Remotely acting SMCHD1 gene regulatory elements: in silico prediction and identification of potential regulatory variants in patients with FSHD

Background: Facioscapulohumeral dystrophy (FSHD) is commonly associated with contraction of the D4Z4 macro-satellite repeat on chromosome 4q35 (FSHD1) or mutations in the SMCHD1 gene (FSHD2). Recent studies have shown that the clinical manifestation of FSHD1 can be modified by mutations in the SMCHD1 gene within a given family. The absence of either D4Z4 contraction or SMCHD1 mutations in a small cohort of patients suggests that the disease could also be due to disruption of gene regulation. In this study, we postulated that mutations responsible for exerting a modifier effect on FSHD might reside within remotely acting regulatory elements that have the potential to interact at a distance with their cognate gene promoter via chromatin looping. To explore this postulate, genome-wide Hi-C data were used to identify genomic fragments displaying the strongest interaction with the SMCHD1 gene. These fragments were then narrowed down to shorter regions using ENCODE and FANTOM data on transcription factor binding sites and epigenetic marks characteristic of promoters, enhancers and silencers

Quasi-Normal Modes of Stars and Black Holes

Perturbations of stars and black holes have been one of the main topics of relativistic astrophysics for the last few decades. They are of particular importance today, because of their relevance to gravitational wave astronomy. In this review we present the theory of quasi-normal modes of compact objects from both the mathematical and astrophysical points of view. The discussion includes perturbations of black holes (Schwarzschild, Reissner-Nordstr\"om, Kerr and Kerr-Newman) and relativistic stars (non-rotating and slowly-rotating). The properties of the various families of quasi-normal modes are described, and numerical techniques for calculating quasi-normal modes reviewed. The successes, as well as the limits, of perturbation theory are presented, and its role in the emerging era of numerical relativity and supercomputers is discussed.Comment: 74 pages, 7 figures, Review article for "Living Reviews in Relativity

Radiocarbon-based source apportionment of elemental carbon aerosols at two South Asian receptor observatories over a full annual cycle

Black carbon (BC) aerosols impact climate and air quality. Since BC from fossil versus biomass combustion have different optical properties and different abilities to penetrate the lungs, it is important to better understand their relative contributions in strongly affected regions such as South Asia. This study reports the first year-round 14C-based source apportionment of elemental carbon (EC), the mass-based correspondent to BC, using as regional receptor sites the international Maldives Climate Observatory in Hanimaadhoo (MCOH) and the mountaintop observatory of the Indian Institute of Tropical Meteorology in Sinhagad, India (SINH). For the highly-polluted winter season (December–March), the fractional contribution to EC from biomass burning (fbio) was 53 ± 5% (n = 6) at MCOH and 56 ± 3% at SINH (n = 5). The fbio for the non-winter remainder was 53 ± 11% (n = 6) at MCOH and 48 ± 8% (n = 7) at SINH. This observation-based constraint on near-equal contributions from biomass burning and fossil fuel combustion at both sites compare with predictions from eight technology-based emission inventory (EI) models for India of (fbio)EI spanning 55–88%, suggesting that most current EI for Indian BC systematically under predict the relative contribution of fossil fuel combustion. A continued iterative testing of bottom-up EI with top-down observational source constraints has the potential to lead to reduced uncertainties regarding EC sources and emissions to the benefit of both models of climate and air quality as well as guide efficient policies to mitigate emissions

Year-round radiocarbon-based source apportionment of carbonaceous aerosols at two background sites in South Asia

Atmospheric Brown Clouds (ABC), regional-scale haze events, are a significant concern for both human cardiopulmonary health and regional climate impacts. In order to effectively mitigate this pollution-based phenomenon, it is imperative to understand the magnitude, scope and source of ABC in regions such as South Asia. Two sites in S. Asia were chosen for a 15-month field campaign focused on isotope-based source apportionment of carbonaceous aerosols in 2008-2009. Both the Maldives Climate Observatory in Hanimaadhoo (MCOH) and a mountaintop site in Sinhagad, India (SINH) act as regionally mixed receptor sites. Annual radiocarbon-based source apportionment for soot elemental carbon (SEC) at MCOH and SINH revealed 73 6 and 59 5 contribution from biomass combustion, respectively (remainder from fossil fuel). The contributions from biogenic/biomass combustion to total organic carbon were similar between MCOH and SINH (69 5 and 64 5, respectively). The biomass combustion contribution for SEC in the current study, especially the results from MCOH, shows good agreement with published black carbon emissions inventories for India. Geographic source assessment, including clustered back trajectory analysis and carbon contribution by source region, indicated that the highest SEC/TOC loads originated from the W. Indian coastal margin, including the coastal city of Mumbai, India. The winter dry season 14C-based source apportionment of the BC-tracing SEC fraction for 2006, 2008, 2009 were not statistically different (p = 0.7) and point to a near-constant two-thirds contribution from biomass combustion practices, including wood and other biofuels as well as burning of agricultural crop residues

Biases in the estimation of transfer function prediction errors

In the quest for more precise sea-surface temperature reconstructions from microfossil assemblages, large modern training sets and new transfer function methods have been developed. Realistic estimates of the predictive power of a transfer function can only be calculated from an independent test set. If the test set is not fully independent, the error estimate will be artificially low. We show that the modern analogue technique using a similarity index (SIMMAX) and the revised analogue method ( RAM), both derived from the modern analogue technique, achieve apparently lower root mean square error of prediction (RMSEP) by failing to ensure statistical independence of samples during cross validation. We also show that when cross validation is used to select the best artificial neural network or modern analogue model, the RMSEP based on cross validation is lower than that for a fully independent test set

Comparative study of the Martian suprathermal electron depletions based on Mars Global Surveyor, Mars Express and Mars Atmosphere and Volatile EvolutioN missions observations

Nightside suprathermal electron depletions have been observed at Mars by three spacecraft to date: Mars Global Surveyor, Mars Express, and the Mars Atmosphere and Volatile EvolutioN (MAVEN) mission. This spatial and temporal diversity of measurements allows us to propose here a comprehensive view of the Martian electron depletions through the first multispacecraft study of the phenomenon. We have analyzed data recorded by the three spacecraft from 1999 to 2015 in order to better understand the distribution of the electron depletions and their creation mechanisms. Three simple criteria adapted to each mission have been implemented to identify more than 134,500 electron depletions observed between 125 and 900 km altitude. The geographical distribution maps of the electron depletions detected by the three spacecraft confirm the strong link existing between electron depletions and crustal magnetic field at altitudes greater than ~170 km. At these altitudes, the distribution of electron depletions is strongly different in the two hemispheres, with a far greater chance to observe an electron depletion in the Southern Hemisphere, where the strongest crustal magnetic sources are located. However, the unique MAVEN observations reveal that below a transition region near 160–170 km altitude the distribution of electron depletions is the same in both hemispheres, with no particular dependence on crustal magnetic fields. This result supports the suggestion made by previous studies that these low-altitudes events are produced through electron absorption by atmospheric CO2

Traces of the Second Demographic Transition in Four Selected Countries in Central and Eastern Europe: Union Formation as a Demographic Manifestation

Using data from the first round of the national Gender and Generations Surveys of Russia, Romania, and Bulgaria, and from a similar survey of Hungary, which were all collected in recent years, we study rates of entry into marital and non-marital unions. We have used elements from the narrative of the Second Demographic Transition (SDT) as a vehicle to give our analysis of the data from the four countries some coherence, and find what can be traces of the SDT in these countries. The details vary by country; in particular, latter-day developments in union formation patterns did not start at the same time in all the countries, but in our assessment it began everywhere before communism fell, that is, before the societal transition to a market economy got underway in 1990

Circulating endothelial cell-derived extracellular vesicles mediate the acute phase response and sickness behaviour associated with CNS inflammation.

Brain injury elicits a systemic acute-phase response (APR), which is responsible for co-ordinating the peripheral immunological response to injury. To date, the mechanisms responsible for signalling the presence of injury or disease to selectively activate responses in distant organs were unclear. Circulating endogenous extracellular vesicles (EVs) are increased after brain injury and have the potential to carry targeted injury signals around the body. Here, we examined the potential of EVs, isolated from rats after focal inflammatory brain lesions using IL-1β, to activate a systemic APR in recipient naïve rats, as well as the behavioural consequences of EV transfer. Focal brain lesions increased EV release, and, following isolation and transfer, the EVs were sequestered by the liver where they initiated an APR. Transfer of blood-borne EVs from brain-injured animals was also enough to suppress exploratory behaviours in recipient naïve animals. EVs derived from brain endothelial cell cultures treated with IL-1β also activated an APR and altered behaviour in recipient animals. These experiments reveal that inflammation-induced circulating EVs derived from endothelial cells are able to initiate the APR to brain injury and are sufficient to generate the associated sickness behaviours, and are the first demonstration that EVs are capable of modifying behavioural responses

Ownership-dependent mating tactics of minor males of the beetle Librodor japonicus (Nitidulidae) with intra-sexual dimorphism of mandibles

Intra-sexual dimorphism is found in the weapons of many male beetles. Different behavioral tactics to access females between major and minor males, which adopt fighting and alternative tactics, respectively, are thought to maintain the male dimorphism. In these species major males have enlarged weapons that they use in fights with rival males. Minor males also have small weapons in some of these species, and it is unclear why these males possess weapons. We examined the hypothesis that minor males might adopt a fighting tactic when their status was relatively high in comparison with that of other males (e.g., ownership of a territory). We observed the behavioral tactics of major and minor males of the beetle Librodor japonicus, whose males have a dimorphism of their mandibles. Major males fought for resources, whereas minor males adopted two status-dependent tactics, fighting and sneaking, to access females, depending on their ownership of a sap site. We suggest that ownership status-dependent mating tactics in minor males may maintain the intra-sexual dimorphism in this beetle.</p