP signal to synaptic regions. Pairing of both targeted pre- and post-t-GRASP constructs resulted in strong preferential GRASP signal in synaptic regions in Drosophila larval sensory neurons, larval neuromuscular junctions, and adult photoreceptor neurons with minimal false-positive signal.Comparison with Existing MethodsActivity-independent t-GRASP exhibits an enhancement of GRASP signal specificity for synaptic contact sites as compared to existing Drosophila GRASP methods. Fly strains were developed for expression of both pre- and post-t-GRASP with each of the three Drosophila binary transcription systems, thus enabling GRASP assays to be performed between any two driver pairs of any transcription system in either direction, an option not available for existing Drosophila GRASP methods.Conclusionst-GRASP is a novel targeted GRASP method for assessing synaptic connectivity between Drosophila neurons. Its flexibility of use with all three Drosophila binary transcription systems significantly expands the potential use of GRASP in Drosophila.
https://ift.tt/2IEfSqY
Performance and microbial community of CIC anaerobic reactor treating food waste under different grease contents and inner circulation ratio
Abstract
High concentrations of grease easily inhibit anaerobic digestion. The stability of the process and microbial responses in the controlling internal circulation (CIC) reactor used for treating food waste were investigated under different grease contents and inner circulation ratios. Results showed that at the grease content of 1 g/L, the removal rates of 94% and 86–93% were achieved for chemical oxygen demand (COD) and NH3–N, respectively. In contrast, when the grease content increased to 7 g/L, removal rates for COD and NH3–N significantly decreased to 42.8 and 10%, respectively. In the three-dimensional excitation and emission matrix (3D-EEM) spectra of LB-EPS (loosely bound extracellular polymeric substances), the fluorescence intensity of coenzyme F420 was weakened in the granular sludge, and the fluorescence peak of aromatic protein disappeared in the TB-EPS (tightly bound EPS). The activity and stability of the granular sludge deteriorated with increasing grease content, in this case at 7 g/L. However, when the inner cycle ratio was increased to 4, the removal rate of COD and NH3–N increased to about 70 and 76%, respectively. The adverse effects of grease could be decreased by increasing the inner cycle ratio. When the grease content increased from 1 to 7 g/L, the abundance of Methanofollis increased from 9.93 to 46.41%, while Methanothrix abundance was reduced from 18.4 to 3.07%. It could indicate that Methanothrix was sensitive to high grease content.
https://ift.tt/2IBAFvA