Dominant-negative mutations potentiated by the HSF1-regulated proteostasis network.

Protein mutational landscapes are sculpted by the impacts of the resulting amino acid substitutions on the protein's stability and folding or aggregation kinetics. These properties can, in turn, be modulated by the composition and activities of the cellular proteostasis network. Heat shock factor 1 (HSF1) is the master regulator of the cytosolic and nuclear proteostasis networks, dynamically tuning the expression of cytosolic and nuclear chaperones and quality control factors to meet demand.

Prognostic Index for Liver Radiation (PILiR).

A Prognostic Index for Liver Radiation (PILiR) for improved patient selection for stereotactic liver-directed radiotherapy (SBRT) was developed. Using a large single-center database, 195 patients treated with SBRT for local control, including 66 with hepatocellular carcinoma (HCC) and 129 with metastatic liver disease, were analyzed. Only patients ineligible for alternative treatments were included.

Mediators of Functional Disability at Mid- and Late-Life.

As the number and proportion of older adults living in the U.S. increases, growing evidence shows that people are entering late life with more functional disability than in previous generations.

Gene Electrotransfer via Conductivity-Clamped Electric Field Focusing Pivots Sensori-Motor DNA Therapeutics: "A Spoonful of Sugar Helps the Medicine Go Down".

Viral vectors and lipofection-based gene therapies have dispersion-dependent transduction/transfection profiles that thwart precise targeting. The study describes the development of focused close-field gene electrotransfer (GET) technology, refining spatial control of gene expression. Integration of fluidics for precise delivery of "naked" plasmid deoxyribonucleic acid (DNA) in sucrose carrier within the focused electric field enables negative biasing of near-field conductivity ("conductivity-clamping"-CC), increasing the efficiency of plasma membrane molecular translocation.

Mental Health, Self-Care, and Engagement in Care among Black Women Living with HIV.

Objectives: Due to sociostructural factors, Black women living with human immunodeficiency virus (HIV) in the United States represent the highest percentage of women with HIV and experience mental health struggles that impact health behaviors. This study examines associations between mental health, self-care, medication adherence, engagement with healthcare, HIV-related healthcare visits, and hospitalization.

Methods: One hundred and nineteen Black women living with HIV in the Southeastern United States completed measures on scheduled visits (general and HIV-related healthcare), visits attended/missed/rescheduled, mental healthcare engagement (therapy and support groups), hospital visits (emergency room and overnight stays), medication adherence, and a clinician-administered interview assessing mental health.

STP13.1 is an H-coupled monosaccharide transporter, present in source leaves and seed coats, with higher substrate affinity at depolarized potentials.

Sugar transport proteins (STPs) are high-affinity H-coupled hexose symporters. Recently, the contribution of STP13 to bacterial and fungal pathogen resistance across multiple plant species has garnered significant interest. Quantitative PCR analysis of source leaves, developing embryos, and seed coats of .

Pyrimidine depletion enhances targeted and immune therapy combinations in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a fatal disease characterized by the accumulation of undifferentiated myeloblasts, and agents that promote differentiation have been effective in this disease but are not curative. Dihydroorotate dehydrogenase inhibitors (DHODHi) have the ability to promote AML differentiation and target aberrant malignant myelopoiesis. We introduce HOSU-53, a DHODHi with significant monotherapy activity, which is further enhanced when combined with other standard-of-care therapeutics.

Digenic inheritance involving a muscle-specific protein kinase and the giant titin protein causes a skeletal muscle myopathy.

In digenic inheritance, pathogenic variants in two genes must be inherited together to cause disease. Only very few examples of digenic inheritance have been described in the neuromuscular disease field. Here we show that predicted deleterious variants in SRPK3, encoding the X-linked serine/argenine protein kinase 3, lead to a progressive early onset skeletal muscle myopathy only when in combination with heterozygous variants in the TTN gene.

Planning for Program Evaluation Improves Implementation and Assessment.

This article offers a general approach to plan and implement an educational program by illustrating the evaluation process and data from the AGE-ADAR Scholars Program. A well-designed program evaluation will also include a plan for stakeholder dissemination. We adapted a framework from the Centers for Disease Control and Prevention which includes hard and soft outcomes.

Developing, implementing, and evaluating the visiting Neighbors' program in rural Appalachia: A quality improvement protocol.

Introduction: Older adults living alone in rural areas frequently experience health declines, social isolation, and limited access to services. To address these challenges, our medical academic university supported a quality improvement project for developing and evaluating the Visiting Neighbors program in two rural Appalachian counties. Our Visiting Neighbors program trained local volunteers to visit and guide rural older adults in healthy activities.

Inclusion of Sex and Gender Differences in U.S. State Action Plans for Opioid Use and Opioid Use Disorder.

States have developed action plans to address the "opioid crisis" over the past several years. While sex- and gender-based differences have been identified in complications of opioid use, risks of addiction to opioids, barriers to treatment of opioid use disorder, and associated stigma, it is unknown if or to what extent opioid plans consider or account for these differences. The objectives of this study were to analyze U.

Structural and functional insights into the Pseudomonas aeruginosa glycosyltransferase WaaG and the implications for lipopolysaccharide biosynthesis.

The glycosyltransferase WaaG in Pseudomonas aeruginosa (PaWaaG) is involved in the synthesis of the core region of lipopolysaccharides. It is a promising target for developing adjuvants that could help in the uptake of antibiotics. Herein, we have determined structures of PaWaaG in complex with the nucleotide-sugars UDP-glucose, UDP-galactose, and UDP-GalNAc.

Facilitated Intubation: Time to Re-examine an Old Technique With Its Associated Risks Mitigated by New Technology.

Background: Facilitated intubation (FI) refers to intubation performed using a sedative or anesthetic drug as an induction agent, without the use of a paralytic (neuromuscular blocking agent). In comparison, rapid sequence intubation (RSI) employs both an induction agent and a paralytic drug. RSI has been seen to outperform FI in terms of first-pass success when performing direct laryngoscopy and was quickly adopted as the gold standard in all situations.

Configuration-independent thermal invariants under flow reversal in thin vascular systems.

Modulating temperature fields is indispensable for advancing modern technologies: space probes, electronic packing, and implantable medical devices, to name a few. Bio-inspired thermal regulation achieved via fluid flow within a network of embedded vesicles is notably desirable for slender synthetic material systems. This far-reaching study-availing theory, numerics, and experiments-reveals a counter-intuitive yet fundamental property of vascular-based fluid-flow-engendered thermal regulation.

Lipid- and substrate-induced conformational and dynamic changes in a glycosyltransferase involved in E. coli LPS synthesis revealed by F and P NMR.

WaaG is a glycosyltransferase (GT) involved in the synthesis of the bacterial cell wall, and in Escherichia coli it catalyzes the transfer of a glucose moiety from the donor substrate UDP-glucose onto the nascent lipopolysaccharide (LPS) molecule which when completed constitutes the major component of the bacterium's outermost defenses. Similar to other GTs of the GT-B fold, having two Rossman-like domains connected by a short linker, WaaG is believed to undergo complex inter-domain motions as part of its function to accommodate the nascent LPS and UDP-glucose in the catalytic site located in the cleft between the two domains. As the nascent LPS is bulky and membrane-bound, WaaG is a peripheral membrane protein, adding to the complexity of studying the enzyme in a biologically relevant environment.

Sugar loading of crop seeds - a partnership of phloem, plasmodesmal and membrane transport.

Sugar loading of developing seeds comprises a cohort of transport events that contribute to reproductive success and seed yield. Understanding these events is most advanced for grain crops (Brassicaceae, Fabaceae and Gramineae) and Arabidopsis. For these species, 75-80% of their final seed biomass is derived from phloem-imported sucrose.

Viral Evolution Shaped by Host Proteostasis Networks.

Understanding the factors that shape viral evolution is critical for developing effective antiviral strategies, accurately predicting viral evolution, and preventing pandemics. One fundamental determinant of viral evolution is the interplay between viral protein biophysics and the host machineries that regulate protein folding and quality control. Most adaptive mutations in viruses are biophysically deleterious, resulting in a viral protein product with folding defects.

An Engineered Nanosugar Enables Rapid and Sustained Glucose-Responsive Insulin Delivery in Diabetic Mice.

Glucose-responsive insulin-delivery platforms that are sensitive to dynamic glucose concentration fluctuations and provide both rapid and prolonged insulin release have great potential to control hyperglycemia and avoid hypoglycemia diabetes. Here, biodegradable and charge-switchable phytoglycogen nanoparticles capable of glucose-stimulated insulin release are engineered. The nanoparticles are "nanosugars" bearing glucose-sensitive phenylboronic acid groups and amine moieties that allow effective complexation with insulin (≈95% loading capacity) to form nanocomplexes.

Fibrillar glomerulonephritis in a patient with systemic lupus erythematosus with no evidence of lupus nephritis.

Fibrillar glomerulonephritis (FGN) is a rare proliferative form of glomerular disease characterised by randomly oriented fibrillar deposits with a mean diameter of 20 nm. It has a rare association with systemic lupus erythematosus (SLE). We report the case of a female in her mid-50's with a 20 year history of SLE, who developed proteinuria due to FGN and had no histological evidence of lupus nephritis.

An Unusual Presentation of Cryoglobulinemia in a Patient With Undiagnosed Sjögren's Syndrome and Treated Marginal Zone Lymphoma.

Our case details a 47-year-old female who presented to our cancer hospital with a petechial rash of the lower extremities as well as a headache and blurred vision for the prior two days. She was found to have systolic pressures in the 200s in the emergency department and was admitted for a hypertensive emergency. Notable medical history includes marginal zone lymphoma (MZL) status post-submandibular resection at an outside institution in 11/2017 (thought to be in remission).

Polymer-derived SiOC reinforced with core-shell nanophase structure of ZrB/ZrO for excellent and stable high-temperature microwave absorption (up to 900 °C).

Microwave absorbing materials for high-temperature harsh environments are highly desirable for aerodynamically heated parts and engine combustion induced hot spots of aircrafts. This study reports ceramic composites with excellent and stable high-temperature microwave absorption in air, which are made of polymer-derived SiOC reinforced with core-shell nanophase structure of ZrB/ZrO. The fabricated ceramic composites have a crystallized t-ZrO interface between ZrB and SiOC domains.