Purifying Selection in Deeply Conserved Human Enhancers Is More Consistent than in Coding Sequences

(c) 2014 De Silva et al. This 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

Are all ‘research fields’ equal? Rethinking practice for the use of data from crowd-sourcing market places

New technologies like large-scale social media sides (e.g., Facebook and Twitter) and crowdsourcing services (e.g., Amazon Mechanical Turk, Crowdflower, Clickworker) impact social science research and provide many new and interesting avenues for research. The use of these new technologies for research has not been without challenges and a recently published psychological study on Facebook led to a widespread discussion on the ethics of conducting large-scale experiments online. Surprisingly little has been said about the ethics of conducting research using commercial crowdsourcing market places. In this paper, I want to focus on the question of which ethical questions are raised by data collection with crowdsourcing tools. I briefly draw on implications of internet research more generally and then focus on the specific challenges that research with crowdsourcing tools faces. I identify fair-pay and related issues of respect for autonomy as well as problems with power dynamics between researcher and participant, which has implications for ‘withdrawal-withoutprejudice’, as the major ethical challenges with crowdsourced data. Further, I will to draw attention on how we can develop a ‘best practice’ for researchers using crowdsourcing tools

Trees and shrubs as sources of fodder in Australia

Experience with browse plants in Australia is briefly reviewed in terms of their forage value to animals, their economic value to the landholder and their ecological contribution to landscape stability. Of the cultivated species only two have achieved any degree of commercial acceptance (Leucaena leucocephala and Chamaecytisus palmensis). Both of these are of sufficiently high forage value to be used as the sole source of feed during seasonal periods of nutritional shortage. Both are also leguminous shrubs that establish readily from seed. It is suggested that a limitation in their present use is the reliance on stands of single species which leaves these grazing systems vulnerable to disease and insects. Grazing systems so far developed for high production and persistence of cultivated species involve short periods of intense grazing followed by long periods of recovery. Similar management may be necessary in the arid and semi-arid rangelands where palatable browse species are in decline

Chromatin loop anchors are associated with genome instability in cancer and recombination hotspots in the germline

Abstract Background Chromatin loops form a basic unit of interphase nuclear organization, with chromatin loop anchor points providing contacts between regulatory regions and promoters. However, the mutational landscape at these anchor points remains under-studied. Here, we describe the unusual patterns of somatic mutations and germline variation associated with loop anchor points and explore the underlying features influencing these patterns. Results Analyses of whole genome sequencing datasets reveal that anchor points are strongly depleted for single nucleotide variants (SNVs) in tumours. Despite low SNV rates in their genomic neighbourhood, anchor points emerge as sites of evolutionary innovation, showing enrichment for structural variant (SV) breakpoints and a peak of SNVs at focal CTCF sites within the anchor points. Both CTCF-bound and non-CTCF anchor points harbour an excess of SV breakpoints in multiple tumour types and are prone to double-strand breaks in cell lines. Common fragile sites, which are hotspots for genome instability, also show elevated numbers of intersecting loop anchor points. Recurrently disrupted anchor points are enriched for genes with functions in cell cycle transitions and regions associated with predisposition to cancer. We also discover a novel class of CTCF-bound anchor points which overlap meiotic recombination hotspots and are enriched for the core PRDM9 binding motif, suggesting that the anchor points have been foci for diversity generated during recent human evolution. Conclusions We suggest that the unusual chromatin environment at loop anchor points underlies the elevated rates of variation observed, marking them as sites of regulatory importance but also genomic fragility

SAS6-like protein in Plasmodium indicates that conoid-associated apical complex proteins persist in invasive stages within the mosquito vector

The SAS6-like (SAS6L) protein, a truncated paralogue of the ubiquitous basal body/centriole protein SAS6, has been characterised recently as a flagellum protein in trypanosomatids, but associated with the conoid in apicomplexan Toxoplasma. The conoid has been suggested to derive from flagella parts, but is thought to have been lost from some apicomplexans including the malaria-causing genus Plasmodium. Presence of SAS6L in Plasmodium, therefore, suggested a possible role in flagella assembly in male gametes, the only flagellated stage. Here, we have studied the expression and role of SAS6L throughout the Plasmodium life cycle using the rodent malaria model P. berghei. Contrary to a hypothesised role in flagella, SAS6L was absent during gamete flagellum formation. Instead, SAS6L was restricted to the apical complex in ookinetes and sporozoites, the extracellular invasive stages that develop within the mosquito vector. In these stages SAS6L forms an apical ring, as we show is also the case in Toxoplasma tachyzoites. The SAS6L ring was not apparent in blood-stage invasive merozoites, indicating that the apical complex is differentiated between the different invasive forms. Overall this study indicates that a conoid-associated apical complex protein and ring structure is persistent in Plasmodium in a stage-specific manner

Impairment of Auditory-Motor Timing and Compensatory Reorganization after Ventral Premotor Cortex Stimulation

Integrating auditory and motor information often requires precise timing as in speech and music. In humans, the position of the ventral premotor cortex (PMv) in the dorsal auditory stream renders this area a node for auditory-motor integration. Yet, it remains unknown whether the PMv is critical for auditory-motor timing and which activity increases help to preserve task performance following its disruption. 16 healthy volunteers participated in two sessions with fMRI measured at baseline and following rTMS (rTMS) of either the left PMv or a control region. Subjects synchronized left or right finger tapping to sub-second beat rates of auditory rhythms in the experimental task, and produced self-paced tapping during spectrally matched auditory stimuli in the control task. Left PMv rTMS impaired auditory-motor synchronization accuracy in the first sub-block following stimulation (p<0.01, Bonferroni corrected), but spared motor timing and attention to task. Task-related activity increased in the homologue right PMv, but did not predict the behavioral effect of rTMS. In contrast, anterior midline cerebellum revealed most pronounced activity increase in less impaired subjects. The present findings suggest a critical role of the left PMv in feed-forward computations enabling accurate auditory-motor timing, which can be compensated by activity modulations in the cerebellum, but not in the homologue region contralateral to stimulation

Examining mindfulness and its relation to self-differentiation and alexithymia

Published online first in 10 July 2013Research supports the association between mindfulness, emotion regulation, stress reduction, and interpersonal/relational wellness. The present study evaluated the potential effect of mindfulness on some indicators of psychological imbalance such as low self-differentiation and alexithymia. In this cross-sectional study, a sample of 168 undergraduates (72 % women) completed measures of perceived mindfulness (CAMS-R and PHLMS), self-differentiation (SIPI), and alexithymia (TAS-20). Results revealed positive correlations between the different dimensions of mindfulness and negative correlations between those dimensions, selfdifferentiation, and alexithymia. The dimensions of quality of mindfulness and acceptance were mediators in the relationship between self-differentiation and alexithymia. A nonsignificant interaction between gender and alexithymia was found. All mindfulness dimensions, but self-differentiation, contributed to explain the allocation of the non-alexithymic group. These results indicate that mindfulness seems to be a construct with great therapeutic and research potential at different levels, suggesting that some aspects of mindfulness seem to promote a better self-differentiation and prevent alexithymia

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Exploring new physics frontiers through numerical relativity

The demand to obtain answers to highly complex problems within strong-field gravity has been met with significant progress in the numerical solution of Einstein's equations - along with some spectacular results - in various setups. We review techniques for solving Einstein's equations in generic spacetimes, focusing on fully nonlinear evolutions but also on how to benchmark those results with perturbative approaches. The results address problems in high-energy physics, holography, mathematical physics, fundamental physics, astrophysics and cosmology