bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses
Authors: Kapeli Katannya , Pratt Gabriel A. , Vu Anthony Q. , Hutt Kasey R. , Martinez Fernando J. , Sundararaman Balaji , Batra Ranjan , Freese Peter , Lambert Nicole J. , Huelga Stephanie C. , Chun Seung J. , Liang Tiffany Y. , Chang Jeremy , Donohue John P. , Shiue Lily , Zhang Jiayu , Zhu Haining , Cambi Franca , Kasarskis Edward , Hoon Shawn , Ares Manuel , Burge Christopher B. , Ravits John , Rigo Frank , Yeo Gene W. 
Published: July 2016

AbstractThe RNA-binding protein (RBP) TAF15 is implicated in amyotrophic lateral sclerosis (ALS). To compare TAF15 function to that of two ALS-associated RBPs, FUS and TDP-43, we integrate CLIP-seq and RNA Bind-N-Seq technologies, and show that TAF15 binds to ∼4,900 RNAs enriched for GGUA motifs in adult mouse brains. TAF15 and FUS exhibit similar binding patterns in introns, are enriched in 3′ untranslated regions and alter genes distinct from TDP-43. However, unlike FUS and TDP-43, TAF15 has a minimal role in alternative splicing. In human neural progenitors, TAF15 and FUS affect turnover of their RNA targets. In human stem cell-derived motor neurons, the RNA profile associated with concomitant loss of both TAF15 and FUS resembles that observed in the presence of the ALS-associated mutation FUS R521G, but contrasts with late-stage sporadic ALS patients. Taken together, our findings reveal convergent and divergent roles for FUS, TAF15 and TDP-43 in RNA metabolism.
A systematic High-Content Screening microscopy approach reveals key roles for Rab33b, OATL1 and Myo6 in nanoparticle trafficking in HeLa cells
Authors: Panarella Angela , Bexiga Mariana G. , Galea George , O’ Neill Elaine D. , Salvati Anna , Dawson Kenneth A. , Simpson Jeremy C. 
Published: July 2016

AbstractSynthetic nanoparticles are promising tools for imaging and drug delivery; however the molecular details of cellular internalization and trafficking await full characterization. Current knowledge suggests that following endocytosis most nanoparticles pass from endosomes to lysosomes. In order to design effective drug delivery strategies that can use the endocytic pathway, or by-pass lysosomal accumulation, a comprehensive understanding of nanoparticle uptake and trafficking mechanisms is therefore fundamental. Here we describe and apply an RNA interference-based high-content screening microscopy strategy to assess the intracellular trafficking of fluorescently-labeled polystyrene nanoparticles in HeLa cells. We screened a total of 408 genes involved in cytoskeleton and membrane function, revealing roles for myosin VI, Rab33b and OATL1 in this process. This work provides the first systematic large-scale quantitative assessment of the proteins responsible for nanoparticle trafficking in cells, paving the way for subsequent genome-wide studies.
A novel role for pigment genes in the stress response in rainbow trout (Oncorhynchus mykiss)
Authors: Khan Uniza Wahid , Øverli Øyvind , Hinkle Patricia M. , Pasha Farhan Ahmad , Johansen Ida Beitnes , Berget Ingunn , Silva Patricia I. M. , Kittilsen Silje , Höglund Erik , Omholt Stig W. , Våge Dag Inge 
Published: July 2016

AbstractIn many vertebrate species visible melanin-based pigmentation patterns correlate with high stress- and disease-resistance, but proximate mechanisms for this trait association remain enigmatic. Here we show that a missense mutation in a classical pigmentation gene, melanocyte stimulating hormone receptor (MC1R), is strongly associated with distinct differences in steroidogenic melanocortin 2 receptor (MC2R) mRNA expression between high- (HR) and low-responsive (LR) rainbow trout (Oncorhynchus mykiss). We also show experimentally that cortisol implants increase the expression of agouti signaling protein (ASIP) mRNA in skin, likely explaining the association between HR-traits and reduced skin melanin patterning. Molecular dynamics simulations predict that melanocortin 2 receptor accessory protein (MRAP), needed for MC2R function, binds differently to the two MC1R variants. Considering that mRNA for MC2R and the MC1R variants are present in head kidney cells, we hypothesized that MC2R activity is modulated in part by different binding affinities of the MC1R variants for MRAP. Experiments in mammalian cells confirmed that trout MRAP interacts with the two trout MC1R variants and MC2R, but failed to detect regulation of MC2R signaling, possibly due to high constitutive MC1R activity.
A Two-Year Treatment of Amnestic Mild Cognitive Impairment using a Compound Chinese Medicine: A Placebo Controlled Randomized Trial
Authors: Zhang Junying , Liu Zhen , Zhang Huamin , Yang Caishui , Li He , Li Xin , Chen Kewei , Zhang Zhanjun 
Published: July 2016

AbstractWe aimed to investigate the long-term therapeutic effects of a compound Chinese medicine, the Bushen capsule, on cognition and brain connectivity in patients with amnestic mild cognitive impairment (aMCI). Thus, sixty aMCI participants were recruited to this 24-month study and were randomly divided into treatment (30 with a Bushen capsule) and placebo (30 with a placebo capsule) groups. Neuropsychological tests with MMSE and episodic memory as the primary outcomes and resting-state functional magnetic resonance imaging (fMRI) were analyzed before and after the treatment over 24 month period. In contrast to the placebo group, the drug group presented improved or stable general cognitive function, memory, language and executive function especially the primary outcomes MMSE and episodic memory with Bushen capsule treatment. FMRI results showed increased connectivity in the right precuneus and the global connectivity indexed with goodness of fit (GOF) of the default mode network (DMN) in the drug group and decreased GOF in the placebo group. More importantly, we found the GOF change was positively correlated with changes in MMSE and memory scores after 24 months in the drug group. Over 24 months, treatment with the compound Chinese medicine Bushen capsule can improve multiple domains of cognition and increase the functional local (right precuneus) and global connectivity within the DMN, which are associated with better performance.
In vivo label-free measurement of lymph flow velocity and volumetric flow rates using Doppler optical coherence tomography
Authors: Blatter Cedric , Meijer Eelco F. J. , Nam Ahhyun S. , Jones Dennis , Bouma Brett E. , Padera Timothy P. , Vakoc Benjamin J. 
Published: July 2016

AbstractDirectin vivoimaging of lymph flow is key to understanding lymphatic system function in normal and disease states. Optical microscopy techniques provide the resolution required for these measurements, but existing optical techniques for measuring lymph flow require complex protocols and provide limited temporal resolution. Here, we describe a Doppler optical coherence tomography platform that allows direct, label-free quantification of lymph velocity and volumetric flow rates. We overcome the challenge of very low scattering by employing a Doppler algorithm that operates on low signal-to-noise measurements. We show that this technique can measure lymph velocity at sufficiently high temporal resolution to resolve the dynamic pulsatile flow in collecting lymphatic vessels.
Comparative genomic analysis of novel Acinetobacter symbionts: A combined systems biology and genomics approach
Authors: Gupta Vipin , Haider Shazia , Sood Utkarsh , Gilbert Jack A. , Ramjee Meenakshi , Forbes Ken , Singh Yogendra , Lopes Bruno S. , Lal Rup 
Published: July 2016

AbstractThe increasing trend of antibiotic resistance in Acinetobacter drastically limits the range of therapeutic agents required to treat multidrug resistant (MDR) infections. This study focused on analysis of novel Acinetobacter strains using a genomics and systems biology approach. Here we used a network theory method for pathogenic and non-pathogenic Acinetobacter spp. to identify the key regulatory proteins (hubs) in each strain. We identified nine key regulatory proteins, guaA, guaB, rpsB, rpsI, rpsL, rpsE, rpsC, rplM and trmD, which have functional roles as hubs in a hierarchical scale-free fractal protein-protein interaction network. Two key hubs (guaA and guaB) were important for insect-associated strains, and comparative analysis identified guaA as more important than guaB due to its role in effective module regulation. rpsI played a significant role in all the novel strains, while rplM was unique to sheep-associated strains. rpsM, rpsB and rpsI were involved in the regulation of overall network topology across all Acinetobacter strains analyzed in this study. Future analysis will investigate whether these hubs are useful as drug targets for treating Acinetobacter infections.
Glycogen synthase kinase 3β suppresses polyglutamine aggregation by inhibiting Vaccinia-related kinase 2 activity
Authors: Lee Eunju , Ryu Hye Guk , Kim Sangjune , Lee Dohyun , Jeong Young-Hun , Kim Kyong-Tai 
Published: July 2016

AbstractHuntington’s disease (HD) is a neurodegenerative disorder caused by an abnormal expansion of polyglutamine repeats in the N-terminal of huntingtin. The amount of aggregate-prone protein is controlled by various mechanisms, including molecular chaperones. Vaccinia-related kinase 2 (VRK2) is known to negatively regulate chaperonin TRiC, and VRK2-facilitated degradation of TRiC increases polyQ protein aggregation, which is involved in HD. We found that VRK2 activity was negatively controlled by glycogen synthase kinase 3β (GSK3β). GSK3β directly bound to VRK2 and inhibited the catalytic activity of VRK2 in a kinase activity-independent manner. Furthermore, GSK3β increased the stability of TRiC and decreased the formation of HttQ103-GFP aggregates by inhibiting VRK2. These results indicate that GSK3β signaling may be a regulatory mechanism of HD progression and suggest targets for further therapeutic trials for HD.
Exotic skyrmion crystals in chiral magnets with compass anisotropy
Authors: Chen J. P. , Zhang Dan-Wei , Liu J. -M. 
Published: July 2016

AbstractThe compass-type anisotropy appears naturally in diverse physical contexts with strong spin-orbit coupling (SOC) such as transition metal oxides and cold atomic gases etc and it has been receiving substantial attention. Motivated by recent studies and particularly recent experimental observations on helimagnet MnGe, we investigate the critical roles of this compass-type anisotropy in modulating various spin textures of chiral magnets with strong SOC, by Monte Carlo simulations based on a classical Heisenberg spin model with Dzyaloshinsky-Moriya interaction and compass anisotropy. A phase diagram with emergent spin orders in the space of compass anisotropy and out-of-plane magnetic field is presented. In this phase diagram, we propose that a hybrid super-crystal structure consisting of alternating half-skyrmion and half-anti-skyrmion is the possible zero-field ground state of MnGe. The simulated evolution of the spin structure driven by magnetic field is in good accordance with experimental observations on MnGe. Therefore, this Heisenberg spin model successfully captures the main physics responsible for the magnetic structures in MnGe and the present work may also be instructive to research on the magnetic states in other systems with strong SOC.
Sharp temporal tuning in the bat auditory midbrain overcomes spectral-temporal trade-off imposed by cochlear mechanics
Authors: Macías Silvio , Hechavarría Julio C. , Kössl Manfred 
Published: July 2016

AbstractIn the cochlea of the mustached bat, cochlear resonance produces extremely sharp frequency tuning to the dominant frequency of the echolocation calls, around 61 kHz. Such high frequency resolution in the cochlea is accomplished at the expense of losing temporal resolution because of cochlear ringing, an effect that is observable not only in the cochlea but also in the cochlear nucleus. In the midbrain, the duration of sounds is thought to be analyzed by duration-tuned neurons, which are selective to both stimulus duration and frequency. We recorded from 57 DTNs in the auditory midbrain of the mustached bat to assess if a spectral-temporal trade-off is present. Such spectral-temporal trade-off is known to occur as sharp tuning in the frequency domain which results in poorer resolution in the time domain, and vice versa. We found that a specialized sub-population of midbrain DTNs tuned to the bat’s mechanical cochlear resonance frequency escape the cochlear spectral-temporal trade-off. We also show evidence that points towards an underlying neuronal inhibition that appears to be specific only at the resonance frequency.
Overexpression of Bmi1 in Lymphocytes Stimulates Skeletogenesis by Improving the Osteogenic Microenvironment
Authors: Zhou Xichao , Dai Xiuliang , Wu Xuan , Ji Ji , Karaplis Andrew , Goltzman David , Yang Xiangjiao , Miao Dengshun 
Published: July 2016

AbstractTo investigate whether overexpression of Bmi1 in lymphocytes can stimulate skeletogenesis by improving the osteogenic microenvironment, we examined the skeletal phenotype of EμBmi1 transgenic mice with overexpression of Bmi1 in lymphocytes. The size of the skeleton, trabecular bone volume and osteoblast number, indices of proliferation and differentiation of bone marrow mesenchymal stem cells (BM-MSCs) were increased significantly, ROS levels were reduced and antioxidative capacity was enhanced in EμBmi1 mice compared to WT mice. In PTHrP1–84 knockin (PthrpKI/KI) mice, the expression levels of Bmi1 are reduced and potentially can mediate the premature osteoporosis observed. We therefore generated a PthrpKI/KI mice overexpressing Bmi1 in lymphocytes and compared them with PthrpKI/KI and WT littermates. Overexpression of Bmi1 in PthrpKI/KI mice resulted in a longer lifespan, increased body weight and improvement in skeletal growth and parameters of osteoblastic bone formation with reduced ROS levels and DNA damage response parameters. Our results demonstrate that overexpression of Bmi1 in lymphocytes can stimulate osteogenesis in vivo and partially rescue defects in skeletal growth and osteogenesis in PthrpKI/KI mice. These studies therefore indicate that overexpression of Bmi1 in lymphocytes can stimulate skeletogenesis by inhibiting oxidative stress and improving the osteogenic microenvironment.
Monolayer MoS2 Bandgap Modulation by Dielectric Environments and Tunable Bandgap Transistors
Authors: Ryou Junga , Kim Yong-Sung , KC Santosh , Cho Kyeongjae 
Published: July 2016

AbstractSemiconductors with a moderate bandgap have enabled modern electronic device technology, and the current scaling trends down to nanometer scale have introduced two-dimensional (2D) semiconductors. The bandgap of a semiconductor has been an intrinsic property independent of the environments and determined fundamental semiconductor device characteristics. In contrast to bulk semiconductors, we demonstrate that an atomically thin two-dimensional semiconductor has a bandgap with strong dependence on dielectric environments. Specifically, monolayer MoS2 bandgap is shown to change from 2.8 eV to 1.9 eV by dielectric environment. Utilizing the bandgap modulation property, a tunable bandgap transistor, which can be in general made of a two-dimensional semiconductor, is proposed.
Soft magnetic memory of silk cocoon membrane
Authors: Roy Manas , Dubey Amarish , Singh Sushil Kumar , Bhargava Kalpana , Sethy Niroj Kumar , Philip Deepu , Sarkar Sabyasachi , Bajpai Alok , Das Mainak 
Published: July 2016

AbstractSilk cocoon membrane (SCM), a solid matrix of protein fiber, responds to light, heat and moisture and converts these energies to electrical signals. Essentially it exhibits photo-electric and thermo-electric properties; making it a natural electro-magnetic sensor, which may influence the pupal development. This raises the question: ‘is it only electricity?’, or ‘it also posses some kind of magnetic memory?’ This work attempted to explore the magnetic memory of SCM and confirm its soft magnetism. Fe, Co, Ni, Mn, Gd were found in SCM, in traces, through energy dispersive X-ray analysis (EDX), X-ray photoelectron spectroscopy (XPS) and inductively coupled plasma mass spectrometry (ICP-MS). Presence of iron was ascertained by electron paramagnetic resonance (EPR). In addition, EPR-spectra showed the presence of a stable pool of carbon-centric free radical in the cocoon structure. Carbon-centric free radicals behaves as a soft magnet inherently. Magnetic-Hysteresis (M-H) of SCM confirmed its soft magnetism. It can be concluded that the soft bio-magnetic feature of SCM is due to the entrapment of ferromagnetic elements in a stable pool of carbon centric radicals occurring on the super-coiled protein structure. Natural soft magnets like SCM provide us with models for developing eco-friendly, protein-based biological soft magnets.
HANDS2: accurate assignment of homoeallelic base-identity in allopolyploids despite missing data
Authors: Khan Amina , Belfield Eric J. , Harberd Nicholas P. , Mithani Aziz 
Published: July 2016

AbstractCharacterization of homoeallelic base-identity in allopolyploids is difficult since homeologous subgenomes are closely related and becomes further challenging if diploid-progenitor data is missing. We present HANDS2, a next-generation sequencing-based tool that enables highly accurate (>90%) genome-wide discovery of homeolog-specific base-identity in allopolyploids even in the absence of a diploid-progenitor. We applied HANDS2 to the transcriptomes of various cruciferous plants belonging to genus Brassica. Our results suggest that the three C genomes in Brassica are more similar to each other than the three A genomes, and provide important insights into the relationships between various Brassica tetraploids and their diploid-progenitors at a single-base resolution.
The modification of the thrombin generation test for the clinical assessment of dabigatran etexilate efficiency
Authors: Gribkova Irina V. , Lipets Elena N. , Rekhtina Irina G. , Bernakevich Alex I. , Ayusheev Dorzho B. , Ovsepyan Ruzanna A. , Ataullakhanov Fazoil I. , Sinauridze Elena I. 
Published: July 2016

AbstractA new oral anticoagulant, dabigatran etexilate (DE, a prodrug of direct thrombin inhibitor (DTI) dabigatran), has been used clinically to prevent thrombosis. The assessment of dabigatran efficiency is necessary in some clinical cases, such as renal insufficiency, risk of bleeding, and drug interactions. However, a specific thrombin generation test (TGT) that is one of the most informative and sensitive to anticoagulant therapy (calibrated automated thrombinography (САТ)) shows a paradoxical increase of test parameters, such as endogenous thrombin potential (ETP) and peak thrombin, in patients receiving DE. The paradoxical behaviour of ETP and peak thrombin in these patients in the presence of DTIs is mostly caused by a decrease in the activity of thrombin in the α2-macroglobulin-thrombin complex that is used as a calibrator in CAT. For a correct estimation of the TGT parameters in patient’s plasma containing DTIs we proposed to use our previously described alternative calibration method that is based on the measurement of the fluorescence signal of a well-known concentration of the reaction product (7-amino-4-methylcoumarin). In this study, the validity of such approach was demonstrated in an ex vivo study in patients with knee replacement and two special patients with multiple myeloma, who received DE for thrombosis prophylaxis.
Conformational stability of digestion-resistant peptides of peanut conglutins reveals the molecular basis of their allergenicity
Authors: Apostolovic Danijela , Stanic-Vucinic Dragana , de Jongh Harmen H. J. , de Jong Govardus A. H. , Mihailovic Jelena , Radosavljevic Jelena , Radibratovic Milica , Nordlee Julie A. , Baumert Joseph L. , Milcic Milos , Taylor Steve L. , Garrido Clua Nuria , Cirkovic Velickovic Tanja , Koppelman Stef J. 
Published: July 2016

AbstractConglutins represent the major peanut allergens and are renowned for their resistance to gastro-intestinal digestion. Our aim was to characterize the digestion-resistant peptides (DRPs) of conglutins by biochemical and biophysical methods followed by a molecular dynamics simulation in order to better understand the molecular basis of food protein allergenicity. We have mapped proteolysis sites at the N- and C-termini and at a limited internal segment, while other potential proteolysis sites remained unaffected. Molecular dynamics simulation showed that proteolysis only occurred in the vibrant regions of the proteins. DRPs appeared to be conformationally stable as intact conglutins. Also, the overall secondary structure and IgE-binding potency of DRPs was comparable to that of intact conglutins. The stability of conglutins toward gastro-intestinal digestion, combined with the conformational stability of the resulting DRPs provide conditions for optimal exposure to the intestinal immune system, providing an explanation for the extraordinary allergenicity of peanut conglutins.
Transition of differential histone H3 methylation in photoreceptors and other retinal cells during retinal differentiation
Authors: Ueno Kazuko , Iwagawa Toshiro , Kuribayashi Hiroshi , Baba Yukihiro , Nakauchi Hiromitsu , Murakami Akira , Nagasaki Masao , Suzuki Yutaka , Watanabe Sumiko 
Published: July 2016

AbstractTo analyze cell lineage-specific transitions in global transcriptional and epigenetic changes during retinogenesis, we purified retinal cells from normal mice during postnatal development into two fractions, namely, photoreceptors and other retinal cells, based on Cd73 expression, and performed RNA sequencing and ChIP sequencing of H3K27me3 and H3K4me3. Genes expressed in the photoreceptor lineage were marked with H3K4me3 in the Cd73-positive cell fraction; however, the level of H3K27me3 was very low in both Cd73-positive and -negative populations. H3K27me3 may be involved in spatio-temporal onset of a subset of bipolar-related genes. Subsets of genes expressed in amacrine and retinal ganglion cells, which are early-born retinal cell types, were suggested to be maintained in a silent state by H3K27me3 during late-stage retinogenesis. In the outer nuclear layer, upregulation of Rho and rod-related genes were observed in Ezh2-ablated retina, suggesting a role for H3K27me3 in the maintenance of proper expression levels. Taken together, our data on the transition of lineage-specific molecular signatures during development suggest that histone methylation is involved in retinal differentiation and maintenance through cell lineage-specific mechanisms.
The normal modes of lattice vibrations of ice XI
Authors: Zhang Peng , Wang Zhe , Lu Ying-Bo , Ding Zheng-Wen 
Published: July 2016

AbstractThe vibrational spectrum of ice XI at thermal wavelengths using the CASTEP code, a first-principles simulation method, is investigated. A dual-track approach is constructed to verify the validity for the computational phonon spectrum: collate the simulated spectrum with inelastic neutron scattering experiments and assign the photon scattering peaks according to the calculated normal vibration frequencies. The 33 optical normal vibrations at the Brillouin center are illustrated definitely from the ab initio outcomes. The depolarizing field effect of the hydrogen bond vibrations at frequencies of 229 cm−1 and 310 cm−1 is found to agree well with the LST relationship. It is a convincing evidence to manifest the LO-TO splitting of hydrogen bonds in ice crystal. We attribute the two hydrogen bond peaks to the depolarization effect and apply this viewpoint to ordinary ice phase, ice Ih, which is difficult to analyse their vibration modes due to proton disorder.