Enhanced Low-Humidity Performance of Polymer Exchange Membrane Fuel Cells via Membrane Surface Engineering.

Polymer electrolyte membrane fuel cells (PEMFCs) play a pivotal role in meeting the energy needs of high-power applications such as construction and agricultural machinery and mobility. High-power operation often exacerbates problems associated with water management within the cell due to excessive water generation, affecting water distribution at the cathode and anode interfaces. Our research recognizes the importance of addressing challenges associated with the high-power operation of polymer electrolyte membrane fuel cells (PEMFCs) for use in high-power fuel cell applications.

Parallel genome-scale CRISPR-Cas9 screens uncouple human pluripotent stem cell identity versus fitness.

Pluripotent stem cells have remarkable self-renewal capacity: the ability to proliferate indefinitely while maintaining the pluripotent identity essential for their ability to differentiate into almost any cell type in the body. To investigate the interplay between these two aspects of self-renewal, we perform four parallel genome-scale CRISPR-Cas9 loss-of-function screens interrogating stem cell fitness in hPSCs and the dissolution of primed pluripotent identity during early differentiation. These screens distinguish genes with distinct roles in pluripotency regulation, including mitochondrial and metabolism regulators crucial for stem cell fitness, and chromatin regulators that control pluripotent identity during early differentiation.

Members of an array of zinc-finger proteins specify distinct Hox chromatin boundaries.

Partitioning of repressive from actively transcribed chromatin in mammalian cells fosters cell-type-specific gene expression patterns. While this partitioning is reconstructed during differentiation, the chromatin occupancy of the key insulator, CCCTC-binding factor (CTCF), is unchanged at the developmentally important Hox clusters. Thus, dynamic changes in chromatin boundaries must entail other activities.

CRISPR screening uncovers a long-range enhancer for ONECUT1 in pancreatic differentiation and links a diabetes risk variant.

Functional enhancer annotation is critical for understanding tissue-specific transcriptional regulation and prioritizing disease-associated non-coding variants. However, unbiased enhancer discovery in disease-relevant contexts remains challenging. To identify enhancers pertinent to diabetes, we conducted a CRISPR interference (CRISPRi) screen in the human pluripotent stem cell (hPSC) pancreatic differentiation system.

A PLURIPOTENT STEM CELL PLATFORM FOR IN VITRO SYSTEMS GENETICS STUDIES OF MOUSE DEVELOPMENT.

The directed differentiation of pluripotent stem cells (PSCs) from panels of genetically diverse individuals is emerging as a powerful experimental system for characterizing the impact of natural genetic variation on developing cell types and tissues. Here, we establish new PSC lines and experimental approaches for modeling embryonic development in a genetically diverse, outbred mouse stock (Diversity Outbred mice). We show that a range of inbred and outbred PSC lines can be stably maintained in the primed pluripotent state (epiblast stem cells -- EpiSCs) and establish the contribution of genetic variation to phenotypic differences in gene regulation and directed differentiation.

CRISPR Screening Uncovers a Long-Range Enhancer for in Pancreatic Differentiation and Links a Diabetes Risk Variant.

Functional enhancer annotation is a valuable first step for understanding tissue-specific transcriptional regulation and prioritizing disease-associated non-coding variants for investigation. However, unbiased enhancer discovery in physiologically relevant contexts remains a major challenge. To discover regulatory elements pertinent to diabetes, we conducted a CRISPR interference screen in the human pluripotent stem cell (hPSC) pancreatic differentiation system.

Home-administered transcranial direct current stimulation is a feasible intervention for depression: an observational cohort study.

Transcranial direct current stimulation (tDCS) is an emerging treatment for major depression. We recruited participants with moderate-to-severe major depressive episodes for an observational clinical trial using Soterix Medical's tDCS telehealth platform as a standard of care. The acute intervention consisted of 28 sessions (5 sessions/week, 6 weeks) of the left anodal dorsolateral prefrontal cortex (DLPFC) tDCS (2.

Immediate and Differential Response to Emotional Stimuli Associated With Transcranial Direct Current Stimulation for Depression: A Visual-Search Task Pilot Study.

Objectives: When administered in repeated daily doses, transcranial direct current stimulation (tDCS) directed to the prefrontal cortex has cumulative efficacy for the treatment of depression. Depression can be marked by altered processing of emotionally salient information. An acute marker of response to tDCS may be measured as an immediate change in emotional information processing.

Dynamic network-guided CRISPRi screen identifies CTCF-loop-constrained nonlinear enhancer gene regulatory activity during cell state transitions.

Comprehensive enhancer discovery is challenging because most enhancers, especially those contributing to complex diseases, have weak effects on gene expression. Our gene regulatory network modeling identified that nonlinear enhancer gene regulation during cell state transitions can be leveraged to improve the sensitivity of enhancer discovery. Using human embryonic stem cell definitive endoderm differentiation as a dynamic transition system, we conducted a mid-transition CRISPRi-based enhancer screen.

Parallel genome-scale CRISPR-Cas9 screens uncouple human pluripotent stem cell identity versus fitness.

Pluripotent stem cells are defined by their self-renewal capacity, which is the ability of the stem cells to proliferate indefinitely while maintaining the pluripotent identity essential for their ability to differentiate into any somatic cell lineage. However, understanding the mechanisms that control stem cell fitness versus the pluripotent cell identity is challenging. To investigate the interplay between these two aspects of pluripotency, we performed four parallel genome-scale CRISPR-Cas9 loss-of-function screens interrogating stem cell fitness in hPSC self-renewal conditions, and the dissolution of the primed pluripotency identity during early differentiation.

Members of an array of zinc finger proteins specify distinct chromatin boundaries.

Partitioning of repressive from actively transcribed chromatin in mammalian cells fosters cell-type specific gene expression patterns. While this partitioning is reconstructed during differentiation, the chromatin occupancy of the key insulator, CTCF, is unchanged at the developmentally important clusters. Thus, dynamic changes in chromatin boundaries must entail other activities.

Moving intra-individual variability (IIV) towards clinical utility: IIV measured using a commercial testing platform.

Objectives: Intra-individual variability (IIV), measured across repeated response times (RT) during continuous psychomotor tasks, is an early marker of cognitive change in the context of neurodegeneration. To advance IIV towards broader application in clinical research, we evaluated IIV from a commercial cognitive testing platform and compared it to the calculation approaches used in experimental cognitive studies.

Methods: Cognitive assessment was administered in participants with multiple sclerosis (MS) during the baseline of an unrelated study.

Effects of attention bias modification for anxiety: Neurophysiological indices and moderation by symptom severity.

Objective: Attention bias modification (ABM) aims to decrease anxiety symptom severity through the reduction of threat-related attention bias (AB). Individual differences in treatment response and poor measurement reliability of AB have called its clinical promise into question. The current study examined whether individual differences in anxiety severity at baseline moderated treatment response, and employed both behavioral and neurophysiological metrics of AB.

JIB-04, a Pan-Inhibitor of Histone Demethylases, Targets Histone-Lysine-Demethylase-Dependent AKT Pathway, Leading to Cell Cycle Arrest and Inhibition of Cancer Stem-Like Cell Properties in Hepatocellular Carcinoma Cells.

JIB-04, a pan-histone lysine demethylase (KDM) inhibitor, targets drug-resistant cells, along with colorectal cancer stem cells (CSCs), which are crucial for cancer recurrence and metastasis. Despite the advances in CSC biology, the effect of JIB-04 on liver CSCs (LCSCs) and the malignancy of hepatocellular carcinoma (HCC) has not been elucidated yet. Here, we showed that JIB-04 targeted KDMs, leading to the growth inhibition and cell cycle arrest of HCC, and abolished the viability of LCSCs.

Transcranial Electrical Stimulation for Psychiatric Disorders in Adults: A Primer.

Transcranial electrical stimulation (tES) comprises noninvasive neuromodulation techniques that deliver low-amplitude electrical currents to targeted brain regions with the goal of modifying neural activities. Expanding evidence from the past decade, specifically using transcranial direct current simulation and transcranial alternating current stimulation, presents promising applications of tES as a treatment for psychiatric disorders. In this review, the authors discuss the basic technical aspects and mechanisms of action of tES in the context of clinical research and practice and review available evidence for its clinical use, efficacy, and safety.

Evaluation of protein descriptors in computer-aided rational protein engineering tasks and its application in property prediction in SARS-CoV-2 spike glycoprotein.

The importance of protein engineering in the research and development of biopharmaceuticals and biomaterials has increased. Machine learning in computer-aided protein engineering can markedly reduce the experimental effort in identifying optimal sequences that satisfy the desired properties from a large number of possible protein sequences. To develop general protein descriptors for computer-aided protein engineering tasks, we devised new protein descriptors, one sequence-based descriptor (PCgrades), and three structure-based descriptors (PCspairs, 3D-SPIEs_5.

Mobile Attention Bias Modification Training Is a Digital Health Solution for Managing Distress in Multiple Sclerosis: A Pilot Study in Pediatric Onset.

Emotional health is important dimension of care for patients living with pediatric onset multiple sclerosis (POMS), but few options are available for stress and anxiety reduction. The high burden of interventions requiring regular in person and onsite visits for treatment are less feasible. Attention bias modification training (ABMT) is effective for anxiety reduction in adult and adolescent populations.

Transcranial Direct Current Stimulation (tDCS) Augments the Effects of Gamified, Mobile Attention Bias Modification.

Anxiety-related attention bias (AB) is the preferential processing of threat observed in clinical and sub-clinical anxiety. Attention bias modification training (ABMT) is a computerized cognitive training technique designed to systematically direct attention away from threat and ameliorate AB, but mixed and null findings have highlighted gaps in our understanding of mechanisms underlying ABMT and how to design the most effective delivery systems. One neuromodulation technique, transcranial direct current stimulation (tDCS) across the pre-frontal cortex (PFC) may augment the effects of ABMT by strengthening top-down cognitive control processes, but the evidence base is limited and has not been generalized to current approaches in digital therapeutics, such as mobile applications.

Absence Makes the Mind Grow Fonder: Reconceptualizing Studies of Safety Learning in Translational Research on Anxiety.

Overgeneralized fear (OGF), or indiscriminate fear responses to signals of threat and nonthreat, is a well-studied cognitive mechanism in human anxiety. Anxiety-related OGF has been studied primarily through fear-learning paradigms and conceptualized as overly exaggerated learning of cues signaling imminent threat. However, the role of safety learning in OGF has not only received much less empirical attention but has been fundamentally conceptualized as learning about the absence of threat rather than the presence of safety.

EEG Correlates of Involuntary Cognitions in the Reflexive Imagery Task.

The Reflexive Imagery Task (RIT) reveals that the activation of sets can result in involuntary cognitions that are triggered by external stimuli. In the basic RIT, subjects are presented with an image of an object (e.g.

The late positive potential as a neurocognitive index of emotion regulatory flexibility.

A growing body of research has examined regulatory flexibility as the ability to dynamically modulate emotional expression and experience (Bonanno & Burton, 2013). The late positive potential (LPP), an event-related potential reflecting processing of emotionally-evocative stimuli, is sensitive to emotion regulation (ER) or the psychological processes that underlie the experience, expression, and management of emotions. However, few studies have used the LPP to index regulatory flexibility or tested its association with self-reported emotional well-being and ER.

Involuntary Entry Into Consciousness From the Activation of Sets: Object Counting and Color Naming.

High-level cognitions can enter consciousness through the activation of certain action sets and the presentation of external stimuli ("set-based entry," for short). Set-based entry arises in a manner that is involuntary and systematic. In the Reflexive Imagery Task, for example, subjects are presented with visual objects and instructed to not think of the names of the objects.

The reflexive imagery task: An experimental paradigm for neuroimaging.

High-level cognitions can be triggered into consciousness through the presentation of external stimuli and the activation of certain action sets. These activations arise in a manner that is involuntary, systematic and nontrivial. For example, in the Reflexive Imagery Task (RIT), subjects are presented with visual objects and instructed to not think of the names of the objects.