Establishment of a Swiss Webster mouse model of pneumonic plague to meet essential data elements under the animal rule.

A recombinant vaccine (rF1V) is being developed for protection against pneumonic plague. This study was performed to address essential data elements to establish a well-characterized Swiss Webster mouse model for licensing the rF1V vaccine using the FDA's Animal Rule. These elements include the documentation of challenge material characteristics, aerosol exposure parameters, details of the onset and severity of clinical signs, pathophysiological response to disease, and relevance to human disease.

Lack of effect of lowering LDL cholesterol on cancer: meta-analysis of individual data from 175,000 people in 27 randomised trials of statin therapy.

Background: Statin therapy reduces the risk of occlusive vascular events, but uncertainty remains about potential effects on cancer. We sought to provide a detailed assessment of any effects on cancer of lowering LDL cholesterol (LDL-C) with a statin using individual patient records from 175,000 patients in 27 large-scale statin trials.

Methods And Findings: Individual records of 134,537 participants in 22 randomised trials of statin versus control (median duration 4.

Optimal use of fresh frozen plasma.

Fresh frozen plasma contains a number of therapeutically useful substances, most notably coagulation factors. As with any transfusion, there are risks associated with plasma transfusion. Ironically, the risk of viral transmission (human immunodeficiency virus or hepatitis), although widely publicized, is extremely small.

Native gel electrophoresis of human telomerase distinguishes active complexes with or without dyskerin.

Telomeres, the ends of linear chromosomes, safeguard against genome instability. The enzyme responsible for extension of the telomere 3' terminus is the ribonucleoprotein telomerase. Whereas telomerase activity can be reconstituted in vitro with only the telomerase RNA (hTR) and telomerase reverse transcriptase (TERT), additional components are required in vivo for enzyme assembly, stability and telomere extension activity.

Empirical classification of eating disorders.

Current diagnostic criteria for anorexia nervosa (AN) and bulimia nervosa (BN) account for a minority of individuals with clinically significant disorders of eating, raising concerns about the clinical utility of current definitions. This review examines evidence for the validity of current and alternative approaches to defining eating disorders and implications for draft criteria for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Although this review largely supports the predictive validity of distinctions among AN, BN, and the newly proposed binge eating disorder (BED), it also highlights that our tendency to "study what we define" has created a gap between the problems that people have and what we know about those problems.

Online enzymatic sequencing of glycans from Trastuzumab by phospholipid-assisted capillary electrophoresis.

CE separations of glycans taken from the cancer drug, Trastuzumab (Herceptin(®)), were accomplished using phospholipid additives. Glycans were labeled with 1-aminopyrene-3,6,8-trisulfonic acid and were separated with efficiencies as high as 510000 theoretical plates in a 60.2 cm 25 μm id fused-silica capillary.

Obesity is associated with impaired immune response to influenza vaccination in humans.

Background: Obesity is an independent risk factor for morbidity and mortality from pandemic influenza H1N1. Influenza is a significant public health threat, killing an estimated 250,000-500,000 people worldwide each year. More than one in ten of the world's adult population is obese and more than two-thirds of the US adult population is overweight or obese.

Analyses of gene function in amphioxus embryos by microinjection of mRNAs and morpholino oligonucleotides.

The invertebrate chordate amphioxus (Branchiostoma), which is the most basal living chordate, has become an accepted model for the vertebrate ancestor in studies of development and evolution. Amphioxus resembles vertebrates in regard to morphology, developmental gene expression, and gene function. In addition, the amphioxus genome has representatives of most vertebrate gene families.

Parental disorders, childhood abuse, and binge eating in a large community sample.

Objective: Genetic and nonshared environmental factors are implicated in the etiology of binge eating behaviors (BEB), with genetic risk expressed as parental psychopathology. Traumatic experiences including child abuse predict onset of BEB. It is not clear if each separately contribute to BEB, or whether parental pathology leads to abuse which in turn influences BEB.

Alternative splicing in development and function of chordate endocrine systems: a focus on Pax genes.

Genome sequencing has facilitated an understanding of gene networks but has also shown that they are only a small part of the answer to the question of how genes translate into a functional organism. Much of the answer lies in epigenetics-heritable traits not directly encoded by the genome. One such phenomenon is alternative splicing, which affects over 75% of protein coding genes and greatly amplifies the number of proteins.

"Insights of early chordate genomics: endocrinology and development in amphioxus, tunicates and lampreys": introduction to the symposium.

This symposium focused on the evolution of chordate genomes, in particular, those events that occurred before the appearance of jawed vertebrates. The aim was to highlight insights that have come from the genome sequences of jawless chordates (lampreys, tunicates, and amphioxus) not only into evolution of chordate genomes, but also into the evolution of the organism. To this end, we brought together researchers whose recent work on these organisms spans the gap from genomics to the evolution of body forms and functions as exemplified by endocrine systems and embryonic development.

"You have to hunt for the fruits, the vegetables": environmental barriers and adaptive strategies to acquire food in a low-income African American neighborhood.

This qualitative study sought to understand food acquisition behaviors and environmental factors that influence those behaviors among women in a low-income African American community with limited food resources. We drew on in-depth interviews with 30 women ages 21 to 45 years recruited from a community health center in Chicago, Illinois. Data were analyzed using qualitative content analysis.

Sublethal exposure to crude oil during embryonic development alters cardiac morphology and reduces aerobic capacity in adult fish.

Exposure to high concentrations of crude oil produces a lethal syndrome of heart failure in fish embryos. Mortality is caused by cardiotoxic polycyclic aromatic hydrocarbons (PAHs), ubiquitous components of petroleum. Here, we show that transient embryonic exposure to very low concentrations of oil causes toxicity that is sublethal, delayed, and not counteracted by the protective effects of cytochrome P450 induction.

A neutral Pt3 stack unsupported by any bridging ligand.

Pt···Pt···Pt interactions via their d(8) orbitals, combined with π-π stacking of deprotonated, chelating 2-(3'-pyrazolyl)pyridine (pyzpy) ligands, are responsible for trans-Pt(pyzpy)(2) (2) crystallization in a stack of three molecules unsupported by any bridging ligand.

Microscale exoglycosidase processing and lectin capture of glycans with phospholipid assisted capillary electrophoresis separations.

Capillary electrophoresis separations of glycans labeled with 1-aminopyrene-3,6,8-trisulfonic acid were achieved with separation efficiencies ranging from 480,000 to 640,000 theoretical plates in a 60.2 cm, 25 μm inner diameter fused silica capillary. Under these separation conditions, the coefficient of variation in peak area is 10%, and if labeling efficiency is estimated at 100%, the limit of detection is 15 fM.

Asymmetric localization of germline markers Vasa and Nanos during early development in the amphioxus Branchiostoma floridae.

The origin of germline cells was a crucial step in animal evolution. Therefore, in both developmental biology and evolutionary biology, the mechanisms of germline specification have been extensively studied over the past two centuries. However, in many animals, the process of germline specification remains unclear.

Citrus flavonoids repress the mRNA for stearoyl-CoA desaturase, a key enzyme in lipid synthesis and obesity control, in rat primary hepatocytes.

Citrus flavonoids have been shown to decrease plasma lipid levels, improve glucose tolerance, and attenuate obesity. One possible mechanism underlying these physiological effects is reduction of hepatic levels of the mRNA for stearoyl-CoA desaturase-1 (SCD1), since repression of this enzyme reduces hyperlipidemia and adiposity. Here, we show that citrus flavonoids of two structural classes reduce SCD1 mRNA concentrations in a dose-dependent manner in rat primary hepatocytes.

Evolution of mating within the Candida parapsilosis species group.

Candida orthopsilosis and Candida metapsilosis are closely related to Candida parapsilosis, a major cause of infection in premature neonates. Mating has not been observed in these species. We show that ∼190 isolates of C.

Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials.

Background: Lowering of LDL cholesterol with standard statin regimens reduces the risk of occlusive vascular events in a wide range of individuals. We aimed to assess the safety and efficacy of more intensive lowering of LDL cholesterol with statin therapy.

Methods: We undertook meta-analyses of individual participant data from randomised trials involving at least 1000 participants and at least 2 years' treatment duration of more versus less intensive statin regimens (five trials; 39 612 individuals; median follow-up 5·1 years) and of statin versus control (21 trials; 129 526 individuals; median follow-up 4·8 years).

Mutation of tagO reveals an essential role for wall teichoic acids in Staphylococcus epidermidis biofilm development.

The icaADBC-encoded polysaccharide intercellular adhesin (PIA) and wall teichoic acids (WTA) are structural components of Staphylococcus epidermidis biofilms. Deletion of tagO, which encodes the first enzymic step in WTA biosynthesis, had pleiotropic effects, including enhanced intercellular aggregation and autolytic activity, and impaired biofilm production. The biofilm-negative phenotype of the tagO mutant, named TAGO1, was associated with increased cell surface hydrophobicity, lower rates of primary attachment to polystyrene, and reduced icaADBC operon and PIA expression.

Laboratory spawning and development of the Bahama lancelet, Asymmetron lucayanum (cephalochordata): fertilization through feeding larvae.

Here we report on spawning and development of the Bahama lancelet, Asymmetron lucayanum. Ripe adults collected in Bimini spawned the same evening when placed in the dark for 90 minutes. The developmental morphology is described from whole mounts and histological sections.

Protection in mice passively immunized with serum from cynomolgus macaques and humans vaccinated with recombinant plague vaccine (rF1V).

Passive transfer models were developed to evaluate the ability of antibodies generated in cynomolgus macaques and humans vaccinated with a recombinant plague vaccine (rF1V) to protect naïve Swiss Webster mice against pneumonic plague. Development of the passive transfer model is intended to support clinical and nonclinical development of the rF1V vaccine. To evaluate protection, unfractionated serum collected from rF1V vaccinated cynomolgus macaques and human volunteers with known antibody titers to rF1, rV and rF1V was transferred into naïve Swiss Webster mice via the intraperitoneal route.

Persistence in darkness of virulent alphaviruses, Ebola virus, and Lassa virus deposited on solid surfaces.

Ebola, Lassa, Venezuelan equine encephalitis, and Sindbis viruses were dried onto solid surfaces, incubated for various time periods under controlled conditions of temperature and relative humidity, and quantitatively eluted from surfaces, and viral titers in the recovered samples were determined. The viral inactivation kinetics that were obtained indicated that viral resistance to natural inactivation in the dark follows (in decreasing order of stability) alphavirus > Lassa virus > Ebola virus. The findings reported in this study on the natural decay in the dark should assist in understanding the biophysical properties of enveloped RNA viruses outside the host and in estimating the persistence of viruses in the environment during epidemics or after an accidental or intentional release.

Steroid determination in fish plasma using capillary electrophoresis.

A capillary separation method that incorporates pH-mediated stacking is employed for the simultaneous determination of circulating steroid hormones in plasma from Perca flavescens (yellow perch) collected from natural aquatic environments. The method can be applied to separate eight steroid standards: progesterone, 17alpha,20beta-dihydroxypregn-4-en-3-one, 17alpha-hydroxyprogesterone, testosterone, estrone, 11-ketotestosterone, ethynyl estradiol, and 17beta-estradiol. Based on screening of plasma, the performance of the analytical method was determined for 17alpha,20beta-dihydroxypregn-4-en-3-one, testosterone, 11-ketotestosterone, and 17beta-estradiol.