Understanding Developmental Cell Death Using as a Model System.

Cell death plays an essential function in organismal development, wellbeing, and ageing. Many types of cell deaths have been described in the past 30 years. Among these, apoptosis remains the most conserved type of cell death in metazoans and the most common mechanism for deleting unwanted cells.

Autophagy captures the retromer-TBC1D5 complex to inhibit receptor recycling.

Retromer prevents the destruction of numerous receptors by recycling them from endosomes to the Golgi network or plasma membrane. This enables retromer to fine-tune the activity of many signaling pathways in parallel. However, the mechanism(s) by which retromer function adapts to environmental fluctuations such as nutrient withdrawal and how this affects the fate of its cargoes remains incompletely understood.

Receptor Recycling by Retromer.

The highly conserved retromer complex controls the fate of hundreds of receptors that pass through the endolysosomal system and is a central regulatory node for diverse metabolic programs. More than 20 years ago, retromer was discovered as an essential regulator of endosome-to-Golgi transport in yeast; since then, significant progress has been made to characterize how metazoan retromer components assemble to enable its engagement with endosomal membranes, where it sorts cargo receptors from endosomes to the -Golgi network or plasma membrane through recognition of sorting motifs in their cytoplasmic tails. In this review, we examine retromer regulation by exploring its assembled structure with an emphasis on how a range of adaptor proteins shape the process of receptor trafficking.

Local Monitoring Should Inform Local Solutions: Morphological Assemblages of Microplastics Are Similar within a Pathway, But Relative Total Concentrations Vary Regionally.

Pathways for microplastics to aquatic ecosystems include agricultural runoff, urban runoff, and treated or untreated wastewater. To better understand the importance of each pathway as a vector for microplastics into waterbodies and for mitigation, we sampled agricultural runoff, urban stormwater runoff, treated wastewater effluent, and the waterbodies downstream in four regions across North America: the Sacramento Delta, the Mississippi River, Lake Ontario, and Chesapeake Bay. The highest concentrations of microplastics in each pathway varied by region: agricultural runoff in the Sacramento Delta and Mississippi River, urban stormwater runoff in Lake Ontario, and treated wastewater effluent in Chesapeake Bay.

A double-blind randomised placebo-controlled trial investigating the effects of lesogaberan on the objective cough frequency and capsaicin-evoked coughs in patients with refractory chronic cough.

Objective: Baclofen is a centrally acting γ-aminobutyric acid type B (GABA) receptor agonist which reduces gastro-oesophageal reflux and suppresses the cough reflex; however, central nervous system side-effects limit its use. Lesogaberan is a novel peripherally acting GABA agonist, but its effects on refractory chronic cough are unknown.

Design: We performed a single-centre, placebo-controlled, double-blind randomised crossover study in patients with chronic cough, refractory to the treatment of underlying conditions.

Resilience of larval wood frogs (Rana sylvatica) to hydrocarbons and other compounds released from naturally weathered diluted bitumen in a boreal lake.

The risks to aquatic wildlife from spills of diluted bitumen (dilbit) into inland waters are poorly understood. In this paper, we describe the response of larval wood frogs (Rana sylvatica) to hydrocarbons and other compounds released from experimental spills of dilbit in a temperate boreal lake. To simulate a wide range of environmentally relevant oil spill scenarios, different volumes of Cold Lake Winter Blend dilbit (0, 1.

Mobile Phone-Based Intervention Among Adolescents Living With Perinatally Acquired HIV Transitioning from Pediatric to Adult Care: Protocol for the Interactive Transition Support for Adolescents Living With HIV using Social Media (InTSHA) Study.

Background: Adolescents living with perinatally acquired HIV often have poor retention in care and viral suppression during the transition from pediatric to adult-based care.

Objective: The aim of this study is to evaluate a mobile phone-based intervention, Interactive Transition Support for Adolescents Living With HIV using Social Media (InTSHA), among adolescents living with perinatally acquired HIV as they transition from pediatric to adult care in South Africa.

Methods: InTSHA uses encrypted, closed group chats delivered via WhatsApp (Meta Platforms Inc) to develop peer support and improve communication between adolescents, their caregivers, and health care providers.

Effect of centrally and peripherally acting GABA agonism on the healthy human cough reflex.

Background: Currently there are no effective licensed anti-tussive therapies. Understanding how the neuronal mechanisms mediating the cough reflex in animal models translate to humans is important for the development of effective therapies. Pre-clinical studies suggest that the activation of GABA receptors in both the peripheral and central nervous systems inhibit cough.

Nuclear data for reactor production of Ba and Ba.

The newest radioisotope for brachytherapy treatment of prostate cancer is Cs (t = 9.69 d, 100% EC). Generated via electron capture decay of Ba (t = 11.

Evaluation of thiobencarb runoff from rice farming practices in a California watershed using an integrated RiceWQ-AnnAGNPS system.

The development of modeling technology to adequately simulate water and pesticide movement within the rice paddy environment faces several challenges. These include: (1) adequately representing ponded conditions; (2) the collection/implementation of temporal/spatial pesticide application data at field scales; (3) the integration of various mixed-landuses simulation schemes. Currently available models do not fully consider these challenges and results may not be sufficiently accurate to represent fate and transport of rice pesticides at watershed scales.

Retromer dysfunction at the nexus of tauopathies.

Tauopathies define a broad range of neurodegenerative diseases that encompass pathological aggregation of the microtubule-associated protein tau. Although tau aggregation is a central feature of these diseases, their underlying pathobiology is remarkably heterogeneous at the molecular level. In this review, we summarize critical differences that account for this heterogeneity and contrast the physiological and pathological functions of tau.

Inhibition of the Complement Alternative Pathway by Chemically Modified DNA Aptamers That Bind with Picomolar Affinity to Factor B.

The complement system is a conserved component of innate immunity that fulfills diverse roles in defense and homeostasis. Inappropriate activation of complement contributes to many inflammatory diseases, however, which has led to a renewed emphasis on development of therapeutic complement inhibitors. Activation of complement component C3 is required for amplification of complement and is achieved through two multisubunit proteases called C3 convertases.

Hyperdipsia in sheep bearing lesions in the medial septal nucleus.

Previous experiments in rodents showed that ablation of the septal brain region caused hyperdipsia. We investigated which part of the septal region needs ablation to produce hyperdipsia in sheep, and whether increased drinking was a primary hyperdipsia. Following ablation of the medial septal region (n = 5), but not parts of the lateral septal region (n = 4), daily water intake increased from ~2.

Cp1/cathepsin L is required for autolysosomal clearance in .

Macroautophagy/autophagy is a highly conserved lysosomal degradative pathway important for maintaining cellular homeostasis. Much of our current knowledge of autophagy is focused on the initiation steps in this process. Recently, an understanding of later steps, particularly lysosomal fusion leading to autolysosome formation and the subsequent role of lysosomal enzymes in degradation and recycling, is becoming evident.

Retromer regulates the lysosomal clearance of MAPT/tau.

The macroautophagy/autophagy-lysosome axis enables the clearance and degradation of cytoplasmic components including protein aggregates, damaged organelles and invading pathogens. Protein aggregation and lysosomal system dysfunction in the brain are common features of several late-onset neurological disorders including Alzheimer disease. Spatial overlap between depletion of the endosomal-sorting complex retromer and MAPT/tau aggregation in the brain have been previously reported.

Drosophila as a model to understand autophagy deregulation in human disorders.

Autophagy has important functions in normal physiology to maintain homeostasis and protect against cellular stresses by the removal of harmful cargos such as dysfunctional organelles, protein aggregates and invading pathogens. The deregulation of autophagy is a hallmark of many diseases and therapeutic targeting of autophagy is highly topical. With the complex role of autophagy in disease it is essential to understand the genetic and molecular basis of the contribution of autophagy to pathogenesis.

Regional brain responses associated with using imagination to evoke and satiate thirst.

In response to dehydration, humans experience thirst. This subjective state is fundamental to survival as it motivates drinking, which subsequently corrects the fluid deficit. To elicit thirst, previous studies have manipulated blood chemistry to produce a physiological thirst stimulus.

The effects of stride frequency manipulation on physiological and perceptual responses during backward and forward running with body weight support.

Purpose: We investigated the influence of a change in stride frequency on physiological and perceptual responses during forward and backward running at different body weight support (BWS) levels.

Methods: Participants ran forward and backward at 0% BWS, 20% BWS, and 50% BWS conditions on a lower body positive pressure treadmill. The stride frequency conditions consisted of forward and backward running at preferred stride frequency (PSF), PSF + 10%, and PSF-10%.

A sensitivity analysis of pesticide concentrations in California Central Valley vernal pools.

Vernal pools are ephemeral wetlands that provide critical habitat to many listed species. Pesticide fate in vernal pools is poorly understood because of uncertainties in the amount of pesticide entering these ecosystems and their bioavailability throughout cycles of wet and dry periods. The Pesticide Water Calculator (PWC), a model used for the regulation of pesticides in the US, was used to predict surface water and sediment pore water pesticide concentrations in vernal pool habitats.

Ecdysone controlled cell and tissue deletion.

The removal of superfluous and unwanted cells is a critical part of animal development. In insects the steroid hormone ecdysone, the focus of this review, is an essential regulator of developmental transitions, including molting and metamorphosis. Like other steroid hormones, ecdysone works via nuclear hormone receptors to direct spatial and temporal regulation of gene transcription including genes required for cell death.

Patient non-attendance at urgent referral appointments for suspected cancer and its links to cancer diagnosis and one year mortality: A cohort study of patients referred on the Two Week Wait pathway.

Background: The 'Two Week Wait' policy aims to ensure patients with suspected cancer are seen within two weeks of referral. However, patient non-attendance can result in this target being missed. This study aimed to identify predictors of non-attendance; and analyse the relationship between attendance and outcomes including cancer diagnosis and early mortality.

Concurrent Quinidine and Phenobarbital in the Treatment of a Patient with 2 Mutations.

Epilepsy of infancy with migrating focal seizures is a devastating pediatric neurologic disorder that often results in treatment-resistant seizure activity and developmental delay. The condition has been associated with mutations in the gene that cause a gain of function in neuronal sodium-activated potassium channels. Quinidine has been shown to reverse this gain of function and has recently been used to reduce seizure activity in patients with these mutations.

Hedgehog and Wingless signaling are not essential for autophagy-dependent cell death.

Autophagy-dependent cell death is a distinct mode of regulated cell death required in a context specific manner. One of the best validated genetic models of autophagy-dependent cell death is the removal of the Drosophila larval midgut during larval-pupal transition. We have previously shown that down-regulation of growth signaling is essential for autophagy induction and larval midgut degradation.