bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-resolution imaging of SNR IC443 and W44 with the Sardinia Radio Telescope
Authors: Egron E. , Pellizzoni A. , Iacolina M. N. , Loru S. , Marongiu M. , Righini S. , Cardillo M. , Giuliani A. , Mulas S. , Murtas G. , Simeone D. 
Published: October 2017

AbstractWe present single-dish imaging of the well-known Supernova Remnants (SNRs) IC443 and W44 at 1.5 GHz and 7 GHz with the recently commissioned 64-m diameter Sardinia Radio Telescope (SRT). Our images were obtained through on-the-fly mapping techniques, providing antenna beam oversampling, automatic baseline subtraction and radio-frequency interference removal. It results in high-quality maps of the SNRs at 7 GHz, which are usually lacking and not easily achievable through interferometry at this frequency due to the very large SNR structures. SRT continuum maps of our targets are consistent with VLA maps carried out at lower frequencies (at 324 MHz and 1.4 GHz), providing a view of the complex filamentary morphology. New estimates of the total flux density are given within 3% and 5% error at 1.5 GHz and 7 GHz respectively, in addition to flux measurements in different regions of the SNRs.
Radio and X-ray observations of supernovae in dense environments
Authors: Chandra Poonam 
Published: October 2017

AbstractHere we discuss the observational properties of supernovae exploding in extremely dense environments, namely Type IIn supernovae (SNe IIn). In SNe IIn, the surrounding environments play significant role in the supernovae energetics and evolution. Thus they are different than other classes of core collapse supernovae, whose energetics are not significantly altered by their environments. Though high density of medium is a prerequisite for radio and X-ray emission, less than 10% on SNe IIn are bright in these bands. This has important implications for their progenitor models. I will discuss the radio and X-ray observations of SNe IIn, which are crucial to unravel their complex environments. We also discuss some individual supernovae belonging to this class and discuss as to how they have refined our understanding of SNe IIn. Finally the importance of well sampled long term light curves in radio and X-ray bands cannot be stressed enough.
Cosmic ray astroparticle physics: current status and future perspectives
Authors: Donato Fiorenza 
Published: October 2017

AbstractThe data we are receiving from galactic cosmic rays are reaching an unprecedented precision, over very wide energy ranges. Nevertheless, many problems are still open, while new ones seem to appear when data happen to be redundant. We will discuss some paths to possible progress in the theoretical modeling and experimental exploration of the galactic cosmic radiation.
Diagnostics of the Supernova Engine
Authors: Fryer Chris L. , Ellinger Carola , Young Patrick A. , Vance Gregory 
Published: October 2017

AbstractThe standard engine behind core-collapse supernovae is continuously evolving with increasingly detailed models. At this time, most simulations focus on an engine invoking turbulence above the proto-neutron star, sometimes termed the “convection-enhanced” engine. Here we review this engine and why it has become the standard for normal supernovae, focusing on a wide set of observations that provide insight into the supernova engine.
Acetoclastic Methanosaeta are dominant methanogens in organic-rich Antarctic marine sediments
Authors: Carr Stephanie A , Schubotz Florence , Dunbar Robert B , Mills Christopher T , Dias Robert , Summons Roger E , Mandernack Kevin W 
Published: October 2017

Abstract
Despite accounting for the majority of sedimentary methane, the physiology and relative abundance of subsurface methanogens remain poorly understood. We combined intact polar lipid and metagenome techniques to better constrain the presence and functions of methanogens within the highly reducing, organic-rich sediments of Antarctica’s Adélie Basin. The assembly of metagenomic sequence data identified phylogenic and functional marker genes of methanogens and generated the first Methanosaeta sp. genome from a deep subsurface sedimentary environment. Based on structural and isotopic measurements, glycerol dialkyl glycerol tetraethers with diglycosyl phosphatidylglycerol head groups were classified as biomarkers for active methanogens. The stable carbon isotope (δ13C) values of these biomarkers and the Methanosaeta partial genome suggest that these organisms are acetoclastic methanogens and represent a relatively small (0.2%) but active population. Metagenomic and lipid analyses suggest that Thaumarchaeota and heterotrophic bacteria co-exist with Methanosaeta and together contribute to increasing concentrations and δ13C values of dissolved inorganic carbon with depth. This study presents the first functional insights of deep subsurface Methanosaeta organisms and highlights their role in methane production and overall carbon cycling within sedimentary environments.
The structure of the human ABC transporter ABCG2 reveals a novel mechanism for drug extrusion
Authors: Khunweeraphong Narakorn , Stockner Thomas , Kuchler Karl 
Published: October 2017

AbstractThe human ABC transporter ABCG2 (Breast Cancer Resistance Protein, BCRP) is implicated in anticancer resistance, in detoxification across barriers and linked to gout. Here, we generate a novel atomic model of ABCG2 using the crystal structure of ABCG5/G8. Extensive mutagenesis verifies the structure, disclosing hitherto unrecognized essential residues and domains in the homodimeric ABCG2 transporter. The elbow helix, the first intracellular loop (ICL1) and the nucleotide-binding domain (NBD) constitute pivotal elements of the architecture building the transmission interface that borders a central cavity which acts as a drug trap. The transmission interface is stabilized by salt-bridge interactions between the elbow helix and ICL1, as well as within ICL1, which is essential to control the conformational switch of ABCG2 to the outward-open drug-releasing conformation. Importantly, we propose that ICL1 operates like a molecular spring that holds the NBD dimer close to the membrane, thereby enabling efficient coupling of ATP hydrolysis during the catalytic cycle. These novel mechanistic data open new opportunities to therapeutically target ABCG2 in the context of related diseases.
The Efficacy and Pharmacological Mechanism of Zn7MT3 to Protect against Alzheimer’s Disease
Authors: Xu Wei , Xu Qiming , Cheng Hao , Tan Xiangshi 
Published: October 2017

AbstractAlzheimer’s disease (AD) is one of the leading causes of death for people over 65 years. Worse still, no completely effective therapeutic agent is available so far. One important pathological hallmark of AD is accumulated amyloid-β (Aβ) plaques with dysregulated metal homeostasis. Human metallothionin 3 (MT3), a regulator of metal homeostasis, is downregulated at least 30% in AD brain. So far, some in vitro studies demonstrated its multiple functions related to AD. However, it is a great pity that systematic in vivo studies of MT3 on AD model animals are still a blank so far. In this study, we treated APP/PS1 mice with sustained drug release of Zn7MT3 directly to the central nervous system, and investigated the role and molecular mechanism of Zn7MT3 to protect against AD mice systematically. The results demonstrated that Zn7MT3 can significantly ameliorate cognitive deficits, regulate metal homeostasis, abolish Aβ plaque load, and reduce oxidative stress. Additionally, it has been confirmed that MT3 is penetrable to the blood brain barrier of AD mice. All these results support that Zn7MT3 is an effective AD suppressing agent and has potential for applications in Alzheimer’s disease therapy.
Identification of candidate drugs using tensor-decomposition-based unsupervised feature extraction in integrated analysis of gene expression between diseases and DrugMatrix datasets
Authors: Taguchi Y.-h. 
Published: October 2017

AbstractIdentifying drug target genes in gene expression profiles is not straightforward. Because a drug targets proteins and not mRNAs, the mRNA expression of drug target genes is not always altered. In addition, the interaction between a drug and protein can be context dependent; this means that simple drug incubation experiments on cell lines do not always reflect the real situation during active disease. In this paper, I applied tensor-decomposition-based unsupervised feature extraction to the integrated analysis using a mathematical product of gene expression in various diseases and gene expression in the DrugMatrix dataset, where comprehensive data on gene expression during various drug treatments of rats are reported. I found that this strategy, in a fully unsupervised manner, enables researchers to identify a combined set of genes and compounds that significantly overlap with gene and drug interactions identified in the past. As an example illustrating the usefulness of this strategy in drug discovery experiments, I considered cirrhosis, for which no effective drugs have ever been proposed. The present strategy identified two promising therapeutic-target genes, CYPOR and HNFA4; for their protein products, bezafibrate was identified as a promising candidate drug, supported by in silico docking analysis.
Resection of high frequency oscillations predicts seizure outcome in the individual patient
Authors: Fedele Tommaso , Burnos Sergey , Boran Ece , Krayenbühl Niklaus , Hilfiker Peter , Grunwald Thomas , Sarnthein Johannes 
Published: October 2017

AbstractHigh frequency oscillations (HFOs) are recognized as biomarkers for epileptogenic brain tissue. A remaining challenge for epilepsy surgery is the prospective classification of tissue sampled by individual electrode contacts. We analysed long-term invasive recordings of 20 consecutive patients who subsequently underwent epilepsy surgery. HFOs were defined prospectively by a previously validated, automated algorithm in the ripple (80–250 Hz) and the fast ripple (FR, 250–500 Hz) frequency band. Contacts with the highest rate of ripples co-occurring with FR over several five-minute time intervals designated the HFO area. The HFO area was fully included in the resected area in all 13 patients who achieved seizure freedom (specificity 100%) and in 3 patients where seizures reoccurred (negative predictive value 81%). The HFO area was only partially resected in 4 patients suffering from recurrent seizures (positive predictive value 100%, sensitivity 57%). Thus, the resection of the prospectively defined HFO area proved to be highly specific and reproducible in 13/13 patients with seizure freedom, while it may have improved the outcome in 4/7 patients with recurrent seizures. We thus validated the clinical relevance of the HFO area in the individual patient with an automated procedure. This is a prerequisite before HFOs can guide surgical treatment in multicentre studies.
A self-feedback network based on liquid chromatography-quadrupole-time of flight mass spectrometry for system identification of β-carboline alkaloids in Picrasma quassioides
Authors: Shi Yuanyuan , Wang Ruoqi , Zhu Xiaoyu , Xu Dongge , Liu Wenyuan , Feng Feng 
Published: October 2017

AbstractProfiling chemical components in herbs by mass spectrometry is a challenging work because of the lack of standard compounds, especially for position isomers. This paper provides a strategy based on a self-feedback network of mass spectra (MS) data to identify chemical constituents in herbs by liquid chromatography-quadrupole-time of flight mass spectrometry without compound standards. Components sharing same skeleton were screened and all ions were classified into a database. All candidates were connected by the selected bridging ions to establish a primary MS network. Benefited from such a network, it is feasible to characterize sequentially the structures of all diagnostic ions and candidates once single component has been de novo identified. TakingPicrasma quassioidesas an example, the primary network of β-carbolines was established with 65 ions (selected from 76 β-carbolines), each of which appeared at least in four compounds. Once an alkaloid has been identified, its logical ions could feedback into primary network to build pathways with other unknown compounds. Moreover, the position of the substituent groups could be deduced through the secondary metabolic pathways of alkaloids (plant secondary metabolism). The network therefore can be utilized for identification of unknown compounds and even their position isomers.
How aging impacts skin biomechanics: a multiscale study in mice
Authors: Lynch Barbara , Bonod-Bidaud Christelle , Ducourthial Guillaume , Affagard Jean-Sébastien , Bancelin Stéphane , Psilodimitrakopoulos Sotiris , Ruggiero Florence , Allain Jean-Marc , Schanne-Klein Marie-Claire 
Published: October 2017

AbstractSkin aging is a complex process that strongly affects the mechanical behavior of skin. This study aims at deciphering the relationship between age-related changes in dermis mechanical behavior and the underlying changes in dermis microstructure. To that end, we use multiphoton microscopy to monitor the reorganization of dermal collagen during mechanical traction assays in ex vivo skin from young and old mice. The simultaneous variations of a full set of mechanical and microstructural parameters are analyzed in the framework of a multiscale mechanical interpretation. They show consistent results for wild-type mice as well as for genetically-modified mice with modified collagen V synthesis. We mainly observe an increase of the tangent modulus and a lengthening of the heel region in old murine skin from all strains, which is attributed to two different origins that may act together: (i) increased cross-linking of collagen fibers and (ii) loss of water due to proteoglycans deterioration, which impedes inner sliding within these fibers. In contrast, the microstructure reorganization upon stretching shows no age-related difference, which can be attributed to opposite effects of the decrease of collagen content and of the increase of collagen cross-linking in old mice.
Genetic Diversity and Phylogenetic Differentiation of Southwestern Chinese Han: a comprehensive and comparative analysis on 21 non-CODIS STRs
Authors: He Guanglin , Wang Zheng , Wang Mengge , Hou Yiping 
Published: October 2017

AbstractShort tandem repeats (STRs), with high polymorphism and complex evolution information, play a significant role in genetic association studies like population genetics, molecular anthropology and human forensics. However, human genetic diversity has only been partially sampled and available for Southwest Chinese Han population, as well as the genetic architecture of this population remains uncharacterized. In this work, 368 unrelated Han individuals from Sichuan province were firstly genotyped with 21 non-CODIS autosomal STRs, and phylogenetic relationships along administrative (Han Chinese from different regions) and ethnic divisions (minority ethnic groups) were subsequently investigated. The CMP and CPE were 6.2796 × 10−20 and 0.9999999, respectively. Analysis of molecular variance (AMOVA), principal component analysis (PCA), multidimensional scaling plots (MDS) and phylogenetic analysis consistently demonstrated that the Southwest Han population had a close genetic relationship with the geographically close population (Hunan Han) and kept a distant genetic relationship with some ethnic groups, most prominently for Gansu Yugu and Fujian She. Furthermore, no significant genetic distinction between the Northern Han and Southern Han was observed. Aforementioned results suggested that these 21 STRs are highly polymorphic and informative, which are suitable for human identification and population genetics.
Role of HIV exposure and infection in relation to neonatal GBS disease and rectovaginal GBS carriage: a systematic review and meta-analysis
Authors: Cools Piet , van de Wijgert Janneke H. H. M. , Jespers Vicky , Crucitti Tania , Sanders Eduard J. , Verstraelen Hans , Vaneechoutte Mario 
Published: October 2017

AbstractStreptococcus agalactiae (GBS) is the leading cause worldwide of neonatal sepsis. We sought to assess to which extent HIV exposure of neonates is associated with GBS neonatal disease. Furthermore, we assessed to which extent HIV infection in women is associated with maternal rectovaginal GBS carriage, the single most important risk factor for GBS neonatal disease. We searched Pubmed, Embase, and Web of Science for studies assessing the association between neonatal GBS disease and HIV-status of the mother and studies that assessed the association between rectovaginal GBS colonization and HIV status in women. HIV-exposed uninfected neonates were more than twice as likely to have neonatal GBS disease compared to unexposed neonates. HIV-exposed neonates were not at increased risk for early-onset neonatal disease, but were 4.43 times more likely to have late-onset neonatal GBS disease. There was no significant association between HIV infection status and rectovaginal GBS carriage. Public health interventions preventing neonatal GBS disease are urgently needed for the increasing group of HIV-exposed neonates. A framework integrating and explaining our findings highlights opportunities for the clinical practice and global health policy to prevent disease. Well-designed studies should clarify the relation between HIV-status and GBS carriage.
Toxoplasma-induced changes in host risk behaviour are independent of parasite-derived AaaH2 tyrosine hydroxylase
Authors: Afonso Cristina , Paixão Vitor B. , Klaus Andreas , Lunghi Matteo , Piro Federica , Emiliani Carla , Di Cristina Manlio , Costa Rui M. 
Published: October 2017

AbstractToxoplasma gondii infects a broad range of hosts and can establish chronic infections with the formation of brain cysts. Infected animals show altered risk behaviour which has been suggested to increase capture probability of hosts, and thus enhance parasite transmission. It has been proposed that the ability of Toxoplasma cysts to secrete tyrosine hydroxylase could mediate these behavioural alterations. We tested the involvement of secreted tyrosine hydroxylase, coded by the parasite AaaH2 gene, in the development of alterations in mouse behaviour, by generating an AaaH2 deletion mutant parasite strain and testing its influence on behaviour. We found that both mice infected with wild type or AaaH2 mutant strains showed changes in risk behaviour. We confirmed these findings using factor analysis of the behaviour, which revealed that behavioural changes happened along a single dimension, and were observed in both infected groups. Furthermore, we developed a new behavioural paradigm in which animals are unpredictably trapped, and observed that both groups of infected animals perceive trapping but fail to adjust their behaviour to avoid further trapping. These results demonstrate that parasite-secreted AaaH2 TH is neither necessary for the generation of risky behaviour nor for the increased trappability observed during chronic Toxoplasma infection.
Regiospecific Synthesis of Ring A Fused Withaferin A Isoxazoline Analogues: Induction of Premature Senescence by W-2b in Proliferating Cancer Cells
Authors: Rasool Faheem , Nayak Debasis , Katoch Archana , Faheem Mir Mohd , Yousuf Syed Khalid , Hussain Nazar , Belawal Chetan , Satti N. K. , Goswami Anindya , Mukherjee Debaraj 
Published: October 2017

AbstractInduction of premature senescence represents a novel functional strategy to curb the uncontrolled proliferation of malignant cancer cells. This study unveils the regiospecific synthesis of novel isoxazoline derivatives condensed to ring A of medicinal plant product Withaferin-A. Intriguingly, the cis fused products with β-oriented hydrogen exhibited excellent cytotoxic activities against proliferating human breast cancer MCF7 and colorectal cancer HCT-116 cells. The most potent derivative W-2b triggered premature senescence along with increase in senescence-associated β-galactosidase activity, G2/M cell cycle arrest, and induction of senescence-specific marker p21Waf1/Cip1 at its sub-toxic concentration. W-2b conferred a robust increase in phosphorylation of mammalian checkpoint kinase-2 (Chk2) in cancer cells in a dose-dependent manner. Silencing of endogenous Chk2 by siRNA divulged that the amplification of p21 expression and senescence by W-2b was Chk2-dependent. Chk2 activation (either by ectopic overexpression or through treatment with W-2b) suppressed NM23-H1 signaling axis involved in cancer cell proliferation. Finally, W-2b showed excellent in vivo efficacy with 83.8% inhibition of tumor growth at a dose of 25 mg/kg, b.w. in mouse mammary carcinoma model. Our study claims that W-2b could be a potential candidate to limit aberrant cellular proliferation rendering promising improvement in the treatment regime in cancer patients.
Aquarius is required for proper CtIP expression and homologous recombination repair
Authors: Sakasai Ryo , Isono Mayu , Wakasugi Mitsuo , Hashimoto Mitsumasa , Sunatani Yumi , Matsui Tadashi , Shibata Atsushi , Matsunaga Tsukasa , Iwabuchi Kuniyoshi 
Published: October 2017

AbstractAccumulating evidence indicates that transcription is closely related to DNA damage formation and that the loss of RNA biogenesis factors causes genome instability. However, whether such factors are involved in DNA damage responses remains unclear. We focus here on the RNA helicase Aquarius (AQR), a known R-loop processing factor, and show that its depletion in human cells results in the accumulation of DNA damage during S phase, mediated by R-loop formation. We investigated the involvement of Aquarius in DNA damage responses and found that AQR knockdown decreased DNA damage-induced foci formation of Rad51 and replication protein A, suggesting that Aquarius contributes to homologous recombination (HR)-mediated repair of DNA double-strand breaks (DSBs). Interestingly, the protein level of CtIP, a DSB processing factor, was decreased in AQR-knockdown cells. Exogenous expression of Aquarius partially restored CtIP protein level; however, CtIP overproduction did not rescue defective HR in AQR-knockdown cells. In accordance with these data, Aquarius depletion sensitized cells to genotoxic agents. We propose that Aquarius contributes to the maintenance of genomic stability via regulation of HR by CtIP-dependent and -independent pathways.
TMAO is Associated with Mortality: Impact of Modestly Impaired Renal Function
Authors: Gruppen Eke G. , Garcia Erwin , Connelly Margery A. , Jeyarajah Elias J. , Otvos James D. , Bakker Stephan J. L. , Dullaart Robin P. F. 
Published: October 2017

AbstractTrimethylamine-N-Oxide (TMAO) is a microbiome-related metabolite that is cleared by the kidney and linked to renal function. We explored the relationship between TMAO and all-cause mortality, and determined whether this association was modified by renal function. A prospective study was performed among PREVEND participants to examine associations of plasma TMAO with all-cause mortality. After median follow-up of 8.3 years in 5,469 participants, 322 subjects died. TMAO was positively associated with age, body mass index, type 2 diabetes mellitus and inversely with estimated glomerular filtration rate (eGFRcreatcysC)(all P < 0.001). Subjects in the highest versus lowest TMAO quartile had a crude 1.86-fold higher mortality risk (Ptrend < 0.001). After adjustment for several risk factors, TMAO remained associated with all-cause mortality [HR:1.36 (95% CI, 0.97–1.91),Ptrend = 0.016]. This association was lost after further adjustment for urinary albumin excretion and eGFR [HR:1.15 (95% CI, 0.81–1.64),Ptrend = 0.22]. The association of TMAO with mortality was modified by eGFR in crude and age- and sex-adjusted analyses (interaction P = 0.002). When participants were stratified by renal function (eGFR < vs. ≥90 mL/min/1.73 m2), TMAO was associated with all-cause mortality only in subjects with eGFR <90 mL/min/1.73 m2 [adjusted HR:1.18 (95% CI, 1.02–1.36),P = 0.023]. In conclusion, TMAO is associated with all-cause mortality, particularly in subjects with eGFR <90 mL/min/1.73 m2.