SUN1/2 Are Essential for RhoA/ROCK-Regulated Actomyosin Activity in Isolated Vascular Smooth Muscle Cells.

Vascular smooth muscle cells (VSMCs) are the predominant cell type in the blood vessel wall. Changes in VSMC actomyosin activity and morphology are prevalent in cardiovascular disease. The actin cytoskeleton actively defines cellular shape and the LInker of Nucleoskeleton and Cytoskeleton (LINC) complex, comprised of nesprin and the Sad1p, UNC-84 (SUN)-domain family members SUN1/2, has emerged as a key regulator of actin cytoskeletal organisation.

A single bout of resistance exercise improves postprandial lipid metabolism in overweight/obese men with prediabetes.

Aims/hypothesis: Prediabetes is associated with postprandial hypertriacylglycerolaemia. Resistance exercise acutely lowers postprandial plasma triacylglycerol (TG); however, the changes in lipid metabolism that mediate this reduction are poorly understood. The aim of this study was to identify the constitutive metabolic mechanisms underlying the changes in postprandial lipid metabolism after resistance exercise in obese men with prediabetes.

Raising Animals Without Antibiotics: U.S. Producer and Veterinarian Experiences and Opinions.

Ensuring the safety, health, and overall well-being of animals raised for food is both an ethical obligation and a critical component of providing safe food products. The use of antibiotics for maintaining animal health has come under scrutiny in recent years due to the rise of antibiotic resistance globally. Some U.

The atypical cyclin-like protein Spy1 overrides p53-mediated tumour suppression and promotes susceptibility to breast tumourigenesis.

Background: Breast cancer is the most common cancer to affect women and one of the leading causes of cancer-related deaths. Proper regulation of cell cycle checkpoints plays a critical role in preventing the accumulation of deleterious mutations. Perturbations in the expression or activity of mediators of cell cycle progression or checkpoint activation represent important events that may increase susceptibility to the onset of carcinogenesis.

Differential Expression of Glucose Transporters and Hexokinases in Prostate Cancer with a Neuroendocrine Gene Signature: A Mechanistic Perspective for F-FDG Imaging of PSMA-Suppressed Tumors.

Although the incidence of de novo neuroendocrine prostate cancer (PC) is rare, recent data suggest that low expression of prostate-specific membrane antigen (PSMA) is associated with a spectrum of neuroendocrine hallmarks and androgen receptor (AR) suppression in PC. Previous clinical reports indicate that PCs with a phenotype similar to neuroendocrine tumors can be more amenable to imaging by F-FDG than by PSMA-targeting radioligands. In this study, we evaluated the association between neuroendocrine gene signature and F-FDG uptake-associated genes including glucose transporters (GLUTs) and hexokinases, with the goal of providing a genomic signature to explain the reported F-FDG avidity of PSMA-suppressed tumors.

Amblyomma americanum ticks utilizes countervailing pro and anti-inflammatory proteins to evade host defense.

Feeding and transmission of tick-borne disease (TBD) agents by ticks are facilitated by tick saliva proteins (TSP). Thus, defining functional roles of TSPs in tick evasion is expected to reveal potential targets in tick-antigen based vaccines to prevent TBD infections. This study describes two types of Amblyomma americanum TSPs: those that are similar to LPS activate macrophage (MΦ) to express pro-inflammation (PI) markers and another set that suppresses PI marker expression by activated MΦ.

Adipose tissue NAD biosynthesis is required for regulating adaptive thermogenesis and whole-body energy homeostasis in mice.

Nicotinamide adenine dinucleotide (NAD) is a critical coenzyme for cellular energy metabolism. The aim of the present study was to determine the importance of brown and white adipose tissue (BAT and WAT) NAD metabolism in regulating whole-body thermogenesis and energy metabolism. Accordingly, we generated and analyzed adipocyte-specific nicotinamide phosphoribosyltransferase () knockout (ANKO) and brown adipocyte-specific knockout (BANKO) mice because NAMPT is the rate-limiting NAD biosynthetic enzyme.

The contribution of age structure to the international homicide decline.

Background: Since 1990, the world's homicide rate has declined by nearly 20%. While prior research has documented parallel homicide declines across many individual countries, the causes of a shared international homicide decline remain unknown. Drawing on a worldwide process of population ageing, and on research linking age to criminal activity, this study investigates the contribution of global demographic shifts to the international homicide decline.

Cyclin-like proteins tip regenerative balance in the liver to favour cancer formation.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. A variety of factors can contribute to the onset of this disease, including viral infection, obesity, alcohol abuse and non-alcoholic fatty liver disease (NAFLD). These stressors predominantly introduce chronic inflammation leading to liver cirrhosis and finally the onset of HCC; however, approximately 20% of HCC cases arise in the absence of cirrhosis via a poorly defined mechanism.

Greater mindfulness associated with lower pain, fatigue, and psychological distress in women with metastatic breast cancer.

Objective: Women with metastatic breast cancer (MBC) report high levels of disease-related symptoms including pain, fatigue, psychological distress, and sleep disturbance. Mindfulness may be particularly relevant to women with MBC given the high symptom burden and psychological toll of this disease; however, the topic is understudied among this patient population. Therefore, we aimed to test the associations between mindfulness and patient-reported symptoms among a sample of women with MBC.

Engineering γδT cells limits tonic signaling associated with chimeric antigen receptors.

Despite the benefits of chimeric antigen receptor (CAR)-T cell therapies against lymphoid malignancies, responses in solid tumors have been more limited and off-target toxicities have been more marked. Among the possible design limitations of CAR-T cells for cancer are unwanted tonic (antigen-independent) signaling and off-target activation. Efforts to overcome these hurdles have been blunted by a lack of mechanistic understanding.

Neuro- and hepatic toxicological profile of (S)-2,4-diaminobutanoic acid in embryonic, adolescent and adult zebrafish.

(S)-2,4-Diaminobutanoic acid (DABA) is a noncanonical amino acid often co-produced by cyanobacteria along with β-N-methylamino-l-alanine (BMAA) in algal blooms. Although BMAA is a well-established neurotoxin, the toxicity of DABA remains unclear. As part of our development of biocompatible materials, we wish to make use of DABA as both a building block and as the end-product of enzymatically induced depolymerization; however, if it is toxic at very low concentrations, this would not be possible.

How to increase community-wide resilience and decrease inequalities due to adverse childhood experiences (ACEs): Strategies from Walla Walla, Washington.

Adverse childhood experiences (ACEs) negatively impact community-level social problems, education, work, mental, and physical health beyond the effects of economic and political inequality. This paper summarizes the evidence that community-wide resilience moderates such impacts and examines how resilience can be increased by strategic interventions focused on community capacity building; Trauma-Informed Practices (TIPs) by staff in community organizations; and cultural change. Findings from three formative research evaluations in Walla Walla, Washington, show how community capacity was increased, trauma-informed practices were implemented across local organizations, and a school's culture was transformed.

Exploring the genetics of lesion and nodal resistance in pea ( L.) to using genome-wide association studies and RNA-Seq.

The disease white mold caused by the fungus is a significant threat to pea production, and improved resistance to this disease is needed. Nodal resistance in plants is a phenomenon where a fungal infection is prevented from passing through a node, and the infection is limited to an internode region. Nodal resistance has been observed in some pathosystems such as the pea ( L.

The gut microbiome and metabolome of saddleback tamarins (Leontocebus weddelli): Insights into the foraging ecology of a small-bodied primate.

Body mass is a strong predictor of diet and nutritional requirements across a wide range of mammalian taxa. In the case of small-bodied primates, because of their limited gut volume, rapid food passage rate, and high metabolic rate, they are hypothesized to maintain high digestive efficiency by exploiting foods rich in protein, fats, and readily available energy. However, our understanding of the dietary requirements of wild primates is limited because little is known concerning the contributions of their gut microbiome to the breakdown and assimilation of macronutrients and energy.

Inaccurate secondary structure predictions often indicate protein fold switching.

Although most proteins conform to the classical one-structure/one-function paradigm, an increasing number of proteins with dual structures and functions have been discovered. In response to cellular stimuli, such proteins undergo structural changes sufficiently dramatic to remodel even their secondary structures and domain organization. This "fold-switching" capability fosters protein multi-functionality, enabling cells to establish tight control over various biochemical processes.

Parenting a child with cancer: a couple-based approach.

Couples co-parenting a child with cancer face significant stressors that can adversely affect their couple relationship. How parents respond as a couple may affect the psychological adjustment of each parent and the child, as well as the ability of the family to cope with the child's illness. The purpose of this study was to assess the feasibility and acceptability of a couple-based intervention for parents of children with cancer.

Using selfies to challenge public stereotypes of scientists.

In an online Qualtrics panel survey experiment (N = 1620), we found that scientists posting self-portraits ("selfies") to Instagram from the science lab/field were perceived as significantly warmer and more trustworthy, and no less competent, than scientists posting photos of only their work. Participants who viewed scientist selfies, especially posts containing the face of a female scientist, perceived scientists as significantly warmer than did participants who saw science-only images or control images. Participants who viewed selfies also perceived less symbolic threat from scientists.

Brittle cornea syndrome: Disease-causing mutations in ZNF469 and two novel variants identified in a patient followed for 26 years.

Aims: Brittle cornea syndrome (BCS) is a rare autosomal recessive disorder. The aim of this study was to review ZNF469 mutations associated with BCS type 1 to date and to describe an additional case of Czech/Polish background.

Methods: Whole genome sequencing was undertaken to identify the molecular genetic cause of disease in the proband.

Amino acid signatures of HLA Class-I and II molecules are strongly associated with SLE susceptibility and autoantibody production in Eastern Asians.

Human leukocyte antigen (HLA) is a key genetic factor conferring risk of systemic lupus erythematosus (SLE), but precise independent localization of HLA effects is extremely challenging. As a result, the contribution of specific HLA alleles and amino-acid residues to the overall risk of SLE and to risk of specific autoantibodies are far from completely understood. Here, we dissected (a) overall SLE association signals across HLA, (b) HLA-peptide interaction, and (c) residue-autoantibody association.

Management of cancer-associated anemia with erythropoiesis-stimulating agents: ASCO/ASH clinical practice guideline update.

Purpose: To update the American Society of Clinical Oncology (ASCO)/American Society of Hematology (ASH) recommendations for use of erythropoiesis-stimulating agents (ESAs) in patients with cancer.

Methods: PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) and meta-analyses of RCTs in patients with cancer published from January 31, 2010, through May 14, 2018. For biosimilar ESAs, the literature search was expanded to include meta-analyses and RCTs in patients with cancer or chronic kidney disease and cohort studies in patients with cancer due to limited RCT evidence in the cancer setting.