julilili42/papers huggingface dataset:
TPC2 polymorphisms associated with a hair pigmentation phenotype in humans result in gain of channel function by independent mechanisms
2017-09-18

Significance Polymorphisms in the endolysosomal cation channel TPC2 have been suggested to lead to a shift in human hair color from brown to blond. In two further studies a role for TPC2 in melanosomal pH regulation was postulated. Electrophysiological data on how these polymorphisms affect channel gating and activity are, however, missing. We show here that both polymorphisms lead to a gain of channel function by different mechanisms. In M484L sensitivity to its endogenous ligand PI(3,5)P 2 is strongly increased while in G734E channel inactivation by ATP is reduced. These findings are corroborated by molecular dynamics and ion substitution experiments. Furthermore, &gt;100 blond- and brown/black-haired human individuals were genotyped and fibroblasts isolated from selected donors to confirm key in vitro findings.
Seasonal and weather variation of sleep and physical activity in 12–14-year-old children
2017-09-18

<i>Background</i>: Understanding variation in physical activity (PA) and sleep is necessary to develop novel intervention strategies targeting adolescents' health behaviors. We examined the extent to which PA and sleep vary by aspects of the physical environment. <i>Participants</i>: We performed a cross-sectional analysis of 669 adolescents in the Project Viva cohort. <i>Methods</i>: We estimated total PA, sleep duration, sleep efficiency, and sleep midpoint timing from wrist accelerometers. We used multivariable linear regression models and generalized estimated equations to assess associations of PA and sleep with season and daily weather conditions obtained from the National Oceanic and Atmospheric Administration archive. <i>Results</i>: Mean age was 12.9 (<i>SD</i> 0.6) years; 51% were female and 68% were white. Mean sleep duration was 466 (<i>SD</i> 42) min per night and total PA was 1,652 (<i>SD</i> 431) counts per min per day. Sleep midpoint time was 41 (95% CI: 27 to 54) min later in summer, 28 (95% CI: -41 to -14) min earlier in spring, and 29 (95% CI: -43 to -15) min earlier in autumn compared to winter. Higher temperature and longer day length both were associated with small reductions of nightly sleep duration. Adolescents were less physically active during winter and on rainy and short sunlight days. There was an inverse U-shaped relationship between PA and mean temperature. <i>Conclusions</i>: Season was associated with large changes in sleep timing, and smaller changes in other sleep and PA measurements. Given the importance of sleep and circadian alignment, future health behavioral interventions may benefit by targeting "season-specific" interventions.
Early Cretaceous exhumation of the Qiangtang Terrane during collision with the Lhasa Terrane, Central Tibet
2017-09-18

Abstract The timing of the closure of the Bangong Ocean between the Lhasa and South Qiangtang Terranes in central Tibet and the resulting crustal thickening are still under debate. We integrate published apatite fission track and (U–Th)/He thermochronometer data with new zircon (U–Th)/He ages from eight samples and with structural profiles to document that the South Qiangtang Terrane experienced slow exhumation between 200 and 150 Ma, associated with the opening of the Bangong Ocean. Accelerated exhumation (around 0.2–0.3 mm/a) of the South Qiangtang Terrane was initiated at around 150 Ma. This exhumation event is interpreted to reflect collision between the Lhasa and South Qiangtang Terranes after closure of the Bangong Ocean, associated with crustal thickening via thick‐skinned folding and thrusting within the South Qiangtang Terrane. The amalgamation of the Lhasa and South Qiangtang Terranes recorded here may represent the first stage of crustal thickening in the central Tibetan Plateau.
High-Sensitivity Cardiac Troponin I as a Gatekeeper for Coronary Computed Tomography Angiography and Stress Testing in Patients with Acute Chest Pain
2017-09-18

Abstract BACKGROUND Most patients presenting to the emergency department (ED) with suspected acute coronary syndrome (ACS) undergo noninvasive cardiac testing with a low diagnostic yield. We determined whether a combination of high-sensitivity cardiac troponin I (hs-cTnI) and cardiovascular risk factors might improve selection of patients for cardiac testing. METHODS We included patients from the Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography (ROMICAT) I and II trials who presented to the ED with acute chest pain and were referred for cardiac testing. Based on serial hs-cTnI measurements and cardiovascular risk factors, we derived and validated the criterion for no need of cardiac testing. We predicted the effect of this criterion on the effectiveness of patient management. RESULTS A combination of baseline hs-cTnI (&amp;lt;4 ng/L) and cardiovascular risk factors (&amp;lt;2) ruled out ACS with a negative predictive value of 100% in ROMICAT I. We validated this criterion in ROMICAT II, identifying 29% patients as not needing cardiac testing. An additional 5% of patients were identified by adding no change or a decrease between baseline and 2 h hs-cTnI as a criterion. Assuming those patients would be discharged from the ED without cardiac testing, implementation of hs-cTnI would increase ED discharge rate (24.3% to 50.2%, P &amp;lt; 0.001) and decrease the length of hospital stay (21.4 to 8.2 h, P &amp;lt; 0.001), radiation dose (10.2 to 7.7 mSv, P &amp;lt; 0.001), and costs of care (4066 to 3342 US$, P &amp;lt; 0.001). CONCLUSIONS We derived and validated a criterion for combined hs-cTnI and cardiovascular risk factors that identified acute chest pain patients with no need for cardiac testing and could improve effectiveness of patient management. ClinicalTrials.gov Identifiers: NCT00990262 and NCT01084239
J(Si,H) Coupling Constants of Activated Si–H Bonds
2017-09-18

We outline in this combined experimental and theoretical NMR study that sign and magnitude of J(Si,H) coupling constants provide reliable indicators to evaluate the extent of the oxidative addition of Si-H bonds in hydrosilane complexes. In combination with experimental electron density studies and MO analyses a simple structure-property relationship emerges: positive J(Si,H) coupling constants are observed in cases where M → L π-back-donation (M = transition metal; L = hydrosilane ligand) dominates. The corresponding complexes are located close to the terminus of the respective oxidative addition trajectory. In contrast negative J(Si,H) values signal the predominance of significant covalent Si-H interactions and the according complexes reside at an earlier stage of the oxidative addition reaction pathway. Hence, in nonclassical hydrosilane complexes such as Cp<sub>2</sub>Ti(PMe<sub>3</sub>)(HSiMe<sub>3-n</sub>Cl<sub>n</sub>) (with n = 1-3) the sign of J(Si,H) changes from minus to plus with increasing number of chloro substituents n and maps the rising degree of oxidative addition. Accordingly, the sign and magnitude of J(Si,H) coupling constants can be employed to identify and characterize nonclassical hydrosilane species also in solution. These NMR studies might therefore help to reveal the salient control parameters of the Si-H bond activation process in transition-metal hydrosilane complexes which represent key intermediates for numerous metal-catalyzed Si-H bond activation processes. Furthermore, experimental high-resolution and high-pressure X-ray diffraction studies were undertaken to explore the close relationship between the topology of the electron density displayed by the η<sup>2</sup>(Si-H)M units and their respective J(Si,H) couplings.
Human Cerebrospinal fluid promotes long-term neuronal viability and network function in human neocortical organotypic brain slice cultures
2017-09-19

Abstract Pathophysiological investigation of CNS-related diseases, such as epilepsy or neurodegenerative disorders, largely relies on histological studies on human post mortem tissue, tissue obtained by biopsy or resective surgery and on studies using disease models including animal models, heterologous expression systems or cell culture based approaches. However, in general it remains elusive to what extent results obtained in model systems can be directly translated to the human brain, calling for strategies allowing validation or even primary investigation in live human CNS tissue. In the work reported here, we prepared human organotypic slice cultures from access tissue of resective epilepsy surgery. Employing different culture conditions, we systematically compared artificial culturing media versus human cerbrospinal fluid (hCSF) obtained from patients with normal pressure hydrocephalus (NPH). Presented data demonstrates sustained cortical neuronal survival including not only maintenance of typical cellular electrophysiological properties and activity, such as robust action potential generation and synaptic connectivity, but also preservation of tonic and phasic network activity up to several weeks in vitro . As clearly delineated by immunocytochemistry, single cell patch clamp and extracellular recordings, we find that in contrast to artificial culturing media, hCSF significantly enhances neuron viability and maintenance of network activity.
Preventing Surgical Site Infections Using a Natural, Biodegradable, Antibacterial Coating on Surgical Sutures
2017-09-19

Surgical site infections (SSIs) are one of the most common nosocomial infections, which can result in serious complications after surgical interventions. Foreign materials such as implants or surgical sutures are optimal surfaces for the adherence of bacteria and subsequent colonization and biofilm formation. Due to a significant increase in antibiotic-resistant bacterial strains, naturally occurring agents exhibiting antibacterial properties have great potential in prophylactic therapies. The aim of this study was to develop a coating for surgical sutures consisting of the antibacterial substance totarol, a naturally occurring diterpenoid isolated from Podocarpus totara in combination with poly(lactide-co-glycolide acid) (PLGA) as a biodegradable drug delivery system. Hence, non-absorbable monofilament and multifilament sutures were coated with solutions containing different amounts and ratios of totarol and PLGA, resulting in a smooth, crystalline coating. Using an agar diffusion test (ADT), it became evident that the PLGA/totarol-coated sutures inhibited the growth of Staphylococcus aureus over a period of 15 days. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that the coated sutures were not cytotoxic to murine fibroblasts. Overall, the data indicates that our innovative, biodegradable suture coating has the potential to reduce the risk of SSIs and postoperative biofilm-formation on suture material without adverse effects on tissue.
CK2β regulates thrombopoiesis and Ca2+-triggered platelet activation in arterial thrombosis
2017-09-19

Key Points CK2β is critically required for thrombopoiesis by regulating tubulin polymerization, MK fragmentation, and proplatelet formation. CK2β facilitates inositol triphosphate–mediated increase of cytosolic Ca2+ and is essential for platelet activation in arterial thrombosis in vivo.
Restraint of presynaptic protein levels by Wnd/DLK signaling mediates synaptic defects associated with the kinesin-3 motor Unc-104
2017-09-19

The kinesin-3 family member Unc-104/KIF1A is required for axonal transport of many presynaptic components to synapses, and mutation of this gene results in synaptic dysfunction in mice, flies and worms. Our studies at the Drosophila neuromuscular junction indicate that many synaptic defects in unc-104-null mutants are mediated independently of Unc-104’s transport function, via the Wallenda (Wnd)/DLK MAP kinase axonal damage signaling pathway. Wnd signaling becomes activated when Unc-104’s function is disrupted, and leads to impairment of synaptic structure and function by restraining the expression level of active zone (AZ) and synaptic vesicle (SV) components. This action concomitantly suppresses the buildup of synaptic proteins in neuronal cell bodies, hence may play an adaptive role to stresses that impair axonal transport. Wnd signaling also becomes activated when pre-synaptic proteins are over-expressed, suggesting the existence of a feedback circuit to match synaptic protein levels to the transport capacity of the axon.
Prognostic value of perfusion CT in hepatocellular carcinoma treatment with sorafenib: comparison with mRECIST in longitudinal follow-up
2017-09-19

Background Targeted therapies are of increasing clinical importance and classic radiologic therapy response-criteria often fail to detect early therapeutic response or failure. For hepatocellular carcinoma (HCC), this is of major importance as therapeutic options are limited. Purpose To investigate the impact of sorafenib-treatment on intralesional perfusion using perfusion computed tomography (PCT) in HCC and to correlate the observed changes with mRECIST and the course of serum alpha-fetoprotein (AFP) for identification of their prognostic value. Material and Methods PCT was performed before and after two months of sorafenib treatment in 28 consecutive HCC patients and AFP levels were registered. Changes in tumor perfusion parameters blood flow (BF), blood volume (BV), mean transit time (MTT), volume transfer constant (K trans ), arterial liver perfusion (ALP), and hepatic perfusion index (HPI) were registered in one target lesion. mRECIST measurements were performed at baseline and after two and four months during sorafenib treatment. Results According to mRECIST, after two months of treatment, all patients showed stable disease (SD), whereas after four months, 13 patients (46%) showed SD and 15 patients (54%) showed progressive disease (PD). A significant decrease was found in perfusion parameters BF, BV, K trans , ALP, and HPI in patients with SD as well as a significant increase in MTT ( P &lt; 0.05) after two months compared to baseline, while patients with PD showed a significant increase in HPI, BF, and BV. There were no correlations between AFP and mRECIST or perfusion parameters. Conclusion Decreased intralesional BF and HPI after two months of sorafenib treatment predicts disease stabilization after four months, whereas AFP dynamics were of limited value.
FDG-PET/MRI in alveolar echinococcosis
2017-09-19

Positron emission tomography–computed tomography (PET/CT) is recommended for the staging and follow-up of alveolar echinococcosis and to guide patient management in affluent healthcare systems (Reuter et al., 2008Reuter S. Grüner B. Buck A.K. Blumstein N. Kern P. Reske S.N. Long-term follow-up of metabolic activity in human alveolar echinococcosis using FDG-PET.Nukl Nucl Med. 2008; 47: 147-152Google Scholar, Brunetti et al., 2010Brunetti Enrico Kern Peter Vuitton Dominique Angèle Writing Panel for the WHO-IWGE Expert consensus for the diagnosis and treatment of cystic and alveolar echinococcosis in humans.Acta Trop. 2010; 114: 1-16https://doi.org/10.1016/j.actatropica.2009.11.001Crossref PubMed Scopus (1222) Google Scholar). However, repeated PET/CT assessments are associated with considerable radiation exposure (Brenner and Hall, 2007Brenner David J. Hall Eric J. Computed tomography — an increasing source of radiation exposure.N Engl J Med. 2007; 357: 2277-2284https://doi.org/10.1056/NEJMra072149Crossref PubMed Scopus (6611) Google Scholar). It has been reported that magnetic resonance imaging (MRI) improves the staging of alveolar echinococcosis compared to CT imaging (Azizi et al., 2015Azizi Amel Blagosklonov Oleg Lounis Ahmed Berthet Louis Vuitton Dominique-Angèle Bresson-Hadni Solange et al.Alveolar echinococcosis: correlation between hepatic MRI findings and FDG-PET/CT metabolic activity.Abdom Imaging. 2015; 40: 56-63https://doi.org/10.1007/s00261-014-0183-0Crossref PubMed Scopus (49) Google Scholar, Kodama et al., 2003Kodama Yoshihisa Fujita Nobuyuki Shimizu Tadashi Endo Hideho Nambu Toshikazu Sato Naoki et al.Alveolar echinococcosis: MR findings in the liver.Radiology. 2003; 228: 172-177https://doi.org/10.1148/radiol.2281020323Crossref PubMed Scopus (106) Google Scholar). With the recent availability of fluorodeoxyglucose (FDG) PET/MRI in clinical practice, this dual imaging modality may improve the management of patients with alveolar echinococcosis and address the above-mentioned limitations of PET/CT imaging at the same time. After obtaining informed consent, PET/CT and PET/MRI were performed in a patient with alveolar echinococcosis. Figure 1 show axial (upper row) and frontal (lower row) FDG PET/CT (left) and FDG PET/MRI (right) images, which demonstrate strong peri-lesional uptake in a hepatic lesion caused by Echinococcus multilocularis – the fox tape worm. This appears to be the first time that PET/MRI has been used for the management of a parasitic disease. Further systematic evaluation will provide information on the prospective use of FDG PET/MRI in the routine management of alveolar echinococcosis. Conflict of interest: None.
Task-induced frequency modulation features for brain-computer interfacing
2017-09-19

Task-induced frequency modulation is robust and straight forward to compute, and increases performance when added to standard amplitude modulation features across paradigms. This allows more information to be extracted from the EEG signal cheaply and can be used throughout the field of BCIs.
The NOVA project: maximizing beam time efficiency through synergistic analyses of SRμCT data
2017-09-19

Beamtime and resulting SRμCT data are a valuable resource for researchers of a broad scientific community in life sciences. Most research groups, however, are only interested in a specific organ and use only a fraction of their data. The rest of the data usually remains untapped. By using a new collaborative approach, the NOVA project (Network for Online Visualization and synergistic Analysis of tomographic data) aims to demonstrate, that more efficient use of the valuable beam time is possible by coordinated research on different organ systems. The biological partners in the project cover different scientific aspects and thus serve as model community for the collaborative approach. As proof of principle, different aspects of insect head morphology will be investigated (e.g., biomechanics of the mouthparts, and neurobiology with the topology of sensory areas). This effort is accomplished by development of advanced analysis tools for the ever-increasing quantity of tomographic datasets. In the preceding project ASTOR, we already successfully demonstrated considerable progress in semi-automatic segmentation and classification of internal structures. Further improvement of these methods is essential for an efficient use of beam time and will be refined in the current NOVAproject. Significant enhancements are also planned at PETRA III beamline p05 to provide all possible contrast modalities in x-ray imaging optimized to biological samples, on the reconstruction algorithms, and the tools for subsequent analyses and management of the data. All improvements made on key technologies within this project will in the long-term be equally beneficial for all users of tomography instrumentations.
Enhanced photoluminescence from a molecular tunneling junction (Conference Presentation)
2017-09-19

We demonstrate enhanced photoluminescence (PL) from an optically pumped bias driven molecular tunneling junction (Au-substrate/self assembled molecular monolayer/Au-tip) with molecules chemically bound to the Au substrate. The gap between a sharp gold tip and a flat gold substrate covered with a self-assembled monolayer (SAM) of 5-chloro-2 mercaptobenzothiazole (Cl-MBT) molecules can be used as an extremely small optical gain medium. When a bias-voltage is applied between tip and sample such that electrons tunnel from the Cl-MBT's highest occupied molecular orbital (HOMO) to the tip, holes are left behind in the molecules. These can be repopulated by hot electrons that are created by the laser-driven plasmon oscillation on the metal surfaces enclosing the molecule. Emission of photons occurs from the recombination of plasmon excited hot electrons with holes in the HOMO of surface bound molecules below the tip. Varying the laser pump power or alternatively the applied bias voltage shows in both cases a distinct threshold above which enhancement of the optical signal occurs. Solving the rate equations for this system shows that optical feed-back by the gap mode's near field can efficiently stimulate the emission process. The system reflects many essential features of a superluminescent organic light emitting diode.
Poster abstracts of the 25th German Conference on Bioinformatics
2017-09-19

The annual German Conference on Bioinformatics (GCB) has brought together renowned international scientists in bioinformatics, computational biology, biostatistics, biology and medicine since 1993. The 25 th GCB was held in Tübingen from 18 th to 21 st of September 2017, making its second appearance at the vivid university city with its internationally renowned medical faculty as well as the faculty of science, and several top research institutes like the Max Planck Institute for Developmental Biology. This environment has created and attracted several internationally recognized research groups in bioinformatics, computational biology, and biomedical data science out of which many have contributed in organizing the GCB 2017. Following are the abstracts of posters accepted for presentation at the conference, showing the wide range of different areas from bioinformatics infrastructure to theoretical approaches in single cell analyses.
Distortion correction of diffusion-weighted magnetic resonance imaging of the head and neck in radiotherapy position
2017-09-20

Simultaneous positron emission tomography/magnetic resonance imaging (PET/MRI) has high potential to improve radiotherapy (RT) planning. Key advantages are increased delineation accuracy and the in...
Archaeological reconnaissance of the Late Pleistocene Red Sea coast in the Danakil
2017-09-20

The paucity of archaeological evidence from the northern Afar Rift and Red Sea littoral remains a major hindrance to testing the hypothesised Out-of-Africa dispersal of early humans via the ‘Southern Route’—across the Bab al-Mandeb into Arabia and beyond. Encouraged by renewed geological studies (e.g. Atnafu et al . 2015), and recent archaeological discoveries (e.g. Walter et al . 2000; Beyin 2013), we initiated a pioneering exploration along the ancient Red Sea coast in the Danakil Depression (Figure 1a–c). The most conspicuous geomorphological features here constitute terraces of reef carbonates and associated marine deposits, formed when the depression was covered by the open Red Sea during the Middle to Late Pleistocene. Initial results of our exploration promise contexts in which the distribution and cultural/behavioural adaptation of early humans during the Out-of-Africa event can be closely investigated.