A Vulnerable Subtype of Dopaminergic Neurons Drives Early Motor Deficits in Parkinson's Disease.

In Parkinson's disease, dopaminergic neurons (DANs) in the midbrain gradually degenerate, with ventral substantia nigra pars compacta (SNc) DANs exhibiting greater vulnerability. However, it remains unclear whether specific molecular subtypes of ventral SNc DANs are more susceptible to degeneration in PD, and if they contribute to the early motor symptoms associated with the disease. We identified a subtype of + DANs, +, which are selectively lost earlier than other DANs, and with a time course that aligns with the development of motor symptoms in MitoPark mice.

Chromatin regulator HELLS mediates SSB repair and responses to DNA alkylation damage.

The SNF2 family chromatin remodeler HELLS has emerged as an important regulator of cell proliferation, genome stability, and several cancer pathways. Significant upregulation of HELLS has been reported in 33 human cancer types. While HELLS has been implicated in DNA damage response, its function in DNA repair is poorly understood.

HIF1α-regulated glycolysis promotes activation-induced cell death and IFN-γ induction in hypoxic T cells.

Hypoxia is a common feature in various pathophysiological contexts, including tumor microenvironment, and IFN-γ is instrumental for anti-tumor immunity. HIF1α has long been known as a primary regulator of cellular adaptive responses to hypoxia, but its role in IFN-γ induction in hypoxic T cells is unknown. Here, we show that the HIF1α-glycolysis axis controls IFN-γ induction in both human and mouse T cells, activated under hypoxia.

Evaluating urine volume and host depletion methods to enable genome-resolved metagenomics of the urobiome.

Background: The gut microbiome has emerged as a clear player in health and disease, in part by mediating host response to environment and lifestyle. The urobiome (microbiota of the urinary tract) likely functions similarly. However, efforts to characterize the urobiome and assess its functional potential have been limited due to technical challenges including low microbial biomass and high host cell shedding in urine.

Sex-specific diet differences in harbor seals () via spatial assortment.

The lack of recovery of Chinook salmon () in the Pacific Northwest has been blamed in part on predation by pinnipeds, particularly the harbor seal (). Previous work at a limited number of locations has shown that male seal diet contains more salmon than that of female seals and that sex ratios at haul-out sites differ spatiotemporally. This intrapopulation variation in predation may result in greater effects on salmon than suggested by models assuming equal spatial distribution and diet proportion.

Behavioral and social drivers of COVID-19 vaccination initiation in the US: a longitudinal study March─ October 2021.

Many studies have examined behavioral and social drivers of COVID-19 vaccination initiation, but few have examined these drivers longitudinally. We sought to identify the drivers of COVID-19 vaccination initiation using the Behavioral and Social Drivers of Vaccination (BeSD) Framework. Participants were a nationally-representative sample of 1,563 US adults who had not received a COVID-19 vaccine by baseline.

HIF1α-glycolysis engages activation-induced cell death to drive IFN-γ induction in hypoxic T cells.

The role of HIF1α-glycolysis in regulating IFN-γ induction in hypoxic T cells is unknown. Given that hypoxia is a common feature in a wide array of pathophysiological contexts such as tumor and that IFN-γ is instrumental for protective immunity, it is of great significance to gain a clear idea on this. Combining pharmacological and genetic gain-of-function and loss-of-function approaches, we find that HIF1α-glycolysis controls IFN-γ induction in both human and mouse T cells activated under hypoxia.

A machine learning one-class logistic regression model to predict stemness for single cell transcriptomics and spatial omics.

Cell annotation is a crucial methodological component to interpreting single cell and spatial omics data. These approaches were developed for single cell analysis but are often biased, manually curated and yet unproven in spatial omics. Here we apply a stemness model for assessing oncogenic states to single cell and spatial omic cancer datasets.

Complete genome sequence of the probiotic strain iVS-1.

iVS-1 is a human-isolated strain known to possess several probiotic properties. Here, its genome was completely sequenced to examine genes associated with lactose metabolism and other potentially beneficial traits, such as the production of folate and gamma-aminobutyric acid (GABA).

Droperidol undermining gastroparesis symptoms (DRUGS) in the emergency department.

Background/purpose: Gastroparesis is a syndrome of delayed gastric emptying without obstruction. There are high rates of Emergency Department (ED) visits due to gastroparesis, and this chronic disease is difficult to treat which often leads to hospital admissions. This study aimed to evaluate the impact droperidol administration has on opioid therapy, symptom relief, co-administration of antiemetic and prokinetic medications, disposition, cost, and length of stay (LOS) of patients presenting to the ED.

Dectin-3-targeted antifungal liposomes efficiently bind and kill diverse fungal pathogens.

DectiSomes are anti-infective drug-loaded liposomes targeted to pathogenic cells by pathogen receptors including the Dectins. We have previously used C-type lectin (CTL) pathogen receptors Dectin-1, Dectin-2, and DC-SIGN to target DectiSomes to the extracellular oligoglycans surrounding diverse pathogenic fungi and kill them. Dectin-3 (also known as MCL, CLEC4D) is a CTL pathogen receptor whose known cognate ligands are partly distinct from other CTLs.

DectiSomes: C-type lectin receptor-targeted liposomes as pan-antifungal drugs.

Combatting the ever-increasing threat from invasive fungal pathogens faces numerous fundamental challenges, including constant human exposure to large reservoirs of species in the environment, the increasing population of immunocompromised or immunosuppressed individuals, the unsatisfactory efficacy of current antifungal drugs and their associated toxicity, and the scientific and economic barriers limiting a new antifungal pipeline. DectiSomes represent a new drug delivery platform that enhances antifungal efficacy for diverse fungal pathogens and reduces host toxicity for current and future antifungals. DectiSomes employ pathogen receptor proteins - C-type lectins - to target drug-loaded liposomes to conserved fungal cognate ligands and away from host cells.

Emerging issues in probiotic safety: 2023 perspectives.

Probiotics are used for both generally healthy consumers and in clinical settings. However, theoretical and proven adverse events from probiotic consumption exist. New probiotic strains and products, as well as expanding use of probiotics into vulnerable populations, warrants concise, and actionable recommendations on how to work toward their safe and effective use.

Assessing the Suitability of a Virtual 'Pink Warrior' for Older Breast Cancer Survivors during COVID-19: A Pilot Study.

The COVID-19 pandemic impacted the conduct of in-person physical activity (PA) interventions among older survivors of BC, who need such interventions to stay active and prevent functional decline. We tested the feasibility of virtually delivering an exergame-based PA intervention to older BC survivors. We enrolled 20 female BC survivors ≥55 years and randomly assigned them to two groups.

Explaining demographic differences in COVID-19 vaccination stage in the United States - April-May 2021.

COVID-19 vaccine coverage in the US has marked demographic and geographical disparities, but few explanations exist for them. Our paper aimed to identify behavioral and social drivers that explain these vaccination disparities. Participants were a national probability sample of 3562 American adults, recruited from the Ipsos KnowledgePanel.

High-plex imaging of RNA and proteins at subcellular resolution in fixed tissue by spatial molecular imaging.

Resolving the spatial distribution of RNA and protein in tissues at subcellular resolution is a challenge in the field of spatial biology. We describe spatial molecular imaging, a system that measures RNAs and proteins in intact biological samples at subcellular resolution by performing multiple cycles of nucleic acid hybridization of fluorescent molecular barcodes. We demonstrate that spatial molecular imaging has high sensitivity (one or two copies per cell) and very low error rate (0.

The Chromatin Remodeler HELLS: A New Regulator in DNA Repair, Genome Maintenance, and Cancer.

Robust, tightly regulated DNA repair is critical to maintaining genome stability and preventing cancer. Eukaryotic DNA is packaged into chromatin, which has a profound, yet incompletely understood, regulatory influence on DNA repair and genome stability. The chromatin remodeler HELLS (helicase, lymphoid specific) has emerged as an important epigenetic regulator of DNA repair, genome stability, and multiple cancer-associated pathways.

Feasibility and Acceptability of an Active Video Game-Based Physical Activity Support Group (Pink Warrior) for Survivors of Breast Cancer: Randomized Controlled Pilot Trial.

Background: Survivors of breast cancer with functional limitations have a 40% higher mortality rate than those without. Despite the known benefits of physical activity (PA), <40% of survivors of breast cancer meet the recommendations for PA. The combination of active video games (AVGs) and group-based PA counseling may hold potential for motivating PA adoption and improving physical function.

Developmental basis of evolutionary lung loss in plethodontid salamanders.

One or more members of four living amphibian clades have independently dispensed with pulmonary respiration and lack lungs, but little is known of the developmental basis of lung loss in any taxon. We use morphological, molecular, and experimental approaches to examine the Plethodontidae, a dominant family of salamanders, all of which are lungless as adults. We confirm an early anecdotal report that plethodontids complete early stages of lung morphogenesis: Transient embryonic lung primordia form but regress by apoptosis before hatching.

A REVIEW OF LAWSUITS RELATED TO POINT-OF-CARE EMERGENCY ULTRASOUND APPLICATIONS.

Background: Previous investigators have assessed United States Case Law to evaluate the medicolegal risk surrounding point-of-care ultrasound applications. These studies have suggested that nonperformance is the primary source of an allegation of medical malpractice.

Objectives: The objective of this study is to update the literature regarding medical malpractice cases involving ultrasound applications that could be used at the point of care, and assess the risk conveyed to advanced practice providers and by application of emerging applications of ultrasound.