bluuebunny/crossref_metadata_2025_split huggingface dataset:
Facing the Adversity: the Role of Internal Assets on Well-Being in Adolescents with Special Needs
Authors: Simões Celeste , Matos Margarida Gaspar , Morgan Antony 
Published: August 2015

AbstractNegative life events are one of the major threats to well-being. Some adolescents are more vulnerable, namely adolescents with special needs that face special challenges for growing up healthy and happy. Nevertheless, internal assets can act as protective factors. The aim of this study is to analyze the factors that moderate the impact of negative life events, among adolescents with special needs, on well-being. The sample included 472 adolescents with special needs, mean age 14 years old. Pupils attended 77 public schools in Portugal. Sample was collected within the HBSC (Health Behavior in School aged Children) Portuguese survey. Questions used in this study, covered well-being, internal assets and life events. Results showed that the well-being of adolescents with special needs who had a set of internal assets (personal and social competences) was protected, even when they faced negative life events. However when several negative life events were present, the assets that continued to be protective were problem solving, F(4, 383) = 3.79, p = .005, η2 = .04, and self-efficacy, F(4, 377) = 3.39, p = .010, η2 = .04, suggesting the resilience properties of these factors.
The mechanochemistry of copper reports on the directionality of unfolding in model cupredoxin proteins
Authors: Beedle Amy E. M. , Lezamiz Ainhoa , Stirnemann Guillaume , Garcia-Manyes Sergi 
Published: August 2015

AbstractUnderstanding the directionality and sequence of protein unfolding is crucial to elucidate the underlying folding free energy landscape. An extra layer of complexity is added in metalloproteins, where a metal cofactor participates in the correct, functional fold of the protein. However, the precise mechanisms by which organometallic interactions are dynamically broken and reformed on (un)folding are largely unknown. Here we use single molecule force spectroscopy AFM combined with protein engineering and MD simulations to study the individual unfolding pathways of the blue-copper proteins azurin and plastocyanin. Using the nanomechanical properties of the native copper centre as a structurally embedded molecular reporter, we demonstrate that both proteins unfold via two independent, competing pathways. Our results provide experimental evidence of a novel kinetic partitioning scenario whereby the protein can stochastically unfold through two distinct main transition states placed at the N and C termini that dictate the direction in which unfolding occurs.
Structural and mechanistic insights into phospholipid transfer by Ups1–Mdm35 in mitochondria
Authors: Watanabe Yasunori , Tamura Yasushi , Kawano Shin , Endo Toshiya 
Published: August 2015

AbstractEukaryotic cells are compartmentalized into membrane-bounded organelles whose functions rely on lipid trafficking to achieve membrane-specific compositions of lipids. Here we focused on the Ups1–Mdm35 system, which mediates phosphatidic acid (PA) transfer between the outer and inner mitochondrial membranes, and determined the X-ray structures of Mdm35 and Ups1–Mdm35 with and without PA. The Ups1–Mdm35 complex constitutes a single domain that has a deep pocket and flexible Ω-loop lid. Structure-based mutational analyses revealed that a basic residue at the pocket bottom and the Ω-loop lid are important for PA extraction from the membrane following Ups1 binding. Ups1 binding to the membrane is enhanced by the dissociation of Mdm35. We also show that basic residues around the pocket entrance are important for Ups1 binding to the membrane and PA extraction. These results provide a structural basis for understanding the mechanism of PA transfer between mitochondrial membranes.
Large-volume en-bloc staining for electron microscopy-based connectomics
Authors: Hua Yunfeng , Laserstein Philip , Helmstaedter Moritz 
Published: August 2015

AbstractLarge-scale connectomics requires dense staining of neuronal tissue blocks for electron microscopy (EM). Here we report a large-volume dense en-bloc EM staining protocol that overcomes the staining gradients, which so far substantially limited the reconstructable volumes in three-dimensional (3D) EM. Our protocol provides densely reconstructable tissue blocks from mouse neocortex sized at least 1 mm in diameter. By relaxing the constraints on precise topographic sample targeting, it makes the correlated functional and structural analysis of neuronal circuits realistic.
Quantitative interactome analysis reveals a chemoresistant edgotype
Authors: Chavez Juan D. , Schweppe Devin K. , Eng Jimmy K. , Zheng Chunxiang , Taipale Alex , Zhang Yiyi , Takara Kohji , Bruce James E. 
Published: August 2015

AbstractChemoresistance is a common mode of therapy failure for many cancers. Tumours develop resistance to chemotherapeutics through a variety of mechanisms, with proteins serving pivotal roles. Changes in protein conformations and interactions affect the cellular response to environmental conditions contributing to the development of new phenotypes. The ability to understand how protein interaction networks adapt to yield new function or alter phenotype is limited by the inability to determine structural and protein interaction changes on a proteomic scale. Here, chemical crosslinking and mass spectrometry were employed to quantify changes in protein structures and interactions in multidrug-resistant human carcinoma cells. Quantitative analysis of the largest crosslinking-derived, protein interaction network comprising 1,391 crosslinked peptides allows for ‘edgotype’ analysis in a cell model of chemoresistance. We detect consistent changes to protein interactions and structures, including those involving cytokeratins, topoisomerase-2-alpha, and post-translationally modified histones, which correlate with a chemoresistant phenotype.
Clinically relevant copy number variations detected in cerebral palsy
Authors: Oskoui Maryam , Gazzellone Matthew J. , Thiruvahindrapuram Bhooma , Zarrei Mehdi , Andersen John , Wei John , Wang Zhuozhi , Wintle Richard F. , Marshall Christian R. , Cohn Ronald D. , Weksberg Rosanna , Stavropoulos Dimitri J. , Fehlings Darcy , Shevell Michael I. , Scherer Stephen W. 
Published: August 2015

AbstractCerebral palsy (CP) represents a group of non-progressive clinically heterogeneous disorders that are characterized by motor impairment and early age of onset, frequently accompanied by co-morbidities. The cause of CP has historically been attributed to environmental stressors resulting in brain damage. While genetic risk factors are also implicated, guidelines for diagnostic assessment of CP do not recommend for routine genetic testing. Given numerous reports of aetiologic copy number variations (CNVs) in other neurodevelopmental disorders, we used microarrays to genotype a population-based prospective cohort of children with CP and their parents. Here we identify de novo CNVs in 8/115 (7.0%) CP patients (∼1% rate in controls). In four children, large chromosomal abnormalities deemed likely pathogenic were found, and they were significantly more likely to have severe neuromotor impairments than those CP subjects without such alterations. Overall, the CNV data would have impacted our diagnosis or classification of CP in 11/115 (9.6%) families.
Ion channel gene expression predicts survival in glioma patients
Authors: Wang Rong , Gurguis Christopher I. , Gu Wanjun , Ko Eun A , Lim Inja , Bang Hyoweon , Zhou Tong , Ko Jae-Hong 
Published: August 2015

AbstractIon channels are important regulators in cell proliferation, migration and apoptosis. The malfunction and/or aberrant expression of ion channels may disrupt these important biological processes and influence cancer progression. In this study, we investigate the expression pattern of ion channel genes in glioma. We designate 18 ion channel genes that are differentially expressed in high-grade glioma as a prognostic molecular signature. This ion channel gene expression based signature predicts glioma outcome in three independent validation cohorts. Interestingly, 16 of these 18 genes were down-regulated in high-grade glioma. This signature is independent of traditional clinical, molecular and histological factors. Resampling tests indicate that the prognostic power of the signature outperforms random gene sets selected from human genome in all the validation cohorts. More importantly, this signature performs better than the random gene signatures selected from glioma-associated genes in two out of three validation datasets. This study implicates ion channels in brain cancer, thus expanding on knowledge of their roles in other cancers. Individualized profiling of ion channel gene expression serves as a superior and independent prognostic tool for glioma patients.
Proximity-induced magnetism in transition-metal substituted graphene
Authors: Crook Charles B. , Constantin Costel , Ahmed Towfiq , Zhu Jian-Xin , Balatsky Alexander V. , Haraldsen Jason T. 
Published: August 2015

AbstractWe investigate the interactions between two identical magnetic impurities substituted into a graphene superlattice. Using a first-principles approach, we calculate the electronic and magnetic properties for transition-metal substituted graphene systems with varying spatial separation. These calculations are compared for three different magnetic impurities, manganese, chromium and vanadium. We determine the electronic band structure, density of states and Millikan populations (magnetic moment) for each atom, as well as calculate the exchange parameter between the two magnetic atoms as a function of spatial separation. We find that the presence of magnetic impurities establishes a distinct magnetic moment in the graphene lattice, where the interactions are highly dependent on the spatial and magnetic characteristic between the magnetic and carbon atoms, which leads to either ferromagnetic or antiferromagnetic behavior. Furthermore, through an analysis of the calculated exchange energies and partial density of states, it is determined that interactions between the magnetic atoms can be classified as an RKKY interaction.
Potential Role of Acetyl-CoA Synthetase (acs) and Malate Dehydrogenase (mae) in the Evolution of the Acetate Switch in Bacteria and Archaea
Authors: Barnhart Elliott P. , McClure Marcella A. , Johnson Kiki , Cleveland Sean , Hunt Kristopher A. , Fields Matthew W. 
Published: August 2015

AbstractAlthough many Archaea have AMP-Acs (acetyl-coenzyme A synthetase) and ADP-Acs, the extant methanogenic genus Methanosarcina is the only identified Archaeal genus that can utilize acetate via acetate kinase (Ack) and phosphotransacetylase (Pta). Despite the importance of ack as the potential urkinase in the ASKHA phosphotransferase superfamily, an origin hypothesis does not exist for the acetate kinase in Bacteria, Archaea, or Eukarya. Here we demonstrate that Archaeal AMP-Acs and ADP-Acs contain paralogous ATPase motifs previously identified in Ack, which demonstrate a novel relation between these proteins in Archaea. The identification of ATPase motif conservation and resulting structural features in AMP- and ADP-acetyl-CoA synthetase proteins in this study expand the ASKHA superfamily to include acetyl-CoA synthetase. Additional phylogenetic analysis showed that Pta and MaeB sequences had a common ancestor and that the Pta lineage within the halophilc archaea was an ancestral lineage. These results suggested that divergence of a duplicated maeB within an ancient halophilic, archaeal lineage formed a putative pta ancestor. These results provide a potential scenario for the establishment of the Ack/Pta pathway and provide novel insight into the evolution of acetate metabolism for all three domains of life.
Superconductivity Series in Transition Metal Dichalcogenides by Ionic Gating
Authors: Shi Wu , Ye Jianting , Zhang Yijin , Suzuki Ryuji , Yoshida Masaro , Miyazaki Jun , Inoue Naoko , Saito Yu , Iwasa Yoshihiro 
Published: August 2015

AbstractFunctionalities of two-dimensional (2D) crystals based on semiconducting transition metal dichalcogenides (TMDs) have now stemmed from simple field effect transistors (FETs) to a variety of electronic and opto-valleytronic devices and even to superconductivity. Among them, superconductivity is the least studied property in TMDs due to methodological difficulty accessing it in different TMD species. Here, we report the systematic study of superconductivity in MoSe2, MoTe2 and WS2 by ionic gating in different regimes. Electrostatic gating using ionic liquid was able to induce superconductivity in MoSe2 but not in MoTe2 because of inefficient electron accumulation limited by electronic band alignment. Alternative gating using KClO4/polyethylene glycol enabled a crossover from surface doping to bulk doping, which induced superconductivities in MoTe2 and WS2 electrochemically. These new varieties greatly enriched the TMD superconductor families and unveiled critical methodology to expand the capability of ionic gating to other materials.
Copy number variation-based genome wide association study reveals additional variants contributing to meat quality in Swine
Authors: Wang Ligang , Xu Lingyang , Liu Xin , Zhang Tian , Li Na , Hay El Hamidi , Zhang Yuebo , Yan Hua , Zhao Kebin , Liu George E , Zhang Longchao , Wang Lixian 
Published: August 2015

AbstractPork quality is important both to the meat processing industry and consumers’ purchasing attitude. Copy number variation (CNV) is a burgeoning kind of variants that may influence meat quality. In this study, a genome-wide association study (GWAS) was performed between CNVs and meat quality traits in swine. After false discovery rate (FDR) correction, a total of 8 CNVs on 6 chromosomes were identified to be significantly associated with at least one meat quality trait. All of the 8 CNVs were verified by next generation sequencing and six of them were verified by qPCR. Only the haplotype block containing CNV12 is adjacent to significant SNPs associated with meat quality, suggesting the effects of those CNVs were not likely captured by tag SNPs. The DNA dosage and EST expression of CNV12, which overlap with an obesity related gene Netrin-1 (Ntn1), were consistent with Ntn1 RNA expression, suggesting the CNV12 might be involved in the expression regulation of Ntn1 and finally influence meat quality. We concluded that CNVs may contribute to the genetic variations of meat quality beyond SNPs and several candidate CNVs were worth further exploration.
BCRP and P-gp relay overexpression in triple negative basal-like breast cancer cell line: a prospective role in resistance to Olaparib
Authors: Dufour Robin , Daumar Pierre , Mounetou Emmanuelle , Aubel Corinne , Kwiatkowski Fabrice , Abrial Catherine , Vatoux Catherine , Penault-Llorca Frédérique , Bamdad Mahchid 
Published: August 2015

AbstractThe triple negative basal-like (TNBL) breast carcinoma is an aggressive and unfavorable prognosis disease. Inhibitors of poly(ADP-ribose) polymerase such as Olaparib could represent a promising targeted therapy but their sensitivity against Multidrug Resistance proteins (MDR), which causes resistance, is not well defined. Thus, our work focused on the analysis of P-gp and BCRP coexpression in the SUM1315 TNBL human cell line, in correlation with Olaparib intracellular concentration. Western blot analyses showed a clear coexpression of P-gp and BCRP in SUM1315 cells. A low cytotoxic Olaparib treatment clearly led to an increased expression of both BCRP and P-gp in these cells. Indeed, after 1.5 h of treatment, BCRP expression was increased with a 1.8 fold increase rate. Then, P-gp took over from 3 h to 15 h with an average increase rate of 1.8 fold and finally returned to control value at 24 h. HPLC-UV analyses showed that, in the same treatment conditions, the intracellular Olaparib concentration increased from 1 h to 3 h and remained relatively stable until 24 h. Results suggest that the resistance mechanism induced by Olaparib in TNBL SUM1315 cell line may be overpassed if a cytotoxic and stable intracellular level of the drug can be maintained.
Sodium butyrate alleviates adipocyte inflammation by inhibiting NLRP3 pathway
Authors: Wang Xukai , He Gang , Peng Yan , Zhong Weitian , Wang Yan , Zhang Bo 
Published: August 2015

AbstractInsulin resistance (IR) is a common feature of Type II diabetes, metabolic disorders, hypertension and other vascular diseases. Recent studies showed that obesity-induced inflammation may be critical for IR. To investigate the anti-inflammatory effect of sodium butyrate (NaB) on obesity-induced inflammation, the db/db mice were intraperitoneally injected with NaB for 6 weeks. Glucose control was evaluated by glucose tolerance test (GTT) and insulin tolerance test (ITT). Adipose tissue was harvested for gene expression analysis. 3T3-L1 adipocytes were treated with Tnf-α to mimic the inflammatory state and gene expression was detected by realtime PCR and Western blotting. Our results showed that NaB treatment improved glucose control in db/db mice as determined by GTT and ITT tests. Gene expression analysis showed that NaB inhibited cytokines and immunological markers including CD68, Interferon-γ and Mcp in adipose tissues in db/db mice. Moreover, NaB inhibited cytokine releasing in 3T3-L1 adipocytes treated with TNF-α. Further analysis of inflammation pathway showed that NLRP3 was activated in db/db mice, which was efficiently inhibited by NaB treatment. Our data suggest that inhibition of obesity-induced inflammation alleviates IR and NaB might be a potential anti-inflammatory agent for obesity.
Adaptation of the human aryl hydrocarbon receptor to sense microbiota-derived indoles
Authors: Hubbard Troy D. , Murray Iain A. , Bisson William H. , Lahoti Tejas S. , Gowda Krishne , Amin Shantu G. , Patterson Andrew D. , Perdew Gary H. 
Published: August 2015

AbstractLigand activation of the aryl hydrocarbon (AHR) has profound effects upon the immunological status of the gastrointestinal tract, establishing and maintaining signaling networks, which facilitate host-microbe homeostasis at the mucosal interface. However, the identity of the ligand(s) responsible for such AHR-mediated activation within the gut remains to be firmly established. Here, we combine in vitro ligand binding, quantitative gene expression, protein-DNA interaction and ligand structure activity analyses together with in silico modeling of the AHR ligand binding domain to identify indole, a microbial tryptophan metabolite, as a human-AHR selective agonist. Human AHR, acting as a host indole receptor may exhibit a unique bimolecular (2:1) binding stoichiometry not observed with typical AHR ligands. Such bimolecular indole-mediated activation of the human AHR within the gastrointestinal tract may provide a foundation for inter-kingdom signaling between the enteric microflora and the immune system to promote commensalism within the gut.
Molecular architecture of silk fibroin of Indian golden silkmoth, Antheraea assama
Authors: Gupta K Adarsh , Mita Kazuei , Arunkumar Kallare P. , Nagaraju Javaregowda 
Published: August 2015

AbstractThe golden silk spun by Indian golden silkmothAntheraea assama,is regarded for its shimmering golden luster, tenacity and value as biomaterial. This report describes the gene coding for golden silk H-fibroin (AaFhc), its expression, full-length sequence and structurally important motifs discerning the underlying genetic and biochemical factors responsible for its much sought-after properties. The coding region, with biased isocodons, encodes highly repetitious crystalline core, flanked by a pair of 5′ and 3′ non-repetitious ends.AaFhcmRNA expression is strictly territorial, confined to the posterior silk gland, encoding a protein of size 230 kDa, which makes homodimers making the elementary structural units of the fibrous core of the golden silk. Characteristic polyalanine repeats that make tight β-sheet crystals alternate with non-polyalanine repeats that make less orderly antiparallel β-sheets, β-turns and partial α-helices. Phylogenetic analysis of the conserved N-terminal amorphous motif and the comparative analysis of the crystalline region with other saturniid H-fibroins reveal that AaFhc has longer, numerous and relatively uniform repeat motifs with lower serine content that assume tighter β-crystals and denser packing, which are speculated to be responsible for its acclaimed properties of higher tensile strength and higher refractive index responsible for golden luster.
Protease recognition sites in Bet v 1a are cryptic, explaining its slow processing relevant to its allergenicity
Authors: Freier Regina , Dall Elfriede , Brandstetter Hans 
Published: August 2015

AbstractDespite a high similarity with homologous protein families, only few proteins trigger an allergic immune response with characteristic TH2 polarization. This puzzling observation is illustrated by the major birch pollen allergen Bet v 1a and its hypoallergenic protein isoforms, e.g., Bet v 1d. Given the key role of proteolytic processing in antigen presentation and T cell polarization, we investigated the recognition of Bet v 1 isoforms by the relevant protease cathepsin S. We found that at moderately acidic pH values Bet v 1a bound to cathepsin S with significantly lower affinity and was more slowly cleaved than its hypoallergenic isoform Bet v 1d. Only at pH values ≤4.5 the known proteolytic cleavage sites in Bet v 1a became accessible, resulting in a strong increase in affinity towards cathepsin S. Antigen processing and class II MHC loading occurs at moderately acidic compartments where processing of Bet v 1a and Bet v 1d differs distinctly. This difference translates into low and high density class II MHC loading and subsequently in TH2 and TH1 polarization, respectively.
Identification of a DYRK1A Inhibitor that Induces Degradation of the Target Kinase using Co-chaperone CDC37 fused with Luciferase nanoKAZ
Authors: Sonamoto Rie , Kii Isao , Koike Yuka , Sumida Yuto , Kato-Sumida Tomoe , Okuno Yukiko , Hosoya Takamitsu , Hagiwara Masatoshi 
Published: August 2015

AbstractThe protein kinase family includes attractive targets for drug development. Methods for screening of kinase inhibitors remain largely limited to in vitro catalytic assays. It has been shown that ATP-competitive inhibitors antagonize interaction between the target kinase and kinase-specific co-chaperone CDC37 in living cells. Here we show a cell-based method to screen kinase inhibitors using fusion protein of CDC37 with a mutated catalytic 19-kDa component of Oplophorus luciferase, nanoKAZ (CDC37-nanoKAZ). A dual-specificity kinase DYRK1A, an importance of which has been highlighted in Alzheimer’s disease, was targeted in this study. We established 293T cells stably expressing CDC37-nanoKAZ and analyzed interaction between CDC37-nanoKAZ and DYRK1A. We revealed that DYRK1A interacted with CDC37-nanoKAZ. Importantly, point mutations that affect autophosphorylation strengthened the interaction, thus improving signal/noise ratio of the interaction relative to non-specific binding of CDC37-nanoKAZ. This high signal/noise ratio enabled screening of chemical library that resulted in identification of a potent inhibitor of DYRK1A, named CaNDY. CaNDY induced selective degradation of DYRK1A and inhibited catalytic activity of recombinant DYRK1A with IC50 value of 7.9 nM by competing with ATP. This method based on a mutant target kinase and a bioluminescence-eliciting co-chaperone CDC37 could be applicable to evaluation and development of inhibitors targeting other kinases.