Chromatin Accessibility Landscape of Cutaneous T Cell Lymphoma and Dynamic Response to HDAC Inhibitors

Publication date: Available online 15 June 2017
Source:Cancer Cell
Author(s): Kun Qu, Lisa C. Zaba, Ansuman T. Satpathy, Paul G. Giresi, Rui Li, Yonghao Jin, Randall Armstrong, Chen Jin, Nathalie Schmitt, Ziba Rahbar, Hideki Ueno, William J. Greenleaf, Youn H. Kim, Howard Y. Chang
Here, we define the landscape and dynamics of active regulatory DNA in cutaneous T cell lymphoma (CTCL) by ATAC-seq. Analysis of 111 human CTCL and control samples revealed extensive chromatin signatures that distinguished leukemic, host, and normal CD4⁺ T cells. We identify three dominant patterns of transcription factor (TF) activation that drive leukemia regulomes, as well as TF deactivations that alter host T cells in CTCL patients. Clinical response to histone deacetylase inhibitors (HDACi) is strongly associated with a concurrent gain in chromatin accessibility. HDACi causes distinct chromatin responses in leukemic and host CD4⁺ T cells, reprogramming host T cells toward normalcy. These results provide a foundational framework to study personal regulomes in human cancer and epigenetic therapy.

Graphical abstract

Teaser

Qu et al. show that the accessible chromatin landscape distinguishes leukemic from host T cells in cutaneous T cell lymphoma (CTCL) patients as well as T cells from healthy individuals. The clinical response of CTCL to HDAC inhibitors strongly associates with a concurrent gain in chromatin accessibility.


http://ift.tt/2s7NyUk

The effect of caloric restriction on the forelimb skeletal muscle fibers of the hypertrophic myostatin null mice

Publication date: Available online 15 June 2017
Source:Acta Histochemica
Author(s): Mohamed I. Elashry, Antonios Matsakas, Sabine Wenisch, Stefan Arnhold, Ketan Patel
Skeletal muscle mass loss has a broad impact on body performance and physical activity. Muscle wasting occurs due to genetic mutation as in muscular dystrophy, age-related muscle loss (sarcopenia) as well as in chronic wasting disorders as in cancer cachexia. Food restriction reduces muscle mass underpinned by increased muscle protein break down. However the influence of dietary restriction on the morphometry and phenotype of forelimb muscles in a genetically modified myostatin null mice are not fully characterized. The effect of a five week dietary limitation on five anatomically and structurally different forelimb muscles was examined. C57/BL6 wild type (Mstn^+/+) and myostatin null (Mstn^−/−) mice were either given a standard rodent normal daily diet ad libitum (ND) or 60% food restriction (FR) for a 5 week period. M. triceps brachii Caput laterale (T.lateral), M. triceps brachii Caput longum (T.long), M. triceps brachii Caput mediale (T.medial), M. extensor carpi ulnaris (ECU) and M. flexor carpi ulnaris (FCU) were dissected, weighted and processed for immunohistochemistry. Muscle mass, fibers cross sectional areas (CSA) and myosin heavy chain types IIB, IIX, IIA and type I were analyzed. We provide evidence that caloric restriction results in muscle specific weight reduction with the fast myofibers being more prone to atrophy. We show that slow fibers are less liable to dietary restriction induced muscle atrophy. The effect of dietary restriction was more pronounced in Mstn^−/− muscles to implicate the oxidative fibers compared to Mstn^+/+. Furthermore, peripherally located myofibers are more susceptible to dietary induced reduction compared to deep fibers. We additionally report that dietary restriction alters the glycolytic phenotype of the Mstn^−/− into the oxidative form in a muscle dependent manner. In summary our study shows that calorie restriction alters muscle fiber profile of forelimb muscles of Myostatin null mice.



http://ift.tt/2rn1zut

Leptin-like immunoreactivity in the central nervous system, digestive organs, and gonads of the giant freshwater prawn, Macrobrachium rosenbergii

Publication date: Available online 16 June 2017
Source:Acta Histochemica
Author(s): Jaruwan Poljaroen, Yotsawan Tinikul, Ruchanok Tinikul, Panat Anurucpreeda, Prasert Sobhon
Leptin, a highly conserved adipocyte-derived hormone, plays important roles in a variety of physiological processes, including the control of fat storage and metabolic status which are linked to food intake, energy homeostasis, and reproduction in all vertebrates. In the present study, we hypothesize that leptin is also present in various organs of the fresh water prawns, Macrobrachium rosenbergii. The existence and distribution of a leptin-like peptide in prawn tissues were verified by using Western blotting (WB) and immunohistochemical detection (ID) using primary antibody against human leptin. With WB, a leptin-like peptide, having a molecular weight of 15kDa, was detected in the brain, thoracic ganglia, abdominal ganglia, parts of the gastro-intestinal tract, hepatopancreas, adipocytes and gonads. By ID, leptin immunoreactivity (leptin-ir) was detected in the brain, thoracic ganglia and intersegmental commissural nerve fibers of abdominal ganglia. In the gastrointestinal tract, there was intense leptin-ir in the apical part of the epithelial cells of the cardiac and pyloric parts of the stomach. In the midgut and hindgut, the leptin-ir was detected in epithelial cells and basal cells located near the basal lamina of the epithelium. In addition, there was leptin-ir in the Restzellen cells in the hepatopancreas which produce digestive enzymes. In the ovary, the strong intensity of a leptin-ir was detected in the cytoplasm of middle to late stage oocytes, whereas no positive staining was detected in follicular cells. An intense leptin-ir was detected in spermatocytes and sustentacular cells in the seminiferous tubules in the testes of small and orange claw males. Taken together, the detection of the leptin-ir in several organs implicates the existence of a leptin-like peptide in various organs of the freshwater prawn; and like in vertebrates this peptide may be an important hormonal factor in controlling feeding and reproductive process.



http://ift.tt/2sFEas8

Nanotechnologies for In Vitro IgE Testing

Abstract

Purpose of Review

This review discusses the recent advances in the development of IgE antibody assays based on nanotechnologies. IgE blood testing is an important part of the diagnostic workup of IgE-mediated hypersentivity. We also address the challenges in moving from an academic proof-of-concept to a product routinely used by allergy experts.

Recent Findings

Several nanotechnologies have been applied to the field of IgE testing: nanoparticles are used either as a support to capture analytes or as a detection tool to enhance the measurement signal. Nanofluidics allows to reduce assay time by enhancing molecular interaction.

Summary

Nanotechnologies bring forth new methods for in vitro IgE testing. Substantial advantages such as lower sample volume, shorter assay time, simplified procedures, and lower analytic sensitivity, without affecting test precision and accuracy, can be achieved thanks to nanotechnologies.

http://ift.tt/2t9bTHB

Acquired Immunity in Chronic Rhinosinusitis

Abstract

Chronic rhinosinusitis (CRS) is a prevalent disease that is associated with significant costs and quality of life impairments. Currently, patients are classified into subgroups based on clinical characteristics, most often the presence or absence of nasal polyps. However, despite medical and surgical treatment, many of these patients continue to have symptoms. Recent efforts have focused on gaining a more complete understanding of the inflammatory mechanisms that drive pathogenesis in CRS, and it is becoming clear that the inflammatory processes in CRS are quite complex. As our understanding of these complex phenotypes improves, it may become possible to classify patients into endotypes based on unique inflammatory patterns within the sinus mucosa. This information may also lead to the identification of appropriate targeted therapies for different endotypes. This review will discuss our current understanding of endotypes in CRS along with the unique adaptive immune responses that may contribute to these different endotypes and, finally, some potential targeted therapeutics for the next generation of CRS treatment strategies.

http://ift.tt/2szlgDl

Nanotechnologies for In Vitro IgE Testing

Abstract

Purpose of Review

This review discusses the recent advances in the development of IgE antibody assays based on nanotechnologies. IgE blood testing is an important part of the diagnostic workup of IgE-mediated hypersentivity. We also address the challenges in moving from an academic proof-of-concept to a product routinely used by allergy experts.

Recent Findings

Several nanotechnologies have been applied to the field of IgE testing: nanoparticles are used either as a support to capture analytes or as a detection tool to enhance the measurement signal. Nanofluidics allows to reduce assay time by enhancing molecular interaction.

Summary

Nanotechnologies bring forth new methods for in vitro IgE testing. Substantial advantages such as lower sample volume, shorter assay time, simplified procedures, and lower analytic sensitivity, without affecting test precision and accuracy, can be achieved thanks to nanotechnologies.

http://ift.tt/2t9bTHB

Acquired Immunity in Chronic Rhinosinusitis

Abstract

Chronic rhinosinusitis (CRS) is a prevalent disease that is associated with significant costs and quality of life impairments. Currently, patients are classified into subgroups based on clinical characteristics, most often the presence or absence of nasal polyps. However, despite medical and surgical treatment, many of these patients continue to have symptoms. Recent efforts have focused on gaining a more complete understanding of the inflammatory mechanisms that drive pathogenesis in CRS, and it is becoming clear that the inflammatory processes in CRS are quite complex. As our understanding of these complex phenotypes improves, it may become possible to classify patients into endotypes based on unique inflammatory patterns within the sinus mucosa. This information may also lead to the identification of appropriate targeted therapies for different endotypes. This review will discuss our current understanding of endotypes in CRS along with the unique adaptive immune responses that may contribute to these different endotypes and, finally, some potential targeted therapeutics for the next generation of CRS treatment strategies.

http://ift.tt/2szlgDl