Undisclosed financial conflicts of interest in DSM-5-TR: cross sectional analysis.

Objective: To assess the extent and types of financial ties to industry of panel and task force members of the American Psychiatric Association's , fifth edition, text revision (DSM-5-TR), published in 2022.

Design: Cross sectional analysis.

Setting: Open Payments database, USA.

Investigating the Potential of Fusarium solani and Phanerochaete chrysosporium in the Removal of 2,4,6-TNT.

Past and  recent applications of 2,4,6-trinitrotoluene (TNT) in military and civilian industries have led to contamination of soil and marine ecosystems. Among various TNT remediation techniques, biological remediation is widely accepted for its sustainability, low cost, and scalable applications. This study was designed to isolate a fungus strain from a TNT-contaminated soil to investigate its tolerance to and potential for removal of TNT.

Optical profiling of autonomous Ca nanodomains generated by lysosomal TPC2 and TRPML1.

Multiple families of Ca-permeable channels co-exist on lysosomal Ca stores but how each family couples to its own unique downstream physiology is unclear. We have therefore investigated the Ca-signalling architecture underpinning different channels on the same vesicle that drive separate pathways, using phagocytosis as a physiological stimulus. Lysosomal Ca-channels are a major Ca source driving particle uptake in macrophages, but different channels drive different aspects of Fc-receptor-mediated phagocytosis: TPC2 couples to dynamin activation, whilst TRPML1 couples to lysosomal exocytosis.

E-cigarette vapor renders neutrophils dysfunctional due to filamentous actin accumulation.

Background: Electronic cigarette (e-cigarette) use continues to rise despite concerns of long-term effects, especially the risk of developing lung diseases such as chronic obstructive pulmonary disease. Neutrophils are central to the pathogenesis of chronic obstructive pulmonary disease, with changes in phenotype and function implicated in tissue damage.

Objective: We sought to measure the impact of direct exposure to nicotine-containing and nicotine-free e-cigarette vapor on human neutrophil function and phenotype.

Mechanistic understanding of perfluorooctane sulfonate (PFOS) sorption by biochars.

Biochar has recently emerged as a cost-effective solution to combat per- and polyfluoroalkyl substances (PFAS) pollution in water, but mechanistic understanding of which physicochemical properties of biochars dictate PFAS sorptive removal from water remains elusive. Herein, 15 biochars were pyrolyzed from five feedstocks (corn, Douglas fir, eucalyptus, poplar, and switchgrass) at three pyrolysis temperatures (500, 700, and 900 °C) to investigate their removal efficiencies and mechanisms of perfluorooctane sulfonate (PFOS) from water. A commercial biochar was also included for comparison.

Two-pore channels: going with the flows.

In recent years, our understanding of the structure, mechanisms and functions of the endo-lysosomal TPC (two-pore channel) family have grown apace. Gated by the second messengers, NAADP and PI(3,5)P2, TPCs are an integral part of fundamental signal-transduction pathways, but their array and plasticity of cation conductances (Na+, Ca2+, H+) allow them to variously signal electrically, osmotically or chemically. Their relative tissue- and organelle-selective distribution, together with agonist-selective ion permeabilities provides a rich palette from which extracellular stimuli can choose.

NAADP-Mediated Ca Signalling.

The discovery of NAADP-evoked Ca release in sea urchin eggs and then as a ubiquitous Ca mobilizing messenger has introduced several novel paradigms to our understanding of Ca signalling, not least in providing a link between cell stimulation and Ca release from lysosomes and other acidic Ca storage organelles. In addition, the hallmark concentration-response relationship of NAADP-mediated Ca release, shaped by striking activation/desensitization mechanisms, influences its actions as an intracellular messenger. There has been recent progress in our understanding of the molecular mechanisms underlying NAADP-evoked Ca release, such as the identification of the endo-lysosomal two-pore channel family of cation channels (TPCs) as their principal target and the identity of NAADP-binding proteins that complex with them.

Predicting the pulmonary effects of long-term e-cigarette use: are the clouds clearing?

Commercially available since 2007, e-cigarettes are a popular electronic delivery device of ever-growing complexity. Given their increasing use by ex-smokers, smokers and never-smokers, it is important to evaluate evidence of their potential pulmonary effects and predict effects of long-term use, since there has been insufficient time to study a chronic user cohort. It is crucial to evaluate indicators of harm seen in cigarette use, and those potentially unique to e-cigarette exposure.

Acidic Ca stores and immune-cell function.

Acidic organelles act as intracellular Ca stores; they actively sequester Ca in their lumina and release it to the cytosol upon activation of endo-lysosomal Ca channels. Recent data suggest important roles of endo-lysosomal Ca channels, the Two-Pore Channels (TPCs) and the TRPML channels (mucolipins), in different aspects of immune-cell function, particularly impacting membrane trafficking, vesicle fusion/fission and secretion. Remarkably, different channels on the same acidic vesicles can couple to different downstream physiology.

Phytostabilization of a contaminated military site using Miscanthus and soil amendments.

Military activities can contaminate productive land with potentially toxic substances. The most common trace metal contaminant on military bases is lead (Pb). A field experiment was begun in 2016 at Fort Riley, KS, in an area with total soil Pb concentrations ranging from 900 to 1,500 mg kg and near-neutral pH.

Choreographing endo-lysosomal Ca throughout the life of a phagosome.

The emergence of endo-lysosomes as ubiquitous Ca stores with their unique cohort of channels has resulted in their being implicated in a growing number of processes in an ever-increasing number of cell types. The architectural and regulatory constraints of these acidic Ca stores distinguishes them from other larger Ca sources such as the ER and influx across the plasma membrane. In view of recent advances in the understanding of the modes of operation, we discuss phagocytosis as a template for how endo-lysosomal Ca signals (generated via TPC and TRPML channels) can be integrated in multiple sophisticated ways into biological processes.

A cellular protection racket: How lysosomal Ca fluxes prevent kidney injury.

LC3-lipidation is activated by lysosomal damage by mechanisms that are unknown and divergent from canonical autophagy. In this study, Nakamura et al, show that lysosomal damage induced by lysosomotropic agents or oxalate in renal proximal tubule cells causes lipidated LC3 to insert into the lysosomal membrane to activate TRPML1 channels and release Ca from lysosomes. This leads to TFEB dephosphorylation and translocation into the nucleus which results in clearance of damaged lysosomes and their contents which may reduce the deleterious effects of crystal nephropathy.

Defective platelet function in Niemann-Pick disease type C1.

Niemann-Pick disease type C (NPC) is a neurodegenerative lysosomal storage disorder caused by mutations in either (95% of cases) or . Reduced late endosome/lysosome calcium (Ca) levels and the accumulation of unesterified cholesterol and sphingolipids within the late endocytic system characterize this disease. We previously reported impaired lysosome-related organelle (LRO) function in Natural Killer cells; however, the potential contribution of impaired acid compartment Ca flux and LRO function in other cell types has not been determined.

Discovery and Characterization of Clinical Candidate LXE408 as a Kinetoplastid-Selective Proteasome Inhibitor for the Treatment of Leishmaniases.

Visceral leishmaniasis is responsible for up to 30,000 deaths every year. Current treatments have shortcomings that include toxicity and variable efficacy across endemic regions. Previously, we reported the discovery of GNF6702, a selective inhibitor of the kinetoplastid proteasome, which cleared parasites in murine models of leishmaniasis, Chagas disease, and human African trypanosomiasis.

NAADP-regulated two-pore channels drive phagocytosis through endo-lysosomal Ca nanodomains, calcineurin and dynamin.

Macrophages clear pathogens by phagocytosis and lysosomes that fuse with phagosomes are traditionally regarded as to a source of membranes and luminal degradative enzymes. Here, we reveal that endo-lysosomes act as platforms for a new phagocytic signalling pathway in which FcγR activation recruits the second messenger NAADP and thereby promotes the opening of Ca -permeable two-pore channels (TPCs). Remarkably, phagocytosis is driven by these local endo-lysosomal Ca nanodomains rather than global cytoplasmic or ER Ca signals.

Benchmarking Psychosocial Skills Important for Talent Development.

How can high potential in childhood be transformed into outstanding adult accomplishment? Research indicates that individuals who become outstanding performers and producers have more than just raw talent in the domain or opportunities to develop their talent-they have the will, drive, and focus to take advantage of the opportunities with which they are presented, and the capacity to persist through failures even as the bar for success gets higher. Despite the importance of these psychosocial facilitators, they are among the least well understood in the field of gifted and talented research. In this study, we reviewed existing literature in order to build comprehensive list of the psychosocial variables associated with talent development across domains (visual art, dance, sports, academics, music, acting, medicine, and software engineering).

A rare case of type 2 entrapment of the median nerve after posterior elbow dislocation with MRI and ultrasound correlation.

A 9-year-old boy sustained an ulnohumeral dislocation with a medial epicondyle fracture and experienced incomplete post-traumatic median nerve palsy in addition to post-traumatic stiffness following closed reduction and cast immobilization. When his motor palsy and stiffness did not improve, MRI and ultrasound were obtained, which demonstrated entrapment of the median nerve in an osseous tunnel at the fracture site, compatible with type 2 median nerve entrapment. Subsequently, the patient underwent surgery to mobilize the medial epicondyle and free the median nerve, resulting in improved range of motion, near complete restoration of motor function, and complete restoration of sensory function in the median nerve distribution within 6 months of surgery.

Revealing the secrets of secretion.

An intracellular ion channel may have a central role in the release of cytokines by macrophages.

Clinical utilization of shear wave elastography in the musculoskeletal system.

Shear wave elastography (SWE) is an emerging technology that provides information about the inherent elasticity of tissues by producing an acoustic radiofrequency force impulse, sometimes called an "acoustic wind," which generates transversely-oriented shear waves that propagate through the surrounding tissue and provide biomechanical information about tissue quality. Although SWE has the potential to revolutionize bone and joint imaging, its clinical application has been hindered by technical and artifactual challenges. Many of the stumbling blocks encountered during musculoskeletal SWE imaging are readily recognizable and can be overcome, but progressive advances in technology and a better understanding of image acquisition are required before SWE can reliably be used in musculoskeletal imaging.

Modulating PCAF/GCN5 Immune Cell Function through a PROTAC Approach.

P300/CBP-associated factor (PCAF) and general control nonderepressible 5 (GCN5) are closely related epigenetic proteins, each containing an acetyltransferase domain and a bromodomain. Consistent with reported roles for these proteins in immune function, we find that PCAF-deficient macrophages exhibit a markedly reduced ability to produce cytokines upon stimulation with lipopolysaccharide (LPS). Investigating the potential to target this pathway pharmacologically, we show that chemical inhibition of the PCAF/GCN5 bromodomains is insufficient to recapitulate the diminished inflammatory response of PCAF-deficient immune cells.

Pathogenic mycobacteria achieve cellular persistence by inhibiting the Niemann-Pick Type C disease cellular pathway.

Background: Tuberculosis remains a major global health concern. The ability to prevent phagosome-lysosome fusion is a key mechanism by which intracellular mycobacteria, including , achieve long-term persistence within host cells. The mechanisms underpinning this key intracellular pro-survival strategy remain incompletely understood.

Implementation of resource facilitation to assess referral needs and promote access to state vocational rehabilitation services in people with traumatic brain injury.

Resource facilitation (RF) has shown promise for improving return to work (RTW) after traumatic brain injury (TBI), but little is known about the RF needs of people recruited from acute trauma settings. In this descriptive study, we sought to track referral needs, describe problems in accessing state vocational rehabilitation (VR) services, and highlight the role of RF in overcoming these difficulties in 45 adults with complicated mild to severe TBI seeking RTW who were recruited from acute trauma care. Participants received a referral to the state VR agency, along with RF services for up to one year.

Proteasome inhibition for treatment of leishmaniasis, Chagas disease and sleeping sickness.

Chagas disease, leishmaniasis and sleeping sickness affect 20 million people worldwide and lead to more than 50,000 deaths annually. The diseases are caused by infection with the kinetoplastid parasites Trypanosoma cruzi, Leishmania spp. and Trypanosoma brucei spp.

Preferential Coupling of the NAADP Pathway to Exocytosis in T-Cells.

A cytotoxic T-lymphocyte (CTL) kills an infected or tumorigenic cell by Ca-dependent exocytosis of cytolytic granules at the immunological synapse formed between the two cells. However, these granules are more than reservoirs of secretory cytolytic proteins but may also serve as unique Ca signaling hubs that autonomously generate their own signals for exocytosis. This review discusses a selective role for the Ca-mobilizing messenger, nicotinic acid adenine dinucleotide phosphate (NAADP) and its molecular targets, two-pore channels (TPCs), in stimulating exocytosis.