Phenotypic and Genetic Divergence among Poison Frog Populations in a Mimetic Radiation.

The evolution of Müllerian mimicry is, paradoxically, associated with high levels of diversity in color and pattern. In a mimetic radiation, different populations of a species evolve to resemble different models, which can lead to speciation. Yet there are circumstances under which initial selection for divergence under mimicry may be reversed.

Dogslife: a web-based longitudinal study of Labrador Retriever health in the UK.

Background: Dogslife is the first large-scale internet-based longitudinal study of canine health. The study has been designed to examine how environmental and genetic factors influence the health and development of a birth cohort of UK-based pedigree Labrador Retrievers.

Results: In the first 12 months of the study 1,407 Kennel Club (KC) registered eligible dogs were recruited, at a mean age of 119 days of age (SD 69 days, range 3 days - 504 days).

Techniques for minimizing the effects of PCR inhibitors in the chytridiomycosis assay.

Chytridiomycosis is an amphibian disease of global conservation concern that is caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd). Since the discovery of Bd in 1998, several methods have been used for detection of Bd; among these polymerase chain reaction (PCR) from skin swabs is accepted as the best method due to its noninvasiveness, high sensitivity and ease of use. However, PCR is not without problems - to be successful, this technique is dependent upon the presence of nondegraded DNA template and reaction contents that are free from inhibitors.

Estimated economic benefits from low-frequency administration of atypical antipsychotics in treatment of schizophrenia: a decision model.

The objective of this study was to quantify the direct medical resources used and the corresponding burden of disease in the treatment of patients with schizophrenia. Because low-frequency administration (LFA) of risperidone guarantees adherence during treatment intervals and offers fewer opportunities to discontinue, adherence and persistence were assumed to improve, thereby reducing relapses of major symptoms.A decision tree model including Markov processes with monthly cycles and a five-year maximum timeframe was constructed.

A gene expression atlas of the domestic pig.

Background: This work describes the first genome-wide analysis of the transcriptional landscape of the pig. A new porcine Affymetrix expression array was designed in order to provide comprehensive coverage of the known pig transcriptome. The new array was used to generate a genome-wide expression atlas of pig tissues derived from 62 tissue/cell types.

Recent developments in the diagnosis of Marfan syndrome and related disorders.

Marfan syndrome is a multisystem disorder of connective tissue that is inherited in an autosomal dominant fashion, and results from mutation of the FBN1 gene on human chromosome 15. There are a number of conditions of the connective tissue with a similar phenotype that can be confused with Marfan syndrome. Modifications of the diagnostic criteria have recently been published, facilitating the differentiation of Marfan syndrome from these conditions.

Population structure and genetic heterogeneity in popular dog breeds in the UK.

There is increasing concern that reproductive isolation related to breed specifications in dogs, while maintaining genetic differences among breeds, is likely to promote breed-specific genetic disorders. This study examined genetic diversity among 13 popular dog breed groups in the UK. Most breeds showed high levels of homozygosity when compared with crossbred animals.

Modeling the Zn(2+) and Cd(2+) metalation mechanism in mammalian metallothionein 1a.

Mammalian metallothioneins (MTs) are a family of small cysteine rich proteins believed to have a number of physiological functions, including both metal ion homeostasis and toxic metal detoxification. Mammalian MTs bind 7 Zn(2+) or Cd(2+) ions into two distinct domains: an N-terminal β-domain that binds 3 Zn(2+) or Cd(2+), and a C-terminal α-domain that binds 4 Zn(2+) or Cd(2+). Although stepwise metalation to the saturated M(7)-MT (where M=Zn(2+) or Cd(2+)) species would be expected to take place via a noncooperative mechanism involving the 20 cysteine thiolate ligands, literature reports suggest a cooperative mechanism involving cluster formation prior to saturation of the protein.

Development of a men's Preference for Testosterone Replacement Therapy (P-TRT) instrument.

Background: This study used a standard research approach to create a final conceptual model and the Preference for the Testosterone Replacement Therapy (P-TRT) instrument.

Methods: A discussion guide was developed from a literature review and expert opinion to direct one-on-one interviews with participants who used testosterone replacement therapy and consented to participate in the study. Data from telephone interviews were transcribed for theme analysis using NVivo 9 qualitative analysis software, analyzed descriptively from a saturation grid, and used to evaluate men's P-TRT.

Structure and function of the mammalian fibrillin gene family: implications for human connective tissue diseases.

Fibrillins and latent transforming growth factor β binding proteins (LTBPs) are components of the extracellular matrix of connective tissue. While fibrillins are integral to the 10nm microfibrils, and often associated with elastin, all family members are likely to have an additional role in regulating the bioavailability of transforming growth factor β (TGBβ). Both fibrillins and LTBPs are large glycoproteins, containing a series of calcium binding epidermal growth factor domains as well as a number of copies of a unique 8 cysteine domain found only in this protein superfamily.

Structural properties of metal-free apometallothioneins.

The metalated forms of metallothionein are well studied (particularly Zn-MT, Cu-MT and Cd-MT), but almost nothing is known about the chemical and structural properties of apometallothioneins despite their importance in initial metalation and subsequent demetalation. Electrospray ionization mass spectrometry was used to provide a detailed view of the structural properties of the metal-free protein. Mass spectra of Zn(7)-MT and apo-MT at pH 7 exhibit the same charge state distribution, indicating that apo-MT is tightly folded like the metallated protein, whereas apo-MT at pH 3 exhibits a charge state spectrum associated with unfolding or denaturation.

Noncooperative metalation of metallothionein 1a and its isolated domains with zinc.

Mammalian metallothioneins (MTs) are a family of small cysteine-rich proteins capable of binding 7 Zn(2+) or Cd(2+) ions into two distinct domains: an N-terminal β-domain that binds 3 Zn(2+) or Cd(2+) and a C-terminal α-domain that binds 4 Zn(2+) or Cd(2+). MT has been implicated in a number of physiological functions, including metal ion homeostasis, toxic metal detoxification, and as a protective agent against oxidative stress. Conventionally, MT has been understood to coordinate metal ions in a cooperative fashion.

Mate choice and the genetic basis for colour variation in a polymorphic dart frog: inferences from a wild pedigree.

Understanding how reproductive barriers evolve during speciation remains an important question in evolution. Divergence in mating preferences may be a common first step in this process. The striking colour pattern diversity of strawberry dart frog (Dendrobates pumilio) populations has likely been shaped by sexual selection.

The early inflammatory response in a mini-cardiopulmonary bypass system: a prospective randomized study.

Objective: The aim of this study was to compare the early systemic inflammatory response of the Resting Heart System (RHS; Medtronic, Minneapolis, MN USA), a miniaturized cardiopulmonary bypass (CPB) system, with two groups using a standard extracorporeal circulation system during on-pump coronary artery bypass grafting (CABG) surgery.

Methods: A total of 60 consecutive patients requiring CABG were prospectively randomized to undergo on-pump CABG using conventional CPB without cardiotomy suction (group A), conventional CPB with cardiotomy suction (group B), or the RHS (group C). Blood samples were collected at five time points: immediately before CPB, 30 minutes into CPB, immediately at the end of CPB, 30 minutes post-CPB, and 1 hour post-CPB.

Male gender promotes an increased inflammatory response to lipopolysaccharide in umbilical vein blood.

Objectives: To establish gender-specific differences in maternal and fetal immune response in healthy human fetuses at term.

Methods: Forty-five women with elective caesarean sections for uncomplicated singleton pregnancies were recruited for two studies. Using a multiplex biomarker immunoassay system, unstimulated maternal and fetal plasma concentrations of interleukin (IL)-1β, IL-1ra, IL-6, IL-8, macrophage inflammatory protein (MIP)-1α, and tumor necrosis factor (TNF)-α were measured from one study population.

Daily average consumption of 2 long-acting opioids: an interrupted time series analysis.

Background: Oxycodone controlled release (CR) and oxymorphone extended release (ER) are frequently prescribed long-acting opioids, which are approved for twice-daily dosing. The US Food and Drug Administration approved a reformulated crush-resistant version of oxycodone CR in April 2010.

Objective: To compare the daily average consumption (DACON) for oxycodone CR and for oxymorphone ER before and after the introduction of the reformulated, crush-resistant version of oxycodone CR.

Phosphorylation: the molecular switch of double-strand break repair.

Repair of double-stranded breaks (DSBs) is vital to maintaining genomic stability. In mammalian cells, DSBs are resolved in one of the following complex repair pathways: nonhomologous end-joining (NHEJ), homologous recombination (HR), or the inclusive DNA damage response (DDR). These repair pathways rely on factors that utilize reversible phosphorylation of proteins as molecular switches to regulate DNA repair.

Young and older adults' beliefs about effective ways to mitigate age-related memory decline.

This study investigated whether young and older adults vary in their beliefs about the impact of various mitigating factors on age-related memory decline. Eighty young (ages 18-23) and 80 older (ages 60-82) participants reported their beliefs about their own memory abilities and the strategies that they use in their everyday lives to attempt to control their memory. Participants also reported their beliefs about memory change with age for hypothetical target individuals who were described as using (or not using) various means to mitigate memory decline.

Genome-wide analysis of mitral valve disease in Cavalier King Charles Spaniels.

The Cavalier King Charles Spaniel (CKCS) is prone to severe early onset mitral valve disease. In this study, 36 purebred CKCS dogs were evaluated for mitral valve murmur and divided into early and late onset groups. A genome-wide genetic approach was used to assess whether the condition is determined by a small number of genetic factors.

Direct and indirect costs of patients treated with extended-release oxymorphone HCl or controlled-release oxycodone HCl.

Objective: Compare direct and indirect costs of oxymorphone extended-release ('oxymorphone') and oxycodone controlled-release ('oxycodone') users.

Methods: Patients, aged 18+, with ≥1 claim for oxymorphone/oxycodone, Q2:2006-Q4:2009, were selected from a de-identified private payer claims database and observed from the first such claim ('index date') until the earliest of: use of comparator drug; end of continuous eligibility; 12 months ('study period'). Patients with claims for any formulation of the comparator drug during the first 30 days of the study period were excluded.

Economic impact of potential drug-drug interactions among osteoarthritis patients taking opioids.

Patients with osteoarthritis (OA) taking at least one CYP450-metabolized opioid concurrently with another CYP450-metabolized medication experience a drug-drug exposure (DDE), which puts them at risk of a pharmacokinetic drug-drug interaction (PK DDI). This study compared patients with and without such an incident DDE to determine healthcare utilization and associated payments. Using a retrospective database analysis, the impact of DDEs was evaluated in terms of associated clinical events, healthcare services utilization (office visits, outpatient visits, ED visits, hospitalization), and payments in patient populations based on age (those under age 65 and those 65 years of age and older), during the 6 months after exposure.

Economic impact of potential CYP450 pharmacokinetic drug-drug interactions among chronic low back pain patients taking opioids.

Chronic low back pain (cLBP) patients who take at least 1 CYP450-metabolized opioid analgesic agent concurrent with at least 1 other CYP450-metabolized medication experience a drug-drug exposure (DDE), which puts them at risk for a pharmacokinetic drug-drug interaction (PK DDI). This study compared utilization of healthcare resources and associated payments in cLBP patients with and without incident DDEs with the potential to cause PK DDIs. A retrospective database analysis examined the associated clinical events, healthcare utilization (measured in terms of claims for office visits, outpatient visits, emergency department visits, and hospitalization), and cost to the health plan, as defined as the sum of health plan payments for resources used.

Imatinib in active diffuse cutaneous systemic sclerosis: Results of a six-month, randomized, double-blind, placebo-controlled, proof-of-concept pilot study at a single center.

Objective: To better understand the feasibility of using imatinib, a tyrosine kinase inhibitor, to treat active diffuse cutaneous systemic sclerosis (dcSSc).

Methods: We performed a 6-month, randomized, double-blind, placebo-controlled, proof-of-concept pilot study of imatinib in patients with active dcSSc. Data on safety, modified Rodnan skin thickness scores (MRSS), Health Assessment Questionnaire (HAQ) scores, patient's and physician's global assessments (100-mm visual analog scale), and biomarkers in serum and skin biopsy samples were collected.

Evidence for acquisition of virulence effectors in pathogenic chytrids.

Background: The decline in amphibian populations across the world is frequently linked to the infection of the chytrid fungus Batrachochytrium dendrobatidis (Bd). This is particularly perplexing because Bd was only recently discovered in 1999 and no chytrid fungus had previously been identified as a vertebrate pathogen.

Results: In this study, we show that two large families of known virulence effector genes, crinkler (CRN) proteins and serine peptidases, were acquired by Bd from oomycete pathogens and bacteria, respectively.