Evolutionary analysis of mitochondrially encoded proteins of toad-headed lizards, Phrynocephalus, along an altitudinal gradient.

BACKGROUND: Animals living at high altitude must adapt to environments with hypoxia and low temperatures, but relatively little is known about underlying genetic changes. Toad-headed lizards of the genus Phrynocephalus cover a broad altitudinal gradient of over 4000 m and are useful models for studies of such adaptive responses. In one of the first studies to have considered selection on mitochondrial protein-coding regions in an ectothermic group distributed over such a wide range of environments, we analysed nineteen complete mitochondrial genomes from all Chinese Phrynocephalus (including eight genomes sequenced for the first time). Initial analyses used site and branch-site model (program: PAML) approaches to examine nonsynonymous: synonymous substitution rates across the mtDNA tree. RESULTS: Ten positively selected sites were discovered, nine of which corresponded to subunits ND2, ND3, ND4, ND5, and ND6 within the respiratory chain enzyme mitochondrial Complex I (NADH Coenzyme Q oxidoreductase). Four of these sites showed evidence of general long-term selection across the group while the remainder showed evidence of episodic selection across different branches of the tree. Some of these branches corresponded to increases in altitude and/or latitude. Analyses of physicochemical changes in protein structures revealed that residue changes at sites that were under selection corresponded to major functional differences. Analyses of coevolution point to coevolution of selected sites within the ND4 subunit, with key sites associated with proton translocation across the mitochondrial membrane. CONCLUSIONS: Our results identify mitochondrial Complex I as a target for environment-mediated selection in this group of lizards, a complex that frequently appears to be under selection in other organisms. This makes these lizards good candidates for more detailed future studies of molecular evolution

Positive predictive value of automated database records for diabetic ketoacidosis (DKA) in children and youth exposed to antipsychotic drugs or control medications: a tennessee medicaid study

<p>Abstract</p> <p>Background</p> <p>Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of treatment with some atypical antipsychotic drugs in children and <b>youth</b>. Because drug-associated DKA is rare, large automated health outcomes databases may be a valuable data source for conducting pharmacoepidemiologic studies of DKA associated with exposure to individual antipsychotic drugs. However, no validated computer case definition of DKA exists. We sought to assess the positive predictive value (PPV) of a computer case definition to detect incident cases of DKA, using automated records of Tennessee Medicaid as the data source and medical record confirmation as a "gold standard."</p> <p>Methods</p> <p>The computer case definition of DKA was developed from a retrospective cohort study of antipsychotic-related type 2 diabetes mellitus (1996-2007) in Tennessee Medicaid enrollees, aged 6-24 years. Thirty potential cases with any DKA diagnosis (ICD-9 250.1, ICD-10 E1x.1) were identified from inpatient encounter claims. Medical records were reviewed to determine if they met the clinical definition of DKA.</p> <p>Results</p> <p>Of 30 potential cases, 27 (90%) were successfully abstracted and adjudicated. Of these, 24 cases were confirmed by medical record review (PPV 88.9%, 95% CI 71.9 to 96.1%). Three non-confirmed cases presented acutely with severe hyperglycemia, but had no evidence of acidosis.</p> <p>Conclusions</p> <p>Diabetic ketoacidosis in children and youth can be identified in a computerized Medicaid database using our case definition, which could be useful for automated database studies in which drug-associated DKA is the outcome of interest.</p

Tailoring hyper-heuristics to specific instances of a scheduling problem using affinity and competence functions

Hyper-heuristics are high level heuristics which coordinate lower level ones to solve a given problem. Low level heuristics, however, are not all as competent/good as each other at solving the given problem and some do not work together as well as others. Hence the idea of measuring how good they are (competence) at solving the problem and how well they work together (their affinity). Models of the affinity and competence properties are suggested and evaluated using previous information on the performance of the simple low level heuristics. The resulting model values are used to improve the performance of the hyper-heuristic by tailoring it not only to the specific problem but the specific instance being solved. The test case is a hard combinatorial problem, namely the Hybrid Flow Shop scheduling problem. Numerical results on randomly generated as well as real-world instances are included

Hepatotoxicity or Hepatoprotection? Pattern Recognition for the Paradoxical Effect of the Chinese Herb Rheum palmatum L. in Treating Rat Liver Injury

The hepatotoxicity of some Chinese herbs has been a cause for concern in recent years. However, some herbs, such as rhubarb, have been documented as having both therapeutic and toxic effects on the liver, leading to the complex problem of distinguishing the benefits from the risks of using this herb. To comparatively analyze the dose-response relationship between rhubarb and hepatic health, we administrated total rhubarb extract(RE) to normal and carbon tetrachloride(CCl4)-treated rats for 12 weeks at 4 dosage levels(2.00, 5.40, 14.69 and 40.00 g·kg−1, measured as the quantity of crude material), followed by biochemical and histopathological tests of the rats' livers. A composite pattern was extracted by factor analysis, using all the biochemical indices as variables, into a visual representation of two mathematically obtained factors, which could be interpreted as the fibrosis factor and the cellular injury factor, according to the values of the variable loadings. The curative effect of administering the two lowest dosages of RE to CCl4-treated rats was mainly expressed as a decrease in the extent of cellular injury. The hepatoprotective mechanism of RE might be related to its antioxidant effect, the antagonism of the free radical damage to hepatocytes caused by CCl4. By contrast, the RE-induced liver damage was mainly expressed as a significant increase in the amount of fibrosis in both normal rats at all dosage levels and CCl4-treated rats at the two highest dosage levels. Therefore, the hepatotoxic potential of RE could be attributable to the liver cell fibrosis induced by high doses of the herb. This study illustrates the bidirectional potential of rhubarb and demonstrates the feasibility of using factor analysis to study the dose-response relationships between herbal medicines and hepatotoxicity or the healing effects of these herbs by extracting the underlying interrelationships among a number of functional bio-indices in a holistic manner

Elasto-Plastic Stress Analysis in Rotating Disks and Pressure Vessels Made of Functionally Graded Materials

Abstract A new elastio-plastic stress solution in axisymmetric problems (rotating disk, cylindrical and spherical vessel) is presented. The rotating disk (cylindrical and spherical vessel) was made of a ceramic/metal functionally graded material, i.e. a particle-reinforced composite. It was assumed that the material's plastic deformation follows an isotropic strain-hardening rule based on the von-Mises yield criterion. The mechanical properties of the graded material were modeled by the modified rule of mixtures. By assuming small strains, Hencky's stress-strain relation was used to obtain the governing differential equations for the plastic region. A numerical method for solving those differential equations was then proposed that enabled the prediction of stress state within the structure. Selected finite element results were also presented to establish supporting evidence for the validation of the proposed approach

RNAseq Analyses Identify Tumor Necrosis Factor-Mediated Inflammation as a Major Abnormality in ALS Spinal Cord

ALS is a rapidly progressive, devastating neurodegenerative illness of adults that produces disabling weakness and spasticity arising from death of lower and upper motor neurons. No meaningful therapies exist to slow ALS progression, and molecular insights into pathogenesis and progression are sorely needed. In that context, we used high-depth, next generation RNA sequencing (RNAseq, Illumina) to define gene network abnormalities in RNA samples depleted of rRNA and isolated from cervical spinal cord sections of 7 ALS and 8 CTL samples. We aligned \u3e50 million 2X150 bp paired-end sequences/sample to the hg19 human genome and applied three different algorithms (Cuffdiff2, DEseq2, EdgeR) for identification of differentially expressed genes (DEG’s). Ingenuity Pathways Analysis (IPA) and Weighted Gene Co-expression Network Analysis (WGCNA) identified inflammatory processes as significantly elevated in our ALS samples, with tumor necrosis factor (TNF) found to be a major pathway regulator (IPA) and TNFα-induced protein 2 (TNFAIP2) as a major network “hub” gene (WGCNA). Using the oPOSSUM algorithm, we analyzed transcription factors (TF) controlling expression of the nine DEG/hub genes in the ALS samples and identified TF’s involved in inflammation (NFkB, REL, NFkB1) and macrophage function (NR1H2::RXRA heterodimer). Transient expression in human iPSC-derived motor neurons of TNFAIP2 (also a DEG identified by all three algorithms) reduced cell viability and induced caspase 3/7 activation. Using high-density RNAseq, multiple algorithms for DEG identification, and an unsupervised gene co-expression network approach, we identified significant elevation of inflammatory processes in ALS spinal cord with TNF as a major regulatory molecule. Overexpression of the DEG TNFAIP2 in human motor neurons, the population most vulnerable to die in ALS, increased cell death and caspase 3/7 activation. We propose that therapies targeted to reduce inflammatory TNFα signaling may be helpful in ALS patients

Effect of a single acupuncture treatment on surgical wound healing in dogs: a randomized, single blinded, controlled pilot study

<p>Abstract</p> <p>Background</p> <p>The aim of the study was to investigate the effect of acupuncture on wound healing after soft tissue or orthopaedic surgery in dogs.</p> <p>Methods</p> <p>29 dogs were submitted to soft tissue and/or orthopaedic surgeries. Five dogs had two surgical wounds each, so there were totally 34 wounds in the study. All owners received instructions for post operative care as well as antibiotic and pain treatment. The dogs were randomly assigned to treatment or control groups. Treated dogs received one dry needle acupuncture treatment right after surgery and the control group received no such treatment. A veterinary surgeon that was blinded to the treatment, evaluated the wounds at three and seven days after surgery in regard to oedema (scale 0-3), scabs (yes/no), exudate (yes/no), hematoma (yes/no), dermatitis (yes/no), and aspect of the wound (dry/humid).</p> <p>Results</p> <p>There was no significant difference between the treatment and control groups in the variables evaluated three and seven days after surgery. However, oedema reduced significantly in the group treated with acupuncture at seven days compared to three days after surgery, possibly due the fact that there was more oedema in the treatment group at day three (although this difference was nor significant between groups).</p> <p>Conclusions</p> <p>The use of a single acupuncture treatment right after surgery in dogs did not appear to have any beneficial effects in surgical wound healing.</p

Quantum-squeezing effects of strained multilayer graphene NEMS

Quantum squeezing can improve the ultimate measurement precision by squeezing one desired fluctuation of the two physical quantities in Heisenberg relation. We propose a scheme to obtain squeezed states through graphene nanoelectromechanical system (NEMS) taking advantage of their thin thickness in principle. Two key criteria of achieving squeezing states, zero-point displacement uncertainty and squeezing factor of strained multilayer graphene NEMS, are studied. Our research promotes the measured precision limit of graphene-based nano-transducers by reducing quantum noises through squeezed states

Disparities and risks of sexually transmissible infections among men who have sex with men in China: a meta-analysis and data synthesis.

BACKGROUND: Sexually transmitted infections (STIs), including Hepatitis B and C virus, are emerging public health risks in China, especially among men who have sex with men (MSM). This study aims to assess the magnitude and risks of STIs among Chinese MSM. METHODS: Chinese and English peer-reviewed articles were searched in five electronic databases from January 2000 to February 2013. Pooled prevalence estimates for each STI infection were calculated using meta-analysis. Infection risks of STIs in MSM, HIV-positive MSM and male sex workers (MSW) were obtained. This review followed the PRISMA guidelines and was registered in PROSPERO. RESULTS: Eighty-eight articles (11 in English and 77 in Chinese) investigating 35,203 MSM in 28 provinces were included in this review. The prevalence levels of STIs among MSM were 6.3% (95% CI: 3.5-11.0%) for chlamydia, 1.5% (0.7-2.9%) for genital wart, 1.9% (1.3-2.7%) for gonorrhoea, 8.9% (7.8-10.2%) for hepatitis B (HBV), 1.2% (1.0-1.6%) for hepatitis C (HCV), 66.3% (57.4-74.1%) for human papillomavirus (HPV), 10.6% (6.2-17.6%) for herpes simplex virus (HSV-2) and 4.3% (3.2-5.8%) for Ureaplasma urealyticum. HIV-positive MSM have consistently higher odds of all these infections than the broader MSM population. As a subgroup of MSM, MSW were 2.5 (1.4-4.7), 5.7 (2.7-12.3), and 2.2 (1.4-3.7) times more likely to be infected with chlamydia, gonorrhoea and HCV than the broader MSM population, respectively. CONCLUSION: Prevalence levels of STIs among MSW were significantly higher than the broader MSM population. Co-infection of HIV and STIs were prevalent among Chinese MSM. Integration of HIV and STIs healthcare and surveillance systems is essential in providing effective HIV/STIs preventive measures and treatments. TRIAL REGISTRATION: PROSPERO NO: CRD42013003721