Functional diversity of Toll/interleukin-1 receptor domains in flowering plants and its translational potential.

Across the Tree of Life, innate immunity and cell death mechanisms protect hosts from potential pathogens. In prokaryotes, animals, and flowering plants, these functions are often mediated by Toll/interleukin-1 receptor (TIR) domain proteins. Here, we discuss recent analyses of TIR biology in flowering plants, revealing (i) TIR functions beyond pathogen recognition, e.

DRAK2 regulates myosin light chain phosphorylation in T cells.

Death-associated protein kinase-related apoptosis-inducing kinase-2 (DRAK2; also known as STK17B) is a serine/threonine kinase expressed in T cells. Drak2-deficient (Drak2-/-) mice respond effectively to tumors and pathogens while displaying resistance to T cell-mediated autoimmune disease. However, the molecular mechanisms by which DRAK2 impacts T cell function remain unclear.

Massachusetts Medicaid ACO Program May Have Improved Care Use And Quality For Pregnant And Postpartum Enrollees.

Value-based care models, such as Medicaid accountable care organizations (ACOs), have the potential to improve access to and quality of care for pregnant and postpartum Medicaid enrollees. We leveraged a natural experiment in Massachusetts to evaluate the effects of Medicaid ACOs on quality-of-care-sensitive measures and care use across the prenatal, delivery, and postpartum periods. Using all-payer claims data on Medicaid-covered live deliveries in Massachusetts, we used a difference-in-differences approach to compare measures before (the first quarter of 2016 through the fourth quarter of 2017) and after (the third quarter of 2018 through the fourth quarter of 2020) Medicaid ACO implementation among ACO and non-ACO patients.

Sonic Hedgehog activates prostaglandin signaling to stabilize primary cilium length.

Sonic Hedgehog (SHH) is a driver of embryonic patterning that, when corrupted, triggers developmental disorders and cancers. SHH effector responses are organized through primary cilia (PC) that grow and retract with the cell cycle and in response to extracellular cues. Disruption of PC homeostasis corrupts SHH regulation, placing significant pressure on the pathway to maintain ciliary fitness.

Mental health screening and referral to treatment in dental practices: A scoping review.

Objective: The purpose of this study was to conduct a scoping review to examine and summarize the characteristics of research related to mental health (MH) screenings and/or referrals to treatment in dental practices.

Methods: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for Scoping Reviews and searched multiple databases for terms connected with dental care, MH concerns, screening, and referral. Included articles: (1) described care provided in a dental practice, (2) described a situation where the patient is experiencing the potential MH problem, (3) did not involve dental anxiety exclusively, and (4) involved some form of MH screening and/or referral to treatment.

Cytoneme signaling provides essential contributions to mammalian tissue patterning.

During development, morphogens pattern tissues by instructing cell fate across long distances. Directly visualizing morphogen transport in situ has been inaccessible, so the molecular mechanisms ensuring successful morphogen delivery remain unclear. To tackle this longstanding problem, we developed a mouse model for compromised sonic hedgehog (SHH) morphogen delivery and discovered that endocytic recycling promotes SHH loading into signaling filopodia called cytonemes.

Ghrelin deletion and conditional ghrelin cell ablation increase pancreatic islet size in mice.

Ghrelin exerts key effects on islet hormone secretion to regulate blood glucose levels. Here, we sought to determine whether ghrelin's effects on islets extend to the alteration of islet size and β cell mass. We demonstrate that reducing ghrelin - by ghrelin gene knockout (GKO), conditional ghrelin cell ablation, or high-fat diet (HFD) feeding - was associated with increased mean islet size (up to 62%), percentage of large islets (up to 854%), and β cell cross-sectional area (up to 51%).

Ghrelin-responsive mediobasal hypothalamic neurons mediate exercise-associated food intake and exercise endurance.

Previous studies have implicated the orexigenic hormone ghrelin as a mediator of exercise endurance and the feeding response postexercise. Specifically, plasma ghrelin levels nearly double in mice when they are subjected to an hour-long bout of high-intensity interval exercise (HIIE) using treadmills. Also, growth hormone secretagogue receptor-null (GHSR-null) mice exhibit decreased food intake following HIIE and diminished running distance (time until exhaustion) during a longer, stepwise exercise endurance protocol.

Effects of thermoneutrality on food intake, body weight, and body composition in a Prader-Willi syndrome mouse model.

Objective: Prader-Willi syndrome (PWS) is a multisystem genetic disorder. Unfortunately, none of several mouse models carrying PWS mutations emulates the entirety of the human PWS phenotype, including hyperphagia plus obesity.

Methods: To determine whether housing at thermoneutrality (TN, 30 °C) permits the development of hyperphagia and obesity in the Snord116del PWS mouse model, the effects of housing three different ages of Snord116del and wild-type (WT) littermates at TN versus room temperature (RT, 22-24 °C) for 8 weeks were compared.

Plant and prokaryotic TIR domains generate distinct cyclic ADPR NADase products.

Toll/interleukin-1 receptor (TIR) domain proteins function in cell death and immunity. In plants and bacteria, TIR domains are often enzymes that produce isomers of cyclic adenosine 5'-diphosphate-ribose (cADPR) as putative immune signaling molecules. The identity and functional conservation of cADPR isomer signals is unclear.

eRNA profiling uncovers the enhancer landscape of oesophageal adenocarcinoma and reveals new deregulated pathways.

Cancer is driven by both genetic and epigenetic changes that impact on gene expression profiles and the resulting tumourigenic phenotype. Enhancers are transcriptional regulatory elements that are key to our understanding of how this rewiring of gene expression is achieved in cancer cells. Here, we have harnessed the power of RNA-seq data from hundreds of patients with oesophageal adenocarcinoma (OAC) or its precursor state Barrett's oesophagus coupled with open chromatin maps to identify potential enhancer RNAs and their associated enhancer regions in this cancer.

Oncogenic ERRB2 signals through the AP-1 transcription factor to control mesenchymal-like properties of oesophageal adenocarcinoma.

Oesophageal adenocarcinoma (OAC) is a deadly disease with poor survival statistics and few targeted therapies available. One of the most common molecular aberrations in OAC is amplification or activation of the gene encoding the receptor tyrosine kinase ERBB2, and ERBB2 is targeted in the clinic for this subset of patients. However, the downstream consequences of these ERBB2 activating events are not well understood.

Regulatory chromatin rewiring promotes metabolic switching during adaptation to oncogenic receptor tyrosine kinase inhibition.

Oesophageal adenocarcinoma (OAC) patients show poor survival rates and there are few targeted molecular therapies available. However, components of the receptor tyrosine kinase (RTK) driven pathways are commonly mutated in OAC, typified by high frequency amplifications of the RTK ERBB2. ERBB2 can be therapeutically targeted, but this has limited clinical benefit due to the acquisition of drug resistance.

Implementation and sustainability of safe consumption sites: a qualitative systematic review and thematic synthesis.

Background: Safe consumption sites (SCSs) serve diverse populations of people who use drugs (PWUD) and public health objectives. SCS implementation began in the 1980s, and today, there are at least 200 known SCSs operating in over twelve countries. While a growing literature supports their effectiveness as a harm reduction strategy, there is limited information on contextual factors that may support or hinder SCS implementation and sustainability.

Fixation of Embryonic Mouse Tissue for Cytoneme Analysis.

Developmental tissue patterning and postdevelopmental tissue homeostasis depend upon controlled delivery of cellular signals called morphogens. Morphogens act in a concentration- and time-dependent manner to specify distinct transcriptional programs that instruct and reinforce cell fate. One mechanism by which appropriate morphogen signaling thresholds are ensured is through delivery of the signaling proteins by specialized filopodia called cytonemes.

Patient perspectives on delays in cervical cancer screening and follow-up care in Botswana: a mixed methods study.

Background: Delays in screening and timely diagnosis contribute significantly to global disparities in cervical cancer mortality in Botswana and other low- and middle-income countries, particularly those with high rates of HIV. Little is known about the modifiable factors shaping these delays from the perspectives of women themselves and how these perspectives may differ between those living with and without HIV.

Methods: From March-May 2019, we conducted a concurrent, mixed methods study of women receiving treatment for cervical cancer at a multidisciplinary oncology clinic in Botswana.

Regulatory mechanisms of cytoneme-based morphogen transport.

During development and tissue homeostasis, cells must communicate with their neighbors to ensure coordinated responses to instructional cues. Cues such as morphogens and growth factors signal at both short and long ranges in temporal- and tissue-specific manners to guide cell fate determination, provide positional information, and to activate growth and survival responses. The precise mechanisms by which such signals traverse the extracellular environment to ensure reliable delivery to their intended cellular targets are not yet clear.

Exploring Why Financial Incentives Fail to Affect At-home Colorectal Cancer Screening: a Mixed Methods Study.

Background: Despite success in increasing other health behaviors, financial incentives have shown limited to no effect on colorectal cancer (CRC screening. Little is known about the factors shaping why and for whom incentives improve screening.

Objective: To explore the perspective of participants enrolled in a larger, four-arm pragmatic trial at urban family medicine practices which assessed and failed to detect significant effects of financial incentives on at-home CRC screening completion.

Persistent Barriers to Colorectal Cancer Screening Completion Amid Centralized Outreach: A Mixed Methods Study.

Purpose: To understand patient experiences and persistent barriers to colorectal cancer (CRC) screening amid centralized outreach at urban family medicine practices.

Approach: Following a pragmatic trial assessing mailed fecal immunochemical test (FIT) outreach, we invited a subset of participants to complete a semi-structured qualitative interview and structured questionnaire.

Setting: Single urban academic healthcare system.