bluuebunny/crossref_metadata_2025_split huggingface dataset:
The binding of DCC-P3 motif and FAK-FAT domain mediates the initial step of netrin-1/DCC signaling for axon attraction
Authors: Xu Shutong , Liu Yiqiong , Li Xiaolong , Liu Ying , Meijers Rob , Zhang Yan , Wang Jia-huai 
Published: February 2018

AbstractNetrin-1 plays a key role in axon guidance through binding to its receptor, Deleted in Colorectal Cancer (DCC). The initial step of signaling inside the cell after netrin-1/DCC ligation is the binding of DCC cytoplasmic P3 motif to focal adhesion targeting (FAT) domain of focal adhesion kinase (FAK). Here we report the crystal structure of P3/FAT complex. The helical P3 peptide interacts with a helix-swapped FAT dimer in a 2:2 ratio. Dimeric FAT binding is P3-specific and stabilized by a calcium ion. Biochemical studies showed that DCC-P3 motif and calcium ion could facilitate FAT dimerization in solution. Axon guidance assays confirm that the DCC/FAK complex is essential for netrin-1-induced chemoattraction. We propose that netrin-1/DCC engagement creates a small cluster of P3/FAT for FAK recruitment close to the cell membrane, which exerts a concerted effect with PIP2 for FAK signaling. We also compare P3/FAT binding with paxillin/FAT binding and discuss their distinct recognition specificity on a common FAT domain for axon attraction versus integrin signaling, respectively.
Increasing temperature of cooling granular gases
Authors: Brilliantov Nikolai V. , Formella Arno , Pöschel Thorsten 
Published: February 2018

AbstractThe kinetic energy of a force-free granular gas decays monotonously due to inelastic collisions of the particles. For a homogeneous granular gas of identical particles, the corresponding decay of granular temperature is quantified by Haff’s law. Here, we report that for a granular gas of aggregating particles, the granular temperature does not necessarily decay but may even increase. Surprisingly, the increase of temperature is accompanied by the continuous loss of total gas energy. This stunning effect arises from a subtle interplay between decaying kinetic energy and gradual reduction of the number of degrees of freedom associated with the particles’ dynamics. We derive a set of kinetic equations of Smoluchowski type for the concentrations of aggregates of different sizes and their energies. We find scaling solutions to these equations and a condition for the aggregation mechanism predicting growth of temperature. Numerical direct simulation Monte Carlo results confirm the theoretical predictions.
A recurrent kinase domain mutation in PRKCA defines chordoid glioma of the third ventricle
Authors: Goode Benjamin , Mondal Gourish , Hyun Michael , Ruiz Diego Garrido , Lin Yu-Hsiu , Van Ziffle Jessica , Joseph Nancy M. , Onodera Courtney , Talevich Eric , Grenert James P. , Hewedi Iman H. , Snuderl Matija , Brat Daniel J. , Kleinschmidt-DeMasters Bette K. , Rodriguez Fausto J. , Louis David N. , Yong William H. , Lopes M. Beatriz , Rosenblum Marc K. , Butowski Nicholas , Tihan Tarik , Bollen Andrew W. , Phillips Joanna J. , Wiita Arun P. , Yeh Iwei , Jacobson Matthew P. , Bastian Boris C. , Perry Arie , Solomon David A. 
Published: February 2018

AbstractChordoid glioma is a rare brain tumor thought to arise from specialized glial cells of the lamina terminalis along the anterior wall of the third ventricle. Despite being histologically low-grade, chordoid gliomas are often associated with poor outcome, as their stereotypic location in the third ventricle makes resection challenging and efficacious adjuvant therapies have not been developed. Here we performed genomic profiling on 13 chordoid gliomas and identified a recurrent D463H missense mutation in PRKCA in all tumors, which localizes in the kinase domain of the encoded protein kinase C alpha (PKCα). Expression of mutant PRKCA in immortalized human astrocytes led to increased phospho-ERK and anchorage-independent growth that could be blocked by MEK inhibition. These studies define PRKCA as a recurrently mutated oncogene in human cancer and identify a potential therapeutic vulnerability in this uncommon brain tumor.
Zebrafish and medaka offer insights into the neurobehavioral correlates of vertebrate magnetoreception
Authors: Myklatun Ahne , Lauri Antonella , Eder Stephan H. K. , Cappetta Michele , Shcherbakov Denis , Wurst Wolfgang , Winklhofer Michael , Westmeyer Gil G. 
Published: February 2018

AbstractAn impediment to a mechanistic understanding of how some species sense the geomagnetic field (“magnetoreception”) is the lack of vertebrate genetic models that exhibit well-characterized magnetoreceptive behavior and are amenable to whole-brain analysis. We investigated the genetic model organisms zebrafish and medaka, whose young stages are transparent and optically accessible. In an unfamiliar environment, adult fish orient according to the directional change of a magnetic field even in darkness. To enable experiments also in juveniles, we applied slowly oscillating magnetic fields, aimed at generating conflicting sensory inputs during exploratory behavior. Medaka (but not zebrafish) increase their locomotor activity in this assay. Complementary brain activity mapping reveals neuronal activation in the lateral hindbrain during magnetic stimulation. These comparative data support magnetoreception in teleosts, provide evidence for a light-independent mechanism, and demonstrate the usefulness of zebrafish and medaka as genetic vertebrate models for studying the biophysical and neuronal mechanisms underlying magnetoreception.
Membrane cholesterol mediates the cellular effects of monolayer graphene substrates
Authors: Kitko Kristina E. , Hong Tu , Lazarenko Roman M. , Ying Da , Xu Ya-Qiong , Zhang Qi 
Published: February 2018

AbstractGraphene possesses extraordinary properties that promise great potential in biomedicine. However, fully leveraging these properties requires close contact with the cell surface, raising the concern of unexpected biological consequences. Computational models have demonstrated that graphene preferentially interacts with cholesterol, a multifunctional lipid unique to eukaryotic membranes. Here we demonstrate an interaction between graphene and cholesterol. We find that graphene increases cell membrane cholesterol and potentiates neurotransmission, which is mediated by increases in the number, release probability, and recycling rate of synaptic vesicles. In fibroblasts grown on graphene, we also find an increase in cholesterol, which promotes the activation of P2Y receptors, a family of receptor regulated by cholesterol. In both cases, direct manipulation of cholesterol levels elucidates that a graphene-induced cholesterol increase underlies the observed potentiation of each cell signaling pathway. These findings identify cholesterol as a mediator of graphene’s cellular effects, providing insight into the biological impact of graphene.
Membrane sculpting by curved DNA origami scaffolds
Authors: Franquelim Henri G. , Khmelinskaia Alena , Sobczak Jean-Philippe , Dietz Hendrik , Schwille Petra 
Published: February 2018

AbstractMembrane sculpting and transformation is essential for many cellular functions, thus being largely regulated by self-assembling and self-organizing protein coats. Their functionality is often encoded by particular spatial structures. Prominent examples are BAR domain proteins, the ‘banana-like’ shapes of which are thought to aid scaffolding and membrane tubulation. To elucidate whether 3D structure can be uncoupled from other functional features of complex scaffolding proteins, we hereby develop curved DNA origami in various shapes and stacking features, following the presumable design features of BAR proteins, and characterize their ability for membrane binding and transformation. We show that dependent on curvature, membrane affinity and surface density, DNA origami coats can indeed reproduce the activity of membrane-sculpting proteins such as BAR, suggesting exciting perspectives for using them in bottom-up approaches towards minimal biomimetic cellular machineries.
Adoptive cancer immunotherapy using DNA-demethylated T helper cells as antigen-presenting cells
Authors: Kirkin Alexei F. , Dzhandzhugazyan Karine N. , Guldberg Per , Fang Johnny Jon , Andersen Rikke S. , Dahl Christina , Mortensen Jann , Lundby Tim , Wagner Aase , Law Ian , Broholm Helle , Madsen Line , Lundell-Ek Christer , Gjerstorff Morten F. , Ditzel Henrik J. , Jensen Martin R. , Fischer Walter 
Published: February 2018

AbstractIn cancer cells, cancer/testis (CT) antigens become epigenetically derepressed through DNA demethylation and constitute attractive targets for cancer immunotherapy. Here we report that activated CD4+ T helper cells treated with a DNA-demethylating agent express a broad repertoire of endogenous CT antigens and can be used as antigen-presenting cells to generate autologous cytotoxic T lymphocytes (CTLs) and natural killer cells. In vitro, activated CTLs induce HLA-restricted lysis of tumor cells of different histological types, as well as cells expressing single CT antigens. In a phase 1 trial of 25 patients with recurrent glioblastoma multiforme, cytotoxic lymphocytes homed to the tumor, with tumor regression ongoing in three patients for 14, 22, and 27 months, respectively. No treatment-related adverse effects were observed. This proof-of-principle study shows that tumor-reactive effector cells can be generated ex vivo by exposure to antigens induced by DNA demethylation, providing a novel, minimally invasive therapeutic strategy for treating cancer.
Molecular demultiplexer as a terminator automaton
Authors: Turan Ilke S. , Gunaydin Gurcan , Ayan Seylan , Akkaya Engin U. 
Published: February 2018

AbstractMolecular logic gates are expected to play an important role on the way to information processing therapeutic agents, especially considering the wide variety of physical and chemical responses that they can elicit in response to the inputs applied. Here, we show that a 1:2 demultiplexer based on a Zn2+-terpyridine-Bodipy conjugate with a quenched fluorescent emission, is efficient in photosensitized singlet oxygen generation as inferred from trap compound experiments and cell culture data. However, once the singlet oxygen generated by photosensitization triggers apoptotic response, the Zn2+ complex then interacts with the exposed phosphatidylserine lipids in the external leaflet of the membrane bilayer, autonomously switching off singlet oxygen generation, and simultaneously switching on a bright emission response. This is the confirmatory signal of the cancer cell death by the action of molecular automaton and the confinement of unintended damage by excessive singlet oxygen production.
Anaesthesia in austere environments: literature review and considerations for future space exploration missions
Authors: Komorowski Matthieu , Fleming Sarah , Mawkin Mala , Hinkelbein Jochen 
Published: February 2018

AbstractFuture space exploration missions will take humans far beyond low Earth orbit and require complete crew autonomy. The ability to provide anaesthesia will be important given the expected risk of severe medical events requiring surgery. Knowledge and experience of such procedures during space missions is currently extremely limited. Austere and isolated environments (such as polar bases or submarines) have been used extensively as test beds for spaceflight to probe hazards, train crews, develop clinical protocols and countermeasures for prospective space missions. We have conducted a literature review on anaesthesia in austere environments relevant to distant space missions. In each setting, we assessed how the problems related to the provision of anaesthesia (e.g., medical kit and skills) are dealt with or prepared for. We analysed how these factors could be applied to the unique environment of a space exploration mission. The delivery of anaesthesia will be complicated by many factors including space-induced physiological changes and limitations in skills and equipment. The basic principles of a safe anaesthesia in an austere environment (appropriate training, presence of minimal safety and monitoring equipment, etc.) can be extended to the context of a space exploration mission. Skills redundancy is an important safety factor, and basic competency in anaesthesia should be part of the skillset of several crewmembers. The literature suggests that safe and effective anaesthesia could be achieved by a physician during future space exploration missions. In a life-or-limb situation, non-physicians may be able to conduct anaesthetic procedures, including simplified general anaesthesia.
Longitudinal change in the serology of antibodies to Chlamydia trachomatis pgp3 in children residing in a trachoma area
Authors: West Sheila K. , Munoz Beatriz , Kaur Hemjot , Dize Laura , Mkocha Harran , Gaydos Charlotte A. , Quinn Thomas C. 
Published: February 2018

AbstractA serologic test for antibodies to chlamydial antigen pgp3 may be a useful tool for trachoma surveillance. However, little is known about the stability of antibody status over time, or factors associated with seroreversion/conversion. A cohort of 2,111 children ages 1–9 years in Tanzania were followed for one year in the absence of mass azithromycin. At baseline and follow-up, they were evaluated for trachoma, chlamydial infection, and antibodies to chlamydial antigen pgp3. At baseline, 31% of children were seropositive for pgp3 antibodies and 6.4% seroreverted to negative over one year. Of those seronegative, 9.8% seroconverted over the year. The seroreverters had lower baseline mean fluorescence intensity (MFI-BG) values compared to the seropositives who remained positive (Odds Ratio = 0.04 for every unit increase in log10MFI-BG, 95% CI = 0.02–0.09), and were more likely to live in communities with trachoma <5% (p < 0.008). While seroconversion was expected, seroreversion was unexpected. The low seroprevalence rate reported from low endemic areas may be due to seroreversion as well as lack of exposure.
Snap-through transition of buckled graphene membranes for memcapacitor applications
Authors: Yamaletdinov Ruslan D. , Ivakhnenko Oleg V. , Sedelnikova Olga V. , Shevchenko Sergey N. , Pershin Yuriy V. 
Published: February 2018

AbstractUsing computational and theoretical approaches, we investigate the snap-through transition of buckled graphene membranes. Our main interest is related to the possibility of using the buckled membrane as a plate of capacitor with memory (memcapacitor). For this purpose, we performed molecular-dynamics (MD) simulations and elasticity theory calculations of the up-to-down and down-to-up snap-through transitions for membranes of several sizes. We have obtained expressions for the threshold switching forces for both up-to-down and down-to-up transitions. Moreover, the up-to-down threshold switching force was calculated using the density functional theory (DFT). Our DFT results are in general agreement with MD and analytical theory findings. Our systematic approach can be used for the description of other structures, including nanomechanical and biological ones, experiencing the snap-through transition.
Changes in Ugandan Climate Rainfall at the Village and Forest Level
Authors: Ssentongo Paddy , Muwanguzi Abraham J. B. , Eden Uri , Sauer Timothy , Bwanga George , Kateregga Geoffrey , Aribo Lawrence , Ojara Moses , Mugerwa Wilberforce Kisamba , Schiff Steven J. 
Published: February 2018

AbstractIn 2013, the US National Oceanographic and Atmospheric Administration (NOAA) refined the historical rainfall estimates over the African Continent and produced the African Rainfall Climate version 2.0 (ARC2) estimator. ARC2 offers a nearly complete record of daily rainfall estimates since 1983 at 0.1° × 0.1° resolution. Despite short-term anomalies, we identify an overall decrease in average rainfall of about 12% during the past 34 years in Uganda. Spatiotemporally, these decreases are greatest in agricultural regions of central and western Uganda, but similar rainfall decreases are also reflected in the gorilla habitat within the Bwindi Forest in Southwest Uganda. The findings carry significant implications for agriculture production, food security, wildlife habitat, and economic impact at the community and societal level.
Identification and characterization of the BRI2 interactome in the brain
Authors: Martins Filipa , Marafona Ana M. , Pereira Cátia D. , Müller Thorsten , Loosse Christina , Kolbe Katharina , da Cruz e Silva Odete A. B. , Rebelo Sandra 
Published: February 2018

AbstractBRI family proteins are ubiquitous type II transmembrane proteins but BRI2 is highly expressed in some neuronal tissues. Possible BRI2 functions include neuronal maturation and differentiation. Protein complexes appear to be important in mediating its functions. Previously described BRI2 interactors include the Alzheimer’s amyloid precursor protein and protein phosphatase 1, but clearly the identification of novel interactors provides an important tool to understand the role and function of BRI2. To this end three rat brain regions (cerebellum, hippocampus, and cerebral cortex) were processed by BRI2 immunoprecipitation; co-precipitating proteins were identified by Nano-HPLC-MS/MS. The pool of the brain regions resulted in 511 BRI2 interacting proteins (BRI2 brain interactome) of which 120 were brain specific and 49 involved in neuronal differentiation. Brain region-specific analyses were also carried out for cerebellum, hippocampus, and cerebral cortex. Several novel BRI2 interactors were identified among them DLG4/PSD-95, which is singularly important as it places BRI2 in the postsynaptic compartment. This interaction was validated as well as the interaction with GAP-43 and synaptophysin. In essence, the resulting BRI2 brain interactome, associates this protein with neurite outgrowth and neuronal differentiation, as well as synaptic signalling and plasticity. It follows that further studies should address BRI2 particularly given its relevance to neuropathological conditions.
Allopurinol partially prevents disuse muscle atrophy in mice and humans
Authors: Ferrando Beatriz , Gomez-Cabrera Mari Carmen , Salvador-Pascual Andrea , Puchades Carlos , Derbré Frederic , Gratas-Delamarche Arlette , Laparre Ludovic , Olaso-Gonzalez Gloria , Cerda Miguel , Viosca Enrique , Alabajos Ana , Sebastiá Vicente , Alberich-Bayarri Angel , García-Castro Fabio , Viña Jose 
Published: February 2018

AbstractDisuse muscle wasting will likely affect everyone in his or her lifetime in response to pathologies such as joint immobilization, inactivity or bed rest. There are no good therapies to treat it. We previously found that allopurinol, a drug widely used to treat gout, protects muscle damage after exhaustive exercise and results in functional gains in old individuals. Thus, we decided to test its effect in the prevention of soleus muscle atrophy after two weeks of hindlimb unloading in mice, and lower leg immobilization following ankle sprain in humans (EudraCT: 2011-003541-17). Our results show that allopurinol partially protects against muscle atrophy in both mice and humans. The protective effect of allopurinol is similar to that of resistance exercise which is the best-known way to prevent muscle mass loss in disuse human models. We report that allopurinol protects against the loss of muscle mass by inhibiting the expression of ubiquitin ligases. Our results suggest that the ubiquitin-proteasome pathway is an appropriate therapeutic target to inhibit muscle wasting and emphasizes the role of allopurinol as a non-hormonal intervention to treat disuse muscle atrophy.
Role of the Metal-Oxide Work Function on Photocurrent Generation in Hybrid Solar Cells
Authors: Thu Chawloon , Ehrenreich Philipp , Wong Ka Kan , Zimmermann Eugen , Dorman James , Wang Wei , Fakharuddin Azhar , Putnik Martin , Drivas Charalampos , Koutsoubelitis Aimilios , Vasilopoulou Maria , Palilis Leonidas C. , Kennou Stella , Kalb Julian , Pfadler Thomas , Schmidt-Mende Lukas 
Published: February 2018

AbstractZnO is a widely used metal-oxide semiconductor for photovoltaic application. In solar cell heterostructures they not only serve as a charge selective contact, but also act as electron acceptor. Although ZnO offers a suitable interface for exciton dissociation, charge separation efficiencies have stayed rather poor and conceptual differences to organic acceptors are rarely investigated. In this work, we employ Sn doping to ZnO nanowires in order to understand the role of defect and surface states in the charge separation process. Upon doping we are able to modify the metal-oxide work function and we show its direct correlation with the charge separation efficiency. For this purpose, we use the polymer poly(3-hexylthiophene) as donor and the squaraine dye SQ2 as interlayer. Interestingly, neither mobilities nor defects are prime performance limiting factor, but rather the density of available states around the conduction band is of crucial importance for hybrid interfaces. This work highlights crucial aspects to improve the charge generation process of metal-oxide based solar cells and reveals new strategies to improve the power conversion efficiency of hybrid solar cells.
Distribution of metals and metalloids in dried seaweeds and health risk to population in southeastern China
Authors: Chen Qing , Pan Xiao-Dong , Huang Bai-Fen , Han Jian-Long 
Published: February 2018

AbstractConcern about metals and metalloids, especially heavy metals in seaweeds has risen due to potential health risk. This study investigated the distribution of 10 metals and metalloids in 295 dried seaweeds (brown and red) and estimated the possible health risk via hazard index (HI). Elements in seaweeds can be sequenced in descending order by mean values: Al > Mn > As > Cu > Cr > Ni > Cd > Se > Pb > Hg. The levels of Cd, Cu, Mn and Ni in red seaweeds were significantly higher than those in brown seaweeds (P < 0.01). Correlation analysis showed contents of Ni-Cr (r = 0.59, P < 0.01) in seaweeds had moderate positive correlations. Seaweeds from different geographical origins had diverse element distribution. Risk assessment showed that HI at mean level was less than the threshold of 1. It indicates that for the general people there is low health risk to these elements by the intake of seaweeds. Furthermore, in terms of the confirmative toxicity of some metals, such as Cd, Pb and Hg, surveillance of metals in seaweeds should be performed continuously.
Exploring the Link between Serum Phosphate Levels and Low Muscle Strength, Dynapenia, and Sarcopenia
Authors: Chen Yuan-Yuei , Kao Tung-Wei , Chou Cheng-Wai , Wu Chen-Jung , Yang Hui-Fang , Lai Ching-Huang , Wu Li-Wei , Chen Wei-Liang 
Published: February 2018

AbstractEmerging evidences addressed an association between phosphate and muscle function. Because little attention was focused on this issue, the objective of our study was to explore the relationship of phosphate with muscle strength, dynapenia, and sarcopenia. From the National Health and Nutrition Examination Survey, a total of 7421 participants aged 20 years or older were included in our study with comprehensive examinations included anthropometric parameters, strength of the quadriceps muscle, and appendicular lean masses. Within the normal range of serum phosphate, we used quartile-based analyses to determine the potential relationships of serum phosphate with dynapenia, and sarcopenia through multivariate regression models. After adjusting for the pertinent variables, an inverse association between the serum phosphate quartiles and muscle strength was observed and the linear association was stronger than other anthropometric parameters. Notably, the significant association between phosphate and muscle strength was existed in >65 years old age group, not in 20–65 years old. The higher quartiles of phosphate had higher likelihood for predicting the presence of dynapenia rather than sarcopenia in entire population. Our study highlighted that higher quartiles of phosphate had significant association with lower muscle strength and higher risks for predicting the presence of dynapenia.