55 research outputs found
The PKC, HOG and Ca2+ signalling pathways co-ordinately regulate chitin synthesis in Candida albicans
No full textOpen Access via PMC2649417Peer reviewe
Increased Carotid Thickness in Subjects with Recently-Diagnosed Diabetes from Rural Cameroon
No full textPMCID: PMC3423396This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Hematodinium sp. infection in Norway lobster Nephrops norvegicus and its effects on meat quality
No full textHematodinium and Hematodinium-like species have emerged in the last 3 decades
as important parasitic pathogens of crustaceans worldwide, causing a significant economic loss to
fisheries and related markets. In some species (notably the Tanner crab Chionoecetes bairdi), the
parasite reportedly causes the cooked meat to taste bitter and aspirin-like. The bitter taste,
together with the gross pathology of the infection, renders these crabs unmarketable. Surprisingly, no organoleptic tests have ever been conducted to date, and the cause for the bitter taste is
still unknown. Nevertheless, it is generally assumed that the bitter taste occurs widely in cooked
meats and products derived from crustaceans infected with Hematodinium. In the present study,
we analysed the meat quality and organoleptic attributes after capture and during storage of Norway lobsters Nephrops norvegicus from Scottish waters that were either asymptomatic or symptomatic of patent Hematodinium infection. Results from the sensory evaluation of the cooked product indicate that tail meat from symptomatic N. norvegicus is bland in flavour and aftertaste, and
more friable or sloppier in texture than meat from asymptomatic animals. As a consequence,
infected meat tends to be less palatable, although surprisingly no bitter taste is reported. From an
analytical point of view, tail meat from patently infected animals is at an advanced stage of auto -
lysis, while no difference in microbial load is detected. These results suggest that Norway lobsters
heavily infected with Hematodinium are of inferior marketing quality even after the tails have
been cooked
International Diabetes Federation guideline for management of postmeal glucose : a review of recommendations
No full textDiabetes is a significant and growing concern, with over 246 million people around the world living with the disease and another 308 million with impaired glucose tolerance. Depending on the resources of different nations, intervention has generally focused on optimizing overall glycaemic control as assessed by glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) values. Nevertheless, increasing evidence supports the importance of controlling all three members of the glucose triad, namely HbA1c, FPG and postmeal glucose (PMG) in order to improve outcome in diabetes. As part of its global mission to promote diabetes care and prevention and to find a cure, the International Diabetes Federation (IDF) recently developed a guideline that reviews evidence to date on PMG and the development of diabetic complications. Based on an extensive database search of the literature, and guided by a Steering and Development Committee including experts from around the world, the IDF Guideline for Management of Postmeal Glucose offers recommendations for appropriate clinical management of PMG. These recommendations are intended to help clinicians and organizations in developing strategies for effective management of PMG in individuals with Type 1 and Type 2 diabetes. The following review highlights the recommendations of the guideline, the supporting evidence provided and the major conclusions drawn. The full guideline is available for download at www.idf.org
Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders
No full textElevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets
Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
No full textWaist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions
Application of the 1994 WHO Classification to Populations Other Than Postmenopausal Caucasian Women: The 2005 ISCD Official Positions
No full textIn 2003, the International Society for Clinical Densitometry (ISCD) developed Official Positions regarding the applicability of the World Health Organization (WHO) classification of bone mineral density to populations other than postmenopausal women. However, these prior Official Positions do not fully address bone mineral density reporting in females prior to menopause, men, and non-whites. During the 2005 ISCD Position Development Conference, members of the ISCD Expert Panel in conjunction with the ISCD Scientific Advisory Committee re-addressed these topics and, based upon stringent reviews of best available data, developed ISCD Official Positions that provide greater specificity and clarification with respect to the following: (1) the utility of the term 'osteopenia'; (2) utilization of T- and Z-scores for bone mineral density reporting; (3) when to apply the WHO densitometric classification; and (4) which normative database(s) should be used for non-white individuals. Briefly, the term osteopenia is retained, but 'low bone mass' or 'low bone density' is preferred. Z-scores, not T-scores, are preferred in females prior to menopause and males under age 50. In these individuals, a Z-score of -2.0 or lower is defined as below the expected range for age and a Z-score above -2.0 is within the expected range for age. T-scores are preferred and the WHO classification is applicable for postmenopausal women and men age 50 and older. 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Impacts of climate driven range changes on the genetics and morphology of butterflies
No full textThis thesis studied the genetic responses of butterflies to climate induced distribution shifts in terms of patterns of genetic diversity at expanding and contracting range margins, the relative importance of genes versus environment on adaptations to dispersal and local adaptation to temperature during range expansion.
Loss of genetic diversity during range expansion in Pararge aegeria was confirmed using neutral genetic markers (AFLPs). High reductions of genetic diversity were discovered at the range margin relative to the distribution core. Range margin populations exhibit a nearly 50% reduction in neutral genetic diversity, and lower genetic divergence between sites.
The contracting southern range margin of the butterfly Erebia aethiops has not suffered a reduction in genetic diversity relative to the distribution core. As genetic diversity remains relatively high population extinction is unlikely to be exacerbated by inbreeding or reduced fitness from low genetic diversity during range contraction.
Contrary to results from laboratory reared butterflies, wild male P. aegeria do not have significant differences in flight morphology between core and margin sites. This suggests developmental influences suppress the expression of genetic adaptations to dispersal. Wild butterflies also represent a smaller range of phenotypes possibly indicating balancing selection on morphological traits.
Little to no evidence for local adaptation to temperature is apparent at the expanding range margin of P. aegeria. Neither was there evidence for reduced fitness due to lower genetic diversity, as F2 butterflies from core sites had poorer survival rates than the less genetically diverse margin sites.
This study found that neutral genetic diversity is unlikely to affect species during distribution shifts as even high losses during distribution expansion do not appear to affect survival rates. Also adaptation to dispersal and temperature may be limited during range expansion both by environmental constraints and limited selection pressure respectively
Hundreds of variants clustered in genomic loci and biological pathways affect human height
No full textMost common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits(1), but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait(2,3). The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways
Pan-pathogen deep sequencing of nosocomial bacterial pathogens in Italy in spring 2020 : a prospective cohort study
No full textBackground: Nosocomial infections pose a considerable risk to patients who are susceptible, and this is particularly acute in intensive care units when hospital-associated bacteria are endemic. During the first wave of the COVID-19 pandemic, the surge of patients presented a significant obstacle to the effectiveness of infection control measures. We aimed to assess the risks and extent of nosocomial pathogen transmission under a high patient burden by designing a novel bacterial pan-pathogen deep-sequencing approach that could be integrated with standard clinical surveillance and diagnostics workflows. Methods: We did a prospective cohort study in a region of northern Italy that was severely affected by the first wave of the COVID-19 pandemic. Inpatients on both ordinary and intensive care unit (ICU) wards at the San Matteo hospital, Pavia were sampled on multiple occasions to identify bacterial pathogens from respiratory, nasal, and rectal samples. Diagnostic samples collected between April 7 and May 10, 2020 were cultured on six different selective media designed to enrich for Acinetobacter baumannii, Escherichia coli, Enterococcus faecium, Enterococcus faecalis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae, and DNA from each plate with positive growth was deep sequenced en masse. We used mSWEEP and mGEMS to bin sequencing reads by sequence cluster for each species, followed by mapping with snippy to generate high quality alignments. Antimicrobial resistance genes were detected by use of ARIBA and CARD. Estimates of hospital transmission were obtained from pairwise bacterial single nucleotide polymorphism distances, partitioned by within-patient and between-patient samples. Finally, we compared the accuracy of our binned Acinetobacter baumannii genomes with those obtained by single colony whole-genome sequencing of isolates from the same hospital. Findings: We recruited patients from March 1 to May 7, 2020. The pathogen population among the patients was large and diverse, with 2148 species detections overall among the 2418 sequenced samples from the 256 patients. In total, 55 sequence clusters from key pathogen species were detected at least five times. The antimicrobial resistance gene prevalence was correspondingly high, with key carbapenemase and extended spectrum ß-lactamase genes detected in at least 50 (40%) of 125 patients in ICUs. Using high-resolution mapping to infer transmission, we established that hospital transmission was likely to be a significant mode of acquisition for each of the pathogen species. Finally, comparison with single colony Acinetobacter baumannii genomes showed that the resolution offered by deep sequencing was equivalent to single-colony sequencing, with the additional benefit of detection of co-colonisation of highly similar strains. Interpretation: Our study shows that a culture-based deep-sequencing approach is a possible route towards improving future pathogen surveillance and infection control at hospitals. Future studies should be designed to directly compare the accuracy, cost, and feasibility of culture-based deep sequencing with single colony whole-genome sequencing on a range of bacterial species. Funding: Wellcome Trust, European Research Council, Academy of Finland Flagship program, Trond Mohn Foundation, and Research Council of Norway.Peer reviewe
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