Spaceflight alters protein levels and gene expression associated with stress response and metabolic characteristics in human cardiac spheroids.

Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) possess tremendous advantage for cardiac regeneration. However, cell survival is challenging upon cell transplantation. Since microgravity can profoundly affect cellular properties, we investigated the effect of spaceflight on hiPSC-CMs.

Action inflexibility and compulsive-like behavior accompany neurobiological alterations in the anterior orbitofrontal cortex and associated striatal nuclei.

The orbitofrontal cortex (OFC) is a large cortical structure, expansive across anterior-posterior axes. It is essential for flexibly updating learned behaviors, and paradoxically, also implicated in inflexible and compulsive-like behaviors. Here, we investigated mice bred to display inflexible reward-seeking behaviors that are insensitive to action consequences.

Ultrastructural Localization of Glutamate Delta Receptor 1 in the Rodent and Primate Lateral Habenula.

Glutamate delta receptor 1 (GluD1) is a unique synaptogenic molecule expressed at excitatory and inhibitory synapses. The lateral habenula (LHb), a subcortical structure that regulates negative reward prediction error and major monoaminergic systems, is enriched in GluD1. LHb dysfunction has been implicated in psychiatric disorders such as depression and schizophrenia, both of which are associated with GRID1, the gene that encodes GluD1.

SIV Env RhmAbs + N-803 at ART initiation prolongs viral decay without disrupting reservoir establishment in SIV-infected infant macaques.

The latent viral reservoir remains the major barrier to HIV cure, placing the burden of strict adherence to antiretroviral therapy (ART) on people living with HIV to prevent recrudescence of viremia. For infants with perinatally acquired HIV, adherence is anticipated to be a lifelong need. In this study, we tested the hypothesis that administration of ART and viral Envelope-specific rhesus-derived IgG1 monoclonal antibodies (RhmAbs) with or without the IL-15 superagonist N-803 early in infection would limit viral reservoir establishment in SIV-infected infant rhesus macaques.

Role of follicular homing natural killer cells in HIV infection.

Purpose Of Review: Natural killer (NK) cells are integral components of the innate immune system, serving a vital function in eliminating virally infected cells. This review highlights the significance of CXCR5+ NK cells in the context of chronic HIV/SIV infection and viral control.

Recent Findings: Controlled HIV/SHIV infection results in a substantial increase in the population of CXCR5+ NK cells within the B-cell follicles of secondary lymphoid organs (SLOs).

Virulence and Replicative Fitness of HIV-1 Transmitted/Founder (T/F) Viruses Harbouring Drug Resistance-Associated Mutation.

The biological characteristics of early transmitted/founder (T/F) variants are crucial factors for viral transmission and constitute key determinants for the development of better therapeutics and vaccine strategies. The present study aimed to generate T/F viruses and to characterize their biological properties. For this purpose, we constructed 18 full-length infectious molecular clones (IMCs) of HIV from recently infected infants.

Induction of Tier 2 HIV-Neutralizing IgA Antibodies in Rhesus Macaques Vaccinated with BG505.664 SOSIP.

Background: A goal of mucosal human immunodeficiency virus type 1 (HIV-1) vaccines is to generate mucosal plasma cells producing polymeric IgA (pIgA)-neutralizing antibodies at sites of viral entry. However, vaccine immunogens capable of eliciting IgA neutralizing antibodies (nAbs) that recognize tier 2 viral isolates have not yet been identified.

Methods: To determine if stabilized native-like HIV-1 envelope (Env) trimers could generate IgA nAbs, we purified total IgA and IgG from the banked sera of six rhesus macaques that had been found in a previous study to develop serum nAbs after subcutaneous immunization with BG505.

Nanomedicine in Ophthalmology: From Bench to Bedside.

Ocular diseases such as cataract, refractive error, age-related macular degeneration, glaucoma, and diabetic retinopathy significantly impact vision and quality of life worldwide. Despite advances in conventional treatments, challenges like limited bioavailability, poor patient compliance, and invasive administration methods hinder their effectiveness. Nanomedicine offers a promising solution by enhancing drug delivery to targeted ocular tissues, enabling sustained release, and improving therapeutic outcomes.

Recurrent activity propagates through labile ensembles in macaque dorsolateral prefrontal microcircuits.

Human and non-human primate studies clearly implicate the dorsolateral prefrontal cortex (dlPFC) as critical for advanced cognitive functions. It is thought that intracortical synaptic architectures within the dlPFC are the integral neurobiological substrate that gives rise to these processes. In the prevailing model, each cortical column makes up one fundamental processing unit composed of dense intrinsic connectivity, conceptualized as the "canonical" cortical microcircuit.

Assessing serial recall as a measure of artificial grammar learning.

Introduction: Implicit statistical learning is, by definition, learning that occurs without conscious awareness. However, measures that putatively assess implicit statistical learning often require explicit reflection, for example, deciding if a sequence is 'grammatical' or 'ungrammatical'. By contrast, 'processing-based' tasks can measure learning without requiring conscious reflection, by measuring processes that are facilitated by implicit statistical learning.

Sequence order resolves ambiguity in a nonlinguistic visual categorization task.

When we encounter an unfamiliar word in a sentence, word order can be used to determine the grammatical category to which that word belongs and clarify ambiguity. However, it is unclear whether a similar categorization effect occurs in nonlinguistic contexts. We created three perceptually distinct categories of shape stimuli-rounded (A); squared (B); pointed (C).

SARS-CoV-2: The Interplay Between Evolution and Host Immunity.

The persistence of SARS-CoV-2 infections at a global level reflects the repeated emergence of variant strains encoding unique constellations of mutations. These variants have been generated principally because of a dynamic host immune landscape, the countermeasures deployed to combat disease, and selection for enhanced infection of the upper airway and respiratory transmission. The resulting viral diversity creates a challenge for vaccination efforts to maintain efficacy, especially regarding humoral aspects of protection.

Pathophysiology of Motor Control Abnormalities in Parkinson's Disease.

Research in the last few decades has brought us closer to an understanding of the brain circuit abnormalities that underlie parkinsonian motor signs. This article summarizes the current knowledge in this rapidly emerging field. Traditional observations of activity changes of basal ganglia neurons that accompany akinesia and bradykinesia have been supplemented with new knowledge regarding specific pathophysiologic changes that are associated with other parkinsonian signs, such as tremor and gait impairments.

Physics-guided multi-dimensional scan optimization and quasi-steady-state reconstruction to enhance CEST MRI sensitivity efficiency and quantification accuracy.

Chemical exchange saturation transfer (CEST) MRI has become increasingly utilized for detecting dilute labile protons and characterizing microenvironment properties. However, the CEST MRI effect is only a few percent, and there is a need for a systematic approach to optimize scan parameters for sensitive and accurate CEST quantification. We propose multi-dimensional adjustments of key parameters such as the repetition time (TR) and RF duty cycle to optimize CEST MRI sensitivity per unit of time and utilization of quasi-steady-state (QUASS) reconstruction to recover the full CEST effect during postprocessing.

Disruption of LEDGF/p75-directed integration derepresses antisense transcription of the HIV-1 genome.

Disruption of HIV-1 Integrase (IN) interactions with the host-factor Lens Epithelium-Derived Growth Factor (LEDGF)/p75 leads to decreased, random integration, increased latent infection, and described here, accumulation of HIV-1 antisense RNA (asRNA). asRNA increase was observed following interruptions of IN-LEDGF/p75 interactions either through pharmacologic perturbations of IN-LEDGF/p75 by treatment with allosteric HIV-1 integrase inhibitors (ALLINIs) or in cell lines with LEDGF genetic knockout. Additionally, by impairing Tat-dependent HIV transcription, asRNA abundance markedly increases.

Transcriptomic landscape of mammalian ventral pallidum at single-cell resolution.

The ventral pallidum (VP) is critical for motivated behaviors. While contemporary work has begun to elucidate the functional diversity of VP neurons, the molecular heterogeneity underlying this functional diversity remains incompletely understood. We used single-nucleus RNA sequencing and in situ hybridization to define the transcriptional taxonomy of VP cell types in mice, macaques, and baboons.

Folate prevents the autism-related phenotype caused by developmental pyrethroid exposure in prairie voles.

Neurodevelopmental disorders (NDDs) have dramatically increased in prevalence to an alarming one in six children, and yet both causes and preventions remain elusive. Recent human epidemiology and animal studies have implicated developmental exposure to pyrethroid pesticides, one of the most common classes of pesticides in the US, as an environmental risk factor for autism and neurodevelopmental disorders. Our previous research has shown that low-dose chronic developmental pyrethroid exposure (DPE) changes folate metabolites in the adult mouse brain.

Effects of early maternal care on anxiety and threat learning in adolescent nonhuman primates.

Early life adverse experiences, including childhood maltreatment, are major risk factors for psychopathology, including anxiety disorders with dysregulated fear responses. Consistent with human studies, maltreatment by the mother (MALT) leads to increased emotional reactivity in rhesus monkey infants. Whether this persists and results in altered emotion regulation, due to enhanced fear learning or impaired utilization of safety signals as shown in human stress-related disorders, is unclear.

Phenotypic Characterization of Subtype A and Recombinant AC Transmitted/Founder Viruses from a Rwandan HIV-1 Heterosexual Transmission Cohort.

HIV-1 subtypes have distinct geographical distributions, with subtypes A, C, and D and inter-subtype recombinants circulating in sub-Saharan Africa. Historically, individuals living with subtype A viruses exhibit slower CD4 decline and progression to AIDS diagnosis. Despite this, there are few authentic infectious molecular clones (IMCs) of subtype A or AC recombinant transmitted founder (TF) viruses with which to investigate viral impacts on pathogenesis.

Comparative lifespan and healthspan of nonhuman primate species common to biomedical research.

There is a critical need to generate age- and sex-specific survival curves to characterize chronological aging consistently across nonhuman primates (NHP) used in biomedical research. Sex-specific Kaplan-Meier survival curves were computed in 12 translational aging models: baboon, bonnet macaque, chimpanzee, common marmoset, coppery titi monkey, cotton-top tamarin, cynomolgus macaque, Japanese macaque, pigtail macaque, rhesus macaque, squirrel monkey, and vervet/African green. After employing strict inclusion criteria, primary results are based on 12,269 NHPs that survived to adulthood and died of natural/health-related causes.

Attrition in serum anti-DENV antibodies correlates with high anti-SARS-CoV-2 IgG levels and low DENV positivity in mosquito vectors-Findings from a state-wide cluster-randomized community-based study in Tamil Nadu, India.

The decline in dengue incidence and/or prevalence during the COVID-19 pandemic (2020-22) appears to be attributed to reduced treatment-seeking rates, under-reporting, misdiagnosis, disrupted health services and reduced exposure to mosquito vectors due to prevailing lockdowns. There is limited scientific data on dengue virus (DENV) disease during the COVID-19 pandemic. Here, we conducted a community-based, cross-sectional, cluster-randomized survey to assess anti-DENV and anti-SARS-CoV-2 seroprevalence, and also estimated the spatial distribution of DENV-positive aedine mosquito vectors during the COVID-19 pandemic across all the 38 districts of Tamil Nadu, India.

Regulator of G protein signalling 14 (RGS14) protein expression profile in the adult mouse brain.

Regulator of G protein signalling 14 (RGS14) is a multifunctional signalling protein that serves as a natural suppressor of synaptic plasticity in the mouse brain. Our previous studies showed that RGS14 is highly expressed in postsynaptic dendrites and spines of pyramidal neurons in hippocampal area CA2 of the developing mouse brain. However, our more recent work with monkey brain shows that RGS14 is found in multiple neuron populations throughout hippocampal area CA1 and CA2, caudate nucleus, putamen, globus pallidus, substantia nigra and amygdala.

New MiniPromoter Ple389 (ADORA2A) drives selective expression in medium spiny neurons in mice and non-human primates.

Compact cell type-specific promoters are important tools for basic and preclinical research and clinical delivery of gene therapy. In this work, we designed novel MiniPromoters to target D1 and D2 type dopaminoceptive medium spiny neurons in the striatum by manually identifying candidate regulatory regions or employing the OnTarget webserver. We then empirically tested the designs in rAAV-PHP.

Intra-tumoral YAP and TAZ heterogeneity drives collective NSCLC invasion that is targeted by SUMOylation inhibitor TAK-981.

Non-small cell lung cancer (NSCLC) collective invasion is supported by cooperativity of proliferative (follower) and invasive (leader) cells. H1299-isolated follower cells exhibit higher Yes-associated protein (YAP) expression, while leader cells were found to express elevated transcriptional coactivator with PDZ-binding motif (TAZ/WWTR1) expression. Suppressing TAZ (not YAP) in leader cells reduced invasion.

Motion and magnetic field inhomogeneity correction techniques for chemical exchange saturation transfer (CEST) MRI: A contemporary review.

Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) has emerged as a powerful imaging technique sensitive to tissue molecular composition, pH, and metabolic processes in situ. CEST MRI uniquely probes the physical exchange of protons between water and specific molecules within tissues, providing a window into physiological phenomena that remain invisible to standard MRI. However, given the very low concentration (millimolar range) of CEST compounds, the effects measured are generally only on the order of a few percent of the water signal.