The relationship between neutral genetic diversity and performance in wild arthropod populations.

Larger effective populations (Ne) are characterized by higher genetic diversity, which is expected to predict population performance (average individual performance that influences fitness). Empirical studies of the relationship between neutral diversity and performance mostly represent species with small Ne, while there is limited data from the species-rich and ecologically important arthropods that are assumed to have large Ne but are threatened by massive declines. We performed a systematic literature search and used meta-analytical models to test the prediction of a positive association between neutral genetic diversity and performance in wild arthropods.

Discovery of the first selective, small-molecule GFRα2/3 inhibitors through DNA-encoded library technology.

Studies have shown that disrupting the formation of the ligand-RET-GFRα complex could be an effective way of treating pain and itch. Compared to traditional high-throughput screens, DNA encoded libraries (DELs) have distinguished themselves as a powerful technology for hit identification in recent years. The present work demonstrates the use of DEL technology identifying compound 16 as the first GFRa2/GFRa3 small molecule inhibitor (0.

Bortezomib-induced neurotoxicity in human neurons is the consequence of nicotinamide adenine dinucleotide depletion.

The proteosome inhibitor bortezomib has revolutionized the treatment of multiple hematologic malignancies, but in many cases, its efficacy is limited by a dose-dependent peripheral neuropathy. We show that human induced pluripotent stem cell (hiPSC)-derived motor neurons and sensory neurons provide a model system for the study of bortezomib-induced peripheral neuropathy, with promising implications for furthering the mechanistic understanding of and developing treatments for preventing axonal damage. Human neurons in tissue culture displayed distal-to-proximal neurite degeneration when exposed to bortezomib.

A Pharmacist-Driven Glycemic Control Protocol to Reduce the Rate of Severe Hypoglycemia in High-Risk Patients.

Hospital pharmacists contribute to patient safety and quality initiatives by overseeing the prescribing of antidiabetic medications. A pharmacist-driven glycemic control protocol was developed to reduce the rate of severe hypoglycemia events (SHE) in high-risk hospitalized patients. We retrospectively analyzed the rates of SHE (defined as blood glucose ≤40 mg/dL), before and after instituting a pharmacist-driven glycemic control protocol over a 4-year period.

An expert-curated global database of online newspaper articles on spiders and spider bites.

Mass media plays an important role in the construction and circulation of risk perception associated with animals. Widely feared groups such as spiders frequently end up in the spotlight of traditional and social media. We compiled an expert-curated global database on the online newspaper coverage of human-spider encounters over the past ten years (2010-2020).

β spectrin-dependent and domain specific mechanisms for Na channel clustering.

Previously, we showed that a hierarchy of spectrin cytoskeletal proteins maintains nodal Na channels (Liu et al., 2020). Here, using mice lacking β1, β4, or β1/β4 spectrins, we show this hierarchy does not function at axon initial segments (AIS).

NuMA1 promotes axon initial segment assembly through inhibition of endocytosis.

Axon initial segments (AISs) initiate action potentials and regulate the trafficking of vesicles between somatodendritic and axonal compartments. However, the mechanisms controlling AIS assembly remain poorly defined. We performed differential proteomics and found nuclear mitotic apparatus protein 1 (NuMA1) is downregulated in AIS-deficient neonatal mouse brains and neurons.

The adhesion-GPCR BAI1 shapes dendritic arbors via Bcr-mediated RhoA activation causing late growth arrest.

Dendritic arbor architecture profoundly impacts neuronal connectivity and function, and aberrant dendritic morphology characterizes neuropsychiatric disorders. Here, we identify the adhesion-GPCR BAI1 as an important regulator of dendritic arborization. BAI1 loss from mouse or rat hippocampal neurons causes dendritic hypertrophy, whereas BAI1 overexpression precipitates dendrite retraction.

Diltiazem Promotes Regenerative Axon Growth.

Axotomy results in permanent loss of function after brain and spinal cord injuries due to the minimal regenerative propensity of the adult central nervous system (CNS). To identify pharmacological enhancers of axon regeneration, 960 compounds were screened for cortical neuron axonal regrowth using an in vitro cortical scrape assay. Diltiazem, verapamil, and bromopride were discovered to facilitate axon regeneration in rat cortical cultures, in the presence of chondroitin sulfate proteoglycans (CSPGs).

Evaluation and management of adult acquired buried penis.

Adult acquired buried penis represents the clinical manifestation of a wide spectrum of pathology due to a variety of etiologies. It can be related to obesity, a laxity in connective tissue, lichen sclerosis (LS), complications from penile/scrotal enlargement surgery, scrotal lymphedema, or hidradenitis suppurativa (HS). Buried penis can be associated with poor cosmesis and hygiene, voiding dysfunction, and sexual dysfunction.

Axonal G3BP1 stress granule protein limits axonal mRNA translation and nerve regeneration.

Critical functions of intra-axonally synthesized proteins are thought to depend on regulated recruitment of mRNA from storage depots in axons. Here we show that axotomy of mammalian neurons induces translation of stored axonal mRNAs via regulation of the stress granule protein G3BP1, to support regeneration of peripheral nerves. G3BP1 aggregates within peripheral nerve axons in stress granule-like structures that decrease during regeneration, with a commensurate increase in phosphorylated G3BP1.

αII Spectrin Forms a Periodic Cytoskeleton at the Axon Initial Segment and Is Required for Nervous System Function.

Spectrins form a submembranous cytoskeleton proposed to confer strength and flexibility to neurons and to participate in ion channel clustering at axon initial segments (AIS) and nodes of Ranvier. Neuronal spectrin cytoskeletons consist of diverse β subunits and αII spectrin. Although αII spectrin is found in neurons in both axonal and somatodendritic domains, using proteomics, biochemistry, and superresolution microscopy, we show that αII and βIV spectrin interact and form a periodic AIS cytoskeleton.

Bladder Recurrence of Clear Cell Sarcoma of the Kidney Seven Years After Initial Presentation.

Clear cell sarcoma of the kidney (CCSK) is the second most common pediatric renal malignancy after Wilms tumor. CCSK has the potential to metastasize to distant sites and was historically known as the bone metastasizing renal tumor. We report an exceedingly rare case of a bladder recurrence of CCSK.

Loss of Frataxin activates the iron/sphingolipid/PDK1/Mef2 pathway in mammals.

Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disease caused by mutations in (). Loss of causes impaired mitochondrial function and iron homeostasis. An elevated production of reactive oxygen species (ROS) was previously proposed to contribute to the pathogenesis of FRDA.

Leading by Success: Impact of a Clinical and Translational Research Infrastructure Program to Address Health Inequities.

Building research infrastructure capacity to address clinical and translational gaps has been a focus of funding agencies and foundations. Clinical and Translational Sciences Awards, Research Centers in Minority Institutions Infrastructure for Clinical and Translational Research (RCTR), and the Institutional Development Award Infrastructure for Clinical and Translational Research funded by the US government to fund clinical translational research programs have existed for over a decade to address racial and ethnic health disparities across the USA. While the impact on the nation's health cannot be made in a short period, assessment of a program's impact could be a litmus test to gauge its effectiveness at the institution and communities.

Loss of Frataxin induces iron toxicity, sphingolipid synthesis, and Pdk1/Mef2 activation, leading to neurodegeneration.

Mutations in Frataxin (FXN) cause Friedreich's ataxia (FRDA), a recessive neurodegenerative disorder. Previous studies have proposed that loss of FXN causes mitochondrial dysfunction, which triggers elevated reactive oxygen species (ROS) and leads to the demise of neurons. Here we describe a ROS independent mechanism that contributes to neurodegeneration in fly FXN mutants.

Testicular Leydig Cell Tumor with Metachronous Lesions: Outcomes after Metastasis Resection and Cryoablation.

Leydig cell tumors represent 3% of testicular masses and usually occur in prepubertal boys and men between 30 and 60 years of age. Leydig cell tumors are benign in children but can be malignant in 10% of adults. This case report describes a 41-year-old patient who was diagnosed with a Leydig cell tumor that originated in his right testicle that subsequently metastasized to his liver, lungs, and retroperitoneum.

Axon initial segment-associated microglia.

Microglia are the brain's resident immune cells and function as the main defense against pathogens or injury. However, in the absence of disease, microglia have other functions in the normal brain. For example, previous studies showed that microglia contribute to circuit refinement and synaptic plasticity in the developing and adult brain, respectively.

A hierarchy of ankyrin-spectrin complexes clusters sodium channels at nodes of Ranvier.

The scaffolding protein ankyrin-G is required for Na(+) channel clustering at axon initial segments. It is also considered essential for Na(+) channel clustering at nodes of Ranvier to facilitate fast and efficient action potential propagation. However, notwithstanding these widely accepted roles, we show here that ankyrin-G is dispensable for nodal Na(+) channel clustering in vivo.

Smoking and risk of low- and high-grade prostate cancer: results from the REDUCE study.

Purpose: Although the relationship between smoking and prostate cancer risk is inconsistent, some studies show that smoking is associated with prostate cancer mortality. Whether this reflects delayed diagnosis or direct smoking-related effects is unknown. REDUCE, which followed biopsy-negative men with protocol-dictated prostate-specific antigen (PSA)-independent biopsies at 2 and 4 years, provides an opportunity to evaluate smoking and prostate cancer diagnosis with minimal confounding from screening biases.

Women and CKD-mineral and bone disorder.

Development of CKD-mineral and bone disorder (MBD) increases morbidity and mortality in men and women with CKD. The corresponding link among bone disease, fracture, and extraskeletal calcifications has been the subject of much focus. In the general population, the incidence of cardiovascular disease is higher in men than women, and this gender differences in degree of calcification and morbidity is maintained in kidney disease.

The adhesion-GPCR BAI1 regulates synaptogenesis by controlling the recruitment of the Par3/Tiam1 polarity complex to synaptic sites.

Excitatory synapses are polarized structures that primarily reside on dendritic spines in the brain. The small GTPase Rac1 regulates the development and plasticity of synapses and spines by modulating actin dynamics. By restricting the Rac1-guanine nucleotide exchange factor Tiam1 to spines, the polarity protein Par3 promotes synapse development by spatially controlling Rac1 activation.

Obesity, prostate-specific antigen nadir, and biochemical recurrence after radical prostatectomy: biology or technique? Results from the SEARCH database.

Background: Obesity is associated with an increased risk of biochemical recurrence (BCR) after radical prostatectomy (RP). It is unclear whether this is due to technical challenges related to operating on obese men or other biologic factors.

Objective: To examine whether obesity predicts higher prostate-specific antigen (PSA) nadir (as a measure of residual PSA-producing tissue) after RP and if this accounts for the greater BCR risk in obese men.

A distal axonal cytoskeleton forms an intra-axonal boundary that controls axon initial segment assembly.

AnkyrinG (ankG) is highly enriched in neurons at axon initial segments (AISs) where it clusters Na(+) and K(+) channels and maintains neuronal polarity. How ankG becomes concentrated at the AIS is unknown. Here, we show that as neurons break symmetry, they assemble a distal axonal submembranous cytoskeleton, comprised of ankyrinB (ankB), αII-spectrin, and βII-spectrin, that defines a boundary limiting ankG to the proximal axon.