Alien Registration- Sonia, Clara Krestence (Bath, Sagadahoc County)

https://digitalmaine.com/alien_docs/8807/thumbnail.jp

Musicianship and melodic predictability enhance neural gain in auditory cortex during pitch deviance detection

When listening to music, pitch deviations are more salient and elicit stronger prediction error responses when the melodic context is predictable and when the listener is a musician. Yet, the neuronal dynamics and changes in connectivity underlying such effects remain unclear. Here, we employed dynamic causal modeling (DCM) to investigate whether the magnetic mismatch negativity response (MMNm)—and its modulation by context predictability and musical expertise—are associated with enhanced neural gain of auditory areas, as a plausible mechanism for encoding precision-weighted prediction errors. Using Bayesian model comparison, we asked whether models with intrinsic connections within primary auditory cortex (A1) and superior temporal gyrus (STG)—typically related to gain control—or extrinsic connections between A1 and STG—typically related to propagation of prediction and error signals—better explained magnetoencephalography responses. We found that, compared to regular sounds, out-of-tune pitch deviations were associated with lower intrinsic (inhibitory) connectivity in A1 and STG, and lower backward (inhibitory) connectivity from STG to A1, consistent with disinhibition and enhanced neural gain in these auditory areas. More predictable melodies were associated with disinhibition in right A1, while musicianship was associated with disinhibition in left A1 and reduced connectivity from STG to left A1. These results indicate that musicianship and melodic predictability, as well as pitch deviations themselves, enhance neural gain in auditory cortex during deviance detection. Our findings are consistent with predictive processing theories suggesting that precise and informative error signals are selected by the brain for subsequent hierarchical processing

Comprehensive proteome analysis of human skeletal muscle in cachexia and sarcopenia:A pilot study

Background Cancer cachexia (cancer‐induced muscle wasting) is found in a subgroup of cancer patients leaving the patients with a poor prognosis for survival due to a lower tolerance of the chemotherapeutic drug. The cause of the muscle wasting in these patients is not fully understood, and no predictive biomarker exists to identify these patients early on. Skeletal muscle loss is an inevitable consequence of advancing age. As cancer frequently occurs in old age, identifying and differentiating the molecular mechanisms mediating muscle wasting in cancer cachexia vs. age‐related sarcopenia are a challenge. However, the ability to distinguish between them is critical for early intervention, and simple measures of body weight may not be sufficiently sensitive to detect cachexia early. Methods We used a range of omics approaches: (i) undepleted proteome was quantified using advanced high mass accuracy mass spectrometers in SWATH‐MS acquisition mode; (ii) phospho epitopes were quantified using protein arrays; and (iii) morphology was assessed using fluorescent microscopy. Results We quantified the soluble proteome of muscle biopsies from cancer cachexia patients and compared them with cohorts of cancer patients and healthy individuals with and without age‐related muscle loss (aka age‐related sarcopenia). Comparing the proteomes of these cohorts, we quantified changes in muscle contractile myosins and energy metabolism allowing for a clear identification of cachexia patients. In an in vitro time lapse experiment, we mimicked cancer cachexia and identified signal transduction pathways governing cell fusion to play a pivotal role in preventing muscle regeneration. Conclusions The work presented here lays the foundation for further understanding of muscle wasting diseases and holds the promise of overcoming ambiguous weight loss as a measure for defining cachexia to be replaced by a precise protein signature.ISSN:2190-5991ISSN:2190-600

Short-term regulation of peptide YY secretion by a mixed meal or peritoneal glucose-based dialysate in patients with chronic renal failure

This is a pre-copyedited, author-produced version of an article accepted for publication in "Nephrology Dialysis Trasnplantation" following peer review. The version of the record is avaliable online at Oxford Academic website.Instituto de Salud Carlos III, PI051024Instituto de Salud Carlos III, PI070413Xunta de Galicia, PS07/12Xunta de Galicia, 2006/2

Reproducibility of an HPLC-ESI-MS/MS Method for the Measurement of Stable-Isotope Enrichment of in Vivo-Labeled Muscle ATP Synthase Beta Subunit

We sought to evaluate the reproducibility of a liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based approach to measure the stable-isotope enrichment of in vivo-labeled muscle ATP synthase β subunit (β-F1-ATPase), a protein most directly involved in ATP production, and whose abundance is reduced under a variety of circumstances. Muscle was obtained from a rat infused with stable-isotope-labeled leucine. The muscle was homogenized, β-F1-ATPase immunoprecipitated, and the protein was resolved using 1D-SDS PAGE. Following trypsin digestion of the isolated protein, the resultant peptide mixtures were subjected to analysis by HPLC-ESI-MS/MS, which resulted in the detection of multiple β-F1-ATPase peptides. There were three β-F1-ATPase unique peptides with a leucine residue in the amino acid sequence, and which were detected with high intensity relative to other peptides and assigned with >95% probability to β-F1-ATPase. These peptides were specifically targeted for fragmentation to access their stable-isotope enrichment based on MS/MS peak areas calculated from extracted ion chromatographs for selected labeled and unlabeled fragment ions. Results showed best linearity (R2 = 0.99) in the detection of MS/MS peak areas for both labeled and unlabeled fragment ions, over a wide range of amounts of injected protein, specifically for the β-F1-ATPase134-143 peptide. Measured stable-isotope enrichment was highly reproducible for the β-F1-ATPase134-143 peptide (CV = 2.9%). Further, using mixtures of synthetic labeled and unlabeled peptides we determined that there is an excellent linear relationship (R2 = 0.99) between measured and predicted enrichment for percent enrichments ranging between 0.009% and 8.185% for the β-F1-ATPase134-143 peptide. The described approach provides a reliable approach to measure the stable-isotope enrichment of in-vivo-labeled muscle β-F1-ATPase based on the determination of the enrichment of the β-F1-ATPase134-143 peptide

An umbrella review of candidate predictors of response, remission, recovery, and relapse across mental disorders

We aimed to identify diagnosis-specific/transdiagnostic/transoutcome multivariable candidate predictors (MCPs) of key outcomes in mental disorders. We conducted an umbrella review (protocol  link ), searching MEDLINE/Embase (19/07/2022), including systematic reviews of studies reporting on MCPs of response, remission, recovery, or relapse, in DSM/ICD-defined mental disorders. From published predictors, we filtered MCPs, validating MCP criteria. AMSTAR2/PROBAST measured quality/risk of bias of systematic reviews/individual studies. We included 117 systematic reviews, 403 studies, 299,888 individuals with mental disorders, testing 796 prediction models. Only 4.3%/1.2% of the systematic reviews/individual studies were at low risk of bias. The most frequently targeted outcome was remission (36.9%), the least frequent was recovery (2.5%). Studies mainly focused on depressive (39.4%), substance-use (17.9%), and schizophrenia-spectrum (11.9%) disorders. We identified numerous MCPs within disorders for response, remission and relapse, but none for recovery. Transdiagnostic MCPs of remission included lower disease-specific symptoms (disorders = 5), female sex/higher education (disorders = 3), and quality of life/functioning (disorders = 2). Transdiagnostic MCPs of relapse included higher disease-specific symptoms (disorders = 5), higher depressive symptoms (disorders = 3), and younger age/higher anxiety symptoms/global illness severity/ number of previous episodes/negative life events (disorders = 2). Finally, positive trans-outcome MCPs for depression included less negative life events/depressive symptoms (response, remission, less relapse), female sex (response, remission) and better functioning (response, less relapse); for schizophrenia, less positive symptoms/higher depressive symptoms (remission, less relapse); for substance use disorder, marital status/higher education (remission, less relapse). Male sex, younger age, more clinical symptoms and comorbid mental/physical symptoms/disorders were poor prognostic factors, while positive factors included social contacts and employment, absent negative life events, higher education, early access/intervention, lower disease-specific and comorbid mental and physical symptoms/conditions, across mental disorders. Current data limitations include high risk of bias of studies and extraction of single predictors from multivariable models. Identified MCPs can inform future development, validation or refinement of prediction models of key outcomes in mental disorders

The Histidine-Rich Calcium Binding Protein in Regulation of Cardiac Rhythmicity

Sudden unexpected cardiac death (SCD) accounts for up to half of all-cause mortality of heart failure patients. Standardized cardiology tools such as electrocardiography, cardiac imaging, electrophysiological and serum biomarkers cannot accurately predict which patients are at risk of life-threatening arrhythmic episodes. Recently, a common variant of the histidine-rich calcium binding protein (HRC), the Ser96Ala, was identified as a potent biomarker of malignant arrhythmia triggering in these patients. HRC has been shown to be involved in the regulation of cardiac sarcoplasmic reticulum (SR) Ca2+ cycling, by binding and storing Ca2+ in the SR, as well as interacting with the SR Ca2+ uptake and release complexes. The underlying mechanisms, elucidated by studies at the molecular, biochemical, cellular and intact animal levels, indicate that transversion of Ser96 to Ala results in abolishment of an HRC phosphorylation site by Fam20C kinase and dysregulation of SR Ca2+ cycling. This is mediated through aberrant SR Ca2+ release by the ryanodine receptor (RyR2) quaternary complex, due to the impaired HRC/triadin interaction, and depressed SR Ca2+ uptake by the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA2) pump, due to the impaired HRC/SERCA2 interaction. Pharmacological intervention with KN-93, an inhibitor of Ca2+ /calmodulin-dependent protein kinase II (CaMKII), in the HRC Ser96Ala mouse model, reduced the occurrence of malignant cardiac arrhythmias. Herein, we summarize the current evidence on the pivotal role of HRC in the regulation of cardiac rhythmicity and the importance of HRC Ser96Ala as a genetic modifier for arrhythmias in the setting of heart failure