The longevity and reversibility of quiescence in are dependent upon the HIRA histone chaperone.

Quiescence (G0) is a reversible non-dividing state that facilitates cellular survival in adverse conditions. Here, we demonstrate that the HIRA histone chaperone complex is required for the reversibility and longevity of nitrogen starvation-induced quiescence in . The HIRA protein, Hip1 is not required for entry into G0 or the induction of autophagy.

A peroxiredoxin-P38 MAPK scaffold increases MAPK activity by MAP3K-independent mechanisms.

Peroxiredoxins (Prdxs) utilize reversibly oxidized cysteine residues to reduce peroxides and promote HO signal transduction, including HO-induced activation of P38 MAPK. Prdxs form HO-induced disulfide complexes with many proteins, including multiple kinases involved in P38 MAPK signaling. Here, we show that a genetically encoded fusion between a Prdx and P38 MAPK is sufficient to hyperactivate the kinase in yeast and human cells by a mechanism that does not require the HO-sensing cysteine of the Prdx.

Effect of an 11-Week Resistance Training Program on Arterial Stiffness in Young Women.

Morgan, B, Mirza, AM, Gimblet, CJ, Ortlip, AT, Ancalmo, J, Kalita, D, Pellinger, TK, Walter, JM, and Werner, TJ. Effect of an 11-week resistance training program on arterial stiffness in young women. J Strength Cond Res 37(2): 315-321, 2023-The current investigation was conducted to determine the effect of 2 resistance training models on indices of arterial stiffness in young, healthy women.

Synthesis and immunological effects of C14-linked 4,5-epoxymorphinan analogues as novel heroin vaccine haptens.

Active immunization is being explored as a potential therapeutic to combat accidental overdose and to mitigate the abuse potential of opioids. Hapten design is one of the crucial factors that determines the efficacy of a candidate vaccine to substance abuse and remains one of the most active areas of research in vaccine development. Herein we report for the first time the synthesis of three novel opiate surrogates with the linker attachment site at C14, (6,14-AmidoHap), (14-AmidoMorHap), and (14-AmidoHerHap) as novel heroin haptens.

Synthesis and Characterization of Segmented Polyurethanes Containing Trisaminocyclopropenium Carbocations.

Diol-functionalized trisaminocyclopropenium (TACP) carbocations were used as chain extenders in a two-step synthesis of a segmented polyurethane. Differential scanning calorimetry demonstrated significant differences in the crystallization behavior of the poly(tetramethylene oxide) soft segment when minor changes were made to the TACP structure and when compared to a control that was chain extended with butane diol. Fourier transform infrared spectroscopy was used to characterize the different level of hydrogen bonding in the polymers and showed that the bulky, charged TACP chain extender limited hydrogen bonding interactions when compared to the control.

Effect of Emergency Physician-Performed Point-of-Care Ultrasound and Radiology Department-Performed Ultrasound Examinations on the Emergency Department Length of Stay Among Pregnant Women at Less Than 20 Weeks' Gestation.

Objectives: We sought to confirm retrospective studies that measured an approximately 20% reduction in emergency department (ED) length of stay (LOS) in early-gestation pregnant women who receive emergency physician-performed point-of-care ultrasound (US) examinations rather than radiology department-performed US examinations for evaluation of intrauterine pregnancy (IUP).

Methods: A randomized controlled clinical trial was performed at an urban academic safety net hospital and 2 Naval medical centers in the United States. The allocation was concealed before enrollment.

Monitoring the Effects of Illumination on the Structure of Conjugated Polymer Gels Using Neutron Scattering.

We demonstrate a protocol to effectively monitor the gelation process of a high concentration solution of conjugated polymer both in the presence and absence of white light exposure. By instituting a controlled temperature ramp, the gelation of these materials can be precisely monitored as they proceed through this structural evolution, which effectively mirrors the conditions experienced during the solution deposition phase of organic electronic device fabrication. Using small angle neutron scattering (SANS) and ultra-small angle neutron scattering (USANS) along with appropriate fitting protocols we quantify the evolution of select structural parameters throughout this process.

Hyperoxidation of Peroxiredoxins: Gain or Loss of Function?

Significance: In 2003, structural studies revealed that eukaryotic 2-Cys peroxiredoxins (Prx) have evolved to be sensitive to inactivation of their thioredoxin peroxidase activity by hyperoxidation (sulfinylation) of their peroxide-reacting catalytic cysteine. This was accompanied by the unexpected discovery, that the sulfinylation of this cysteine was reversible in vivo and the identification of a new enzyme, sulfiredoxin, that had apparently co-evolved specifically to reduce hyperoxidized 2-Cys Prx, restoring their peroxidase activity. Together, these findings have provided the impetus for multiple studies investigating the purpose of this reversible, Prx hyperoxidation.

Cranium-Penetrating Mass Detected by Ultrasound Expedited Management of Langerhans Cell Histiocytosis.

A 6-year-old boy presented to the pediatric emergency department with a unilateral 5 × 3-cm superficial mass on the postauricular region growing for 1 month. Point-of-care ultrasound was used to evaluate the mass, which revealed a complex cystic mass penetrating the temporal bone. After confirmatory magnetic resonance imaging, the patient was transferred for neurosurgical evaluation, and the tumor was excised.

The importance of solvent quality on the modification of conjugated polymer conformation and thermodynamics with illumination.

Device efficiency in key organic electronic devices such as organic photovoltaics, field transistors, and light emitting diodes has long been known to be closely tied to the conformation of the conjugated polymer chains which make up the active layers. Our previous results show that light exposure can have a profound effect on the structure and assembly of these optoelectronic materials in solution. In order to advance our understanding of the role which solvent quality plays in this phenomenon, we have further studied the modulation of these illumination dependent structural changes on the key benchmark conjugated polymers P3HT and MEH-PPV as a function of solvent quality over a wide range of polymer solubilities.

Blocking two-component signalling enhances Candida albicans virulence and reveals adaptive mechanisms that counteract sustained SAPK activation.

The Ypd1 phosphorelay protein is a central constituent of fungal two-component signal transduction pathways. Inhibition of Ypd1 in Saccharomyces cerevisiae and Cryptococcus neoformans is lethal due to the sustained activation of the 'p38-related' Hog1 stress-activated protein kinase (SAPK). As two-component signalling proteins are not found in animals, Ypd1 is considered to be a prime antifungal target.

Safety and utilization of peripherally inserted central catheters versus midline catheters at a large academic medical center.

Background: Peripherally inserted central catheters (PICCs) are a commonly used central intravenous (IV) access device, which can be associated with significant complications. Midline catheters (MCs) are peripheral IV access devices that may reduce the need for central lines and hence decrease central line-associated bloodstream infections. The objective of this study is to compare the utilization and safety of PICCs and MCs.

SQSTM1/p62 mediates crosstalk between autophagy and the UPS in DNA repair.

SQSTM1/p62 (sequestosome 1) selectively targets polyubiquitinated proteins for degradation via macroautophagy and the proteasome. Additionally, SQSTM1 shuttles between the cytoplasmic and nuclear compartments, although its role in the nucleus is relatively unknown. Here, we report that SQSTM1 dynamically associates with DNA damage foci (DDF) and regulates DNA repair.

Sampangine (a Copyrine Alkaloid) Exerts Biological Activities through Cellular Redox Cycling of Its Quinone and Semiquinone Intermediates.

The cananga tree alkaloid sampangine (1) has been extensively investigated for its antimicrobial and antitumor potential. Mechanistic studies have linked its biological activities to the reduction of cellular oxygen, the induction of reactive oxygen species (ROS), and alterations in heme biosynthesis. Based on the yeast gene deletion library screening results that indicated mitochondrial gene deletions enhanced the sensitivity to 1, the effects of 1 on cellular respiration were examined.

Kalkitoxin inhibits angiogenesis, disrupts cellular hypoxic signaling, and blocks mitochondrial electron transport in tumor cells.

The biologically active lipopeptide kalkitoxin was previously isolated from the marine cyanobacterium Moorea producens (Lyngbya majuscula). Kalkitoxin exhibited N-methyl-D-aspartate (NMDA)-mediated neurotoxicity and acted as an inhibitory ligand for voltage-sensitive sodium channels in cultured rat cerebellar granule neurons. Subsequent studies revealed that kalkitoxin generated a delayed form of colon tumor cell cytotoxicity in 7-day clonogenic cell survival assays.

Nutritional armor for the injured warfighter: omega-3 fatty acids in surgery, trauma, and intensive care.

Nutrients have traditionally been viewed as a means to provide basic energy for cellular homeostasis and amino acids for protein synthesis in all humans. Young, healthy men and women in the military today are presumed to be well nourished and mentally and physically fit to perform their duties in austere environments. Exposure to high-intensity projectiles, blast injuries, and other wounds of war, however, is an everyday occurrence during deployment that potentially challenges all homeostatic mechanisms.

The fission yeast Schizosaccharomyces pombe as a model to understand how peroxiredoxins influence cell responses to hydrogen peroxide.

As a more selectively reactive oxygen species, H2O2 (hydrogen peroxide) has been co-opted as a signalling molecule, but high levels can still lead to lethal amounts of cell damage. 2-Cys Prxs (peroxiredoxins) are ubiquitous thioredoxin peroxidases which utilize reversibly oxidized catalytic cysteine residues to reduce peroxides. As such, Prxs potentially make an important contribution to the repertoire of cell defences against oxidative damage.

A peroxiredoxin promotes H2O2 signaling and oxidative stress resistance by oxidizing a thioredoxin family protein.

H2O2 can cause oxidative damage associated with age-related diseases such as diabetes and cancer but is also used to initiate diverse responses, including increased antioxidant gene expression. Despite significant interest, H2O2-signaling mechanisms remain poorly understood. Here, we present a mechanism for the propagation of an H2O2 signal that is vital for the adaptation of the model yeast, Schizosaccharomyces pombe, to oxidative stress.

Ybp1 and Gpx3 signaling in Candida albicans govern hydrogen peroxide-induced oxidation of the Cap1 transcription factor and macrophage escape.

Aims: As Candida albicans is the major fungal pathogen of humans, there is an urgent need to understand how this pathogen evades toxic reactive oxygen species (ROS) generated by the host immune system. A key regulator of antioxidant gene expression, and thus ROS resistance, in C. albicans is the AP-1-like transcription factor Cap1.

Toward a Virtual Lifetime Electronic Record: the Department of Veterans Affairs experience with the Nationwide Health Information Network.

Health information exchange is expected of all electronic health records (EHRs) in order to ensure safe, quality care coordination. The U.S.

An Atg10-like E2 enzyme is essential for cell cycle progression but not autophagy in Schizosaccharomyces pombe.

Many proteins involved in autophagy have been identified in the yeast Saccharomyces cerevisiae. For example, Atg3 and Atg10 are two E2 enzymes that facilitate the conjugation of the ubiquitin-like proteins (Ubls) Atg8 and Atg12, respectively. Here, we describe the identification and characterization of the predicted Atg10 homolog (SpAtg10) of the evolutionarily distant Schizosaccharomyces pombe.

Protein kinase C regulates late cell cycle-dependent gene expression.

The control of the cell cycle in eukaryotes is exerted in part by the coordinated action of a series of transcription factor complexes. This is exemplified by the Mcm1p-Fkh2p-Ndd1p complex in Saccharomyces cerevisiae, which controls the cyclical expression of the CLB2 cluster of genes at the G(2)/M phase transition. The activity of this complex is positively controlled by cyclin-dependent kinase (CDK) and polo kinases.

Oxidative stress responses involve oxidation of a conserved ubiquitin pathway enzyme.

Although it is vital that cells detect and respond to oxidative stress to allow adaptation and repair damage, the underlying sensing and signaling mechanisms that control these responses are unclear. Protein ubiquitinylation plays an important role in controlling many biological processes, including cell division. In Saccharomyces cerevisiae, ubiquitinylation involves a single E1 enzyme, Uba1, with multiple E2s and E3s providing substrate specificity.