The Hao-Fountain syndrome protein USP7 regulates neuronal connectivity in the brain via a novel p53-independent ubiquitin signaling pathway.

Mutation or deletion of the deubiquitinase USP7 causes Hao-Fountain syndrome (HAFOUS), which is characterized by speech delay, intellectual disability, and aggressive behavior and highlights important unknown roles of USP7 in the nervous system. Here, we conditionally delete USP7 in glutamatergic neurons in the mouse forebrain, triggering disease-relevant phenotypes, including sensorimotor deficits, impaired cognition, and aggressive behavior. Although USP7 deletion induces p53-dependent neuronal apoptosis, most behavioral abnormalities in USP7 conditional knockout mice persist following p53 loss.

Substitution load revisited: a high proportion of deaths can be selective.

Haldane's Dilemma refers to the concern that the need for many "selective deaths" to complete a substitution (i.e. selective sweep) creates a speed limit to adaptation.

Recent Development of Nanoparticle Platforms for Organophosphate Nerve Agent Detoxification.

Poisoning by organophosphate (OP) nerve agents remains a pressing global threat due to their extensive use in chemical warfare agents and pesticides, potentially causing high morbidity and mortality worldwide. This urgent need for effective countermeasures has driven considerable interest in innovative detoxification approaches. Among these, nanoparticle technology stands out for its multifunctional potential and wide-ranging applications.

Impact of Combined Antiretroviral Treatment (cART) on Latent Cytomegalovirus Infection.

Cytomegalovirus infections and reactivations are more frequent in people living with HIV (PLWH) and have been associated with increased risk of HIV progression and immunosenescence. We explored the impact of combination antiretroviral therapy (cART) on latent CMV infection in 225 young adults parenterally infected with HIV during childhood. Anti-CMV IgG antibodies were present in 93.

Identifying Allosteric Small-Molecule Binding Sites of Inactive NS2B-NS3 Proteases of Pathogenic .

Dengue, West Nile, Zika, Yellow fever, and Japanese encephalitis viruses persist as significant global health threats. The development of new therapeutic strategies based on inhibiting essential viral enzymes or viral-host protein interactions is problematic due to the fast mutation rate and rapid emergence of drug resistance. This study focuses on the NS2B-NS3 protease as a promising target for antiviral drug development.

A Pilot Study Exploring the Relationship Between Milk Composition and Microbial Capacity in Breastfed Infants.

Background: Maternal obesity may contribute to childhood obesity in a myriad of ways, including through alterations of the infant gut microbiome. For example, maternal obesity may contribute both directly by introducing a dysbiotic microbiome to the infant and indirectly through the altered composition of human milk that fuels the infant gut microbiome. In particular, indigestible human milk oligosaccharides (HMOs) are known to shape the composition of the infant gut microbiome.

Alcohol Use Disorder and the Gut-Brain Axis: A Narrative Review of the Role of Gut Microbiota and Implications for Treatment.

Alcohol use disorder (AUD) affects millions of people worldwide and can lead to deleterious physical and social consequences. Recent research has highlighted not only the effect of alcohol on the gut microbiome, but also the role of the gut microbiome and the gut-brain axis in the development and maintenance of alcohol use disorder. This review provides an overview of the reciprocal relationship between alcohol consumption and the gut microbiome, including the effects of alcohol on gut microbial composition, changes in gut microbial metabolites in response to alcohol consumption, and how gut microbial metabolites may modulate alcohol use behavior.

A Biopsychosocial Overview of Speech Disorders: Neuroanatomical, Genetic, and Environmental Insights.

Speech disorders encompass a complex interplay of neuroanatomical, genetic, and environmental factors affecting individuals' communication ability. This review synthesizes current insights into the neuroanatomy, genetic underpinnings, and environmental influences contributing to speech disorders. Neuroanatomical structures, such as Broca's area, Wernicke's area, the arcuate fasciculus, and basal ganglia, along with their connectivity, play critical roles in speech production, comprehension, and motor coordination.

Outcomes of Idecabtagene Vicleucel Therapy in Patients with Relapsed/Refractory Multiple Myeloma: A Single-Institution Experience.

Idecabtagene vicleucel (ide-cel), an anti-B-cell maturation chimeric antigen receptor T-cell therapy, represents an unprecedented treatment option for relapsed/refractory multiple myeloma (R/R MM). Nevertheless, given its limitations, including the risk of adverse effects and unclear durability of efficacy, there remains a need to report the real-world clinical outcomes of ide-cel therapy in patients with R/R MM, as well as explore host predictive factors for therapy. We performed a single-center retrospective analysis of 25 adult patients with R/R MM who received ide-cel between 2021 and 2023 at the University of California San Diego Health.

Adaptive Evolutionary Optimization of Deep Learning Architectures for Focused Liver Ultrasound Image Segmentation.

Liver ultrasound segmentation is challenging due to low image quality and variability. While deep learning (DL) models have been widely applied for medical segmentation, generic pre-configured models may not meet the specific requirements for targeted areas in liver ultrasound. Quantitative ultrasound (QUS) is emerging as a promising tool for liver fat measurement; however, accurately segmenting regions of interest within liver ultrasound images remains a challenge.

Multiple regulators constrain the abundance of C. elegans DLK-1 in ciliated sensory neurons.

The conserved MAP3K DLKs are widely known for their functions in synapse formation, axonal regeneration and degeneration, and neuronal survival, notably under traumatic injury and chronic disease conditions. In contrast, their roles in other neuronal compartments are much less explored. Through an unbiased forward genetic screening in C.

Optimized genetic tools for neuroanatomical and functional mapping of the Aedes aegypti olfactory system.

The mosquito Aedes aegypti is an emerging model insect for invertebrate neurobiology. We detail the application of a dual transgenesis marker system that reports the nature of transgene integration with circular donor template for CRISPR-Cas9-mediated homology-directed repair at target mosquito chemoreceptor genes. Employing this approach, we demonstrate the establishment of cell-type-specific T2A-QF2 driver lines for the A.

Talin, a Rap1 effector for integrin activation at the plasma membrane, also promotes Rap1 activity by disrupting sequestration of Rap1 by SHANK3.

Talin regulates the adhesion and migration of cells in part by promoting the affinity of integrins for extracellular matrix proteins, a process that in cells such as endothelial cells and platelets requires the direct interaction of talin with both the small GTPase, Rap1-GTP, and the integrin β3 cytoplasmic tail. To study this process in more detail, we employed an optogenetic approach in living, immortalized endothelial cells to be able to regulate talin interaction with the plasma membrane. Previous studies identified talin as the Rap1-GTP effector for β3 integrin activation.

Antibody-Based Antigen Delivery to Dendritic Cells as a Vaccination Strategy Against Ebola Virus Disease.

Dendritic cells connect innate and adaptive immune responses. This is a particularly important immune checkpoint in the case of emerging infections against which most of the population does not have preexisting antibody immunity. In this study, we sought to test whether antibody-based delivery of Ebola virus (EBOV) antigens to dendritic cells could be used as a vaccination strategy against Ebola virus disease.

Delirium Management Quality Improvement Project to Improve Awareness and Screening in a Medical ICU.

Although delirium is common during critical illness, standard-of-care detection and prevention practices in real-world intensive care unit (ICU) settings remain inconsistent, often due to a lack of provider education. Despite availability for over 20 years of validated delirium screening tools such as the Confusion Assessment Method in the ICU (CAM-ICU), feasible and rigorous educational efforts continue to be needed to address persistent delirium standard-of-care practice gaps. Spanning an 8-month quality improvement project period, our single-ICU interdisciplinary effort involved delivery of CAM-ICU pocket cards to bedside nurses, and lectures by experienced champions that included a live delirium detection demonstration using the CAM-ICU, and a comprehensive discussion of evidence-based delirium prevention strategies (e.

Increased Growth Differentiation Factor 15 Levels Are Associated with HIV-Associated Neurocognitive Impairment: A Pilot Study.

: HIV-associated neurocognitive impairment (NCI) remains a prevalent issue among people with HIV (PWH) despite advancements in antiretroviral therapy (ART). The pathogenesis of HIV-associated NCI is linked to chronic neuroinflammation caused by HIV, even in those with successful viral suppression. Growth Differentiation Factor 15 (GDF15), a protein involved in inflammatory and metabolic stress responses, has emerged as a key player and potential biomarker for various neurological conditions.

Selectivity Effects of Hydrogen Acceptors and Catalyst Structures in Alcohol Oxidations Using (Cyclopentadienone)iron Tricarbonyl Compounds.

Oppenauer-type oxidations are catalyzed by air- and moisture-stable, sustainable, (cyclopentadienone)iron carbonyl compounds, but the substrate scope is limited due to the low reduction potential of acetone, which is the most commonly used hydrogen acceptor. We discovered that furfural, an aldehyde derived from cellulosic biomass, is an effective hydrogen acceptor with this class of catalysts. In general, reactions using furfural as the hydrogen acceptor led to higher isolated yields of ketones and aldehydes compared to those using acetone.

Through-the-sensor sub-bottom imaging using the self-noise of an autonomous underwater vehiclea).

This work demonstrates the feasibility of performing through-the-sensor (TTS) sub-bottom imaging using low-frequency ([100 Hz-1kHz]) self-noise generated by the propulsion of an autonomous underwater vehicle (AUV) acting as a source of opportunity. The self-noise was recorded by a short towed horizontal line array (11.4 m aperture) by the same AUV while it operated ∼35 m above the seabed along a range-dependent section at the New England shelf break.

Molecular-Scale Insights into the Heterogeneous Interactions between an -Terphenyl Isocyanide Ligand and Noble Metal Nanoparticles.

The structural and chemical properties of metal nanoparticles are often dictated by their interactions with molecular ligand shells. These interactions are highly material-specific and can vary significantly even among elements within the same group or materials with similar crystal structure. In this study, we surveyed the heterogeneous interactions between an -terphenyl isocyanide ligand and Au and Ag nanoparticles (NPs) at the single-molecule limit.

Deciphering the toxic effects of polystyrene nanoparticles on erythropoiesis at single-cell resolution.

Polystyrene nanoparticles pose significant toxicological risks to aquatic ecosystems, yet their impact on zebrafish ( ) embryonic development, particularly erythropoiesis, remains underexplored. This study used single-cell RNA sequencing to comprehensively evaluate the effects of polystyrene nanoparticle exposure on erythropoiesis in zebrafish embryos. validation experiments corroborated the transcriptomic findings, revealing that polystyrene nanoparticle exposure disrupted erythrocyte differentiation, as evidenced by the decrease in mature erythrocytes and concomitant increase in immature erythrocytes.

Production of real signs but not pseudosigns affected by age of acquisition in American Sign Language.

Research shows that insufficient language access in early childhood significantly affects language processing. While the majority of this work focuses on syntax, phonology also appears to be affected, though it is unclear exactly how. Here we investigated phonological production across age of acquisition of American Sign Language (ASL).

Redefining diagnostic lesional status in temporal lobe epilepsy with artificial intelligence.

Despite decades of advancements in diagnostic MRI, 30-50% of temporal lobe epilepsy (TLE) patients remain categorized as "non-lesional" (i.e., MRI negative or MRI-) based on visual assessment by human experts.