Cortical Representation of Lateralized Grasping in Chimpanzees (Pan troglodytes): A Combined MRI and PET Study

Functional imaging studies in humans have localized the motor-hand region to a neuroanatomical landmark call the KNOB within the precentral gyrus. It has also been reported that the KNOB is larger in the hemisphere contralateral to an individual's preferred hand, and therefore may represent the neural substrate for handedness. The KNOB has also been neuronatomically described in chimpanzees and other great apes and is similarly associated with handedness. However, whether the chimpanzee KNOB represents the hand region is unclear from the extant literature. Here, we used PET to quantify neural metabolic activity in chimpanzees when engaged in unilateral reach-and-grasping responses and found significantly lateralized activation of the KNOB region in the hemisphere contralateral to the hand used by the chimpanzees. We subsequently constructed a probabilistic map of the KNOB region in chimpanzees in order to assess the overlap in consistency in the anatomical landmarks of the KNOB with the functional maps generated from the PET analysis. We found significant overlap in the anatomical and functional voxels comprising the KNOB region, suggesting that the KNOB does correspond to the hand region in chimpanzees. Lastly, from the probabilistic maps, we compared right- and left-handed chimpanzees on lateralization in grey and white matter within the KNOB region and found that asymmetries in white matter of the KNOB region were larger in the hemisphere contralateral to the preferred hand. These results suggest that neuroanatomical asymmetries in the KNOB likely reflect changes in connectivity in primary motor cortex that are experience dependent in chimpanzees and possibly humans

A population of luminous accreting black holes with hidden mergers

Major galaxy mergers are thought to play an important part in fuelling the growth of supermassive black holes. However, observational support for this hypothesis is mixed, with some studies showing a correlation between merging galaxies and luminous quasars and others showing no such association. Recent observations have shown that a black hole is likely to become heavily obscured behind merger-driven gas and dust, even in the early stages of the merger, when the galaxies are well separated (5 to 40 kiloparsecs). Merger simulations further suggest that such obscuration and black-hole accretion peaks in the final merger stage, when the two galactic nuclei are closely separated (less than 3 kiloparsecs). Resolving this final stage requires a combination of high-spatial-resolution infrared imaging and high-sensitivity hard-X-ray observations to detect highly obscured sources. However, large numbers of obscured luminous accreting supermassive black holes have been recently detected nearby (distances below 250 megaparsecs) in X-ray observations. Here we report high-resolution infrared observations of hard-X-ray-selected black holes and the discovery of obscured nuclear mergers, the parent populations of supermassive-black-hole mergers. We find that obscured luminous black holes (bolometric luminosity higher than 2x10^44 ergs per second) show a significant (P<0.001) excess of late-stage nuclear mergers (17.6 per cent) compared to a sample of inactive galaxies with matching stellar masses and star formation rates (1.1 per cent), in agreement with theoretical predictions. Using hydrodynamic simulations, we confirm that the excess of nuclear mergers is indeed strongest for gas-rich major-merger hosts of obscured luminous black holes in this final stage.Comment: To appear in the 8 November 2018 issue of Nature. This is the authors' version of the wor

An update on the strategies in multicomponent activity monitoring within the phytopharmaceutical field

<p>Abstract</p> <p>Background</p> <p>To-date modern drug research has focused on the discovery and synthesis of single active substances. However, multicomponent preparations are gaining increasing importance in the phytopharmaceutical field by demonstrating beneficial properties with respect to efficacy and toxicity.</p> <p>Discussion</p> <p>In contrast to single drug combinations, a botanical multicomponent therapeutic possesses a complex repertoire of chemicals that belong to a variety of substance classes. This may explain the frequently observed pleiotropic bioactivity spectra of these compounds, which may also suggest that they possess novel therapeutic opportunities. Interestingly, considerable bioactivity properties are exhibited not only by remedies that contain high doses of phytochemicals with prominent pharmaceutical efficacy, but also preparations that lack a sole active principle component. Despite that each individual substance within these multicomponents has a low molar fraction, the therapeutic activity of these substances is established via a potentialization of their effects through combined and simultaneous attacks on multiple molecular targets. Although beneficial properties may emerge from such a broad range of perturbations on cellular machinery, validation and/or prediction of their activity profiles is accompanied with a variety of difficulties in generic risk-benefit assessments. Thus, it is recommended that a comprehensive strategy is implemented to cover the entirety of multicomponent-multitarget effects, so as to address the limitations of conventional approaches.</p> <p>Summary</p> <p>An integration of standard toxicological methods with selected pathway-focused bioassays and unbiased data acquisition strategies (such as gene expression analysis) would be advantageous in building an interaction network model to consider all of the effects, whether they were intended or adverse reactions.</p

Effects of Simulated Microgravity on Embryonic Stem Cells

There have been many studies on the biological effects of simulated microgravity (SMG) on differentiated cells or adult stem cells. However, there has been no systematic study on the effects of SMG on embryonic stem (ES) cells. In this study, we investigated various effects (including cell proliferation, cell cycle distribution, cell differentiation, cell adhesion, apoptosis, genomic integrity and DNA damage repair) of SMG on mouse embryonic stem (mES) cells. Mouse ES cells cultured under SMG condition had a significantly reduced total cell number compared with cells cultured under 1 g gravity (1G) condition. However, there was no significant difference in cell cycle distribution between SMG and 1G culture conditions, indicating that cell proliferation was not impaired significantly by SMG and was not a major factor contributing to the total cell number reduction. In contrast, a lower adhesion rate cultured under SMG condition contributed to the lower cell number in SMG. Our results also revealed that SMG alone could not induce DNA damage in mES cells while it could affect the repair of radiation-induced DNA lesions of mES cells. Taken together, mES cells were sensitive to SMG and the major alterations in cellular events were cell number expansion, adhesion rate decrease, increased apoptosis and delayed DNA repair progression, which are distinct from the responses of other types of cells to SMG

Patients’ Perceptions and Experiences of Familial Hypercholesterolemia, Cascade Genetic Screening and Treatment

Background: Familial hypercholesterolemia (FH) is a serious genetic disorder affecting approximately 1 in every 300 to 500 individuals and is characterised by excessively high low-density lipoprotein (LDL) cholesterol levels, substantially increased risk of early-onset coronary heart disease (CHD) and premature mortality. If FH is untreated, it leads to a greater than 50 % risk of CHD in men by the age of 50 and at least 30 % in women by the age of 60. FH can be diagnosed through genetic screening and effectively managed through pharmacological treatment and lifestyle changes. Purpose: Familial hypercholesterolemia (FH) is a genetic health condition that increases the risk of cardiovascular disease. Although FH can be effectively managed with appropriate pharmacological and dietary interventions, FH detection rate through genetic screening remains low. The present study explored perceptions and experiences of FH patients (N = 18) involved in a genetic cascade screening programme. Methods: Face-to-face interviews were conducted to assess patients’ knowledge and understanding of FH, explore factors linked to adherence to health-protective behaviours and examine perceptions of genetic screening. Results: Thematic analysis of interviews revealed four themes: disease knowledge, severity of FH, lifestyle behavioural change and barriers to cascade screening and treatment. Participants recognised FH as a permanent, genetic condition that increased their risk of CHD and premature mortality. Many participants dismissed the seriousness of FH and the importance of lifestyle changes because they perceived it to be effectively managed through medication. Despite positive attitudes toward screening, many participants reported that relatives were reluctant to attend screening due to their relatives’ ‘fatalistic’ outlook or low motivation. Participants believed that they had insufficient authority or control to persuade family members to attend screening and welcomed greater hospital assistance for contact with relatives. Conclusions: Findings support the adoption of direct methods of recruitment to cascade screening led by medical professionals, who were perceived as having greater authority. Other implications included the need for clinicians to provide clear information, particularly to those who are asymptomatic, related to the seriousness of FH and the necessity for adherence to medication and lifestyle changes

Effect of propofol and etomidate on normoxic and chronically hypoxic pulmonary artery

BACKGROUND: Chronic alveolar hypoxia results in sustained arterial constriction, and increase in pulmonary vascular resistance leading to pulmonary artery hypertension (PAHT). The aim of this study was to investigate the effect of propofol and etomidate on pulmonary artery (PA) reactivity in chronically hypoxic (CH) rats, a model of pulmonary arterial hypertension (PAHT), in normoxic animals, and human PA. METHODS: CH rats were maintained 14 days at 380 mmHg pressure in a hypobaric chamber. Human tissue was retrieved from histological lung pieces from patients undergoing resection for carcinoma. Cumulative concentrations of anaesthetics were tested on isolated vascular rings precontracted with phenylephrine (PHE) or 100 mM KCl. Statistical comparisons were done by ANOVA, followed, when needed, by Student t tests with Bonferroni correction as post-hoc tests. RESULTS: In normoxic rat PA, maximal relaxation (R(max)) induced by etomidate and propofol was 101.3 ± 0.8% and 94.0 ± 2.3%, respectively, in KCl-precontracted rings, and 63.3 ± 9.7% and 46.1 ± 9.1%, respectively, in PHE-precontracted rings (n = 7). In KCl-precontracted human PA, R(max )was 84.7 ± 8.6 % and 66.5 ± 11.8%, for etomidate and propofol, respectively, and 154.2 ± 22.4 % and 51.6 ± 15.1 %, respectively, in PHE-precontracted human PA (n = 7). In CH rat PA, the relaxant effect of both anaesthetics was increased in PHE-precontracted and, for etomidate only, in KCl-precontracted PA. In aorta, CH induced no change in the relaxant effect of anaesthetics. CONCLUSION: Propofol and etomidate have relaxant properties in PA from human and normoxic rat. The relaxant effect is specifically accentuated in PA from CH rat, mainly via an effect on the pharmacomechanical coupling. Etomidate appears to be more efficient than propofol at identical concentration, but, taking into account clinical concentrations, etomidate is less potent than propofol, which effect was in the range of clinical doses. Although these findings provide experimental support for the preferential use of etomidate for haemodynamic stability in patients suffering from PAHT, the clinical relevance of the observations requires further investigation

Shady business: understanding the spatial ecology of exophilic Anopheles mosquitoes

Background: Understanding the ecology of exophilic anophelines is a key step toward developing outdoor control strategies to complement existing indoor control tools against malaria vectors. This study was conducted to assess the movement pattern of exophilic Anopheles mosquitoes between blood meal sources and resting habitats, and the landscape factors dictating their resting habitat choice. Results: Resting clay pots were placed at 5 m, 25 m, 50 m, 75 m and 100 m away from isolated focal houses, radiating from them in four directions. The locations of the clay pots represent heterogeneous land cover types at a relatively fine spatial scale in the landscape. The effect of the landscape characters on the number of both female and male anophelines caught was modelled using zero-inflated negative binomial regression with a log link function. A total of 420 Anopheles mosquitoes (353 females and 67 males) belonging to three species; Anopheles arabiensis, Anopheles pharoensis, and Anopheles tenebrosus were caught in the resting clay pots, with An. arabiensis being the dominant species. Canopy cover, distance from the house, and land cover type were the significant landscape characters influencing the aggregation of resting mosquitoes. Both the count and binary models showed that canopy cover was the strongest predictor variable on the counts and the presence of Anopheles mosquitoes in the clay pots. Female Anopheles were most frequently found resting in the pots placed in banana plantations, and at sampling points that were at the greater distances (75 m and 100 m) from the focal house. Conclusions: This study showed that exophilic Anopheles mosquitoes tend to rest in shaded areas some distance away from human habitation. These findings are important when targeting mosquitoes outdoors, complementing the existing effort being made to control malaria vectors indoors

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV