The Influence of Dopaminergic Medication on Regularity and Determinism of Gait and Balance in Parkinson's Disease: A Pilot Analysis.

: Understanding how dual-tasking and Parkinson's disease medication affect gait and balance regularity can provide valuable insights to patients, caregivers, and clinicians regarding frailty and fall risk. However, dual-task gait and balance studies in PD most often only employ linear measures to describe movement regularity. Some have used nonlinear techniques to analyze PD performances, but only in the on-medication state.

Ebi3 Binding to IFN-γ and IL-10 Limits Their Function.

EBV-induced gene 3 (Ebi3) is a β subunit within the IL-12 cytokine family that canonically binds to α subunits p19, p28, or p35 to form the heterodimeric cytokines IL-39, IL-27, and IL-35, respectively. In the last decade, the binding partners for Ebi3 have continued to expand to include IL-6 and the other IL-12 family β subunit p40, revealing the possibility that Ebi3 may be able to bind to other cytokines and have distinct functions. We first explored this possibility utilizing an in vivo mouse model of regulatory T cell-restricted deletions of the subunits composing the cytokine IL-35, p35, and Ebi3, and we observed a differential impact on CD8+ T cell inhibitory receptor expression despite comparable reduction in tumor growth.

Blockade of LAG-3 and PD-1 leads to co-expression of cytotoxic and exhaustion gene modules in CD8 T cells to promote antitumor immunity.

Relatlimab (rela; anti-LAG-3) plus nivolumab (nivo; anti-PD-1) is safe and effective for treatment of advanced melanoma. We designed a trial (NCT03743766) where advanced melanoma patients received rela, nivo, or rela+nivo to interrogate the immunologic mechanisms of rela+nivo. Analysis of biospecimens from this ongoing trial demonstrated that rela+nivo led to enhanced capacity for CD8 T cell receptor signaling and altered CD8 T cell differentiation, leading to heightened cytotoxicity despite the retention of an exhaustion profile.

LAG-3 and PD-1 synergize on CD8 T cells to drive T cell exhaustion and hinder autocrine IFN-γ-dependent anti-tumor immunity.

Overcoming immune-mediated resistance to PD-1 blockade remains a major clinical challenge. Enhanced efficacy has been demonstrated in melanoma patients with combined nivolumab (anti-PD-1) and relatlimab (anti-LAG-3) treatment, the first in its class to be FDA approved. However, how these two inhibitory receptors synergize to hinder anti-tumor immunity remains unknown.

Multimodal investigation of neuropathology and neurometabolites in mild cognitive impairment and late-life depression with C-PiB beta-amyloid PET and 7T magnetic resonance spectroscopy.

Positron emission tomography (PET) and magnetic resonance spectroscopy (H-MRS) are complementary techniques that can be applied to study how proteinopathy and neurometabolism relate to cognitive deficits in preclinical stages of Alzheimer's disease (AD)-mild cognitive impairment (MCI) and late-life depression (LLD). We acquired beta-amyloid (Aβ) PET and 7 T H-MRS measures of GABA, glutamate, glutathione, N-acetylaspartate, N-acetylaspartylglutamate, myo-inositol, choline, and lactate in the anterior and posterior cingulate cortices (ACC, PCC) in 13 MCI and 9 LLD patients, and 13 controls. We used linear regression to examine associations between metabolites, Aβ, and cognitive scores, and whether metabolites and Aβ explained cognitive scores better than Aβ alone.

First impressions: Do faces with scars and palsies influence warmth, competence and humanization?

A glance is enough to assign psychological attributes to others. Attractiveness is associated with positive attributes ('beauty-is-good' stereotype). Here, we raise the question of a similar but negative bias.

Two high-quality genomes provide new insights into their evolution as obligate algal heterotrophs and their pathogenicity.

Unlabelled: The majority of the nearly 10,000 described species of green algae are photoautotrophs; however, some species have lost their ability to photosynthesize and become obligate heterotrophs that rely on parasitism for survival. Two high-quality genomes of the heterotrophic algae Pz20 and Pz23 were obtained using short- and long-read genomic as well as transcriptomic data. The genome sizes were 31.

A pilot dose-finding study of Terazosin in humans.

Background: Parkinson's disease (PD) is a prevalent neurodegenerative disorder where progressive neuron loss is driven by impaired brain bioenergetics, particularly mitochondrial dysfunction and disrupted cellular respiration. Terazosin (TZ), an α-1 adrenergic receptor antagonist with a known efficacy in treating benign prostatic hypertrophy and hypertension, has shown potential in addressing energy metabolism deficits associated with PD due to its action on phosphoglycerate kinase 1 (PGK1). This study aimed to investigate the safety, tolerability, bioenergetic target engagement, and optimal dose of TZ in neurologically healthy subjects.

Aplp1 interacts with Lag3 to facilitate transmission of pathologic α-synuclein.

Pathologic α-synuclein (α-syn) spreads from cell-to-cell, in part, through binding to the lymphocyte-activation gene 3 (Lag3). Here we report that amyloid β precursor-like protein 1 (Aplp1) interacts with Lag3 that facilitates the binding, internalization, transmission, and toxicity of pathologic α-syn. Deletion of both Aplp1 and Lag3 eliminates the loss of dopaminergic neurons and the accompanying behavioral deficits induced by α-syn preformed fibrils (PFF).

Cutting Edge: LAG3 Dimerization Is Required for TCR/CD3 Interaction and Inhibition of Antitumor Immunity.

Lymphocyte activation gene 3 (LAG3) is an inhibitory receptor that plays a critical role in controlling T cell tolerance and autoimmunity and is a major immunotherapeutic target. LAG3 is expressed on the cell surface as a homodimer but the functional relevance of this is unknown. In this study, we show that the association between the TCR/CD3 complex and a murine LAG3 mutant that cannot dimerize is perturbed in CD8+ T cells.

Variations in household water affordability and water insecurity: An intersectional perspective from 18 low- and middle-income countries.

Compounding systems of marginalization differentiate and shape water-related risks. Yet, quantitative water security scholarship rarely assesses such risks through intersectionality, a paradigm that conceptualizes and examines racial, gendered, class, and other oppressions as interdependent. Using an intersectionality approach, we analyze the relationships between household head gender and self-reported socio-economic status, and water affordability (proportion of monthly income spent on water) and water insecurity (a composite measure of 11 self-reported experiences) for over 4000 households across 18 low- and middle-income countries in Central and South America, Africa, and Asia.

Water Supply Interruptions Are Associated with More Frequent Stressful Behaviors and Emotions but Mitigated by Predictability: A Multisite Study.

Water supply interruptions contribute to household water insecurity. Unpredictable interruptions may particularly exacerbate water insecurity, as uncertainty limits households' ability to optimize water collection and storage or to modify other coping behaviors. This study used regression models of survey data from 2873 households across 10 sites in 9 middle-income countries to assess whether water supply interruptions and the predictability of interruptions were related to composite indicators of stressful behaviors and emotional distress.

Art therapy masks reflect emotional changes in military personnel with PTSS.

Among disabling post-traumatic stress symptoms (PTSS) are irritability, aggressive behavior, distressing memories and general impaired cognition and negative mood. Art therapy interventions, including mask-making, can potentially alleviate these symptoms. We tested the hypothesis that art conveys emotions and predicted that blinded viewers would be able to perceive changes in theoretically derived emotional profiles expressed in art made by military personnel with PTSS from the onset to the end of therapy.

The Effect of a Required 48-Hour Window to Schedule Genetic Counseling on Time From Diagnosis of Breast Cancer to Surgery.

Background: The length of time from diagnosis of breast cancer to surgery has steadily increased. Consultations and tests, in addition to a lack of available counseling programs, contribute to delays. Evidence suggests that delays between diagnosis and surgery may adversely affect patients.

Desert diversity: genome sequence of cluster DJ phage Mossy and cluster DV phage Erutan.

Lytic bacteriophages Mossy and Erutan were directly isolated from desert soil on and characterized by their morphologies and genomes. Mossy, part of the DJ cluster of Actinobacteriophage, has a genome of 61,183 bp. The genome of Erutan, part of the DV cluster, is 66,957 bp.

Musculoskeletal injuries during trail sports: Sex- and age-specific analyses over 20 years from a national injury database.

Introduction: Musculoskeletal (MSK) injuries in US trail sports are understudied as trail sport popularity grows. This study describes MSK injury patterns among hikers, trail runners, and mountain bikers from 2002 through 2021 and investigates MSK injury trends acquired during mountain sports.

Methods: The National Electronic Injury Surveillance System (NEISS) was used to identify US emergency department (ED) patients from 2002-2021 (inclusive) who endured MSK injuries during hiking, trail running, or mountain biking.

Codon-tRNA Coadaptation Bias for Identifying Strong Native Promoters in .

Promoters are crucial elements for engineering microbial production strains used in bioprocesses. For the increasingly popular chassis (formerly ), a limited number of well-characterized promoters constrain the data-driven engineering of production strains. Here, we present an approach for condition-independent identification of strong native promoters.