Microevolution of neuroendocrine mechanisms regulating reproductive timing in Peromyscus leucopus

A key question in the evolution of life history and in evolutionary physiology asks how reproductive and other life-history traits evolve. Genetic variation in reproductive control systems may exist in many elements of the complex inputs that call affect the hypothalamic-pituitary-gonadal (HPG) or reproductive axis. Such variation could include numbers and other traits of secretory cells, the amount and pattern of chemical message released, transport and clearance mechanisms, and the number and other traits of receptor cells. Selection lines created from a natural population of white-footed mice (Peromyscus leucopus) that contains substantial genetic variation in reproductive inhibition in response to short winter daylength (SD) have been used to examine neuroendocrine variation in reproductive timing. We hypothesized that natural genetic variation would be most likely to occur in the inputs to GnRH neurons and/or in GnRH neurons themselves, but not in elements of the photoperiodic pathway that would have pleiotropic effects oil nonreproductive functions as well as oil reproductive functions. Significant genetic variation has been found in the GnRH neuronal system. The number of GnRH neurons immunoreactive to all antibody to mature GnRH peptide under conditions maximizing detection of stained neurons was significantly heritable in an unselected control (C) line. Furthermore, a selection line that suppresses reproduction in SD (photoperiod responsive, R) had fewer IR-GnRH neurons than a selection line that maintains reproduction in SD (photoperiod nonresponsive, NR). This supports the hypothesis that genetic variation in characteristics of GnRH neurons themselves may be responsible for the observed phenotypic variation in reproduction in SD. The R and NR lines differ genetically in food intake and iodo-melatonin receptor binding, as well as in other characteristics. The latter findings are consistent with the hypothesis that genetic variation occurs in the nutritional and hormonal inputs to GnRH neurons. Genetic variation also exists in the phenotypic plasticity of responses to two combinations of treatments, (1) food and photoperiod, and (2) photoperiod and age, indicating genetic variation in individual norms of reaction within this population. Overall, the apparent multiple sources of genetic variation within this population suggest that there may be multiple alternative combinations of alleles for both the R and NR phenotypes. If that interpretation is correct, we suggest that this offers some support for the evolutionary potential hypothesis and is inconsistent with the evolutionary constraint and symmorphosis hypotheses for the evolution of complex neuroendocrine pathways

The UK on the spot accident data collection study – phase II report

The aims and objectives of the On the Spot (OTS) Phase II project are summarised below. • The aim of the OTS Accident Data Collection Study is to provide a uniquely valuable information resource concerning real-world road accidents. The OTS Accident Data Collection Study provides the data to enable the development of evidence-led innovative policy and countermeasures to reduce road traffic casualties. • The objective of the project was to investigate 1,500 road traffic accidents in the OTS-defined Nottinghamshire and Thames Valley Police areas in order to collect high-quality crash data to improve the understanding of human involvement, vehicle design and highway design in accident causation and injury mechanisms. This was achieved by experienced researchers attending the scenes of a known sample of road traffic accidents notified to the emergency services. It is necessary to attend the scene of the road traffic accident while the vehicles, and possibly victims, are still in place to enable the capture of ‘perishable’ information that is only available for a very short time. Capture of the ‘perishable’ or ‘volatile’ information provides a more complete picture of the accident, potentially allowing for a greater understanding. Further data required to provide a complete understanding of the accident are collected later, through follow-up visits and other information collection procedures. During Phases I and II of the OTS project, the Transport Research Laboratory (TRL) and the Vehicle Safety Research Centre (VSRC) at Loughborough University attended and investigated over 3,000 accidents within the Nottinghamshire and Thames Valley regions

Evaluation of Germline BMP4 Mutation as a Cause of Colorectal Cancer

Transforming growth factor-â (TGF-â) signalling plays a key role in colorectal cancer (CRC). Bone morphogenetic protein-4 (BMP4) is a member of the TGF-â family of signal transduction molecules. To examine if germline mutation in BMP4 causes CRC we analysed 504 genetically enriched CRC cases (by virtue of early-onset disease, family history of CRC) for mutations in the coding sequence of BMP4. We identified three pathogenic mutations, p.R286X (g.8330C>T), p.W325C (g.8449G>T) and p.C373S (g.8592G>C), amongst the CRC cases which were not observed in 524 healthy controls. p.R286X localizes to the N-terminal of the TGF-â1 prodomain truncating the protein prior to the active domain. p.W325C and p.C373S mutations are predicted from protein homology modelling with BMP2 to impact deleteriously on BMP4 function. Segregation of p.C373S with adenoma and hyperplastic polyp in first-degree relatives of the case suggests germline mutations may confer a juvenile polyposis-type phenotype. These findings suggest mutation of BMP4is a cause of CRC and the value of protein-based modelling in the elucidation of rare disease-causing variants. © 2010 Wiley-Liss, Inc

Dynamic testing and transfer: An examination of children's problem-solving strategies

This study examined the problem-solving behaviour of 104 children (aged 7–8 years) when tackling construction-analogy tasks. Children were allocated to one of two conditions: either a form of unguided practice alone or this in combination with training based on graduated prompt techniques. Children's ability to solve figural open-ended analogy-problems was investigated as well as their ability to construct new analogy problems themselves. We examined children's progression in solving analogy problems and the variability in their strategy-use. Results showed that the group that received training made greater progress in solving analogy problems than children who only received unguided practice opportunities. However, the training appeared to give no additional improvement in performance on the transfer task over that of repeated unguided practice alone. Findings from this study demonstrate that an open construction task can provide additional information about children's cognitive learning potential

ZMYND10 Is Mutated in Primary Ciliary Dyskinesia and Interacts with LRRC6

Defects of motile cilia cause primary ciliary dyskinesia (PCD), characterized by recurrent respiratory infections and male infertility. Using whole-exome resequencing and high-throughput mutation analysis, we identified recessive biallelic mutations in ZMYND10 in 14 families and mutations in the recently identified LRRC6 in 13 families. We show that ZMYND10 and LRRC6 interact and that certain ZMYND10 and LRRC6 mutations abrogate the interaction between the LRRC6 CS domain and the ZMYND10 C-terminal domain. Additionally, ZMYND10 and LRRC6 colocalize with the centriole markers SAS6 and PCM1. Mutations in ZMYND10 result in the absence of the axonemal protein components DNAH5 and DNALI1 from respiratory cilia. Animal models support the association between ZMYND10 and human PCD, given that zmynd10 knockdown in zebrafish caused ciliary paralysis leading to cystic kidneys and otolith defects and that knockdown in Xenopus interfered with ciliogenesis. Our findings suggest that a cytoplasmic protein complex containing ZMYND10 and LRRC6 is necessary for motile ciliary function

Models of marine fish biodiversity : assessing predictors from three habitat classification schemes

Prioritising biodiversity conservation requires knowledge of where biodiversity occurs. Such knowledge, however, is often lacking. New technologies for collecting biological and physical data coupled with advances in modelling techniques could help address these gaps and facilitate improved management outcomes. Here we examined the utility of environmental data, obtained using different methods, for developing models of both uni- and multivariate biodiversity metrics. We tested which biodiversity metrics could be predicted best and evaluated the performance of predictor variables generated from three types of habitat data: acoustic multibeam sonar imagery, predicted habitat classification, and direct observer habitat classification. We used boosted regression trees (BRT) to model metrics of fish species richness, abundance and biomass, and multivariate regression trees (MRT) to model biomass and abundance of fish functional groups. We compared model performance using different sets of predictors and estimated the relative influence of individual predictors. Models of total species richness and total abundance performed best; those developed for endemic species performed worst. Abundance models performed substantially better than corresponding biomass models. In general, BRT and MRTs developed using predicted habitat classifications performed less well than those using multibeam data. The most influential individual predictor was the abiotic categorical variable from direct observer habitat classification and models that incorporated predictors from direct observer habitat classification consistently outperformed those that did not. Our results show that while remotely sensed data can offer considerable utility for predictive modeling, the addition of direct observer habitat classification data can substantially improve model performance. Thus it appears that there are aspects of marine habitats that are important for modeling metrics of fish biodiversity that are not fully captured by remotely sensed data. As such, the use of remotely sensed data to model biodiversity represents a compromise between model performance and data availability

ZMYND10 Is Mutated in Primary Ciliary Dyskinesia and Interacts with LRRC6

Defects of motile cilia cause primary ciliary dyskinesia (PCD), characterized by recurrent respiratory infections and male infertility. Using whole-exome resequencing and high-throughput mutation analysis, we identified recessive biallelic mutations in ZMYND10 in 14 families and mutations in the recently identified LRRC6 in 13 families. We show that ZMYND10 and LRRC6 interact and that certain ZMYND10 and LRRC6 mutations abrogate the interaction between the LRRC6 CS domain and the ZMYND10 C-terminal domain. Additionally, ZMYND10 and LRRC6 colocalize with the centriole markers SAS6 and PCM1. Mutations in ZMYND10 result in the absence of the axonemal protein components DNAH5 and DNALI1 from respiratory cilia. Animal models support the association between ZMYND10 and human PCD, given that zmynd10 knockdown in zebrafish caused ciliary paralysis leading to cystic kidneys and otolith defects and that knockdown in Xenopus interfered with ciliogenesis. Our findings suggest that a cytoplasmic protein complex containing ZMYND10 and LRRC6 is necessary for motile ciliary function

Analysis of shared common genetic risk between amyotrophic lateral sclerosis and epilepsy

Because hyper-excitability has been shown to be a shared pathophysiological mechanism, we used the latest and largest genome-wide studies in amyotrophic lateral sclerosis (n = 36,052) and epilepsy (n = 38,349) to determine genetic overlap between these conditions. First, we showed no significant genetic correlation, also when binned on minor allele frequency. Second, we confirmed the absence of polygenic overlap using genomic risk score analysis. Finally, we did not identify pleiotropic variants in meta-analyses of the 2 diseases. Our findings indicate that amyotrophic lateral sclerosis and epilepsy do not share common genetic risk, showing that hyper-excitability in both disorders has distinct origins

Loneliness and social media: A qualitative investigation of young people's motivations for use and perceptions of social networking sites

The democratisation of Internet access has incrementally changed every domain of activity and has created new business and economic models. From answering work emails to learning a new language, shopping, booking medical appointments or managing one’s finances, almost everything is attainable at the click of a button. The added implications of the rapid rise of social networking websites (SNSs), such as Facebook, Twitter, Instagram or Snapchat, have further contributed to changing the way we communicate and build new friendships. Indeed most of our social relationships are now being ‘increasingly developed and maintained online’ (Nowland, Necka & Cacioppo, 2017: 1). Ostensibly, despite improved Internet access and enhanced social connectedness, modern societies are struggling to combat loneliness. It is reported to affect people of all ages, especially young adults (16-24 and 25-34 years old) who are avid Internet and social media users (see Office for National Statistics, 2018)