Demographic disparities in access to COVID-19 clinical trial sites across the United States: a geospatial analysis.

Throughout the COVID-19 pandemic, underserved populations, such as racial and ethnic minority communities, were disproportionately impacted by illness and death. Ensuring people from diverse backgrounds have the ability to participate in clinical trials is key to advancing health equity. We sought to analyze the spatial variability in locations of COVID-19 trials sites and to test associations with demographic correlates.

BCL6 coordinates muscle mass homeostasis with nutritional states.

Nutritional status is a determining factor for growth during development and homeostatic maintenance in adulthood. In the context of muscle, growth hormone (GH) coordinates growth with nutritional status; however, the detailed mechanisms remain to be fully elucidated. Here, we show that the transcriptional repressor B cell lymphoma 6 (BCL6) maintains muscle mass by sustaining GH action.

Targeting ROR2 homooligomerization disrupts ROR2-dependent signaling and suppresses stem-like cell properties of human breast adenocarcinoma.

Breast cancer stem-like cells (CSCs) are enriched following treatment with chemotherapy, and posited as having a high level of plasticity and enhanced tumor-initiation capacity, which can enable cancer relapse. Here, we show that such features are shared by breast cancer (BCA) cells that express receptor tyrosine kinase-like orphan receptor (ROR2), which is expressed primarily during embryogenesis and by various cancers. We find that Wnt5a can induce ROR2 homooligomerization to activate noncanonical Wnt signaling and enhance tumor-initiation capacity of BCA cells.

Tailoring implementation strategies for the healthy actions and lifestyles to Avoid Dementia or Hispanos y el ALTo a la Demencia Program: Lessons learned from a survey study.

Background: Healthy Actions and Lifestyles to Avoid Dementia Program (HALT-AD) or Hispanos y el ALTo a la Demencia is a recently-developed online educational platform to help individuals identify and modify their own dementia modifiable risk factors (MRF). In light of known challenges in recruiting and retaining diverse participants in research studies, there is a need to identify data-informed strategies that will contribute to effective outreach and tailored implementation of HALT-AD among its intended users of Hispanic and non-Hispanic midlife and older adults in the US.

Objectives: To identify factors (i.

Targeting CD45 by gene-edited CAR T cells for leukemia eradication and hematopoietic stem cell transplantation preconditioning.

Hematopoietic stem cell transplantation (HSCT) is widely used to treat patients with life-threatening hematologic and immune system disorders. Current nontargeted chemo-/radiotherapy conditioning regimens cause tissue injury and induce an array of immediate and delayed adverse effects, limiting the application of this life-saving treatment. The growing demand to replace canonical conditioning regimens has led to the development of alternative approaches, such as antibody-drug conjugates, naked antibodies, and CAR T cells.

Optimization of a micro-scale air-liquid-interface model of human proximal airway epithelium for moderate throughput drug screening for SARS-CoV-2.

Background: Many respiratory viruses attack the airway epithelium and cause a wide spectrum of diseases for which we have limited therapies. To date, a few primary human stem cell-based models of the proximal airway have been reported for drug discovery but scaling them up to a higher throughput platform remains a significant challenge. As a result, most of the drug screening assays for respiratory viruses are performed on commercial cell line-based 2D cultures that provide limited translational ability.

A Roadmap Towards the Identification and Validation of Conserved T Cell Epitope Regions in Viral Pathogen Families with Pandemic Potential.

The SARS-CoV-2 pandemic has highlighted the need for society, as a whole, to be prepared against potential pandemics caused by a variety of different viral families of concern. Here, we describe a roadmap towards the identification and validation of conserved T cell epitope regions from Viral Families of Pandemic Potential (VFPP). For each viral family, we select a prototype virus, the sequence of which could be utilized in epitope identification screens.

Random noise promotes slow heterogeneous synaptic dynamics important for robust working memory computation.

Recurrent neural networks (RNNs) based on model neurons that communicate via continuous signals have been widely used to study how cortical neural circuits perform cognitive tasks. Training such networks to perform tasks that require information maintenance over a brief period (i.e.

Brain aging rejuvenation factors in adults with genetic and sporadic neurodegenerative disease.

The largest risk factor for dementia is age. Heterochronic blood exchange studies have uncovered age-related blood factors that demonstrate 'pro-aging' or 'pro-youthful' effects on the mouse brain. The clinical relevance and combined effects of these factors for humans is unclear.

Advances in the development of microarray patches in biomedicine.

Microarray patches (MAPs) have been employed to deliver therapeutic payloads and for detection purposes. Research has been conducted to develop novel designs in material chemistry and the architecture of microarray, which have opened up the possibility for broader applications of MAPs. However, MAPs have yet to be clinically implemented fully.

CFTR dictates monocyte adhesion by facilitating integrin clustering but not activation.

Monocytes are critical in controlling tissue infections and inflammation. Monocyte dysfunction contributes to the inflammatory pathogenesis of cystic fibrosis (CF) caused by CF transmembrane conductance regulator (CFTR) mutations, making CF a clinically relevant disease model for studying the contribution of monocytes to inflammation. Although CF monocytes exhibited adhesion defects, the precise mechanism is unclear.

Antibody-drug conjugates targeting SSEA-4 inhibits growth and migration of SSEA-4 positive breast cancer cells.

Although breast cancer treatment has evolved significantly in recent years, drug resistance remains a major challenge. To identify new targets for breast cancer, we found that stage-specific embryonic antigen 4 (SSEA-4) is expressed in all subtypes of breast cancer cell lines, and the increased expression of the associated enzymes β3GalT5 and ST3Gal2 correlates with poor recurrence-free survival (RFS) in breast cancer. We also found that SSEA-4 antibodies can be rapidly internalized into breast cancer cells, a property that makes SSEA-4 an attractive target for antibody-drug conjugates (ADCs).

Visualizing lipid nanoparticle trafficking for mRNA vaccine delivery in non-human primates.

mRNA delivered using lipid nanoparticles (LNPs) has become an important subunit vaccine modality, but mechanisms of action for mRNA vaccines remain incompletely understood. Here, we synthesized a metal chelator-lipid conjugate enabling positron emission tomography (PET) tracer labeling of LNP/mRNA vaccines for quantitative visualization of vaccine trafficking in live mice and non-human primates (NHPs). Following i.

Identifying Strong Neoantigen MHC-I/II Binding Candidates for Targeted Immunotherapy with SINE.

The discovery of tumor-derived neoantigens which elicit an immune response through major histocompatibility complex (MHC-I/II) binding has led to significant advancements in immunotherapy. While many neoantigens have been discovered through the identification of non-synonymous mutations, the rate of these is low in some cancers, including head and neck squamous cell carcinoma. Therefore, the identification of neoantigens through additional means, such as aberrant splicing, is necessary.

A single-nuclei transcriptome census of the Arabidopsis maturing root identifies that MYB67 controls phellem cell maturation.

The periderm provides a protective barrier in many seed plant species. The development of the suberized phellem, which forms the outermost layer of this important tissue, has become a trait of interest for enhancing both plant resilience to stresses and plant-mediated CO sequestration in soils. Despite its importance, very few genes driving phellem development are known.

Radiosynthesis and evaluation of novel F labeled PET ligands for imaging monoacylglycerol lipase.

Monoacylglycerol lipase (MAGL) is a 33 kDa cytosolic serine hydrolase that is widely distributed in the central nervous system and peripheral tissues. MAGL hydrolyzes monoacylglycerols into fatty acids and glycerol, playing a crucial role in endocannabinoid degradation. Inhibition of MAGL in the brain elevates levels of 2-arachidonoylglycerol and leads to decreased pro-inflammatory prostaglandin and thromboxane production.

Tungsten is utilized for lactate consumption and SCFA production by a dominant human gut microbe .

is a dominant member of the human gut microbiome and produces short-chain fatty acids (SCFAs). These promote immune system function and inhibit inflammation, making this microbe important for human health. Lactate is a primary source of gut SCFAs but its utilization by has not been explored.

ANAC044 orchestrates mitochondrial stress signaling to trigger iron-induced stem cell death in root meristems.

While iron (Fe) is essential for life and plays important roles for almost all growth related processes, it can trigger cell death in both animals and plants. However, the underlying mechanisms for Fe-induced cell death in plants remain largely unknown. S-nitrosoglutathione reductase (GSNOR) has previously been reported to regulate nitric oxide homeostasis to prevent Fe-induced cell death within root meristems.

Astrocytes in aging.

The mammalian nervous system is impacted by aging. Aging alters brain architecture, is associated with molecular damage, and can manifest with cognitive and motor deficits that diminish the quality of life. Astrocytes are glial cells of the CNS that regulate the development, function, and repair of neural circuits during development and adulthood; however, their functions in aging are less understood.

Physiologic and structural characterization of desisobutyryl-ciclesonide, a selective glucocorticoid receptor modulator in newborn rats.

Bronchopulmonary dysplasia, the most prevalent chronic lung disease of prematurity, is often treated with glucocorticoids (GCs) such as dexamethasone (DEX), but their use is encumbered with several adverse somatic, metabolic, and neurologic effects. We previously reported that systemic delivery of the GC prodrug ciclesonide (CIC) in neonatal rats activated glucocorticoid receptor (GR) transcriptional responses in lung but did not trigger multiple adverse effects caused by DEX. To determine whether limited systemic metabolism of CIC was solely responsible for its enhanced safety profile, we treated neonatal rats with its active metabolite desisobutyryl-ciclesonide (Des-CIC).

YAP-driven malignant reprogramming of oral epithelial stem cells at single cell resolution.

Tumor initiation represents the first step in tumorigenesis during which normal progenitor cells undergo cell fate transition to cancer. Capturing this process as it occurs in vivo, however, remains elusive. Here we employ spatiotemporally controlled oncogene activation and tumor suppressor inhibition together with multiomics to unveil the processes underlying oral epithelial progenitor cell reprogramming into tumor initiating cells at single cell resolution.

Induced cell phenotype activity recording of DNA-tagged ligands.

Based on their ability to canvas vast genetic or chemical space at low cost and high speed, DNA-encoded libraries (DEL) have served to enable both genomic and small molecule discovery. Current DEL chemical library screening approaches focus primarily on target-based affinity or activity. Here we describe an approach to record the phenotype-based activity of DNA-encoded small molecules on their cognate barcode in living cells.

Tungsten-catalyzed stereodivergent isomerization of terminal olefins.

Catalytic alkene isomerization is a powerful synthetic strategy for preparing valuable internal alkenes from simple feedstocks. The utility of olefin isomerization hinges on the ability to control both positional and stereoisomerism to access a single product among numerous potential isomers. Within base-metal catalysis, relatively little is known about how to modulate reactivity and selectivity with group 6 metal-catalyzed isomerization.