mTOR signalling controls protein aggregation during heat stress and cellular aging in a translation- and Hsf1-independent manner.

The mTOR (mechanistic target of rapamycin) signaling pathway appears central to the aging process as genetic or pharmacological inhibition of mTOR extends lifespan in most eukaryotes tested. While the regulation of protein synthesis by mTOR has been studied in great detail, its impact on protein misfolding and aggregation during stress and aging is less explored. In this study, we identified the mTOR signaling pathway and the linked SEA complex as central nodes of protein aggregation during heat stress and cellular aging, using Saccharomyces cerevisiae as a model organism.

Early extubation after elective surgical aortic valve replacement during the COVID-19 pandemic.

Background: Surgical aortic valve replacement (SAVR) is an established therapy for severe calcific aortic stenosis. Enhanced recovery after cardiac surgery (ERACS) protocols have been shown to improve outcomes for elective cardiac procedures. The COVID-19 pandemic prompted early extubation post-elective surgeries to preserve critical care resources.

The Ventilatory Ratio as a Predictor of Successful Weaning from a Veno-Venous Extracorporeal Membrane Oxygenator.

Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is a critical intervention for patients with severe lung failure, especially acute respiratory distress syndrome (ARDS). The weaning process from ECMO relies largely on expert opinion due to a lack of evidence-based guidelines. The ventilatory ratio (VR), which correlates with dead space and mortality in ARDS, is calculated as [minute ventilation (mL/min) x arterial pCO (mmHg)]/[predicted body weight × 100 × 37.

Gender and Autism Program: A novel clinical service model for gender-diverse/transgender autistic youth and young adults.

Situated in Children's National Hospital (CNH)'s Neuropsychology Division, the Gender and Autism Program (GAP) is the first clinical service dedicated to the needs of autistic gender-diverse/transgender youth. This study describes GAP clinical assessment profiles and presents a multi-perspective programmatic review of GAP evaluation services. Seventy-five consecutive gender- and neuropsychologically-informed GAP evaluations were analyzed, including demographics, gender and autism characterization, and primary domains evaluated.

Seven Tesla Evidence for Columnar and Rostral-Caudal Organization of the Human Periaqueductal Gray Response in the Absence of Threat: A Working Memory Study.

The periaqueductal gray (PAG) is a small midbrain structure that surrounds the cerebral aqueduct, regulates brain-body communication, and is often studied for its role in "fight-or-flight" and "freezing" responses to threat. We used ultra-high-field 7 T fMRI to resolve the PAG in humans and distinguish it from the cerebral aqueduct, examining its in vivo function during a working memory task ( = 87). Both mild and moderate cognitive demands elicited spatially similar patterns of whole-brain blood oxygenation level-dependent (BOLD) response, and moderate cognitive demand elicited widespread BOLD increases above baseline in the brainstem.

Autistic and non-autistic transgender youth are similar in gender development and sexuality phenotypes.

Increasing rhetoric regarding the common intersection of autism and gender diversity has resulted in legislation banning autistic transgender youth from accessing standard of care supports, as well as legislative efforts banning all youth gender care in part justified by the proportional over-occurrence of autism. Yet, no study has investigated whether autistic and non-autistic transgender youth present fundamentally different gender-related phenotypes. To address this gap, we extensively characterized autism, gender diversity, and sexuality among autistic and non-autistic transgender binary youth (N = 66, M = 17.

Elimination of virus-like particles reduces protein aggregation and extends replicative lifespan in .

A major consequence of aging and stress, in yeast to humans, is an increased accumulation of protein aggregates at distinct sites within the cells. Using genetic screens, immunoelectron microscopy, and three-dimensional modeling in our efforts to elucidate the importance of aggregate annexation, we found that most aggregates in yeast accumulate near the surface of mitochondria. Further, we show that virus-like particles (VLPs), which are part of the retrotransposition cycle of Ty elements, are markedly enriched in these sites of protein aggregation.

Early Blood Clot Detection Using Forward Scattering Light Measurements Is Not Superior to Delta Pressure Measurements.

The occurrence of thrombus formation within an extracorporeal membrane oxygenator is a common complication during extracorporeal membrane oxygenation therapy and can rapidly result in a life-threatening situation due to arterial thromboembolism, causing stroke, pulmonary embolism, and limb ischemia in the patient. The standard clinical practice is to monitor the pressure at the inlet and outlet of oxygenators, indicating fulminant, obstructive clot formation indicated by an increasing pressure difference (ΔP). However, smaller blood clots at early stages are not detectable.

Cognitive and Developmental Profiles Associated with Self-Reported Sexual and Gender Minority Stigmatization Among Binary Transgender Adolescents.

Objective: Sexual and gender minority (SGM) stigmatization is a key factor related to transgender adolescent mental health. While previous research has focused on direct associations between stigmatization and mental health, the present study of transgender youth, equitably recruited across the autism spectrum, examines cognitive and developmental factors in relation to the self-report of experienced and perceived SGM stigmatization.

Method: 65 binary transgender adolescents (43% transfeminine; ages 13-21 years) were intentionally recruited across the spectrum of autism traits from no traits to full criteria autism.

Neuromyths and knowledge about intellectual giftedness in a highly educated multilingual country.

Introduction: Understanding brain functioning and intellectual giftedness can be challenging and give rise to various misconceptions. Nonetheless, there seems to be a widespread fascination and appetite for these subjects among the lay public and diverse professionals. The present study is the first to investigate general knowledge about the brain, neuromyths and knowledge about giftedness in a highly multilingual and educated country.

Common Intersection of Autism and Gender Diversity in Youth: Clinical Perspectives and Practices.

Autism and gender diversity often intersect. Many transgender youth seeking gender-related medical interventions are autistic. Clinicians serving these youth lack an autism-specific evidence base to guide gender care decisions.

and in resident wildlife species in Arctic Alaska.

and are zoonotic protozoan parasites that can infect humans and other taxa, including wildlife, often causing gastrointestinal illness. Both have been identified as One Health priorities in the Arctic, where climate change is expected to influence the distribution of many wildlife and zoonotic diseases, but little is known about their prevalence in local wildlife. To help fill information gaps, we collected fecal samples from four wildlife species that occur seasonally on the northern Alaska coastline or in nearshore marine waters-Arctic fox (), polar bear (), Pacific walrus (), and caribou ()-and used immunofluorescence assays to screen for cysts and oocysts.

The yeast guanine nucleotide exchange factor Sec7 is a bottleneck in spatial protein quality control and detoxifies neurological disease proteins.

ER-to-Golgi trafficking partakes in the sorting of misfolded cytoplasmic proteins to reduce their cytological toxicity. We show here that yeast Sec7, a protein involved in proliferation of the Golgi, is part of this pathway and participates in an Hsp70-dependent formation of insoluble protein deposits (IPOD). Sec7 associates with the disaggregase Hsp104 during a mild heat shock and increases the rate of Hsp104 diffusion in an Hsp70-dependent manner when overproduced.

Design Optimization of a Phototherapy Extracorporeal Membrane Oxygenator for Treating Carbon Monoxide Poisoning.

We designed a photo-ECMO device to speed up the rate of carbon monoxide (CO) removal by using visible light to dissociate CO from hemoglobin (Hb). Using computational fluid dynamics, fillets of different radii (5 cm and 10 cm) were applied to the square shape of a photo-ECMO device to reduce stagnant blood flow regions and increase the treated blood volume while being constrained by full light penetration. The blood flow at different flow rates and the thermal load imposed by forty external light sources at 623 nm were modeled using the Navier-Stokes and convection-diffusion equations.

Calcineurin stimulation by Cnb1p overproduction mitigates protein aggregation and α-synuclein toxicity in a yeast model of synucleinopathy.

The calcium-responsive phosphatase, calcineurin, senses changes in Ca concentrations in a calmodulin-dependent manner. Here we report that under non-stress conditions, inactivation of calcineurin signaling or deleting the calcineurin-dependent transcription factor CRZ1 triggered the formation of chaperone Hsp100p (Hsp104p)-associated protein aggregates in Saccharomyces cerevisiae. Furthermore, calcineurin inactivation aggravated α-Synuclein-related cytotoxicity.

The Gender-Diversity and Autism Questionnaire: A Community-Developed Clinical, Research, and Self-Advocacy Tool for Autistic Transgender and Gender-Diverse Young Adults.

Background: Autistic transgender people face unique risks in society, including inequities in accessing needed care and related mental health disparities. Given the need for specific and culturally responsive accommodations/supports, the characterization of key experiences, challenges, needs, and resilience factors within this population is imperative. This study developed a structured self-report tool for autistic transgender young adults to communicate their experiences and needs in a report format attuned to common autistic thinking and communication styles.

Syntaxin 5-dependent phosphorylation of the small heat shock protein Hsp42 and its role in protein quality control.

The small heat shock protein Hsp42 and the t-SNARE protein Sed5 have central roles in the sequestration of misfolded proteins into insoluble protein deposits in the yeast Saccharomyces cerevisiae. However, whether these proteins/processes interact in protein quality control (PQC) is not known. Here, we show that Sed5 and anterograde trafficking modulate phosphorylation of Hsp42 partially via the MAPK kinase Hog1.

Extracorporeal membrane oxygenators with light-diffusing fibers for treatment of carbon monoxide poisoning: Experiments, mathematical modeling, and performance assessment with unit cells.

Unlabelled: BACKGROUND AND OBJECTIVES: Approximately 50,000 emergency department visits per year due to carbon monoxide (CO) poisoning occur in the United States alone. Tissue hypoxia can occur at very low CO concentration exposures because CO binds with a 250-fold higher affinity than oxygen to hemoglobin. The most effective therapy is 100% hyperbaric oxygen (HBO) respiration.

Artificial Hsp104-mediated systems for re-localizing protein aggregates.

Spatial Protein Quality Control (sPQC) sequesters misfolded proteins into specific, organelle-associated inclusions within the cell to control their toxicity. To approach the role of sPQC in cellular fitness, neurodegenerative diseases and aging, we report on the construction of Hsp100-based systems in budding yeast cells, which can artificially target protein aggregates to non-canonical locations. We demonstrate that aggregates of mutant huntingtin (mHtt), the disease-causing agent of Huntington's disease can be artificially targeted to daughter cells as well as to eisosomes and endosomes with this approach.

Bioimpedance Analysis as Early Predictor for Clot Formation Inside a Blood-Perfused Test Chamber: Proof of Concept Using an In Vitro Test-Circuit.

Clot formation inside a membrane oxygenator (MO) due to blood-to-foreign surface interaction represents a frequent complication during extracorporeal membrane oxygenation. Since current standard monitoring methods of coagulation status inside the MO fail to detect clot formation at an early stage, reliable sensors for early clot detection are in demand to reduce associated complications and adverse events. Bioimpedance analysis offers a monitoring concept by integrating sensor fibers into the MO.

Optical, flow, and thermal analysis of a phototherapy extracorporeal membrane oxygenator for treating carbon monoxide poisoning.

Background: Extracorporeal membrane oxygenators (ECMO) are currently utilized to mechanically ventilate blood when lung or lung and heart function are impaired, like in cases of acute respiratory distress syndrome (ARDS). ARDS can be caused by severe cases of carbon monoxide (CO) inhalation, which is the leading cause of poison-related deaths in the United States. ECMOs can be further optimized for severe CO inhalation using visible light to photo-dissociate CO from hemoglobin (Hb).

Alternative and facile production pathway towards obtaining high surface area PtCo/C intermetallic catalysts for improved PEM fuel cell performance.

The design of catalysts with stable and finely dispersed platinum or platinum alloy nanoparticles on the carbon support is key in controlling the performance of proton exchange membrane (PEM) fuel cells. In the present work, an intermetallic PtCo/C catalyst is synthesized double-passivation galvanic displacement. TEM and XRD confirm a significantly narrowed particle size distribution for the catalyst particles compared to commercial benchmark catalysts (Umicore PtCo/C).