How important is sexual isolation to speciation?

K.L.S. was supported by Cornell University and the U.S. NSF during this project. C.R.C was supported by a Natural Environment Research Council Independent Research Fellowship (NE/T01105X/1). T.C.M. is supported by U.S. NSF 2026334. M.G.R. is supported by the Natural Environment Research Council (UK, NE/V001566/1).A central role for sexual isolation in the formation of new species and establishment of species boundaries has been noticed since Darwin and is frequently emphasized in the modern literature on speciation. However, an objective evaluation of when and how sexual isolation plays a role in speciation has been carried out in few taxa. We discuss three approaches for assessing the importance of sexual isolation relative to other reproductive barriers, including the relative evolutionary rate of sexual trait differentiation, the relative strength of sexual isolation in sympatry, and the role of sexual isolation in the long-term persistence of diverging forms. First, we evaluate evidence as to whether sexual isolation evolves faster than other reproductive barriers during the early stages of divergence. Second, we discuss available evidence as to whether sexual isolation is as strong or stronger than other barriers between closely related sympatric species. Finally, we consider the effect of sexual isolation on long-term species persistence, relative to other reproductive barriers. We highlight challenges to our knowledge of and opportunities to improve upon our understanding of sexual isolation from different phases of the speciation process.Peer reviewe

Group-Based Parent Training Interventions for Parents of Children with Autism Spectrum Disorders: a Literature Review

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Parents of children with autism spectrum disorders should have access to interventions to help them understand and support their child. This literature review examines the existing evidence for group-based parent training interventions that support parents of children with autism. From the literature, core intervention processes and outcomes are identified and include parenting and parent behaviour, parent health, child behaviour and peer and social support. Results show a positive trend for intervention effectiveness, but findings are limited by low-quality studies and heterogeneity of intervention content, outcomes and outcome measurement. Future research should focus on specifying effective intervention ingredients and modes of delivery, consistent and reliable outcome measurement, and improving methodological rigour to build a more robust evidence base

Selective release of muscle-specific, extracellular microRNAs during myogenic differentiation

MyomiRs are muscle-specific microRNAs (miRNAs) that regulate myoblast proliferation and differentiation. Extracellular myomiRs (ex-myomiRs) are highly enriched in the serum of Duchenne Muscular Dystrophy (DMD) patients and dystrophic mouse models and consequently have potential as disease biomarkers. The biological significance of miRNAs present in the extracellular space is not currently well understood. Here we demonstrate that ex-myomiR levels are elevated in perinatal muscle development, during the regenerative phase that follows exercise-induced myoinjury, and concomitant with myoblast differentiation in culture. Whereas ex-myomiRs are progressively and specifically released by differentiating human primary myoblasts and C2C12 cultures, chemical induction of apoptosis in C2C12 cells results in indiscriminate miRNA release. The selective release of myomiRs as a consequence of cellular differentiation argues against the idea that they are solely waste products of muscle breakdown, and suggests they may serve a biological function in specific physiological contexts. Ex-myomiRs in culture supernatant and serum are predominantly non-vesicular, and their release is independent of ceramide-mediated vesicle secretion. Furthermore, ex-myomiRs levels are reduced in aged dystrophic mice, likely as a consequence of chronic muscle wasting. In conclusion, we show that myomiR release accompanies periods of myogenic differentiation in cell culture and in vivo. Serum myomiR abundance is therefore a function of the regenerative/degenerative status of the muscle, overall muscle mass, and tissue expression levels. These findings have implications for the use of ex-myomiRs as biomarkers for DMD disease progression and monitoring response to therapy

Rossby wave dynamics of the North Pacific extra-tropical response to El Niño: importance of the basic state in coupled GCMs

The extra-tropical response to El Nino in a "low" horizontal resolution coupled climate model, typical of the Intergovernmental Panel on Climate Change fourth assessment report simulations, is shown to have serious systematic errors. A high resolution configuration of the same model has a much improved response that is similar to observations. The errors in the low resolution model are traced to an incorrect representation of the atmospheric teleconnection mechanism that controls the extra-tropical sea surface temperatures (SSTs) during El Nino. This is due to an unrealistic atmospheric mean state, which changes the propagation characteristics of Rossby waves. These erroneous upper tropospheric circulation anomalies then induce erroneous surface circulation features over the North Pacific. The associated surface wind speed and direction errors create erroneous surface flux and upwelling anomalies which finally lead to the incorrect extra-tropical SST response to El Nino in the low resolution model. This highlights the sensitivity of the climate response to a single link in a chain of complex climatic processes. The correct representation of these processes in the high resolution model indicates the importance of horizontal resolution in resolving such processes

Big data and data repurposing – using existing data to answer new questions in vascular dementia research

Introduction: Traditional approaches to clinical research have, as yet, failed to provide effective treatments for vascular dementia (VaD). Novel approaches to collation and synthesis of data may allow for time and cost efficient hypothesis generating and testing. These approaches may have particular utility in helping us understand and treat a complex condition such as VaD. Methods: We present an overview of new uses for existing data to progress VaD research. The overview is the result of consultation with various stakeholders, focused literature review and learning from the group’s experience of successful approaches to data repurposing. In particular, we benefitted from the expert discussion and input of delegates at the 9th International Congress on Vascular Dementia (Ljubljana, 16-18th October 2015). Results: We agreed on key areas that could be of relevance to VaD research: systematic review of existing studies; individual patient level analyses of existing trials and cohorts and linking electronic health record data to other datasets. We illustrated each theme with a case-study of an existing project that has utilised this approach. Conclusions: There are many opportunities for the VaD research community to make better use of existing data. The volume of potentially available data is increasing and the opportunities for using these resources to progress the VaD research agenda are exciting. Of course, these approaches come with inherent limitations and biases, as bigger datasets are not necessarily better datasets and maintaining rigour and critical analysis will be key to optimising data use

Pulsar Results with the Fermi Large Area Telescope

The launch of the Fermi Gamma-ray Space Telescope has heralded a new era in the study of gamma-ray pulsars. The population of confirmed gamma-ray pulsars has gone from 6-7 to more than 60, and the superb sensitivity of the Large Area Telescope (LAT) on Fermi has allowed the detailed study of their spectra and light curves. Twenty-four of these pulsars were discovered in blind searches of the gamma-ray data, and twenty-one of these are, at present, radio quiet, despite deep radio follow-up observations. In addition, millisecond pulsars have been confirmed as a class of gamma-ray emitters, both individually and collectively in globular clusters. Recently, radio searches in the direction of LAT sources with no likely counterparts have been highly productive, leading to the discovery of a large number of new millisecond pulsars. Taken together, these discoveries promise a great improvement in the understanding of the gamma-ray emission properties and Galactic population of pulsars. We summarize some of the results stemming from these newly-detected pulsars and their timing and multi-wavelength follow-up observations.Comment: 21 pages, 9 figures, to appear in Proceedings of ICREA Workshop on The High-Energy Emission from Pulsars and their Systems, Sant Cugat, Spain, 2010 April 12-16 (Springer

Preserving the impossible: conservation of soft-sediment hominin footprint sites and strategies for three-dimensional digital data capture.

Human footprints provide some of the most publically emotive and tangible evidence of our ancestors. To the scientific community they provide evidence of stature, presence, behaviour and in the case of early hominins potential evidence with respect to the evolution of gait. While rare in the geological record the number of footprint sites has increased in recent years along with the analytical tools available for their study. Many of these sites are at risk from rapid erosion, including the Ileret footprints in northern Kenya which are second only in age to those at Laetoli (Tanzania). Unlithified, soft-sediment footprint sites such these pose a significant geoconservation challenge. In the first part of this paper conservation and preservation options are explored leading to the conclusion that to 'record and digitally rescue' provides the only viable approach. Key to such strategies is the increasing availability of three-dimensional data capture either via optical laser scanning and/or digital photogrammetry. Within the discipline there is a developing schism between those that favour one approach over the other and a requirement from geoconservationists and the scientific community for some form of objective appraisal of these alternatives is necessary. Consequently in the second part of this paper we evaluate these alternative approaches and the role they can play in a 'record and digitally rescue' conservation strategy. Using modern footprint data, digital models created via optical laser scanning are compared to those generated by state-of-the-art photogrammetry. Both methods give comparable although subtly different results. This data is evaluated alongside a review of field deployment issues to provide guidance to the community with respect to the factors which need to be considered in digital conservation of human/hominin footprints

UNCLES: Method for the identification of genes differentially consistently co-expressed in a specific subset of datasets

Background: Collective analysis of the increasingly emerging gene expression datasets are required. The recently proposed binarisation of consensus partition matrices (Bi-CoPaM) method can combine clustering results from multiple datasets to identify the subsets of genes which are consistently co-expressed in all of the provided datasets in a tuneable manner. However, results validation and parameter setting are issues that complicate the design of such methods. Moreover, although it is a common practice to test methods by application to synthetic datasets, the mathematical models used to synthesise such datasets are usually based on approximations which may not always be sufficiently representative of real datasets. Results: Here, we propose an unsupervised method for the unification of clustering results from multiple datasets using external specifications (UNCLES). This method has the ability to identify the subsets of genes consistently co-expressed in a subset of datasets while being poorly co-expressed in another subset of datasets, and to identify the subsets of genes consistently co-expressed in all given datasets. We also propose the M-N scatter plots validation technique and adopt it to set the parameters of UNCLES, such as the number of clusters, automatically. Additionally, we propose an approach for the synthesis of gene expression datasets using real data profiles in a way which combines the ground-truth-knowledge of synthetic data and the realistic expression values of real data, and therefore overcomes the problem of faithfulness of synthetic expression data modelling. By application to those datasets, we validate UNCLES while comparing it with other conventional clustering methods, and of particular relevance, biclustering methods. We further validate UNCLES by application to a set of 14 real genome-wide yeast datasets as it produces focused clusters that conform well to known biological facts. Furthermore, in-silico-based hypotheses regarding the function of a few previously unknown genes in those focused clusters are drawn. Conclusions: The UNCLES method, the M-N scatter plots technique, and the expression data synthesis approach will have wide application for the comprehensive analysis of genomic and other sources of multiple complex biological datasets. Moreover, the derived in-silico-based biological hypotheses represent subjects for future functional studies.The National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-0310-1004)

The challenges faced in the design, conduct and analysis of surgical randomised controlled trials

Randomised evaluations of surgical interventions are rare; some interventions have been widely adopted without rigorous evaluation. Unlike other medical areas, the randomised controlled trial (RCT) design has not become the default study design for the evaluation of surgical interventions. Surgical trials are difficult to successfully undertake and pose particular practical and methodological challenges. However, RCTs have played a role in the assessment of surgical innovations and there is scope and need for greater use. This article will consider the design, conduct and analysis of an RCT of a surgical intervention. The issues will be reviewed under three headings: the timing of the evaluation, defining the research question and trial design issues. Recommendations on the conduct of future surgical RCTs are made. Collaboration between research and surgical communities is needed to address the distinct issues raised by the assessmentof surgical interventions and enable the conduct of appropriate and well-designed trials.The Health Services Research Unit is funded by the Scottish Government Health DirectoratesPeer reviewedPublisher PD