Adiponectin Reverses the Proliferative Effects of Estradiol and IGF-1 in Human Epithelial Ovarian Cancer Cells by Downregulating the Expression of Their Receptors

Abstract

The expression of adiponectin receptors AdipoR1 and AdipoR2 has been reported in the human ovary and ovarian cancer tissues. Moreover, adiponectin has been reported to act as an anti-tumor factor by inhibiting cancer cell proliferation. Thus, we investigate whether adiponectin and its receptors influence ovarian cancer development. In the present study, we found that adiponectin was not expressed in the granulosa cell line (COV434), and epithelial ovarian cancer cell lines (OVCAR-3, SKOV-3, and Caov-3). Additionally, we found that AdipoR1 and AdipoR2 expression is lower in epithelial ovarian cancer cells than in granulosa tumor cells. Endogenous 17β-estradiol as well as exogenous estrogens, such as bisphenol A and its chlorinated and brominated analogs do not affect adiponectin receptor expression. We found that adiponectin inhibited the growth of OVCAR-3 and SKOV-3 cells, and that this effect was independent of apoptosis. Moreover, adiponectin reverses the stimulatory effects of 17β-estradiol and insulin-like growth factor 1 on cell proliferation by downregulating the expression of their receptors, whereas progesterone increased the sensitivity of cancer cells to adiponectin by upregulating AdipoR1 and AdipoR2 expression. These results suggest interactions between adiponectin and various ovarian steroid hormone and growth factor pathways in ovarian cancer cells.

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Agraphia with reversible splenial corpus callosum lesion caused by hypoglycemia

Publication date: Available online 30 March 2018
Source:Brain and Development
Author(s): Yukari Miyakawa, Tatsuo Fuchigami, Masako Aoki, Yusuke Mine, Junichi Suzuki, Tatsuhiko Urakami, Shori Takahashi
BackgroundNeurological manifestations caused by hypoglycemia range from reversible focal deficits and transient encephalopathy to irreversible coma or death. Recently, high signal intensity lesions in the splenium of the corpus callosum on diffusion-weighted magnetic resonance imaging were reported in adults experiencing hypoglycemia. However, patients presenting with agraphia are rare.Subject and methodsWe examined a 17-year-old left-handed female patient with type 1 diabetes who exhibited transient left agraphia with a reversible splenium lesion of the corpus callosum on diffusion-weighted imaging caused by hypoglycemia, which was improved with blood glucose management alone.ConclusionThis rare case indicates that agraphia, a sign of callosal disconnection syndrome, can result from a reversible splenial lesion of the corpus callosum caused by hypoglycemia.



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Accelerated Long-Term Forgetting and Behavioural Difficulties in Children with Epilepsy

Publication date: Available online 30 March 2018
Source:Cortex
Author(s): Michael B. Gascoigne, Mary Lou Smith, Belinda Barton, Richard Webster, Deepak Gill, Suncica Lah
Patients with epilepsy have been shown to exhibit a range of memory deficits, including the rapid forgetting of newly-learned material over long, but not short, delays (termed accelerated long-term forgetting; ALF). Behavioural problems, such as mood disorders and social difficulties, are also overrepresented among children with epilepsy, when compared to patients with other chronic diseases and the general population. We investigated whether ALF was associated with behavioural or psychosocial deficits in children with epilepsy. Patients with either idiopathic generalised epilepsy (IGE; n = 20) or temporal lobe epilepsy (TLE; n = 23) and healthy controls (n = 53) of comparable age, sex, and socioeconomic status completed a battery of neuropsychological tests, including a list-learning task that required recall after short (30-min) and long (7-day) delays. Parents or guardians of all participants also completed the Child Behavior Checklist (CBCL). Compared to control participants, patients with IGE and TLE had higher scores on all but one of the indices of behavioural problems. When patients with IGE and TLE were merged into a single group, they were found to have negative correlations between 7-day recall and internalising, social and total problem behaviour domains, where poorer 7-day recall was associated with behavioural problems of greater severity. These findings suggest that impaired episodic recall is associated with behavioural deficits, including social problems, which are routinely observed in patients with epilepsy.



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Knowledge about writing influences reading: Dynamic visual information about letter production facilitates letter identification

Publication date: Available online 30 March 2018
Source:Cortex
Author(s): Teresa Schubert, Caroline Reilhac, Michael McCloskey
How are reading and writing related? In this study, we address the relationship between letter identification and letter production, uncovering a link in which production information can be used to identify letters presented dynamically. By testing an individual with a deficit in letter identification, we identified a benefit which would be masked by ceiling effects in unimpaired readers. In Experiment 1 we found that letter stimuli defined by the direction of dot motion (tiny dots within letter move leftward, background dots move rightward) provided no advantage over static letters. In Experiment 2, we tested dynamic stimuli in which the letter shapes emerged over time: drawn as they would be written, drawn in reverse, or with the letter shape filled in randomly. Improved identification was observed only for letters drawn as they are typically written. These results demonstrate that information about letter production can be integrated into letter identification, and point to bi-directional connections between stored letter production information (used for writing) and abstract letter identity representations (used in both reading and writing). The links from stored production information to abstract letter identities allow the former to activate the latter. We also consider the implications of our results for remediation of acquired letter identification deficits, including letter-drawing treatments and the underlying cause of their efficacy.



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Cognitive and functional correlates of accelerated long-term forgetting in temporal lobe epilepsy

Publication date: Available online 30 March 2018
Source:Cortex
Author(s): Samantha Audrain, Mary Pat McAndrews
While we know that hippocampal dysfunction is responsible for the memory deficits that patients with temporal lobe epilepsy exhibit at relatively short study-test delays, the role of this region in accelerated long-term forgetting (ALF) is not yet clear. In the present study, we probed the role of the hippocampus in ALF by directly comparing memory for associations to memory that could be supported by item recognition during a forced choice recognition task over delays ranging from 15-minutes to 72-hours. We additionally examined resting-state functional connectivity between the hippocampus and cortical regions known to be involved in processing these types of stimuli, as well as the relationship between ALF and various clinical variables including structural abnormality in the hippocampus, lateralization of epileptic focus, presence of seizures across the retention period, and standardized composite memory scores. We found evidence of accelerated forgetting for item stimuli (but not associative stimuli) by 6 hours post-learning, which became statistically reliable by 72-hours. This finding suggests that unlike controls, patients were unable to utilize novelty to reject the incorrect object-scene pair. While none of the examined clinical variables were related to long-term forgetting, reduced resting-state functional connectivity between the affected anterior hippocampus and unaffected lateral temporal cortex predicted forgetting of item stimuli over the 72-hour delay. Implications for the role of the hippocampus in accelerated long-term forgetting, and existing theories of systems consolidation in this context are discussed.



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Parallel reaction monitoring on a Q Exactive mass spectrometer increases reproducibility of phosphopeptide detection in bacterial phosphoproteomics measurements

Publication date: Available online 29 March 2018
Source:Journal of Proteomics
Author(s): Christoph Taumer, Lena Griesbaum, Alen Kovacevic, Boumediene Soufi, Nicolas C. Nalpas, Boris Macek
Increasing number of studies report the relevance of protein Ser/Thr/Tyr phosphorylation in bacterial physiology, yet the analysis of this type of modification in bacteria still presents a considerable challenge. Unlike in eukaryotes, where tens of thousands of phosphorylation events likely occupy more than two thirds of the proteome, the abundance of protein phosphorylation is much lower in bacteria. Even the state-of-the-art phosphopeptide enrichment protocols fail to remove the high background of abundant unmodified peptides, leading to low signal intensity and undersampling of phosphopeptide precursor ions in consecutive data-dependent MS runs. Consequently, large-scale bacterial phosphoproteomic datasets often suffer from poor reproducibility and a high number of missing values. Here we explore the application of parallel reaction monitoring (PRM) on a Q Exactive mass spectrometer in bacterial phosphoproteome analysis, focusing especially on run-to-run sampling reproducibility. In multiple measurements of identical phosphopeptide-enriched samples, we show that PRM outperforms data-dependent acquisition (DDA) in terms of detection frequency, reaching almost complete sampling efficiency, compared to 20% in DDA. We observe a similar trend over multiple heterogeneous phosphopeptide-enriched samples and conclude that PRM shows a great promise in bacterial phosphoproteomics analyses where reproducible detection and quantification of a relatively small set of phosphopeptides is desired.SignificanceBacterial phosphorylated peptides occur in low abundance compared to their unmodified counterparts, and are therefore rarely reproducibly detected in shotgun (DDA) proteomics measurements. Here we show that parallel reaction monitoring complements DDA analyses and makes detection of known, targeted phosphopeptides more reproducible. This will be of significance in replicated MS measurements that have a goal to reproducibly detect and quantify phosphopeptides of interest.



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Proteomic analysis revealed proteins induced upon Azotobacter vinelandii encystment

Publication date: Available online 29 March 2018
Source:Journal of Proteomics
Author(s): Sangita Chowdhury-Paul, Victoria Pando-Robles, Verónica Jiménez-Jacinto, Daniel Segura, Guadalupe Espín, Cinthia Núñez

Graphical abstract

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