A novel mouse model for developmental and epileptic encephalopathy by Purkinje cell-specific deletion of .

Loss of function variants of are associated with a range of developmental and epileptic encephalopathies (DEEs), including Dravet syndrome. These DEEs feature a wide range of severe neurological disabilities, including changes to social, motor, mood, sleep, and cognitive function which are notoriously difficult to treat, and high rates of early mortality. While the symptomology of -associated DEEs indicates broad changes in neural function, most research has focused on epilepsy-related brain structures and function.

A continuum from predictive to online feedback in visuomotor interception.

Interception, essential for activities like driving and sports, can be characterized by varying degrees of predictive behaviour. We developed a visually guided task to explore how target predictability and visibility influenced interception actions. The task featured a falling dot influenced by horizontal velocity, gravity and air friction, with predictability manipulated through external forces that altered the target's trajectory.

Perilipin 5 Phosphorylation is Dispensable for Upregulation of Hepatic Lipid Metabolism Genes upon Fasting but Required for Insulin Receptor Substrate 2 Expression in Male Mice.

Objective: Perilipin 5 (PLIN5) is a lipid droplet protein highly expressed in cells that actively oxidize fatty acids. Previous in vitro studies have revealed that PLIN5 phosphorylation (p-PLIN5) at serine 155 by PKA is critical for transcriptional regulation of PPARa target genes by which PLIN5 adapt cells for fatty acid oxidation. We aim to determine the extent of p-PLIN5 in vivo and the consequence of impaired PLIN5 phosphorylation in the liver by using a whole-body knock-in of phosphorylation resistant PLIN5 (SA/SA) in mice.

Blood flow restriction increases motor unit firing rates and input excitation of the biceps brachii during a moderate-load muscle action.

This study examined the effects of blood flow restriction (BFR) on motor unit (MU) behaviour of the biceps brachii (BB) during a single non-exhausting submaximal muscle action. Twenty adults performed maximal voluntary contractions (MVCs) of the elbow flexors, followed by an isometric trapezoidal muscle action at 40% MVC during BFR and control (CON) visits. Surface electromyographic signals recorded from the BB during the 40% MVCs were decomposed.

Expression, purification, and characterization of diacylated Lipo-YcjN from Escherichia coli.

YcjN is a putative substrate binding protein expressed from a cluster of genes involved in carbohydrate import and metabolism in Escherichia coli. Here, we determine the crystal structure of YcjN to a resolution of 1.95 Å, revealing that its three-dimensional structure is similar to substrate binding proteins in subcluster D-I, which includes the well-characterized maltose binding protein.

Pupillary responses to directional uncertainty while intercepting a moving target.

Pupillary responses serve as sensitive indicators of cognitive processes, attentional shifts and decision-making dynamics. Our study investigates how directional uncertainty and target speed ( ) influence pupillary responses in a foveal tracking task involving the interception of a moving dot. Directional uncertainty, reflecting the unpredictability of the target's direction changes, was manipulated by altering the angular range (AR) from which random directions for the moving dot were extracted.

Visuomotor predictors of interception.

Intercepting moving targets is a fundamental skill in human behavior, influencing various domains such as sports, gaming, and other activities. In these contexts, precise visual processing and motor control are crucial for adapting and navigating effectively. Nevertheless, there are still some gaps in our understanding of how these elements interact while intercepting a moving target.

Expression, purification, and characterization of diacylated Lipo-YcjN from .

YcjN is a putative substrate-binding protein expressed from a cluster of genes involved in carbohydrate import and metabolism in . Here, we determine the crystal structure of YcjN to a resolution of 1.95 Å, revealing that its three-dimensional structure is similar to substrate binding proteins in subcluster D-I, which includes the well-characterized maltose binding protein (MBP).

A Moderate Blood Flow Restriction Pressure Does Not Affect Maximal Strength or Neuromuscular Responses.

Lubiak, SM, Lawson, JE, Gonzalez Rojas, DH, Proppe, CE, Rivera, PM, Hammer, SM, Trevino, MA, Dinyer-McNeely, TK, Montgomery, TR, Olmos, AA, Sears, KN, Bergstrom, HC, Succi, PJ, Keller, JL, and Hill, EC. A moderate blood flow restriction pressure does not affect maximal strength or neuromuscular responses. J Strength Cond Res XX(X): 000-000, 2024-The purpose of this study was to examine the acute effects of blood flow restriction (BFR) applied at 60% of total arterial occlusion pressure (AOP) on maximal strength.

National Institute on Aging's 50th Anniversary: Advancing Cognitive Aging Research and the Cognitive Health of Older Adults.

In celebration of the National Institute on Aging's (NIA) 50th anniversary, this paper highlights the significant advances in cognitive aging research and the promotion of cognitive health among older adults. Since its inception in 1974, the NIA has played a pivotal role in understanding cognitive aging, including cognitive epidemiology, interventions, and methods, for measuring cognitive change. Key milestones include the shift toward understanding cognitive impairment and Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD), the development of large-scale longitudinal studies, and the incorporation of AD/ADRD-related biomarkers in cognitive aging cohorts.

Influence of Blood Flow Restriction on Neuromuscular Function and Fatigue During Forearm Flexion in Men.

Montgomery, TR Jr, Olmos, A, Sears, KN, Succi, PJ, Hammer, SM, Bergstrom, HC, Hill, EC, Trevino, MA, and Dinyer-McNeely, TK. Influence of blood flow restriction on neuromuscular function and fatigue during forearm flexion in men. J Strength Cond Res 38(7): e349-e358, 2024-To determine the effects of blood flow restriction (BFR) on the mean firing rate (MFR) and motor unit action potential amplitude (MUAPAMP) vs.

Does Box Height Matter? A Comparative Analysis of Box Height on Box Jump Performance in Men and Women.

This study aimed to analyze the effect of box height on box jump performance among recreationally active college students. Fourteen males (age = 20.8 ± 4.

Dentate gyrus is needed for memory retrieval.

The hippocampus is crucial for acquiring and retrieving episodic and contextual memories. In previous studies, the inactivation of dentate gyrus (DG) neurons by chemogenetic- and optogenetic-mediated hyperpolarization led to opposing conclusions about DG's role in memory retrieval. One study used Designer Receptors Exclusively Activated by Designer Drugs (DREADD)-mediated clozapine N-oxide (CNO)-induced hyperpolarization and reported that the previously formed memory was erased, thus concluding that denate gyrus is needed for memory maintenance.

Alternative low-populated conformations prompt phase transitions in polyalanine repeat expansions.

Abnormal trinucleotide repeat expansions alter protein conformation causing malfunction and contribute to a significant number of incurable human diseases. Scarce structural insights available on disease-related homorepeat expansions hinder the design of effective therapeutics. Here, we present the dynamic structure of human PHOX2B C-terminal fragment, which contains the longest polyalanine segment known in mammals.

Point of care thoracic ultrasound versus chest computed tomography in the approach of febrile neutropenia patients: A diagnostic accuracy cohort study.

Single-center prospective cohort diagnostic accuracy study. Our study aimed to evaluate the accuracy and reproducibility of Thoracic Ultrasound (TUS) in detecting pulmonary pathology in immunosuppressed patients. We conducted a single-center prospective study.

Blood flow restriction increases necessary muscle excitation of the elbow flexors during a single high-load contraction.

Purpose: To investigate the effects of blood flow restriction (BFR) on electromyographic amplitude (EMG)-force relationships of the biceps brachii (BB) during a single high-load muscle action.

Methods: Twelve recreationally active males and eleven recreationally active females performed maximal voluntary contractions (MVCs), followed by an isometric trapezoidal muscle action of the elbow flexors at 70% MVC. Surface EMG was recorded from the BB during BFR and control (CON) visits.

Effect of Propranolol on Motor Cortex Excitability in Essential Tremor: An Exploratory Study.

Background: Essential tremor, the world's most prevalent movement disorder, lacks a clear understanding of its pathophysiology. Propranolol, a non-specific beta-blocker capable of crossing the blood-brain barrier, is a primary choice for essential tremor treatment. While its tremor-reducing effects are generally attributed to peripheral actions, various uses hint at central adrenergic effects.

Exploring Health Care Access Among Lesbian, Gay, Bisexual, and Transgender Populations in Orange County, California: A Pilot Cross-sectional Study.

There are approximately 90 000 lesbian, gay, bisexual, and transgender (LGBT) individuals in Orange County, California. LGBT individuals have significant health disparities, particularly if they are from racial or ethnic minority groups and/or have a disability. There are structural and access barriers in the health care system that increase these health disparities.

Noise-Induced Hearing Threshold Shift Correlated with Body Weight and External-Ear Amplification in Chinchilla: a Preliminary Analysis.

Background: External-ear amplification (EEA) has been shown to vary from 5-19 dB-A in large datasets of pediatric, adolescent, and adult human participants. However, variable EEA is an overlooked characteristic that likely plays a role in individual noise-induced hearing loss (NIHL) susceptibility. A noise exposure varying 5-19 dB-A translates to high-EEA individuals theoretically experiencing 3-4 times greater NIHL risk than low-EEA individuals.

Precise Modeling of the Particle Size Distribution in Emulsion Polymerization: Numerical and Experimental Studies for Model Validation under Ab Initio Conditions.

The particle size distribution (PSD) in emulsion polymerization (EP) has been modeled in the past using either the pseudo bulk (PB) or the 0-1/0-1-2 approaches. There is some controversy on the proper type of model to be used to simulate the experimental PSDs, which are apparently broader than the theoretical ones. Additionally, the numerical technique employed to solve the model equations, involving hyperbolic partial differential equations (PDEs) with moving and possibly steep fronts, has to be precise and robust, which is not a trivial matter.

Directional uncertainty in chase and escape dynamics.

Intercepting and avoiding collisions with moving targets are crucial skills for survival. However, little is known about how these behaviors are implemented when the trajectory of the moving target introduces variability and ambiguity into the perceptual-motor system. We developed a simple visuomotor task in which participants used a joystick to interact with a computer-controlled dot that moved along two-dimensional trajectories.

Sex differences in muscle contraction-induced limb blood flow limitations.

Purpose: To determined sex differences in absolute- and %-reductions in blood flow during intermittent muscular contractions as well as relationships between blood flow reductions and time to task failure (TTF).

Methods: Thirteen males (25 ± 4 years) and 13 females (22 ± 5 years) completed intermittent isometric trapezoidal forearm flexion at 50% maximal voluntary contraction until task failure. Doppler ultrasound was used to measure brachial artery blood flow (BABF) during the 12-s plateau phase and 12-s relaxation phase.

Pre- and postsynaptic N-methyl-D-aspartate receptors are required for sequential printing of fear memory engrams.

The organization of fear memory involves the participation of multiple brain regions. However, it is largely unknown how fear memory is formed, which circuit pathways are used for "printing" memory engrams across brain regions, and the role of identified brain circuits in memory retrieval. With advanced genetic methods, we combinatorially blocked presynaptic output and manipulated N-methyl-D-aspartate receptor (NMDAR) in the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC) before and after cued fear conditioning.

Young Children's Development and Behavior: Associations with Timing of Household Food Insecurity in a Racially and Ethnically Diverse Early Head Start Sample.

Objective: The objective of this study was to assess the impact of household food insecurity (HFI) over time on behavioral and developmental health in early childhood while considering the impact of timing/persistence of HFI and potential differences among racially or ethnically minoritized children.

Methods: Families from the Early Head Start Family and Child Experiences Study (N = 760) were followed longitudinally until age 3 years. Caregiver interview data were collected on HFI, problem behaviors (PBs), delays in development (DD), and sociodemographic information.

SARS-CoV-2 Nsp8 N-terminal domain folds autonomously and binds dsRNA.

The SARS-CoV-2 Nsp8 protein is a critical component of the RNA replicase, as its N-terminal domain (NTD) anchors Nsp12, the RNA, and Nsp13. Whereas its C-terminal domain (CTD) structure is well resolved, there is an open debate regarding the conformation adopted by the NTD as it is predicted as disordered but found in a variety of complex-dependent conformations or missing from many other structures. Using NMR spectroscopy, we show that the SARS CoV-2 Nsp8 NTD features both well folded secondary structure and disordered segments.