White shark genome reveals ancient elasmobranch adaptations associated with wound healing and the maintenance of genome stability.

The white shark (; Chondrichthyes, Elasmobranchii) is one of the most publicly recognized marine animals. Here we report the genome sequence of the white shark and comparative evolutionary genomic analyses to the chondrichthyans, whale shark (Elasmobranchii) and elephant shark (Holocephali), as well as various vertebrates. The 4.

Renal mineralocorticoid receptor expression is reduced in lipoatrophy.

Obesity is a condition characterized by adipose tissue hypertrophy; it is estimated that the obesity epidemic accounted for 4 million deaths in 2015 and that 70% of these were due to cardiovascular disease (CVD). One of the mechanisms linking obesity to CVD is the ability of adipose tissue to secrete circulating factors. We hypothesized that adipose tissue and its secretory products may influence mineralocorticoid receptor (MR) expression.

Impact of Genetic Variants on HIV-1 Infection and Disease Progression.

Apolipoprotein L1 (APOL1) has broad innate immune functions and has been shown to restrict HIV replication by multiple mechanisms. Coding variants in are strongly associated with HIV-associated nephropathy (HIVAN) in persons with untreated HIV infection; however, the mechanism by which variant protein potentiates renal injury in the presence of high viral load is not resolved. Little is known about the association of genotypes with HIV viral load, HIV acquisition, or progression to AIDS.

Activation of group 2 innate lymphoid cells after allergen challenge in asthmatic patients.

Background: Group 2 innate lymphoid cells (ILC2s) are effective producers of IL-5 and IL-13 during allergic inflammation and bridge the innate and adaptive immune responses. ILC2 numbers are increased in asthmatic patients compared with healthy control subjects. Thus far, human data describing their phenotype during acute allergic inflammation in the lung are incomplete.

Management of delirium in Parkinson's disease.

Delirium is an acute and fluctuating disturbance of attention and awareness. Pre-existing cognitive disturbances or dementia are the most significant risk factors for developing delirium and precipitating factors such as drug treatment, infections, trauma, or surgery may trigger delirium. Patients with Parkinson's disease (PD) are at an increased risk for delirium which may be underdiagnosed due to phenomenological overlap between delirium and chronic neuropsychiatric features of PD or side effects of dopaminergic medication.

IFITM Genes, Variants, and Their Roles in the Control and Pathogenesis of Viral Infections.

Interferon-induced transmembrane proteins (IFITMs) are a family of small proteins that localize in the plasma and endolysosomal membranes. IFITMs not only inhibit viral entry into host cells by interrupting the membrane fusion between viral envelope and cellular membranes, but also reduce the production of infectious virions or infectivity of progeny virions. Not surprisingly, some viruses can evade the restriction of IFITMs and even hijack the antiviral proteins to facilitate their infectious entry into host cells or promote the assembly of virions, presumably by modulating membrane fusion.

Mechanistic Studies of Fatty Acid Activation by CYP152 Peroxygenases Reveal Unexpected Desaturase Activity.

The majority of cytochrome P450 enzymes (CYPs) predominantly operate as monooxygenases, but recently a class of P450 enzymes was discovered, that can act as peroxygenases (CYP152). These enzymes convert fatty acids through oxidative decarboxylation, yielding terminal alkenes, and through α- and β-hydroxylation to yield hydroxy-fatty acids. Bioderived olefins may serve as biofuels, and hence understanding the mechanism and substrate scope of this class of enzymes is important.

Genetically Regulated Bilirubin and Risk of Non-alcoholic Fatty Liver Disease: A Mendelian Randomization Study.

Mildly elevated serum bilirubin levels were reported to be associated with decreased risk of non-alcoholic fatty liver disease (NAFLD). Whether this is a causal relationship remains unclear. We tested the hypothesis that genetically elevated plasma bilirubin levels are causally related to reduce risk of NAFLD.

Latin Americans show wide-spread Converso ancestry and imprint of local Native ancestry on physical appearance.

Historical records and genetic analyses indicate that Latin Americans trace their ancestry mainly to the intermixing (admixture) of Native Americans, Europeans and Sub-Saharan Africans. Using novel haplotype-based methods, here we infer sub-continental ancestry in over 6,500 Latin Americans and evaluate the impact of regional ancestry variation on physical appearance. We find that Native American ancestry components in Latin Americans correspond geographically to the present-day genetic structure of Native groups, and that sources of non-Native ancestry, and admixture timings, match documented migratory flows.

Enhanced release of palladium and platinum from catalytic converter materials exposed to ammonia and chloride bearing solutions.

The environmental levels of platinum group elements (PGEs) are steadily rising, primarily due to exhaust emissions of vehicle catalytic converter (VCC) materials containing solid PGEs. Once these VCC materials reach soil and water, the PGEs may be transported in the form of nanoparticles (dimensions 1-100 nm) or they may be mobilized by forming coordination complexes with ligands in the environment. Chloride (Cl-) and ammonia (NH3) are two ligands of particular concern due to their ubiquity as well as their potential to form the chemotherapy drug cisplatin (Pt(NH3)2Cl2) or other potentially bioactive complexes.

Lack of Adipocytes Alters Hematopoiesis in Lipodystrophic Mice.

Adult hematopoiesis takes place in the perivascular zone of the bone cavity, where endothelial cells, mesenchymal stromal/stem cells and their derivatives such as osteoblasts are key components of bone marrow (BM) niches. Defining the contribution of BM adipocytes to the hematopoietic stem cell niche remains controversial. While an excess of medullar adiposity is generally considered deleterious for hematopoiesis, an active role for adipocytes in shaping the niche has also been proposed.

V260E Is a Frequent Cause of Steroid-Resistant Nephrotic Syndrome in Black South African Children.

Introduction: In South Africa (SA), steroid-resistant nephrotic syndrome (SRNS) is more frequent in black than in Indian children.

Methods: Seeking a genetic basis for this disparity, we enrolled 33 Indian and 31 black children with steroid-sensitive nephrotic syndrome (SSNS) and SRNS from KwaZulu-Natal, SA; SRNS children underwent kidney biopsy. We sequenced and genotyped in 15 SSNS and 64 SRNS unrelated patients and 104 controls and replicated results in 18 black patients with steroid-resistant focal segmental glomerulosclerosis (SR-FSGS).

APOL1 risk allele RNA contributes to renal toxicity by activating protein kinase R.

risk alleles associate with chronic kidney disease in African Americans, but the mechanisms remain to be fully understood. We show that risk alleles activate protein kinase R (PKR) in cultured cells and transgenic mice. This effect is preserved when a premature stop codon is introduced to risk alleles, suggesting that RNA but not protein is required for the effect.

Sclerotherapy needle injections can expand the subserosal and muscularis propria layers and cause a stable mucosal lift in ESD/EMR patients.

Background: A mucosal lift is needed for ESD and EMR. Most lifts are made via sclerotherapy needle injection. The firm push needed to penetrate the mucosa often leaves the needle tip in the deep wall.

Progression from islet autoimmunity to clinical type 1 diabetes is influenced by genetic factors: results from the prospective TEDDY study.

Background: Progression time from islet autoimmunity to clinical type 1 diabetes is highly variable and the extent that genetic factors contribute is unknown.

Methods: In 341 islet autoantibody-positive children with the human leucocyte antigen (HLA) DR3/DR4-DQ8 or the HLA DR4-DQ8/DR4-DQ8 genotype from the prospective TEDDY (The Environmental Determinants of Diabetes in the Young) study, we investigated whether a genetic risk score that had previously been shown to predict islet autoimmunity is also associated with disease progression.

Results: Islet autoantibody-positive children with a genetic risk score in the lowest quartile had a slower progression from single to multiple autoantibodies (p=0.

Intrawound Vancomycin Powder Reduces Bacterial Load in Contaminated Open Fracture Model.

Objectives: To compare the effectiveness of both vancomycin powder and antibiotic bead placement to irrigation and debridement alone in prevention of infection in a contaminated open fracture model in rats.

Methods: In a previously described model of contaminated open fractures, 45 rats had simulated open fractures created, stabilized, and contaminated with Staphylococcus aureus. They were then treated 6 hours later with 3 interventions: irrigation and debridement alone (control group) or in combination with placement of polymethyl methacrylate beads containing vancomycin and tobramycin powders (antibiotic bead group) or placement of 10 mg of intrawound vancomycin powder (powder group).

Physical activity is associated with lower insulin and C-peptide during glucose challenge in children and adolescents with family background of diabetes.

Aims: Children and adolescents with a family history of diabetes are at increased risk of overweight, but little is known about the potentially beneficial effects of physical activity on these children. The objective of this study was to investigate the association between moderate to vigorous physical activity (MVPA) and metabolic and inflammatory risks in children and adolescents with a family background of Type 1 diabetes or gestational diabetes.

Methods: Valid MVPA measurements, made with accelerometers, were available from 234 participants (median age, 10.

A genome-wide association and admixture mapping study of bronchodilator drug response in African Americans with asthma.

Short-acting β-adrenergic receptor agonists (SABAs) are the most commonly prescribed asthma medications worldwide. Response to SABAs is measured as bronchodilator drug response (BDR), which varies among racial/ethnic groups in the United States. However, the genetic variation that contributes to BDR is largely undefined in African Americans with asthma.

An admixture mapping meta-analysis implicates genetic variation at 18q21 with asthma susceptibility in Latinos.

Background: Asthma is a common but complex disease with racial/ethnic differences in prevalence, morbidity, and response to therapies.

Objective: We sought to perform an analysis of genetic ancestry to identify new loci that contribute to asthma susceptibility.

Methods: We leveraged the mixed ancestry of 3902 Latinos and performed an admixture mapping meta-analysis for asthma susceptibility.

Accuracy in orthognathic surgery─comparison of preoperative plan and postoperative outcome using computer-assisted two-dimensional cephalometry by the Onyx Ceph system.

Purpose: This retrospective study analyzes deviations between preoperative planning and postoperative outcome in orthognathic surgery using 2D Onyx Ceph-cephalometric analyzing and planning system.

Materials And Methods: A total of 100 patients with a mean age 25.1 of years were included in this study.

Fetal-Not Maternal-APOL1 Genotype Associated with Risk for Preeclampsia in Those with African Ancestry.

Black Americans are at increased risk for preeclampsia. Genetic variants in apolipoprotein L1 (APOL1) account for much of the increased risk for kidney disease in blacks. APOL1 is expressed in human placenta and transgenic mice expressing APOL1 develop preeclampsia.

An evaluation of body condition and morphometric relationships within southern California juvenile white sharks Carcharodon carcharias.

Length, mass and girth relationships are presented for 112 juvenile white sharks (JWS) Carcharodon carcharias caught in the Southern California Bight (SCB) nursery area between June 2008 and August 2017. No difference was found between male and female JWS length-mass relationships, but data suggest that JWS in the SCB gain more mass per unit length for the juvenile size classes compared with other C. carcharias populations.

A substrate-trapping strategy for protein phosphatase PP1 holoenzymes using hypoactive subunit fusions.

The protein Ser/Thr phosphatase PP1 catalyzes an important fraction of protein dephosphorylation events and forms highly specific holoenzymes through an association with regulatory interactors of protein phosphatase one (RIPPOs). The functional characterization of individual PP1 holoenzymes is hampered by the lack of straightforward strategies for substrate mapping. Because efficient substrate recruitment often involves binding to both PP1 and its associated RIPPO, here we examined whether PP1-RIPPO fusions can be used to trap substrates for further analysis.

Genetics, Genomics, and Precision Medicine in End-Stage Kidney Disease.

Recent advances in genetics of renal disease have deepened our understanding of progressive kidney disease. Here, we review genetic variants that are of particular importance to progressive glomerular disease that result in end-stage kidney disease (ESKD). Some of the most striking findings relate to APOL1 genetic variants, seen exclusively in individuals of sub-Saharan African descent, that create a predisposition to particular renal disorders, including focal segmental glomerulosclerosis and arterionephrosclerosis.