Despite their high clinical relevance, obtaining structural and biophysical data on transmembrane proteins has been hindered by challenges involved in their expression and extraction in a homogeneous, functionally-active form. The inherent enzymatic activity of receptor tyrosine kinases (RTKs) presents additional challenges. Oncogenic fusions of RTKs with heterologous partners represent a particularly difficult-to-express protein subtype due to their high flexibility, aggregation propensity and the lack of a known method for extraction within the native lipid environment.
View Article and Find Full Text PDFWe describe the novel occurrence of a adenocarcinoma involving the trachea, with distinct solid and glandular components, in a 34-year-old patient. We illustrate its morphological and immunophenotypic features and describe the molecular finding of an EWSR1::BEND2 gene fusion detected by next-generation sequencing (NGS). We discuss the findings in comparison to BEND2-fusion associated neoplasms reported in the head and neck region in the literature to date.
View Article and Find Full Text PDFVisualizing the subcellular localization of presynaptic proteins with fluorescent proteins is a powerful tool to dissect the genetic and molecular mechanisms underlying synapse formation and patterning in live animals. Here, we utilize split green and red fluorescent proteins to visualize the localization of endogenously expressed presynaptic proteins at a single neuron resolution in Caenorhabditis elegans. By using CRISPR/Cas9 genome editing, we generated a collection of C.
View Article and Find Full Text PDFSynaptotagmin-1 (syt1) functions as the Ca-dependent sensor that triggers the rapid and synchronous release of neurotransmitters from neurotransmitter-containing vesicles during neuronal exocytosis. The syt1 protein has two homologous tandem C2 domains that interact with phospholipids in a Ca-dependent manner. Despite the crucial role of syt1 in exocytosis, the precise interactions between Ca, syt1, and phospholipids are not fully understood.
View Article and Find Full Text PDFA20 is a dual-function ubiquitin-editing enzyme that maintains immune homeostasis by restraining inflammation. Although A20 serves a similar negative feedback function for T-cell receptor (TCR) signaling, the molecular mechanisms utilized and their ultimate impact on human T-cell function remain unclear. TCR engagement triggers the assembly of the CARD11-BCL10-MALT1 (CBM) protein complex, a signaling platform that governs the activation of downstream transcription factors including NF-κB and c-Jun/AP-1.
View Article and Find Full Text PDFObjectives: To describe contraceptive use for pregnancy prevention among transgender men and gender diverse (TGD) individuals assigned female or intersex at birth (AFIAB) and explore whether contraceptive use differs by testosterone use.
Study Design: We analyzed data from a cross-sectional, online survey of N = 1694 TGD individuals AFIAB recruited in 2019 through a community-facing website and a national community-engaged cohort study of sexual and/or gender minority (SGM) adults in the US. Descriptive and regression analyses characterized the current and ever use of contraceptive methods for pregnancy prevention, stratified by testosterone use, and described reasons for contraceptive use/non-use.
J Huntingtons Dis
September 2024
Background: Huntington's disease (HD) presents patients and individuals at risk for HD with significant levels of stress. However, relatively little research has examined how individuals cope with stress related to the disease or the association of specific coping strategies with psychological symptoms.
Objective: This study examined the ways in which HD patients and at-risk individuals cope with HD-related stress using a control-based model of coping and the association of coping strategies with symptoms of depression and anxiety.
Successful pregnancy relies on a coordinated interplay between endocrine, immune, and metabolic processes to sustain fetal growth and development. The orchestration of these processes involves multiple signaling pathways driving cell proliferation, differentiation, angiogenesis, and immune regulation necessary for a healthy pregnancy. Among the molecules supporting placental development and maternal tolerance, the families of pregnancy-specific glycoproteins and galectins are of great interest in reproductive biology.
View Article and Find Full Text PDFNursing homes struggle with safety issues, despite decades of intervention. This may, in part, stem from a reliance on a historical perspective that views safety as an intrinsic part of well-designed systems, with errors resulting from knowable, fixable causes. A new perspective (Resilient Health Care) assumes, instead, that in complex systems such as nursing homes, uncertainties and trade-offs occur in the course of everyday work.
View Article and Find Full Text PDFNursing homes struggle with safety issues, despite decades of intervention. This may, in part, stem from a reliance on a historical perspective that views safety as an intrinsic part of well-designed systems, with errors resulting from knowable, fixable causes. A new perspective (Resilient Health Care) assumes, instead, that in complex systems such as nursing homes, uncertainties and trade-offs occur in the course of everyday work.
View Article and Find Full Text PDFThis paper uses Normalization Process Theory (NPT) to examine staff impressions of Montessori-based program training and implementation at Veterans Affairs Community Living Centers (VA CLCs; nursing homes). We conducted a mixed-methods evaluation of Montessori Approaches to Person-Centered Care (MAP-VA) at eight VA CLCs. Trainings were conducted as either a live virtual course or a pre-recorded asynchronous class.
View Article and Find Full Text PDFIn 2006 following several years of preliminary study, the American Society of Clinical Oncology (ASCO) launched the Quality Oncology Practice Initiative (QOPI). This cancer-focused quality initiative evolved considerably over the next decade-and-a-half and is expanding globally. QOPI is undoubtedly the leading standard-bearer for quality cancer care and contemporary medical oncology practice.
View Article and Find Full Text PDFThe rigors of graduate nursing education create significant stress for nurse anesthesia students. The taxing background of an intensive care nurse, especially during the COVID-19 pandemic, compounds the inherent pressures of doctoral study. Students often experience symptoms of burnout, complicating their ability to learn and retain critical information.
View Article and Find Full Text PDFGlioblastoma, IDH-wild type, the most common malignant primary central nervous system tumor, represents a formidable challenge in clinical management due to its poor prognosis and limited therapeutic responses. With an evolving understanding of its underlying biology, there is an urgent need to identify prognostic molecular groups that can be subject to targeted therapy. This study established a cohort of 124 sequential glioblastomas from a tertiary hospital and aimed to find correlations between molecular features and survival outcomes.
View Article and Find Full Text PDFBackground: Huntington's disease (HD) is a neurodegenerative disease that presents families with significant numbers of stressful events. However, relatively little empirical research has characterized the stressors encountered by members of HD-affected families and their correlations with psychological symptoms.
Objective: This study examined frequencies of specific stressors in HD patients and at-risk individuals and the correlates of these stressors with demographics, disease characteristics, and symptoms of depression and anxiety.
The solute-binding protein (SBP) components of periplasmic binding protein-dependent ATP-binding cassette (ABC)-type transporters often possess exquisite selectivity for their cognate ligands. Maltose binding protein (MBP), the best studied of these SBPs, has been extensively used as a fusion partner to enable the affinity purification of recombinant proteins. However, other SBPs and SBP-ligand based affinity systems remain underexplored.
View Article and Find Full Text PDFA remarkably high rate of post-transplant relapse in patients with TP53-mutated myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) calls to question the utility of allogeneic stem cell transplant (HSCT). We, therefore, performed a retrospective analysis to compare the outcomes between HSCT (N = 38) versus non-HSCT (N = 45) approaches. Patients in the HSCT cohort were younger (median age 63 vs.
View Article and Find Full Text PDFIntroduction: Falls in nursing homes are a major cause for decreases in residents' quality of life and overall health. This study aims to reduce resident falls by implementing the LOCK Falls Programme, an evidence-based quality improvement intervention. The LOCK Falls Programme involves the entire front-line care team in (1) focusing on evidence of positive change, (2) collecting data through systematic observation and (3) facilitating communication and coordination of care through the practice of front-line staff huddles.
View Article and Find Full Text PDFThe hydrolytic susceptibility of sulfobetaine-siloxane surfactants is investigated by comparison of a homologous series in this subclass of surfactants (R-(CH)N(Me)(CH)SO; R = (MeSiO)Si-, (MeSiO)Si(Me)-, (MeSiO)-Si(Me)-) with an analogue series of oxyethylene-siloxane surfactants (R-(CH)(OCHCH)OH; R = (MeSiO)Si-, (MeSiO)Si(Me)-, (MeSiO)-Si(Me)-). Nuclear magnetic resonance (NMR) monitoring of these surfactants in an aqueous solution shows that the presence of the sulfobetaine head structure greatly enhances the hydrolysis rate of the siloxane tail as compared with oxyethylene-siloxane analogue control experiments. This sulfobetaine effect is confirmed by adding a model compound, (Me)N(CH)SO, to the oxyethylene-siloxane surfactants and observing the large hydrolysis enhancement.
View Article and Find Full Text PDFThe caspase activation and recruitment domain 11 (CARD11) gene encodes a scaffold protein required for lymphocyte antigen receptor signaling. Dominant-negative, loss-of-function (LOF) pathogenic variants in CARD11 result in CARD11-associated atopy with dominant interference of NF-κB signaling (CADINS) disease. Patients with CADINS suffer with severe atopic manifestations including atopic dermatitis, food allergy, and chronic spontaneous urticaria in addition to recurrent infections and autoimmunity.
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