Probing temperature- and solvent-dependent protein dynamics using terahertz time-domain spectroscopy

The effect of temperature on the terahertz-frequency-range material properties of lyophilized and single-crystal hen egg-white lysozyme has been measured using terahertz time-domain spectroscopy, with the results presented and discussed in the context of protein and solvent dynamical and glass transitions. Lyophilized hen egg-white lysozyme was measured over a temperature range from 4 to 290 K, and a change in the dynamical behaviour of the sample at around 100 K was observed through a change in the terahertz absorption spectrum. Additionally, the effect of cryoprotectants on the temperature-dependent absorption coefficient is studied, and it is demonstrated that terahertz time-domain spectroscopy is capable of resolving the true glass transition temperature of single-crystal hen egg-white lysozyme at 150 K, which is in agreement with literature values measured using differential scanning calorimetry

Terahertz time-domain spectroscopy of lysozyme and mouse urinary protein single crystals

Broadband time-domain spectroscopy was used to measure the terahertz frequency absorption of protein single crystals in order to study global protein dynamics. Temperature dependent dynamics were measured for lysozyme, and the terahertz frequency spectrum of mouse urinary protein was compared to calculated spectra

Proposal for a unified nomenclature for target site mutations associated with resistance to fungicides

Evolved resistance to fungicides is a major problem limiting our ability to control agricultural, medical and veterinary pathogens and is frequently associated with substitutions in the amino acid sequence of the target protein. The convention for describing amino-acid substitutions is to cite the wild type amino acid, the codon number and the new amino acid, using the one letter amino acid code. It has frequently been observed that orthologous amino acid mutations have been selected in different species by fungicides from the same mode of action class, but the amino acids have different numbers. These differences in numbering arise from the different lengths of the proteins in each species. The purpose of the current paper is to propose a system for unifying the labelling of amino acids in fungicide target proteins. To do this we have produced alignments between fungicide target proteins of relevant species fitted to a well-studied “archetype” species. Orthologous amino acids in all species are then assigned numerical “labels” based on the position of the amino acid in the archetype protein

Study of Zγ events and limits on anomalous ZZγ and Zγγ couplings in pp̄ collisions at s=1.96TeV

We present a measurement of the Zγ production cross section and limits on anomalous ZZγ and Zγγ couplings for form-factor scales of Λ=750 and 1000 GeV. The measurement is based on 138 (152) candidates in the eeγ (μμγ) final state using 320(290)pb-1 of pp̄ collisions at s=1.96TeV. The 95% C.L. limits on real and imaginary parts of individual anomalous couplings are |h10,30Z|<0.23, |h20,40Z|<0.020, |h10,30γ|<0.23, and |h20,40γ|<0.019 for Λ=1000GeV. © 2005 The American Physical Society

Increased Seroreactivity to Glioma-Expressed Antigen 2 in Brain Tumor Patients under Radiation

Background: Surgery and radiation are the mainstays of therapy for human gliomas that are the most common primary brain tumors. Most recently, cell culture and animal studies provided the first convincing evidence that radiation not only eliminates tumor cells, but also modulates the immune response and likely improves anti-tumor immunotherapy. Methology/Pricipal Findings: We present an in vivo study that analyzes the effects of radiation on the immune response in tumor patients. As readout system, we utilized the reactivity of glioma patients ’ sera against antigen GLEA2 as the most frequent antigen immunogenic in glioblastoma patients. We established an ELISA assay to analyze reactivity of 24 glioblastoma patients over a period of several months. As control we used 30 sera from healthy donors as well as 30 sera from lung cancer patients. We compared the course of GLEA2 seroreactivity at different times prior, during and after radiation. The GLEA2 seroreactivity was increased by the time of surgery, decreased after surgery, increased again under radiation, and slightly decreased after radiation. Conclusions/Significance: Our results provide in vivo evidence for an increased antibody response against tumor antigens under radiation. Antigens that become immunogenic with an increased antibody response as result of radiation can serv

The effect of Puerariae radix on lipoprotein metabolism in liver and intestinal cells

BACKGROUND: Animal studies investigating the beneficial effects of Puerariae radix on cardiovascular disease have suggested this plant possesses anti-diabetic and lipid lowering properties. However, the exact mechanism by which Puerariae radix affects lipid metabolism is currently unknown. The aim of this study was to investigate the effect of the water extract of Puerariae radix on the secretion of VLDL and chylomicrons from HepG2 liver cells and CaCo2 cells, respectively, in humans. METHODS: The amount of apoB(100 )(a protein marker for VLDL) and apoB(48 )(a protein marker for chylomicrons) in cells and media were quantified by Western Blotting and enhanced chemiluminescence (ECL). Total, free and esterified cholesterol concentrations were measured by gas liquid chromatography. RESULTS: Treatment of cells with water extract of Puerariae radix significantly decreased apoB(100 )production and secretion from HepG2 cells up to 66% in a dose dependent manner. The intracellular total cholesterol and free cholesterol concentration in HepG2 cells also decreased with increasing concentration of the Puerariae radix. In contrast, water extract of Puerariae radix attenuated apoB(48 )concentrations in cells, but not apoB(48 )secretion from CaCo2 enterocytes. CONCLUSIONS: Collectively, our findings suggest that the water extract of Puerariae radix attenuates the hepatic lipoprotein production and secretion. Our present cell culture findings may explain why circulating VLDL and LDL levels were attenuated in animals supplemented with Puerariae radix. Since decreasing the production and secretion of atherogenic lipoproteins decreases the risk of development of cardiovascular disease, diets supplemented with radix may provide a safe and effective beneficial cardioprotective effects in humans

The Clinical Assessment Study of the Hand (CAS-HA): a prospective study of musculoskeletal hand problems in the general population

<p>Abstract</p> <p>Background</p> <p>Pain in the hand affects an estimated 12–21% of the population, and at older ages the hand is one of the most common sites of pain and osteoarthritis. The association between symptomatic hand osteoarthritis and disability in everyday life has not been studied in detail, although there is evidence that older people with hand problems suffer significant pain and disability. Despite the high prevalence of hand problems and the limitations they cause in older adults, little attention has been paid to the hand by health planners and policy makers. We plan to conduct a prospective, population-based, observational cohort study designed in parallel with our previously reported cohort study of knee pain, to describe the course of musculoskeletal hand problems in older adults and investigate the relative merits of different approaches to classification and defining prognosis.</p> <p>Methods/Design</p> <p>All adults aged 50 years and over registered with two general practices in North Staffordshire will be invited to take part in a two-stage postal survey. Respondents to the survey who indicate that they have experienced hand pain or problems within the previous 12 months will be invited to attend a research clinic for a detailed assessment. This will consist of clinical interview, hand assessment, screening test of lower limb function, digital photography, plain x-rays, anthropometric measurement and brief self-complete questionnaire. All consenting clinic attenders will be followed up by (i) general practice medical record review, (ii) repeat postal questionnaire at 18-months, and (iii) repeat postal questionnaire at 3 years.</p> <p>Discussion</p> <p>This paper describes the protocol for the Clinical Assessment Study of the Hand (CAS-HA), a prospective, population-based, observational cohort study of community-dwelling older adults with hand pain and hand problems based in North Staffordshire.</p

“We wouldn’t of made friends if we didn’t come to Football United”: the impacts of a football program on young people’s peer, prosocial and cross-cultural relationships

Background Sport as a mechanism to build relationships across cultural boundaries and to build positive interactions among young people has often been promoted in the literature. However, robust evaluation of sport-for-development program impacts is limited. This study reports on an impact evaluation of a sport-for-development program in Australia, Football United®. Methods A quasi-experimental mixed methods design was employed using treatment partitioning (different groups compared had different levels of exposure to Football United). A survey was undertaken with 142 young people (average age of 14.7 years with 22.5% of the sample comprising girls) in four Australian schools. These schools included two Football United and two Comparison schools where Football United was not operating. The survey instrument was composed of previously validated measures, including emotional symptoms, peer problems and relationships, prosocial behaviour, other-group orientation, feelings of social inclusion and belonging and resilience. Face to face interviews were undertaken with a purposeful sample (n = 79) of those who completed the survey. The participants in the interviews were selected to provide a diversity of age, gender and cultural backgrounds. Results Young people who participated in Football United showed significantly higher levels of other-group orientation than a Comparison Group (who did not participate in the program). The Football United boys had significantly lower scores on the peer problem scale and significantly higher scores on the prosocial scale than boys in the Comparison Group. Treatment partitioning analyses showed positive, linear associations between other-group orientation and total participation in the Football United program. A lower score on peer problems and higher scores on prosocial behaviour in the survey were associated with regularity of attendance at Football United. These quantitative results are supported by qualitative data analysed from interviews. Conclusions The study provides evidence of the effects of Football United on key domains of peer and prosocial relationships for boys and other-group orientation for young people in the program sites studied. The effects on girls, and the impacts of the program on the broader school environment and at the community level, require further investigation

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Between-day reliability of electromechanical delay of selected neck muscles during performance of maximal isometric efforts

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to assess the between-day reliability of the electromechanical delay (EMD) of selected neck muscles during the performance of maximal isometric contractions in five different directions.</p> <p>Methods</p> <p>Twenty-one physically active males participated in two testing sessions separated by seven to eight days. Using a custom-made fixed frame dynamometer, cervical force and surface electromyography (EMG) were recorded bilaterally from the splenius capitis, upper trapezius and sternocleidomastoid muscles during the performance of efforts in extension, flexion, left and right lateral bending, and protraction. The EMD was extracted using the Teager-Kaiser Energy Operator. Reliability indices calculated for each muscle in each testing direction were: the difference in scores between the two testing sessions and corresponding 95% confidence intervals, the standard error of measurement (SEM) and intra-class correlation coefficients (ICC).</p> <p>Results</p> <p>EMD values showed no evidence of systematic difference between the two testing sessions across all muscles and testing directions. The SEM for extension, flexion and lateral bending efforts ranged between 2.5 ms to 4.8 ms, indicating a good level of measurement precision. For protraction, SEM values were higher and considered to be imprecise for research and clinical purposes. ICC values for all muscles across all testing directions ranged from 0.23 to 0.79.</p> <p>Conclusion</p> <p>EMD of selected neck muscles can be measured with sufficient precision for the assessment of neck muscle function in an athletic population in the majority of directions tested.</p