Pyroptotic cell corpses are crowned with F-actin-rich filopodia that engage CLEC9A signaling in incoming dendritic cells.

While apoptosis dismantles the cell to enforce immunological silence, pyroptotic cell death provokes inflammation. Little is known of the structural architecture of cells undergoing pyroptosis, and whether pyroptotic corpses are immunogenic. Here we report that inflammasomes trigger the Gasdermin-D- and calcium-dependent eruption of filopodia from the plasma membrane minutes before pyroptotic cell rupture, to crown the resultant corpse with filopodia.

Estimates of Effective Number of Breeders Identify Drivers of Decline in Mid-Atlantic Brook Trout Populations.

Brook Trout () populations have experienced marked declines throughout their native range and are presently threatened due to isolation in small habitat fragments, land use changes, and climate change. The existence of numerous, spatially distinct populations poses substantial challenges for monitoring population status (e.g.

Promiscuous potato: elucidating genetic identity and the complex genetic relationships of a cultivated potato germplasm collection.

A total of 3,860 accessions from the global clonal potato germplasm collection w3ere genotyped with the Illumina Infinium SolCAP V2 12K potato SNP array to evaluate genetic diversity and population structure within the potato germplasm collection. Diploid, triploid, tetraploid, and pentaploid accessions were included representing the cultivated potato taxa. Heterozygosity ranged from 9.

Engineered CAR-T cells targeting the non-functional P2X purinoceptor 7 (P2X7) receptor as a novel treatment for ovarian cancer.

Objectives: Recent studies have identified expression of the non-functional P2X7 (nfP2X7) receptor on various malignant cells including ovarian cancer, but not on normal cells, which makes it a promising tumour-associated antigen candidate for chimeric antigen receptor (CAR)-T-cell immunotherapies. In this study, we assessed the cytotoxic effects of nfP2X7-CAR-T cells on ovarian cancer using and models.

Methods: We evaluated the effects of nfP2X7-CAR-T cells on ovarian cancer cell lines (SKOV-3, OVCAR3, OVCAR5), normal peritoneal cells (LP-9) and primary serous ovarian cancer cells derived from patient ascites using monolayer and 3D spheroid assays.

The septin modifier, forchlorfenuron, activates NLRP3 via a potassium-independent mitochondrial axis.

The Nod-like receptor protein 3 (NLRP3) inflammasome is activated by stimuli that induce perturbations in cell homeostasis, which commonly converge on cellular potassium efflux. NLRP3 has thus emerged as a sensor for ionic flux. Here, we identify forchlorfenuron (FCF) as an inflammasome activator that triggers NLRP3 signaling independently of potassium efflux.

Genotype-by-environment interactions and local adaptation shape selection in the US National Chip Processing Trial.

We find evidence of selection for local adaptation and extensive genotype-by-environment interaction in the potato National Chip Processing Trial (NCPT). We present a novel method for dissecting the interplay between selection, local adaptation and environmental response in plant breeding schemes. Balancing local adaptation and the desire for widely adapted cultivars is challenging for plant breeders and makes genotype-by-environment interactions (GxE) an important target of selection.

NLRP12 interacts with NLRP3 to block the activation of the human NLRP3 inflammasome.

Inflammasomes are multiprotein complexes that drive inflammation and contribute to protective immunity against pathogens and immune pathology in autoinflammatory diseases. Inflammasomes assemble when an inflammasome scaffold protein senses an activating signal and forms a signaling platform with the inflammasome adaptor protein ASC. The NLRP subfamily of NOD-like receptors (NLRs) includes inflammasome nucleators (such as NLRP3) and also NLRP12, which is genetically linked to familial autoinflammatory disorders that resemble diseases caused by gain-of-function NLRP3 mutants that generate a hyperactive NLRP3 inflammasome.

Impact of Integrated Pharmacology Instruction by Principal Faculty Pharmacists in Two Physician Assistant Programs: A Retrospective Study.

Purpose: In recent years, there has been a growing trend toward integrating pharmacology instruction into physician assistant (PA) programs by dedicated PA faculty pharmacists. Pharmacists train to become medication experts. Incorporating pharmacist instruction in a PA program during the didactic year provides PA students with an early opportunity to experience interprofessional education and interdisciplinary synergy through clinical application.

Academic Rank Disparities in Minoritized and Racialized Physician Assistant Educators.

Purpose: The aim of this study was to investigate the disparities in career progression and the need for inclusive mentorship in the physician assistant (PA) profession, specifically focusing on racial/ethnic minority faculty.

Methods: Pooled data from the Physician Assistant Education Association Program Survey in 2015, 2017, and 2019 were analyzed to examine the effect of PA faculty race/ethnicity on academic rank promotion. Logistic regression models were used to assess the association between faculty race/ethnicity and the likelihood of being in a middle/late-career (associate/professor) or early-career status (instructor/assistant), adjusting for confounding factors.

Pre-clinical validation of a pan-cancer CAR-T cell immunotherapy targeting nfP2X7.

Chimeric antigen receptor (CAR)-T cell immunotherapy is a novel treatment that genetically modifies the patients' own T cells to target and kill malignant cells. However, identification of tumour-specific antigens expressed on multiple solid cancer types, remains a major challenge. P2X purinoceptor 7 (P2X7) is a cell surface expressed ATP gated cation channel, and a dysfunctional version of P2X7, named nfP2X7, has been identified on cancer cells from multiple tissues, while being undetectable on healthy cells.

Professionalism in Physician Assistant Education as a Predictor of Future Licensing Board Disciplinary Actions.

Purpose: The purpose of this study was to evaluate associations between postgraduate disciplinary actions (PGDA) by state licensing boards and physician assistant (PA) school documented professionalism violations (DPV) and academic probation.

Methods: This was a retrospective cohort study comprising PA graduates from 2001 to 2011 at 3 institutions (n = 1364) who were evaluated for the main outcome of PGDA and independent variable of DPV and academic probation. Random-effects multiple logistic regression and accelerated failure time parametric survival analysis were used to investigate the association of PGDA with DPV and academic probation.

Gender Disparities in Physician Assistant Educator Promotion and Compensation: A Mixed Methods Approach.

Introduction: The gender wage gap is well documented in many industries. A disparity in salary between female and male physician assistant (PA) educators has been demonstrated, but disparities in academic rank have not been shown. The purpose of this study was to re-examine gender disparities in compensation to PA educators and to explore whether gender-based disparities exist in promotion to higher academic rank in this field.

Current Concept Review: Risk Factors for Infection Following Open Fractures.

Infection following open fracture is a significant source of morbidity and mortality. Therefore, a central tenet of treatment is to minimize the risk of infection. The initial risk of infection is determined by wound characteristics, such as size, soft tissue coverage, vascular injury, and contamination.

Identifying mechanisms underlying individual body size increases in a changing, highly seasonal environment: The growing trout of West brook.

As air temperature increases, it has been suggested that smaller individual body size may be a general response to climate warming. However, for ectotherms inhabiting cold, highly seasonal environments, warming temperatures may increase the scope for growth and result in larger body size. In a long-term study of individual brook trout Salvelinus fontinalis and brown trout Salmo trutta inhabiting a small stream network, individual lengths increased over the course of 15 years.

Dinickel Catalyzed Vinylidene-Alkene Cyclization Reactions.

A dinickel catalyst promotes reductive cyclization reactions of 1,1-dichloroalkenes containing pendant olefins. The reactions can be conducted with a Zn reductant or electrocatalytically using a carbon working electrode. Mechanistic studies are consistent with the intermediacy of a Ni(vinylidene) species, which adds to the alkene and generates a metallacyclic intermediate.

Transfer of Extended Spectrum Cephalosporin Resistant Enterobacteriaceae Among Patients on an HSCT Unit and the Value of Surveillance and Contact Isolation.

The mechanism(s) of acquisition of extended-spectrum cephalosporin-resistant Enterobacteriaceae (ESCRE) on inpatient hospital units dedicated to hematopoietic stem cell transplantation (HSCT) is unclear. The objectives of this study were to determine whether ESCRE organisms are transmitted among patients housed on a HSCT unit, clarify the mechanisms involved, and determine whether routine surveillance for ESCRE carriage and contact isolation for ESCRE carriers is beneficial. The study was conducted on a 30-bed inpatient unit dedicated to the care of patients with hematologic malignancies and HSCT recipients.