bluuebunny/crossref_metadata_2025_split huggingface dataset:
Opposing regulation of the late phase TNF response by mTORC1-IL-10 signaling and hypoxia in human macrophages
Authors: Huynh Linda , Kusnadi Anthony , Park Sung Ho , Murata Koichi , Park-Min Kyung-Hyun , Ivashkiv Lionel B. 
Published: August 2016

AbstractTumor necrosis factor (TNF) is best known for inducing a rapid but transient NF-κB-mediated inflammatory response. We investigated later phases of TNF signaling, after the initial transient induction of inflammatory genes has subsided, in primary human macrophages. TNF signaling induced expression of late response genes, including inhibitors of NF-κB and TLR signaling, with delayed and sustained kinetics 6–24 hr after TNF stimulation. A subset of late phase genes was expressed in rheumatoid arthritis synovial macrophages, confirming their expression under chronic inflammatory conditions in vivo. Expression of a subset of late phase genes was mediated by autocrine IL-10, which activated STAT3 with delayed kinetics. Hypoxia, which occurs at sites of infection or inflammation where TNF is expressed, suppressed this IL-10-STAT3 autocrine loop and expression of late phase genes. TNF-induced expression of IL-10 and downstream genes was also dependent on signaling by mTORC1, which senses the metabolic state of cells and is modulated by hypoxia. These results reveal an mTORC1-dependent IL-10-mediated late phase response to TNF by primary human macrophages, and identify suppression of IL-10 responses as a new mechanism by which hypoxia can promote inflammation. Thus, hypoxic and metabolic pathways may modulate TNF responses during chronic inflammation.
Arterialized Venous Bone Flaps: An Experimental Investigation
Authors: Borumandi Farzad , Higgins James P. , Buerger Heinz , Vasilyeva Anna , Benlidayi Memmet Emre , Sencar Leman , Gaggl Alexander 
Published: August 2016

AbstractIn arterialized venous flaps (AVFs) the venous network is used to revascularize the flap. While the feasibility of AVFs in soft tissues has been reported there is no study on osseous AVFs. In this study we aim to assess the flap survival of osseous AVFs in a pig model. Medial femoral condyle flaps were elevated in 18 pigs. Three groups were created: AVF (n = 6), conventional arterial flap (cAF, n = 6) and bone graft (BG, n = 6). The AVFs were created by anastomosis of genicular artery with one vena comitans while leaving one efferent vein for drainage. After 6 months the specimens were harvested. The histology and histomorphometry of of the bone in cAF and AVF was significantly superior to bone grafts with a higher bone volume in AVFs (p = 0.01). This study demonstrates that osseous free flaps may be supported and survive using the technique of arterialization of the venous network. The concept of AVFs in osseous flaps may be feasible for revascularization of free flaps with an inadequate artery but well developed veins. Further experimental and clinical studies are needed to assess the feasibility of clinical use of arterialized venous bone flaps.
Patterning nanofibrils through the templated growth of multiple modified amyloid peptides
Authors: Sakai Hiroki , Watanabe Ken , Kudoh Fuki , Kamada Rui , Chuman Yoshiro , Sakaguchi Kazuyasu 
Published: August 2016

AbstractThere has been considerable interest in the patterning of functionalized nanowires because of the potential applications of these materials to the construction of nanodevices. A variety of biomolecular building blocks containing amyloid peptides have been used to functionalize nanowires. However, the patterning of self-assembled nanowires can be challenging because of the difficulties associated with controlling the self-assembly of these functionalized building blocks. Herein, we present a versatile approach for the patterning of nanowires based on the combination of templated fibril growth with a versatile functionalization method using our structure-controllable amyloid peptides (SCAPs). Using this approach, we have succeeded in the formation of multi-type nanowires with tandem domain structures in high yields. Given that the mixing-SCAP method can lead to the formation of tandem fibrils, it is noteworthy that our method allowed us to control the initiation of fibril formation from the gold nanoparticles, which were attached to a short fibril as initiation points. This approach could be used to prepare a wide variety of fibril patterns and therefore holds great potential for the development of novel self-assembled nanodevices.
Quantitative proteomic comparison of stationary/G0 phase cells and tetrads in budding yeast
Authors: Kumar Ravinder , Srivastava Sanjeeva 
Published: August 2016

AbstractMost of the microbial cells on earth under natural conditions exist in a dormant condition, commonly known as quiescent state. Quiescent cells exhibit low rates of transcription and translation suggesting that cellular abundance of proteins may be similar in quiescent cells. Therefore, this study aim to compare the proteome of budding yeast cells from two quiescent states viz. stationary phase/G0 and tetrads. Using iTRAQ (isobaric tag for relative and absolute quantitation) based quantitative proteomics we identified 289 proteins, among which around 40 proteins exhibited ±1.5 fold change consistently from the four biological replicates. Proteomics data was validated by western blot and denstiometric analysis of Hsp12 and Spg4. Level of budding yeast 14-3-3 proteins was found to be similar in both the quiescent states, whereas Hsp12 and Spg4 expressed only during stress. FACS (fluorescence-activated cell sorting) analysis showed that budding yeast cells were arrested at G1 stages both in tetrads as well as in stationary phase. We also observed that quiescent states did not express Ime1 (inducer of meiosis). Taken together, our present study demonstrates that the cells in quiescent state may have similar proteome and accumulation of proteins like Hsp12, Hsp26 and Spg4 may play an important role in retaining viability of the cells during dormancy.
Exactin: A specific inhibitor of Factor X activation by extrinsic tenase complex from the venom of Hemachatus haemachatus
Authors: Girish Vallerinteavide Mavelli , Kini R. Manjunatha 
Published: August 2016

AbstractUnwanted clots lead to heart attack and stroke that result in a large number of deaths. Currently available anticoagulants have some drawbacks including their non-specific actions. Therefore novel anticoagulants that target specific steps in the coagulation pathway are being sought. Here we describe the identification and characterization of a novel anticoagulant protein from the venom of Hemachatus haemachatus (African Ringhals cobra) that specifically inhibits factor X (FX) activation by the extrinsic tenase complex (ETC) and thus named as exactin. Exactin belongs to the three-finger toxin (3FTx) family, with high sequence identity to neurotoxins and low identity to the well-characterized 3FTx anticoagulants-hemextin and naniproin. It is a mixed-type inhibitor of ETC with the kinetic constants, Ki’ and Ki determined as 30.62 ± 7.73 nM and 153.75 ± 17.96 nM, respectively. Exactin does not bind to the active site of factor VIIa and factor Xa based on its weak inhibition (IC50 ≫ 300 μM) to the amidolytic activities of these proteases. Exactin shows exquisite macromolecular specificity to FX activation as compared to factor IX activation by ETC. Exactin thus displays a distinct mechanism when compared to other anticoagulants targeting ETC, with its selective preference to ETC-FX [ES] complex.
Detection of nucleotide-specific CRISPR/Cas9 modified alleles using multiplex ligation detection
Authors: KC R. , Srivastava A. , Wilkowski J. M. , Richter C. E. , Shavit J. A. , Burke D. T. , Bielas S. L. 
Published: August 2016

AbstractCRISPR/Cas9 genome-editing has emerged as a powerful tool to create mutant alleles in model organisms. However, the precision with which these mutations are created has introduced a new set of complications for genotyping and colony management. Traditional gene-targeting approaches in many experimental organisms incorporated exogenous DNA and/or allele specific sequence that allow for genotyping strategies based on binary readout of PCR product amplification and size selection. In contrast, alleles created by non-homologous end-joining (NHEJ) repair of double-stranded DNA breaks generated by Cas9 are much less amenable to such strategies. Here we describe a novel genotyping strategy that is cost effective, sequence specific and allows for accurate and efficient multiplexing of small insertion-deletions and single-nucleotide variants characteristic of CRISPR/Cas9 edited alleles. We show that ligation detection reaction (LDR) can be used to generate products that are sequence specific and uniquely detected by product size and/or fluorescent tags. The method works independently of the model organism and will be useful for colony management as mutant alleles differing by a few nucleotides become more prevalent in experimental animal colonies.
A Quantitative Characterization of Nucleoplasmin/Histone Complexes Reveals Chaperone Versatility
Authors: Fernández-Rivero Noelia , Franco Aitor , Velázquez-Campoy Adrian , Alonso Edurne , Muga Arturo , Prado Adelina 
Published: August 2016

AbstractNucleoplasmin (NP) is an abundant histone chaperone in vertebrate oocytes and embryos involved in storing and releasing maternal histones to establish and maintain the zygotic epigenome. NP has been considered a H2A–H2B histone chaperone and recently it has been shown that it can also interact with H3-H4. However, its interaction with different types of histones has not been quantitatively studied so far. We show here that NP binds H2A–H2B, H3-H4 and linker histones with Kd values in the subnanomolar range, forming different complexes. Post-translational modifications of NP regulate exposure of the polyGlu tract at the disordered distal face of the protein and induce an increase in chaperone affinity for all histones. The relative affinity of NP for H2A–H2B and linker histones and the fact that they interact with the distal face of the chaperone could explain their competition for chaperone binding, a relevant process in NP-mediated sperm chromatin remodelling during fertilization. Our data show that NP binds H3-H4 tetramers in a nucleosomal conformation and dimers, transferring them to DNA to form disomes and tetrasomes. This finding might be relevant to elucidate the role of NP in chromatin disassembly and assembly during replication and transcription.
Association between mannose-binding lectin variants, haplotypes and risk of hepatocellular carcinoma: A case-control study
Authors: Su Chenghao , Lin Yong , Cai Lin , Mao Qianguo , Niu Jianjun 
Published: August 2016

AbstractThe innate immunity gene mannose-binding lectin2 (MBL2) has played an important role in hepatitis B virus (HBV) infection, and the relationship between MBL2 variants and hepatocellular carcinoma (HCC) risk has not yet been identified. In total, 315 HCC cases and 315 healthy controls were enrolled and blood samples were acquired. High resolution melt analysis (HRM) was employed to genotype 6 polymorphisms in MBL2 gene. Increased HCC risk in carriers of LL genotype of −550 polymorphism with an adjusted OR (AOR) of 1.61 (95%CI = 1.00–2.57) was observed but no significant association detected in HL genotype. Both YX and XX genotype demonstrated a significantly elevated HCC risk in the analysis of −221 polymorphism. The B variants in codon 54 was also significantly associated with elevated HCC risk. HYB was identified as the protective factor of HCC while LXB was significantly associated with increase HCC risk. ELISA technique revealed that the MBL2 protein was significantly reduced in HCC cases. Moreover, both IL-1β and IL-6 were inversely associated with plasma MBL2 level.The mutations in MBL2 could lead to compromised innate immunity, and possibly lead to elevated HCC risk, and a novel haplotype HXB has been identified with a rate of 12.5%.
Small secreted proteins enable biofilm development in the cyanobacterium Synechococcus elongatus
Authors: Parnasa Rami , Nagar Elad , Sendersky Eleonora , Reich Ziv , Simkovsky Ryan , Golden Susan , Schwarz Rakefet 
Published: August 2016

AbstractSmall proteins characterized by a double-glycine (GG) secretion motif, typical of secreted bacterial antibiotics, are encoded by the genomes of diverse cyanobacteria, but their functions have not been investigated to date. Using a biofilm-forming mutant of Synechococcus elongatus PCC 7942 and a mutational approach, we demonstrate the involvement of four small secreted proteins and their GG-secretion motifs in biofilm development. These proteins are denoted EbfG1-4 (enable biofilm formation with a GG-motif). Furthermore, the conserved cysteine of the peptidase domain of the Synpcc7942_1133 gene product (dubbed PteB for peptidase transporter essential for biofilm) is crucial for biofilm development and is required for efficient secretion of the GG-motif containing proteins. Transcriptional profiling of ebfG1-4 indicated elevated transcript levels in the biofilm-forming mutant compared to wild type (WT). However, these transcripts decreased, acutely but transiently, when the mutant was cultured in extracellular fluids from a WT culture and biofilm formation was inhibited. We propose that WT cells secrete inhibitor(s) that suppress transcription of ebfG1-4, whereas secretion of the inhibitor(s) is impaired in the biofilm-forming mutant, leading to synthesis and secretion of EbfG1-4 and supporting the formation of biofilms.
Mapping concentrations of posttraumatic stress and depression trajectories following Hurricane Ike
Authors: Gruebner Oliver , Lowe Sarah R. , Tracy Melissa , Joshi Spruha , Cerdá Magdalena , Norris Fran H. , Subramanian S. V. , Galea Sandro 
Published: August 2016

AbstractWe investigated geographic concentration in elevated risk for a range of postdisaster trajectories of chronic posttraumatic stress symptom (PTSS) and depression symptoms in a longitudinal study (N = 561) of a Hurricane Ike affected population in Galveston and Chambers counties, TX. Using an unadjusted spatial scan statistic, we detected clusters of elevated risk of PTSS trajectories, but not depression trajectories, on Galveston Island. We then tested for predictors of membership in each trajectory of PTSS and depression (e.g., demographic variables, trauma exposure, social support), not taking the geographic nature of the data into account. After adjusting for significant predictors in the spatial scan statistic, we noted that spatial clusters of PTSS persisted and additional clusters of depression trajectories emerged. This is the first study to show that longitudinal trajectories of postdisaster mental health problems may vary depending on the geographic location and the individual- and community-level factors present at these locations. Such knowledge is crucial to identifying vulnerable regions and populations within them, to provide guidance for early responders, and to mitigate mental health consequences through early detection of mental health needs in the population. As human-made disasters increase, our approach may be useful also in other regions in comparable settings worldwide.
Autophagy-associated dengue vesicles promote viral transmission avoiding antibody neutralization
Authors: Wu Yan-Wei , Mettling Clément , Wu Shang-Rung , Yu Chia-Yi , Perng Guey-Chuen , Lin Yee-Shin , Lin Yea-Lih 
Published: August 2016

AbstractOne of the major defense mechanisms against virus spread in vivo is the blocking of viral infectibility by neutralizing antibodies. We describe here the identification of infectious autophagy-associated dengue vesicles released from infected cells. These vesicles contain viral proteins E, NS1, prM/M and viral RNA, as well as host lipid droplets and LC3-II, an autophagy marker. The viral RNA can be protected within the autophagic organelles since anti-dengue neutralizing antibodies do not have an effect on the vesicle-mediated transmission that is able to initiate a new round of infection in target cells. Importantly, such infectious vesicles were also detected in a patient serum. Our study suggests that autophagy machinery plays a new role in dengue virus transmission. This discovery explains the inefficiency of neutralizing antibody upon dengue infection as a potential immune evasion mechanism in vivo.
Novel nanoscale bacteriophage-based single-domain antibodies for the therapy of systemic infection caused by Candida albicans
Authors: Dong Shuai , Shi Hongxi , Cao Donghui , Wang Yicun , Zhang Xintong , Li Yan , Gao Xiang , Wang Li 
Published: August 2016

AbstractCandida albicans (C. albicans) is an important human commensal and opportunistic fungal pathogen. Secreted aspartyl proteinases (Saps) are a major virulence trait of C. albicans, and among these proteases Sap2 has the highest expression levels. It is possible that antibodies against Sap2 could provide an antifungal effect. In this study, two phages displaying anti-rSap2 single chain variable fragments (scFvs) were screened from human single fold scFv libraries, and their potential therapeutic roles were evaluated using a murine model infected by C. albicans. The in vivo efficacies were assessed by mortality rates, fungal burden and histological examination. Overall survival rates were significantly increased while the colony counts and infectious foci were significantly decreased after treatment with the scFv-phages relative to the control groups. In order to investigate the immune response provoked by scFv-phages, three kinds of cytokines (Th1, Th2 and Th17 types) were measured and a clear immune response was observed. These findings suggest that anti-rSap2 scFv-phages have potential in the therapy of systemic infection caused by C. albicans.
Down-regulation of SerpinB2 is associated with gefitinib resistance in non-small cell lung cancer and enhances invadopodia-like structure protrusions
Authors: Bae Song Yi , Park Hyen Joo , Hong Ji-Young , Lee Hye-Jung , Lee Sang Kook 
Published: August 2016

AbstractThe failure of targeted therapy due to the resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, is considered a major problem in the treatment of non-small cell lung cancer (NSCLC) patients. SerpinB2, a component of the urokinase plasminogen activator (uPA) system, has been recognized as a biomarker for the progression and metastasis of lung cancer. Nevertheless, the relationship between SerpinB2 and EGFR-TKI resistance has not been elucidated. Here, we report that SerpinB2 is down-regulated in gefitinib-resistant (H292-Gef) cells compared to gefitinib-sensitive (H292) cells. The low SerpinB2 levels in H292-Gef cells were also associated with an enhancement in invasiveness and increase in the length of invadopodia-like structures in the cells. The effect on invasiveness and gefitinib sensitivity was confirmed by knockdown and overexpression of SerpinB2. In addition, the possibility to overcome the resistance through the up-regulation of SerpinB2 was supported by employing an antitumor agent yuanhuadine (YD). Treatment with YD effectively elevated SerpinB2 levels and suppressed invasive properties in H292-Gef cells. Collectively, these findings demonstrate the prospective role of SerpinB2 as a novel biomarker for acquired gefitinib resistance and a potential target for NSCLC treatment.
The Role of Emergent Bilingualism in the Development of Morphological Awareness in Arabic and Hebrew
Authors: Schwartz Mila , Taha Haitham , Assad Hanan , Khamaisi Ferdos , Eviatar Zohar 
Published: August 2016

Purpose
The purpose of the present study was to investigate the role of dual language development and cross-linguistic influence on morphological awareness in young bilinguals' first language (L1) and second language (L2). We examined whether (a) the bilingual children (L1/L2 Arabic and L1/L2 Hebrew) precede their monolingual Hebrew- or Arabic-speaking peers in L1 and L2 morphological awareness, and (b) 1 Semitic language (Arabic) has cross-linguistic influence on another Semitic language (Hebrew) in morphological awareness.

Method
The study sample comprised 93 six-year-old children. The bilinguals had attended bilingual Hebrew−Arabic kindergartens for 1 academic year and were divided into 2 groups: home language Hebrew (L1) and home language Arabic (L1). These groups were compared to age-matched monolingual Hebrew speakers and monolingual Arabic speakers. We used nonwords similar in structure to familiar words in both target languages, representing 6 inflectional morphological categories.

Results
L1 Arabic and L1 Hebrew bilinguals performed significantly better than Arabic- and Hebrew-speaking monolinguals in the respective languages. Differences were not found between the bilingual groups. We found evidence of cross-linguistic transfer of morphological awareness from Arabic to Hebrew in 2 categories−bound possessives and dual number−probably because these categories are more salient in Palestinian Spoken Arabic than in Hebrew.

Conclusions
We conclude that children with even an initial exposure to L2 reveal acceleration of sensitivity to word structure in both of their languages. We suggest that this is due to the fact that two Semitic languages, Arabic and Hebrew, share a common core of linguistic features, together with favorable contextual factors and instructional factors.
Evaluating interdisciplinary research: the elephant in the peer-reviewers’ room
Authors: McLeish Tom , Strang Veronica 
Published: August 2016

AbstractWe review a selection of published reports on the evaluation and wider peer-review of interdisciplinary research (IDR), drawing on an in-depth examination of a range of interdisciplinary projects and the work of a UK-based working group of funders and researchers. Our aim is to elucidate best practice. We focus the study on integrative, interdisciplinary projects, rather than those at the level of “multidisciplinary dialogue”. Five areas of evaluation (publishing, research grants, careers, IDR centres, institutions) demonstrate both commonality and difference in the task of measuring added value in IDR collaborations. We find that, although single-discipline peer review processes are poorly suited to address IDR, a framework that starts with the assumption that IDR is a fundamental academic research practice is effective for single-discipline evaluation as well. This article is published as part of a collection on interdisciplinarity.
Wettability control on multiphase flow in patterned microfluidics
Authors: Zhao Benzhong , MacMinn Christopher W. , Juanes Ruben 
Published: August 2016

Significance
The simultaneous flow of multiple fluid phases through a porous solid occurs in many natural and industrial processes—for example, rainwater infiltrates into soil by displacing air, and carbon dioxide is stored in deep saline aquifers by displacing brine. It has been known for decades that wetting—the affinity of the solid to one of the fluids—can have a strong impact on the flow, but the microscale physics and macroscopic consequences remain poorly understood. Here, we study this in detail by systematically varying the wetting properties of a microfluidic porous medium. Our high-resolution images reveal the fundamental control of wetting on multiphase flow, elucidate the inherently 3D pore-scale mechanisms, and help explain the striking macroscopic displacement patterns that emerge.