Distinct outcomes from targeted perturbations of the multi-subunit SCF E3 ubiquitin ligase in blocking Trp53/Rb1-null prostate tumorigenesis.

Identifying effective therapies targeting multi-protein complexes that lack catalytic sites or cofactor pockets remains a long-standing challenge. The proto-oncogene, ubiquitin E3 ligase SCF, is one such target. SCF promotes the proteasomal degradation of the cyclin-dependent kinase inhibitor p27, which controls cell cycle progression.

Variation in plumage reflectance but not song reflects spatial cognitive performance in black-capped chickadees (Poecile atricapillus).

In seasonally variable environments, enhanced cognitive abilities may allow animals to adjust their behavior to changing conditions. Nonmigratory food-caching birds, like chickadees, rely on specialized spatial cognition to successfully cache and retrieve food items and survive the winter. Previous studies have linked spatial cognitive performance in chickadees to enhanced fitness, including survival and reproduction; however, it remains unknown whether females assess male cognitive ability via direct observation or secondary sexual traits.

Intranasal long R3 insulin-like growth factor-1 treatment promotes amyloid plaque remodeling in cerebral cortex but fails to preserve cognitive function in male 5XFAD mice.

Background: Insulin-like growth factor-1 (IGF-1) promotes neurogenesis, cell survival, and glial function, making it a promising candidate therapy in Alzheimer's disease (AD).

Objective: Long arginine 3-IGF-1 (LR3-IGF-1) is a potent IGF-1 analogue. We sought to determine whether intranasal (IN) LR3 treatment would delay cognitive decline and pathology in 5XFAD mice.

Drug-drug interactions in HIV-infected patients receiving chemotherapy.

Introduction: Coadministration of antiretrovirals and anti-cancer medications may present many complex clinical scenarios. This is characterized by the potential for drug-drug interactions (DDIs) and the challenges that arise in patient management. In this article, we investigate the potential for DDIs between antiretrovirals, including protease inhibitors (PIs), non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs), integrase strand transfer inhibitors (INSTIs), and anti-cancer medications.

Spatial cognitive ability is associated with longevity in food-caching chickadees.

Cognitive abilities are hypothesized to affect survival and life span in nonhuman animals. However, most tests of this hypothesis have relied on interspecific comparisons of indirect measures of cognitive ability, such as brain size. We present direct evidence that individual variation in cognitive abilities is associated with differences in life span in a wild food caching bird.

Relative breeding timing and reproductive success of a resident montane bird species.

Wild populations appear to synchronize their reproductive phenology based on numerous environmental and ecological factors; yet, there is still individual variation in the timing of reproduction within populations and such variation may be associated with fitness consequences. For example, many studies have documented a seasonal decline in reproductive fitness, but breeding timing may have varying consequences across different environments. Using 11 years of data, we investigated the relationship between relative breeding timing and reproductive success in resident mountain chickadees () across two elevational bands in the Sierra Nevada mountains, USA.

Racial (In)Equity in South Los Angeles-Community Centered Experiences with COVID-19 Syndemics.

Objectives: To analyze community experiences involving COVID-19 vaccination access and equity in Black and Latina/o/x communities within South Los Angeles, using a socioecological framework.

Methods: We conducted four virtual focus groups ( = 33 total participants) in 2021, with Black and Latina/o/x community members, community leaders, and community-based providers in South Los Angeles, a region highly impacted by the COVID-19 pandemic. We used a grounded theory approach to guide the analysis and generate data shaped by participant perspectives.

Genes and gene networks underlying spatial cognition in food-caching chickadees.

Substantial progress has been made in understanding the genetic architecture of phenotypes involved in a variety of evolutionary processes. Behavioral genetics remains, however, among the least understood. We explore the genetic architecture of spatial cognitive abilities in a wild passerine bird, the mountain chickadee (Poecile gambeli).

ANKS1B encoded AIDA-1 regulates social behaviors by controlling oligodendrocyte function.

Heterozygous deletions in the ANKS1B gene cause ANKS1B neurodevelopmental syndrome (ANDS), a rare genetic disease characterized by autism spectrum disorder (ASD), attention deficit/hyperactivity disorder, and speech and motor deficits. The ANKS1B gene encodes for AIDA-1, a protein that is enriched at neuronal synapses and regulates synaptic plasticity. Here we report an unexpected role for oligodendroglial deficits in ANDS pathophysiology.

Evolving brain and behaviour changes in rats following repetitive subconcussive head impacts.

There is growing concern that repetitive subconcussive head impacts, independent of concussion, alter brain structure and function, and may disproportionately affect the developing brain. Animal studies of repetitive subconcussive head impacts are needed to begin to characterize the pathological basis and mechanisms underlying imaging and functional effects of repetitive subconcussive head impacts seen in humans. Since repetitive subconcussive head impacts have been largely unexplored in animals, we aimed to characterize the evolution of imaging, behavioural and pathological effects of repetitive subconcussive head impacts in awake adolescent rodents.

What's in a mate? Social pairing decisions and spatial cognitive ability in food-caching mountain chickadees.

While researchers have investigated mating decisions for decades, gaps remain in our understanding of how behaviour influences social mate choice. We compared spatial cognitive performance and food caching propensity within social pairs of mountain chickadees inhabiting differentially harsh winter climates to understand how these measures contribute to social mate choice. Chickadees rely on specialized spatial cognitive abilities to recover food stores and survive harsh winters, and females can discriminate among males with varying spatial cognition.

Food-caching chickadees with specialized spatial cognition do not use scrounging as a stable strategy when learning a spatial task.

Social animals may use alternative strategies when foraging, with producer-scrounger being one stable dichotomy of strategies. While 'producers' search and discover new food sources, 'scroungers' obtain food discovered by producers. Previous work suggests that differences in cognitive abilities may influence tendencies toward being either a producer or a scrounger, but scrounging behaviour in the context of specialized cognitive abilities is less understood.

Complex relationships between climate and reproduction in a resident montane bird.

Animals use climate-related environmental cues to fine-tune breeding timing and investment to match peak food availability. In birds, spring temperature is a commonly documented cue used to initiate breeding, but with global climate change, organisms are experiencing both directional changes in ambient temperatures and extreme year-to-year precipitation fluctuations. Montane environments exhibit complex climate patterns where temperatures and precipitation change along elevational gradients, and where exacerbated annual variation in precipitation has resulted in extreme swings between heavy snow and drought.

The 17-Gene Genomic Prostate Score Assay Is Prognostic for Biochemical Failure in Men With Localized Prostate Cancer After Radiation Therapy at a Community Cancer Center.

Purpose: The objective of this study was to assess the association between the Oncotype DX Genomic Prostate Score (GPS) assay and long-term outcomes in men with localized prostate cancer (PCa) after radiation therapy (RT). We hypothesized that the GPS assay is prognostic for biochemical failure (BCF), along with distant metastasis (DM) and PCa-specific mortality in patients with PCa receiving RT.

Methods And Materials: We retrospectively studied men with localized PCa treated with definitive RT at Georgia Urology from 2010 to 2016.

Lessons Learned about Developing Faith and Public Health Partnerships to Address Health Disparities.

Partnerships between public health and faith-based organizations draw on the strengths of both sectors to achieve a shared interest in promoting health and reducing disparities. However, information about implementation of faith and public health partnerships-particularly those involving diverse racial-ethnic groups-is limited. This paper reports on findings from qualitative interviews conducted with 16 public health and congregational leaders around the country as part of the early phase of the development of a faith and public health partnership to address health disparities in Los Angeles, CA.

Evidence for preserved insulin responsiveness in the aging rat brain.

Insulin appears to exert salutary effects in the central nervous system (CNS). Thus, brain insulin resistance has been proposed to play a role in brain aging and dementia but is conceptually complex and unlikely to fit classic definitions established in peripheral tissues. Thus, we sought to characterize brain insulin responsiveness in young (4-5 months) and old (24 months) FBN male rats using a diverse set of assays to determine the extent to which insulin effects in the CNS are impaired with age.

Corrected cerebral blood flow and reduced cerebral inflammation in berk sickle mice with higher fetal hemoglobin.

Fetal hemoglobin (HbF) is known to lessen the severity of sickle cell disease (SCD), through reductions in peripheral vaso-occlusive disease and reduced risk for cerebrovascular events. However, the influence of HbF on oxygen delivery to high metabolism tissues like the brain, or its influence on cerebral perfusion, metabolism, inflammation or function have not been widely studied. We employed a Berkley mouse model (BERK) of SCD with gamma transgenes q3 expressing exclusively human α- and β-globins with varying levels of γ globin expression to investigate the effect of HbF expression on the brain using magnetic resonance imaging (MRI), MRI diffusion tensor imaging (DTI) and spectroscopy (MRS) and hematological parameters.

The genetic basis of spatial cognitive variation in a food-caching bird.

Spatial cognition is used by most organisms to navigate their environment. Some species rely particularly heavily on specialized spatial cognition to survive, suggesting that a heritable component of cognition may be under natural selection. This idea remains largely untested outside of humans, perhaps because cognition in general is known to be strongly affected by learning and experience.

Quercetin Completely Ameliorates Hypoxia-Reoxygenation-Induced Pathophysiology Severity in NY1DD Transgenic Sickle Mice: Intrinsic Mild Steady State Pathophysiology of the Disease in NY1DD Is Also Reversed.

The vaso-occlusive crisis (VOC) is a major complication of sickle cell disease (SCD); thus, strategies to ameliorate vaso-occlusive episodes are greatly needed. We evaluated the therapeutic benefits of quercetin in a SCD transgenic sickle mouse model. This disease model exhibited very mild disease pathophysiology in the steady state.

Defective myelination in an RNA polymerase III mutant leukodystrophic mouse.

RNA polymerase (Pol) III synthesizes abundant short noncoding RNAs that have essential functions in protein synthesis, secretion, and other processes. Despite the ubiquitous functions of these RNAs, mutations in Pol III subunits cause Pol III-related leukodystrophy, an early-onset neurodegenerative disease. The basis of this neural sensitivity and the mechanisms of disease pathogenesis are unknown.