Best practice guidelines for the molecular genetic diagnosis of maturity-onset diabetes of the young

Member of the EMQN MODY group: Gisela GasparAIMS/HYPOTHESIS: Mutations in the GCK and HNF1A genes are the most common cause of the monogenic forms of diabetes known as 'maturity-onset diabetes of the young'. GCK encodes the glucokinase enzyme, which acts as the pancreatic glucose sensor, and mutations result in stable, mild fasting hyperglycaemia. A progressive insulin secretory defect is seen in patients with mutations in the HNF1A and HNF4A genes encoding the transcription factors hepatocyte nuclear factor-1 alpha and -4 alpha. A molecular genetic diagnosis often changes management, since patients with GCK mutations rarely require pharmacological treatment and HNF1A/4A mutation carriers are sensitive to sulfonylureas. These monogenic forms of diabetes are often misdiagnosed as type 1 or 2 diabetes. Best practice guidelines for genetic testing were developed to guide testing and reporting of results

Considering Intra-individual Genetic Heterogeneity to Understand Biodiversity

In this chapter, I am concerned with the concept of Intra-individual Genetic Hetereogeneity (IGH) and its potential influence on biodiversity estimates. Definitions of biological individuality are often indirectly dependent on genetic sampling -and vice versa. Genetic sampling typically focuses on a particular locus or set of loci, found in the the mitochondrial, chloroplast or nuclear genome. If ecological function or evolutionary individuality can be defined on the level of multiple divergent genomes, as I shall argue is the case in IGH, our current genetic sampling strategies and analytic approaches may miss out on relevant biodiversity. Now that more and more examples of IGH are available, it is becoming possible to investigate the positive and negative effects of IGH on the functioning and evolution of multicellular individuals more systematically. I consider some examples and argue that studying diversity through the lens of IGH facilitates thinking not in terms of units, but in terms of interactions between biological entities. This, in turn, enables a fresh take on the ecological and evolutionary significance of biological diversity

Neonicotinoid pesticide limits improvement in buzz pollination by bumblebees

Neonicotinoid pesticides have been linked to global declines of beneficial insects such as bumblebees. Exposure to trace levels of these chemicals causes sub-lethal effects, such as reduced learning and foraging efficiency. Complex behaviours may be particularly vulnerable to the neurotoxic effects of neonicotinoids. Such behaviours may include buzz pollination (sonication), in which pollinators, usually bees, use innate and learned behaviours to generate high-frequency vibrations to release pollen from flowers with specialised anther morphologies. This study assesses the effect of field-realistic, chronic exposure to the widely-used neonicotinoid thiamethoxam on the development of sonication buzz characteristics over time, as well as the collection of pollen from buzz-pollinated flowers. We found that the pollen collection of exposed bees improved less with increasing experience than that of unexposed bees, with exposed bees collecting between 47% and 56% less pollen by the end of 10 trials. We also found evidence of two distinct strategies for maximising pollen collection: (1) extensions to the duration of individual buzzes and (2) extensions of the overall time spent buzzing. We find new complexities in buzz pollination, and conclude that the impacts of field-realistic exposure to a neonicotinoid pesticide may seriously compromise this important ecosystem service

Structure of hadron resonances with a nearby zero of the amplitude

We discuss the relation between the analytic structure of the scattering amplitude and the origin of an eigenstate represented by a pole of the amplitude.If the eigenstate is not dynamically generated by the interaction in the channel of interest, the residue of the pole vanishes in the zero coupling limit. Based on the topological nature of the phase of the scattering amplitude, we show that the pole must encounter with the Castillejo-Dalitz-Dyson (CDD) zero in this limit. It is concluded that the dynamical component of the eigenstate is small if a CDD zero exists near the eigenstate pole. We show that the line shape of the resonance is distorted from the Breit-Wigner form as an observable consequence of the nearby CDD zero. Finally, studying the positions of poles and CDD zeros of the KbarN-piSigma amplitude, we discuss the origin of the eigenstates in the Lambda(1405) region.Comment: 7 pages, 3 figures, v2: published versio

The value of CCTV surveillance cameras as an investigative tool: an empirical analysis

There has been extensive research on the value of closed-circuit television (CCTV) for preventing crime, but little on its value as an investigative tool. This study sought to establish how often CCTV provides useful evidence and how this is affected by circumstances, analysing 251,195 crimes recorded by British Transport Police that occurred on the British railway network between 2011 and 2015. CCTV was available to investigators in 45% of cases and judged to be useful in 29% (65% of cases in which it was available). Useful CCTV was associated with significantly increased chances of crimes being solved for all crime types except drugs/weapons possession and fraud. Images were more likely to be available for more-serious crimes, and less likely to be available for cases occurring at unknown times or in certain types of locations. Although this research was limited to offences on railways, it appears that CCTV is a powerful investigative tool for many types of crime. The usefulness of CCTV is limited by several factors, most notably the number of public areas not covered. Several recommendations for increasing the usefulness of CCTV are discussed

Mobilization of genomic islands of Staphylococcus aureus by temperate bacteriophage

The virulence of Staphylococcus aureus, in both human and animal hosts, is largely influenced by the acquisition of mobile genetic elements (MGEs). Most S. aureus strains carry a variety of MGEs, including three genomic islands (νSaα, νSaβ, νSaγ) that are diverse in virulence gene content but conserved within strain lineages. Although the mobilization of pathogenicity islands, phages and plasmids has been well studied, the mobilization of genomic islands is poorly understood. We previously demonstrated the mobilization of νSaβ by the adjacent temperate bacteriophage ϕSaBov from strain RF122. In this study, we demonstrate that ϕSaBov mediates the mobilization of νSaα and νSaγ, which are located remotely from ϕSaBov, mostly to recipient strains belonging to ST151. Phage DNA sequence analysis revealed that chromosomal DNA excision events from RF122 were highly specific to MGEs, suggesting sequence-specific DNA excision and packaging events rather than generalized transduction by a temperate phage. Disruption of the int gene in ϕSaBov did not affect phage DNA excision, packaging, and integration events. However, disruption of the terL gene completely abolished phage DNA packing events, suggesting that the primary function of temperate phage in the transfer of genomic islands is to allow for phage DNA packaging by TerL and that transducing phage particles are the actual vehicle for transfer. These results extend our understanding of the important role of bacteriophage in the horizontal transfer and evolution of genomic islands in S. aureus

Associated Factors for Falls among the Community-Dwelling Older People Assessed by Annual Geriatric Health Examinations

BACKGROUND: Falls are very common among the older people. Nearly one-third older people living in a community fall each year. However, few studies have examined factors associated with falls in a community-dwelling population of older Taiwanese adults. OBJECTIVES: To identify the associated factors for falls during the previous 12 months among the community-dwelling Taiwanese older people receiving annual geriatric health examinations. PARTICIPANTS: People aged sixty-five years or older, living in the community, assessed by annual geriatric health examinations METHODS: 1377 community-dwellers aged ≥65 years who received annual geriatric health examinations at one hospital in northern Taiwan between March and November of 2008. They were asked about their history of falls during the year prior to their most recent health examination. RESULTS: The average age of the 1377 participants was 74.9±6.8 years, 48.9% of which were women. Three-hundred and thirteen of the participants (22.7%) had at least one fall during the previous year. Multivariate analysis showed that odds ratio for the risk of falling was 1.94 (95% CI 1.36-2.76) when the female gender group is compared with the male gender group. The adjusted odds ratios of age and waist circumference were 1.03 (95% CI 1.00-1.06) and 1.03 (95% CI 1.01-1.05) respectively. The adjusted odds ratios of visual acuity, Karnofsky scale, and serum albumin level were 0.34 (95% CI 0.15-0.76), 0.94 (95% CI 0.89-0.98), and 0.37 (95% CI 0.18-0.76) respectively. Larger waist circumference, older age, female gender, poorer visual acuity, lower score on the Karnofsky Performance Scale, and lower serum albumin level were the independent associated factors for falls. CONCLUSION: In addition to other associated factors, waist circumference should be included as a novel risk factor for falls

Sperm Length Variation as a Predictor of Extrapair Paternity in Passerine Birds

The rate of extrapair paternity is a commonly used index for the risk of sperm competition in birds, but paternity data exist for only a few percent of the approximately 10400 extant species. As paternity analyses require extensive field sampling and costly lab work, species coverage in this field will probably not improve much in the foreseeable future. Recent findings from passerine birds, which constitute the largest avian order (∼5,900 species), suggest that sperm phenotypes carry a signature of sperm competition. Here we examine how well standardized measures of sperm length variation can predict the rate of extrapair paternity in passerine birds.We collected sperm samples from 55 passerine species in Canada and Europe for which extrapair paternity rates were already available from either the same (n = 24) or a different (n = 31) study population. We measured the total length of individual spermatozoa and found that both the coefficient of between-male variation (CV(bm)) and within-male variation (CV(wm)) in sperm length were strong predictors of the rate of extrapair paternity, explaining as much as 65% and 58%, respectively, of the variation in extrapair paternity among species. However, only the CV(bm) predictor was independent of phylogeny, which implies that it can readily be converted into a currency of extrapair paternity without the need for phylogenetic correction.We propose the CV(bm) index as an alternative measure to extrapair paternity for passerine birds. Given the ease of sperm extraction from male birds in breeding condition, and a modest number of sampled males required for a robust estimate, this new index holds a great potential for mapping the risk of sperm competition across a wide range of passerine birds

Chicken genome analysis reveals novel genes encoding biotin-binding proteins related to avidin family

BACKGROUND: A chicken egg contains several biotin-binding proteins (BBPs), whose complete DNA and amino acid sequences are not known. In order to identify and characterise these genes and proteins we studied chicken cDNAs and genes available in the NCBI database and chicken genome database using the reported N-terminal amino acid sequences of chicken egg-yolk BBPs as search strings. RESULTS: Two separate hits showing significant homology for these N-terminal sequences were discovered. For one of these hits, the chromosomal location in the immediate proximity of the avidin gene family was found. Both of these hits encode proteins having high sequence similarity with avidin suggesting that chicken BBPs are paralogous to avidin family. In particular, almost all residues corresponding to biotin binding in avidin are conserved in these putative BBP proteins. One of the found DNA sequences, however, seems to encode a carboxy-terminal extension not present in avidin. CONCLUSION: We describe here the predicted properties of the putative BBP genes and proteins. Our present observations link BBP genes together with avidin gene family and shed more light on the genetic arrangement and variability of this family. In addition, comparative modelling revealed the potential structural elements important for the functional and structural properties of the putative BBP proteins

Body mass index and outcome in renal transplant recipients: a systematic review and meta-analysis

BACKGROUND: Whether overweight or obese end stage renal disease (ESRD) patients are suitable for renal transplantation (RT) is often debated. The objective of this review and meta-analysis was to systematically investigate the outcome of low versus high BMI recipients after RT. METHODS: Comprehensive searches were conducted in MEDLINE OvidSP, Web of Science, Google Scholar, Embase, and CENTRAL (the Cochrane Library 2014, issue 8). We reviewed four major guidelines that are available regarding (potential) RT recipients. The methodology was in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and written based on the PRISMA statement. The quality assessment of studies was performed by using the GRADE tool. A meta-analysis was performed using Review Manager 5.3. Random-effects models were used. RESULTS: After identifying 5,526 studies addressing this topic, 56 studies were included. We extracted data for 37 outcome measures (including data of more than 209,000 RT recipients), of which 26 could be meta-analysed. The following outcome measures demonstrated significant differences in favour of low BMI (<30) recipients: mortality (RR = 1.52), delayed graft function (RR = 1.52), acute rejection (RR = 1.17), 1-, 2-, and 3-year graft survival (RR = 0.97, 0.95, and 0.97), 1-, 2-, and 3-year patient survival (RR = 0.99, 0.99, and 0.99), wound infection and dehiscence (RR = 3.13 and 4.85), NODAT (RR = 2.24), length of hospital stay (2.31 days), operation duration (0.77 hours), hypertension (RR = 1.35), and incisional hernia (RR = 2.72). However, patient survival expressed in hazard ratios was in significant favour of high BMI recipients. Differences in other outcome parameters were not significant. CONCLUSIONS: Several of the pooled outcome measurements show significant benefits for ‘low’ BMI (<30) recipients. Therefore, we postulate that ESRD patients with a BMI >30 preferably should lose weight prior to RT. If this cannot be achieved with common measures, in morbidly obese RT candidates, bariatric surgery could be considered. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-015-0340-5) contains supplementary material, which is available to authorized users