Biomarker discovery and redundancy reduction towards classification using a multi-factorial MALDI-TOF MS T2DM mouse model dataset

Diabetes like many diseases and biological processes is not mono-causal. On the one hand multifactorial studies with complex experimental design are required for its comprehensive analysis. On the other hand, the data from these studies often include a substantial amount of redundancy such as proteins that are typically represented by a multitude of peptides. Coping simultaneously with both complexities (experimental and technological) makes data analysis a challenge for Bioinformatics.

Combined oral contraceptive pills containing desogestrel or drospirenone enhance large vessel and microvasculature vasodilation in healthy premenopausal women

OBJECTIVE: To determine the effects of different COCs on endothelial function. BACKGROUND: COCs all contain ethinylestradiol, but different progestins; three of the more common progestins are DSG, LN, and DR. Ethinylestradiol enhances some measures of vascular reactivity, but certain progestins may increase risk of vascular diseases and impair endothelial vasodilation. METHODS: Twenty-nine healthy women taking COCs containing 30 μg ethinylestradiol and 150 μg DSG (Marvelon, n = 10), 150 μg LN (Microgynon, n = 10), or 3 mg DR (Yasmin, n = 9) had their vascular reactivity measured using various techniques during their pill-free week (days 5-7) and the third week of active pills (days 26-28). A reference group (n = 10) underwent the same measurements on two consecutive cycles. RESULTS: FMD and LDI were significantly higher during active-pill visits than pill-free visits in women taking DSG and DR (p < 0.02), but not in women taking LN. There were no differences between the duplicate measures in the reference group. CONCLUSIONS: COCs containing 150 μg DSG or 3 mg DR significantly increase endothelium-dependent vasodilation in both large vessels and peripheral microvasculature. These effects may be due to the progestins exhibiting differential effects on eNOS expression.

Local management and landscape drivers of pollination and biological control services in a Kenyan agro-ecosystem

Arthropods that have a direct impact on crop production (i.e. pests, natural enemies and pollinators) can be influenced by both local farm management and the context within which the fields occur in the wider landscape. However, the contributions and spatial scales at which these drivers operate and interact are not fully understood, particularly in the developing world. The impact of both local management and landscape context on insect pollinators and natural enemy communities and on their capacity to deliver related ecosystem services to an economically important tropical crop, pigeonpea was investigated. The study was conducted in nine paired farms across a gradient of increasing distance to semi-native vegetation in Kibwezi, Kenya. Results show that proximity of fields to semi-native habitats negatively affected pollinator and chewing insect abundance. Within fields, pesticide use was a key negative predictor of pollinator, pest and foliar active predator abundance. On the contrary, fertilizer application significantly enhanced pollinator and both chewing and sucking insect pest abundance. At a 1 km spatial scale of fields, there were significant negative effects of the number of semi-native habitat patches within fields dominated by mass flowering pigeonpea on pollinators abundance. For service provision, a significant decline in fruit set when insects were excluded from flowers was recorded. This study reveals the interconnections of pollinators, predators and pests with pigeonpea crop. For sustainable yields and to conserve high densities of both pollinators and predators of pests within pigeonpea landscapes, it is crucial to target the adoption of less disruptive farm management practices such as reducing pesticide and fertilizer inputs.

Dietary intakes and food sources of phytoestrogens in the European Prospective Investigation into Cancer and Nutrition (EPIC) 24-hour dietary recall cohort

BACKGROUND/OBJECTIVES: Phytoestrogens are estradiol-like natural compounds found in plants that have been associated with protective effects against chronic diseases, including some cancers, cardiovascular diseases and osteoporosis. The purpose of this study was to estimate the dietary intake of phytoestrogens, identify their food sources and their association with lifestyle factors in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. SUBJECTS/METHODS: Single 24-hour dietary recalls were collected from 36 037 individuals from 10 European countries, aged 35–74 years using a standardized computerized interview programe (EPIC-Soft). An ad hoc food composition database on phytoestrogens (isoflavones, lignans, coumestans, enterolignans and equol) was compiled using data from available databases, in order to obtain and describe phytoestrogen intakes and their food sources across 27 redefined EPIC centres. RESULTS: Mean total phytoestrogen intake was the highest in the UK health-conscious group (24.9 mg/day in men and 21.1 mg/day in women) whereas lowest in Greece (1.3 mg/day) in men and Spain-Granada (1.0 mg/day) in women. Northern European countries had higher intakes than southern countries. The main phytoestrogen contributors were isoflavones in both UK centres and lignans in the other EPIC cohorts. Age, body mass index, educational level, smoking status and physical activity were related to increased intakes of lignans, enterolignans and equol, but not to total phytoestrogen, isoflavone or coumestan intakes. In the UK cohorts, the major food sources of phytoestrogens were soy products. In the other EPIC cohorts the dietary sources were more distributed, among fruits, vegetables, soy products, cereal products, non-alcoholic and alcoholic beverages. CONCLUSIONS: There was a high variability in the dietary intake of total and phytoestrogen subclasses and their food sources across European regions.

The socioeconomics of food crop production and climate change vulnerability: a global scale quantitative analysis of how grain crops are sensitive to drought

Many studies warn that climate change may undermine global food security. Much work on this topic focuses on modelling crop-weather interactions but these models do not generally account for the ways in which socio-economic factors influence how harvests are affected by weather. To address this gap, this paper uses a quantitative harvest vulnerability index based on annual soil moisture and grain production data as the dependent variables in a Linear Mixed Effects model with national scale socio-economic data as independent variables for the period 1990-2005. Results show that rice, wheat and maize production in middle income countries were especially vulnerable to droughts. By contrast, harvests in countries with higher investments in agriculture (e.g higher amounts of fertilizer use) were less vulnerable to drought. In terms of differences between the world's major grain crops, factors that made rice and wheat crops vulnerable to drought were quite consistent, whilst those of maize crops varied considerably depending on the type of region. This is likely due to the fact that maize is produced under very different conditions worldwide. One recommendation for reducing drought vulnerability risks is coordinated development and adaptation policies, including institutional support that enables farmers to take proactive action.

Natal nest locations of the Asian house rat (Rattus tanezumi) in lowland rice–coconut cropping systems: a coconut penthouse or rice bunds with water frontage?

CONTEXT. Rattus tanezumi is a serious crop pest within the island of Luzon, Philippines. In intensive flood-irrigated rice field ecosystems of Luzon, female R. tanezumi are known to primarily nest within the tillers of ripening rice fields and along the banks of irrigation canals. The nesting habits of R. tanezumi in complex rice–coconut cropping systems are unknown. AIMS. To identify the natal nest locations of R. tanezumi females in rice–coconut systems of the Sierra Madre Biodiversity Corridor (SMBC), Luzon, during the main breeding season to develop a management strategy that specifically targets their nesting habitat. METHODS. When rice was at the booting to ripening stage, cage-traps were placed in rice fields adjacent to coconut habitat. Thirty breeding adult R. tanezumi females were fitted with radio-collars and successfully tracked to their nest sites. KEY RESULTS. Most R. tanezumi nests (66.7%) were located in coconut groves, five nests (16.7%) were located in rice fields and five nests (16.7%) were located on the rice field edge. All nests were located above ground level and seven nests were located in coconut tree crowns. The median distance of nest sites to the nearest rice field was 22.5m. Most nest site locations had good cover of ground vegetation and understorey vegetation, but low canopy cover. Only one nest location had an understorey vegetation height of less than 20 cm. CONCLUSIONS. In the coastal lowland rice–coconut cropping systems of the SMBC, female R. tanezumi showed a preference for nesting in adjacent coconut groves. This is contrary to previous studies in intensive flood-irrigated rice ecosystems of Luzon, where the species nests mainly in the banks of irrigation canals. It is important to understand rodent breeding ecology in a specific ecosystem before implementing appropriate management strategies. IMPLICATIONS. In lowland rice–coconut cropping systems, coconut groves adjacent to rice fields should be targeted for the 20 management of R. tanezumi nest sites during the main breeding season as part of an integrated ecologically based approach to rodent pest management.

Poisoning the mind: Arsenic contamination of drinking water wells and children's educational achievement in rural Bangladesh

Bangladesh has experienced the largest mass poisoning of a population in history owing to contamination of groundwater with naturally occurring inorganic arsenic. Prolonged drinking of such water risks development of diseases and therefore has implications for children's cognitive and psychological development. This study examines the effect of arsenic contamination of tubewells, the primary source of drinking water at home, on the learning outcome of school-going children in rural Bangladesh using recent nationally representative data on secondary school children. We unambiguously find a negative and statistically significant correlation between mathematics scores and arsenic-contaminated drinking tubewells at home, net of the child's socio-economic status, parental background and school specific unobserved correlates of learning. Similar correlations are found for an alternative measure of student achievement and subjective well-being (i.e. self-reported measure of life satisfaction), of the student. We conclude by discussing the policy implication of our findings in the context of the current debate over the adverse effect of arsenic poisoning on children.

Climate change impacts on crop productivity in Africa and South Asia

Climate change is a serious threat to crop productivity in regions that are already food insecure. We assessed the projected impacts of climate change on the yield of eight major crops in Africa and South Asia using a systematic review and meta-analysis of data in 52 original publications from an initial screen of 1144 studies. Here we show that the projected mean change in yield of all crops is − 8% by the 2050s in both regions. Across Africa, mean yield changes of − 17% (wheat), − 5% (maize), − 15% (sorghum) and − 10% (millet) and across South Asia of − 16% (maize) and − 11% (sorghum) were estimated. No mean change in yield was detected for rice. The limited number of studies identified for cassava, sugarcane and yams precluded any opportunity to conduct a meta-analysis for these crops. Variation about the projected mean yield change for all crops was smaller in studies that used an ensemble of > 3 climate (GCM) models. Conversely, complex simulation studies that used biophysical crop models showed the greatest variation in mean yield changes. Evidence of crop yield impact in Africa and South Asia is robust for wheat, maize, sorghum and millet, and either inconclusive, absent or contradictory for rice, cassava and sugarcane.

Competitive exclusion by Bacillus subtilis spores of Salmonella enterica serotype Enteritidis and Clostridium perfringens in young chickens

Cost effective control of avian diseases and food borne pathogens remains a high priority for all sectors of the poultry industry with cleansing and disinfection, vaccination and competitive exclusion approaches being used widely. Previous studies showed that Bacillus subtilis PY79(hr) was an effective competitive exclusion agent for use in poultry to control avian pathogenic Escherichia coli serotype O78:K80. Here we report experiments that were undertaken to test the efficacy of B. subtilis PY79(hr) in the control of Salmonella enterica serotype Enteritidis and Clostridium perfringens in young chickens. To do this, 1-day-old and 20-day-old specific pathogen free (SPF) chicks were dosed with a suspension of B. subtilis spores prior to challenge with S. Enteritidis (S1400) and C. perfringens, respectively. For both challenge models, a single oral inoculum of 1 x 10(9) spores given 24 h prior to challenge was sufficient to suppress colonisation and persistence of both S. Enteritidis and C perfringens. In particular, the faecal shedding of S. Enteritidis, as measured by a semi-quantitative cloacal swabbing technique, was reduced significantly for the 36 days duration of the experiment. B. subtilis persisted in the intestine although with decreasing numbers over the same period. These data add further evidence that B. subtilis spores may be effective agents in the control of avian diseases and food borne pathogens.

Trafficking and signaling of G protein-coupled receptors in the nervous system: implications for disease and therapy

G protein-coupled receptors (GPCRs) are expressed throughout the nervous system where they regulate multiple physiological processes, participate in neurological diseases, and are major targets for therapy. Given that many GPCRs respond to neurotransmitters and hormones that are present in the extracellular fluid and which do not readily cross the plasma membrane, receptor trafficking to and from the plasma membrane is a critically important determinant of cellular responsiveness. Moreover, trafficking of GPCRs throughout the endosomal system can initiate signaling events that are mechanistically and functionally distinct from those operating at the plasma membrane. This review discusses recent advances in the relationship between signaling and trafficking of GPCRs in the nervous system. It summarizes how receptor modifications influence trafficking, discusses mechanisms that regulate GPCR trafficking to and from the plasma membrane, reviews the relationship between trafficking and signaling, and considers the implications of GPCR trafficking to drug development.

Insights into the molecular architecture of a peptide nanotube using FTIR and solid-state NMR spectroscopic measurements on an aligned sample

The self-assembly of proteins and peptides into b-sheet-rich amyloid fibers is a process that has gained notoriety because of its association with human diseases and disorders. Spontaneous self-assembly of peptides into nonfibrillar supramolecular structures can also provide a versatile and convenient mechanism for the bottom-up design of biocompatible materials with functional properties favoring a wide range of practical applications.[1] One subset of these fascinating and potentially useful nanoscale constructions are the peptide nanotubes, elongated cylindrical structures with a hollow center bounded by a thin wall of peptide molecules.[2] A formidable challenge in optimizing and harnessing the properties of nanotube assemblies is to gain atomistic insight into their architecture, and to elucidate precisely how the tubular morphology is constructed from the peptide building blocks. Some of these fine details have been elucidated recently with the use of magic-angle-spinning (MAS) solidstate NMR (SSNMR) spectroscopy.[3] MAS SSNMR measurements of chemical shifts and through-space interatomic distances provide constraints on peptide conformation (e.g., b-strands and turns) and quaternary packing. We describe here a new application of a straightforward SSNMR technique which, when combined with FTIR spectroscopy, reports quantitatively on the orientation of the peptide molecules within the nanotube structure, thereby providing an additional structural constraint not accessible to MAS SSNMR.

Increases in the longevity of desiccation-phase developing rice seeds: response to high temperature drying depends on harvest moisture content

• Background and Aims Earlier studies have suggested that the drying conditions routinely used by genebanks may not be optimal for subsequent seed longevity. The aim of this study was to compare the effect of hot-air drying with low temperature drying on subsequent seed longevity for 20 diverse rice accessions and to consider how factors related to seed production history might influence the results. • Methods Seeds were produced according to normal regeneration procedures at IRRI. They were harvested at different times (harvest date and days after anthesis (DAA), once for each accession) and dried either in a drying room (DR; 15% RH, 15°C), or in a flat-bed heated-air batch dryer (BD; 45°C, 8 h d-1) for up to 6 daily cycles followed by drying in the DR. Relative longevity was assessed by storage at 10.9% moisture content (m.c.) and 45°C. • Key Results Initial drying in the BD resulted in significantly greater longevity compared with the DR for 14 accessions (seed lots): the period of time for viability to fall to 50% for seeds dried in the BD as a percentage of that for seeds dried throughout in the DR varied between 1.3 and 372.2% for these 14 accessions. The seed lots that responded the most were harvested earlier in the season and at higher moisture content. Drying in the BD did not reduce subsequent longevity compared with DR drying for any of the remaining accessions. • Conclusions Seeds harvested at a m.c. where, according to the moisture desorption isotherm, they could still be metabolically active (>16.2%), may be in the first stage of the post-mass maturity, desiccation phase of seed development and able to increase longevity in response to hot-air drying. The genebank standards regarding seed drying for rice and, perhaps, for other tropical species should be reconsidered.

Children’s physic: medical perceptions and treatment of sick children in early modern England, c. 1580-1720

Historians of medicine, childhood, and paediatrics, have often assumed that early modern doctors neither treated children, nor adapted their medicines to suit the peculiar temperaments of the young. Through an examination of medical textbooks and doctors’ casebooks, this article refutes these assumptions. It argues that medical authors and practising doctors regularly treated children, and were careful to tailor their remedies to complement the distinctive constitutions of children. Thus, this article proposes that a concept of ‘children’s physic’ existed in early modern England: this term refers to the notion that children were physiologically distinct, requiring special medical care. Children’s physic was rooted in the ancient traditions of Hippocratic and Galenic medicine: it was the child’s humoral makeup that underpinned all medical ideas about children’s bodies, minds, diseases, and treatments. Children abounded in the humour blood, which made them humid and weak, and in need of medicines of a particularly gentle nature.

p22phox C242T SNP inhibits inflammatory oxidative damage to endothelial cells and vessels

Background— T NADPH oxidase, by generating reactive oxygen species, is involved in the pathophysiology of many cardiovascular diseases and represents a therapeutic target for the development of novel drugs. A single-nucleotide polymorphism (SNP) C242T of the p22phox subunit of NADPH oxidase has been reported to be negatively associated with coronary heart disease (CHD) and may predict disease prevalence. However, the underlying mechanisms remain unknown. Methods and Results— Using computer molecular modelling we discovered that C242T SNP causes significant structural changes in the extracellular loop of p22phox and reduces its interaction stability with Nox2 subunit. Gene transfection of human pulmonary microvascular endothelial cells showed that C242T p22phox reduced significantly Nox2 expression but had no significant effect on basal endothelial O2.- production or the expression of Nox1 and Nox4. When cells were stimulated with TNFα (or high glucose), C242T p22phox inhibited significantly TNFα-induced Nox2 maturation, O2.- production, MAPK and NFκB activation and inflammation (all p<0.05). These C242T effects were further confirmed using p22phox shRNA engineered HeLa cells and Nox2-/- coronary microvascular endothelial cells. Clinical significance was investigated using saphenous vein segments from non CHD subjects after phlebectomies. TT (C242T) allele was common (prevalence of ~22%) and compared to CC, veins bearing TT allele had significantly lower levels of Nox2 expression and O2.- generation in response to high glucose challenge. Conclusions— C242T SNP causes p22phox structural changes that inhibit endothelial Nox2 activation and oxidative response to TNFα or high glucose stimulation. C242T SNP may represent a natural protective mechanism against inflammatory cardiovascular diseases.

Physical disability, recent illnesses and health self-assessment in a population-based study in Sao Paulo, Brazil

Objectives. To investigate health self-assessment and to estimate the prevalence of chronic diseases and recent illnesses in people with and without physical disabilities (PD) in the state of Sao Paulo, southeastern Brazil. Study design. A Cross-sectional study comprising two population-based health surveys conducted in 2002 and 2003. Methods. A total of 8317 persons (165 with PD) were interviewed in the two studies. Variables concerning to health self-assessment; chronic disease and recent illness were compared in the people with and without PD. Negative binomial regression was used in the analysis. Results. Subjects with PD more often assessed their health as poor/very poor compared to non-disabled ones. They reported more illnesses in the 15 days prior to interview as well as more chronic diseases (skin conditions, anaemia, chronic kidney disease, stroke, depression/anxiety, migraine/headache, pulmonary diseases, hypertension, diabetes, arthritis/arthrosis/rheumatic conditions and heart disease). This higher disease prevalence can be either attributed to disability itself or be associated to gender, age and schooling. Conclusions. Subjects with PD had more recent illnesses and chronic diseases and poorer health self-assessment than non-disabled ones. Age, gender, schooling and disability have individual roles in disease development among disabled people.