bluuebunny/crossref_metadata_2025_split huggingface dataset:
The end-joining factor Ku acts in the end-resection of double strand break-free arrested replication forks
Authors: Teixeira-Silva Ana , Ait Saada Anissia , Hardy Julien , Iraqui Ismail , Nocente Marina Charlotte , Fréon Karine , Lambert Sarah A. E. 
Published: December 2017

AbstractReplication requires homologous recombination (HR) to stabilize and restart terminally arrested forks. HR-mediated fork processing requires single stranded DNA (ssDNA) gaps and not necessarily double strand breaks. We used genetic and molecular assays to investigate fork-resection and restart at dysfunctional, unbroken forks in Schizosaccharomyces pombe. Here, we report that fork-resection is a two-step process regulated by the non-homologous end joining factor Ku. An initial resection mediated by MRN-Ctp1 removes Ku from terminally arrested forks, generating ~110 bp sized gaps obligatory for subsequent Exo1-mediated long-range resection and replication restart. The mere lack of Ku impacts the processing of arrested forks, leading to an extensive resection, a reduced recruitment of RPA and Rad51 and a slower fork-restart process. We propose that terminally arrested forks undergo fork reversal, providing a single DNA end for Ku binding. We uncover a role for Ku in regulating end-resection of unbroken forks and in fine-tuning HR-mediated replication restart.
Observation of superparamagnetism in coexistence with quantum anomalous Hall C = ±1 and C = 0 Chern states
Authors: Lachman Ella O. , Mogi Masataka , Sarkar Jayanta , Uri Aviram , Bagani Kousik , Anahory Yonathan , Myasoedov Yuri , Huber Martin E. , Tsukazaki Atsushi , Kawasaki Masashi , Tokura Yoshinori , Zeldov Eli 
Published: December 2017

AbstractSimultaneous transport and scanning nanoSQUID-on-tip magnetic imaging studies in Cr-(Bi,Sb)2Te3 modulation-doped films reveal the presence of superparamagnetic order within the quantum anomalous Hall regime. In contrast to the expectation that a long-range ferromagnetic order is required for establishing the quantum anomalous Hall state, superparamagnetic dynamics of weakly interacting nanoscale magnetic islands is observed both in the plateau transition regions, as well as within the fully quantized C = ±1 Chern plateaus. Modulation doping of the topological insulator films is found to give rise to significantly larger superparamagnetic islands as compared to uniform magnetic doping, evidently leading to enhanced robustness of the quantum anomalous Hall effect. Nonetheless, even in this more robust quantum state, attaining full quantization of transport coefficients requires magnetic alignment of at least 95% of the superparamagnetic islands. The superparamagnetic order is also found within the incipient C = 0 zero Hall plateau, which may host an axion state if the top and bottom magnetic layers are magnetized in opposite directions. In this regime, however, a significantly lower level of island alignment is found in our samples, hindering the formation of the axion state. Comprehension and control of superparamagnetic dynamics is thus a key factor in apprehending the fragility of the quantum anomalous Hall state and in enhancing the endurance of the different quantized states to higher temperatures for utilization of robust topological protection in novel devices.
The evolution of the macrophage-specific enhancer (Fms intronic regulatory element) within the CSF1R locus of vertebrates
Authors: Hume David A. , Wollscheid-Lengeling Evi , Rojo Rocio , Pridans Clare 
Published: December 2017

AbstractThe Csf1r locus encodes the receptor for macrophage colony-stimulating factor, which controls the proliferation, differentiation and survival of macrophages. The 300 bp Fms intronic regulatory element (FIRE), within the second intron of Csf1r, is necessary and sufficient to direct macrophage-specific transcription. We have analysed the conservation and divergence of the FIRE DNA sequence in vertebrates. FIRE is present in the same location in the Csf1r locus in reptile, avian and mammalian genomes. Nearest neighbor analysis based upon this element alone largely recapitulates phylogenies inferred from much larger genomic sequence datasets. One core element, containing binding sites for AP1 family and the macrophage-specific transcription factor, PU.1, is conserved from lizards to humans. Around this element, the FIRE sequence is conserved within clades with the most conserved elements containing motifs for known myeloid-expressed transcription factors. Conversely, there is little alignment between clades outside the AP1/PU.1 element. The analysis favours a hybrid between “enhanceosome” and “smorgasbord” models of enhancer function, in which elements cooperate to bind components of the available transcription factor milieu.
MicroRNA-like RNAs from the same miRNA precursors play a role in cassava chilling responses
Authors: Zeng Changying , Xia Jing , Chen Xin , Zhou Yufei , Peng Ming , Zhang Weixiong 
Published: December 2017

AbstractMicroRNAs (miRNAs) are known to play important roles in various cellular processes and stress responses. MiRNAs can be identified by analyzing reads from high-throughput deep sequencing. The reads realigned to miRNA precursors besides canonical miRNAs were initially considered as sequencing noise and ignored from further analysis. Here we reported a small-RNA species of phased and half-phased miRNA-like RNAs different from canonical miRNAs from cassava miRNA precursors detected under four distinct chilling conditions. They can form abundant multiple small RNAs arranged along precursors in a tandem and phased or half-phased fashion. Some of these miRNA-like RNAs were experimentally confirmed by re-amplification and re-sequencing, and have a similar qRT-PCR detection ratio as their cognate canonical miRNAs. The target genes of those phased and half-phased miRNA-like RNAs function in process of cell growth metabolism and play roles in protein kinase. Half-phased miR171d.3 was confirmed to have cleavage activities on its target gene P-glycoprotein 11, a broad substrate efflux pump across cellular membranes, which is thought to provide protection for tropical cassava during sharp temperature decease. Our results showed that the RNAs from miRNA precursors are miRNA-like small RNAs that are viable negative gene regulators and may have potential functions in cassava chilling responses.
Active-site plasticity revealed in the asymmetric dimer of AnPrx6 the 1-Cys peroxiredoxin and molecular chaperone from Anabaena sp. PCC 7120
Authors: Mishra Yogesh , Hall Michael , Locmelis Roland , Nam Kwangho , Söderberg Christopher A. G. , Storm Patrik , Chaurasia Neha , Rai Lal Chand , Jansson Stefan , Schröder Wolfgang P. , Sauer Uwe H. 
Published: December 2017

AbstractPeroxiredoxins (Prxs) are vital regulators of intracellular reactive oxygen species levels in all living organisms. Their activity depends on one or two catalytically active cysteine residues, the peroxidatic Cys (CP) and, if present, the resolving Cys (CR). A detailed catalytic cycle has been derived for typical 2-Cys Prxs, however, little is known about the catalytic cycle of 1-Cys Prxs. We have characterized Prx6 from the cyanobacteriumAnabaenasp. strain PCC7120 (AnPrx6) and found that in addition to the expected peroxidase activity, AnPrx6 can act as a molecular chaperone in its dimeric state, contrary to other Prxs. The AnPrx6 crystal structure at 2.3 Å resolution reveals different active site conformations in each monomer of the asymmetric obligate homo-dimer. Molecular dynamic simulations support the observed structural plasticity. A FSH motif, conserved in 1-Cys Prxs, precedes the active site PxxxTxxCp signature and might contribute to the 1-Cys Prx reaction cycle.
Pre-treatment inflammatory indexes as predictors of survival and cetuximab efficacy in metastatic colorectal cancer patients with wild-type RAS
Authors: Yang Jing , Guo Xinli , Wang Manni , Ma Xuelei , Ye Xiaoyang , Lin Panpan 
Published: December 2017

AbstractThis study aims at evaluating the prognostic significance of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation indexes (SII) in metastatic colorectal cancer (mCRC) patients treated with cetuximab. Ninety-five patients receiving cetuximab for mCRC were categorized into the high or low NLR, PLR, LMR, and SII groups based on their median index values. Univariate and multivariate survival analysis were performed to identify the indexes’ correlation with progression-free survival (PFS) and overall survival (OS). In the univariate analysis, ECOG performance status, neutrphil counts, lymphocyte counts, monocyte counts, NLR, PLR, and LDH were associated with survival. Multivariate analysis showed that ECOG performance status of 0 (hazard ratio [HR] 3.608, p < 0.001; HR 5.030, p < 0.001, respectively), high absolute neutrophil counts (HR 2.837, p < 0.001; HR 1.922, p = 0.026, respectively), low lymphocyte counts (HR 0.352, p < 0.001; HR 0.440, p = 0.001, respectively), elevated NLR (HR 3.837, p < 0.001; HR 2.467, p = 0.006) were independent predictors of shorter PFS and OS. In conclusion, pre-treatment inflammatory indexes, especially NLR were potential biomarkers to predict the survival of mCRC patients with cetuximab therapy.
Proteomics and antivenomics of Echis carinatus carinatus venom: Correlation with pharmacological properties and pathophysiology of envenomation
Authors: Patra Aparup , Kalita Bhargab , Chanda Abhishek , Mukherjee Ashis K. 
Published: December 2017

AbstractThe proteome composition of Echis carinatus carinatus venom (ECV) from India was studied for the first time by tandem mass spectrometry analysis. A total of 90, 47, and 22 distinct enzymatic and non-enzymatic proteins belonging to 15, 10, and 6 snake venom protein families were identified in ECV by searching the ESI-LC-MS/MS data against non-redundant protein databases of Viperidae (taxid 8689), Echis (taxid 8699) and Echis carinatus (taxid 40353), respectively. However, analysis of MS/MS data against the Transcriptome Shotgun Assembly sequences (87 entries) of conger E. coloratus identified only 14 proteins in ECV. Snake venom metalloproteases and snaclecs, the most abundant enzymatic and non-enzymatic proteins, respectively in ECV account for defibrinogenation and the strong in vitro pro-coagulant activity. Further, glutaminyl cyclase, aspartic protease, aminopeptidase, phospholipase B, vascular endothelial growth factor, and nerve growth factor were reported for the first time in ECV. The proteome composition of ECV was well correlated with its biochemical and pharmacological properties and clinical manifestations observed in Echis envenomed patients. Neutralization of enzymes and pharmacological properties of ECV, and immuno-cross-reactivity studies unequivocally point to the poor recognition of <20 kDa ECV proteins, such as PLA2, subunits of snaclec, and disintegrin by commercial polyvalent antivenom.
Semantic discrimination impacts tDCS modulation of verb processing
Authors: Niccolai Valentina , Klepp Anne , Indefrey Peter , Schnitzler Alfons , Biermann-Ruben Katja 
Published: December 2017

AbstractMotor cortex activation observed during body-related verb processing hints at simulation accompanying linguistic understanding. By exploiting the up- and down-regulation that anodal and cathodal transcranial direct current stimulation (tDCS) exert on motor cortical excitability, we aimed at further characterizing the functional contribution of the motor system to linguistic processing. In a double-blind sham-controlled within-subjects design, online stimulation was applied to the left hemispheric hand-related motor cortex of 20 healthy subjects. A dual, double-dissociation task required participants to semantically discriminate concrete (hand/foot) from abstract verb primes as well as to respond with the hand or with the foot to verb-unrelated geometric targets. Analyses were conducted with linear mixed models. Semantic priming was confirmed by faster and more accurate reactions when the response effector was congruent with the verb’s body part. Cathodal stimulation induced faster responses for hand verb primes thus indicating a somatotopical distribution of cortical activation as induced by body-related verbs. Importantly, this effect depended on performance in semantic discrimination. The current results point to verb processing being selectively modifiable by neuromodulation and at the same time to a dependence of tDCS effects on enhanced simulation. We discuss putative mechanisms operating in this reciprocal dependence of neuromodulation and motor resonance.
Effect of canola oil consumption on memory, synapse and neuropathology in the triple transgenic mouse model of Alzheimer’s disease
Authors: Lauretti Elisabetta , Praticò Domenico 
Published: December 2017

AbstractIn recent years consumption of canola oil has increased due to lower cost compared with olive oil and the perception that it shares its health benefits. However, no data are available on the effect of canola oil intake on Alzheimer’s disease (AD) pathogenesis. Herein, we investigated the effect of chronic daily consumption of canola oil on the phenotype of a mouse model of AD that develops both plaques and tangles (3xTg). To this end mice received either regular chow or a chow diet supplemented with canola oil for 6 months. At this time point we found that chronic exposure to the canola-rich diet resulted in a significant increase in body weight and impairments in their working memory together with decrease levels of post-synaptic density protein-95, a marker of synaptic integrity, and an increase in the ratio of insoluble Aβ 42/40. No significant changes were observed in tau phosphorylation and neuroinflammation. Taken together, our findings do not support a beneficial effect of chronic canola oil consumption on two important aspects of AD pathophysiology which includes memory impairments as well as synaptic integrity. While more studies are needed, our data do not justify the current trend aimed at replacing olive oil with canola oil.
ciaR impacts biofilm formation by regulating an arginine biosynthesis pathway in Streptococcus sanguinis SK36
Authors: Zhu Bin , Ge Xiuchun , Stone Victoria , Kong Xiangzhen , El-Rami Fadi , Liu Yan , Kitten Todd , Xu Ping 
Published: December 2017

AbstractStreptococcus sanguinis is an early colonizer of the tooth surface and competes with oral pathogens such as Streptococcus mutans to maintain oral health. However, little is known about its mechanism of biofilm formation. Here, we show that mutation of the ciaR gene, encoding the response regulator of the CiaRH two-component system in S. sanguinis SK36, produced a fragile biofilm. Cell aggregation, gtfP gene expression and water-insoluble glucan production were all reduced, which suggested polysaccharide production was decreased in ΔciaR. RNA sequencing and qRT-PCR revealed that arginine biosynthesis genes (argR, argB, argC, argG, argH and argJ) and two arginine/histidine permease genes (SSA_1568 and SSA_1569) were upregulated in ΔciaR. In contrast to ΔciaR, most of strains constructed to contain deletions in each of these genes produced more biofilm and water-insoluble glucan than SK36. A ΔciaRΔargB double mutant was completely restored for the gtfP gene expression, glucan production and biofilm formation ability that was lost in ΔciaR, indicating that argB was essential for ciaR to regulate biofilm formation. We conclude that by promoting the expression of arginine biosynthetic genes, especially argB gene, the ciaR mutation reduced polysaccharide production, resulting in the formation of a fragile biofilm in Streptococcus sanguinis.
Tumor necrosis factor-alpha regulates photoreceptor cell autophagy after retinal detachment
Authors: Xie Jia , Zhu Ruilin , Peng Yuan , Gao Wenna , Du Jiantong , Zhao Liang , Chi Ying , Yang Liu 
Published: December 2017

AbstractPhotoreceptor cell death is the ultimate process underlying many retinal diseases, including retinal detachment (RD). Both autophagy and inflammatory factors, such as tumor necrosis factor-alpha (TNF-α), participate in photoreceptor cell death after RD. In this study, we examined whether TNF-α inhibition would impact the autophagy of photoreceptors and reduce the death of photoreceptors after retinal detachment (RD). RD models were created in C57BL/6J mice by a subretinal injection of 1% hyaluronic acid. The TNF-α inhibitor infliximab was administered via intraperitoneal injection two hours before RD. The levels of TNF-α and the autophagy-related proteins Atg5 and LC3B were assayed by immunofluorescence at 1 day, 3 days, and 7 days following RD. Apoptosis was examined at 3 days post-detachment via TUNEL assays. Photoreceptor cell counts were assessed at 7 days after RD. After RD, the protein levels of LC3B and Atg5 increased and reached a peak at 3 days, which decreased at 7 days. The expression of LC3B and Atg5 was prolonged and increased at a slower rate with TNF-α inhibition. The moderate augmentation and extension of autophagy through TNF-α inhibition resulted in the reduction of apoptosis and the enhancement of photoreceptor cell survival.
Structural analysis of the complex between influenza B nucleoprotein and human importin-α
Authors: Labaronne Alice , Milles Sigrid , Donchet Amélie , Jensen Malene Ringkjøbing , Blackledge Martin , Bourhis Jean-Marie , Ruigrok Rob W. H. , Crépin Thibaut 
Published: December 2017

AbstractInfluenza viruses are negative strand RNA viruses that replicate in the nucleus of the cell. The viral nucleoprotein (NP) is the major component of the viral ribonucleoprotein. In this paper we show that the NP of influenza B has a long N-terminal tail of 70 residues with intrinsic flexibility. This tail contains the Nuclear Location Signal (NLS). The nuclear trafficking of the viral components mobilizes cellular import factors at different stages, making these host-pathogen interactions promising targets for new therapeutics. NP is imported into the nucleus by the importin-α/β pathway, through a direct interaction with importin-α isoforms. Here we provide a combined nuclear magnetic resonance and small-angle X-ray scattering (NMR/SAXS) analysis to describe the dynamics of the interaction between influenza B NP and the human importin-α. The NP of influenza B does not have a single NLS nor a bipartite NLS but our results suggest that the tail harbors several adjacent NLS sequences, located between residues 30 and 71.
Local Production of Activated Factor X in Atherosclerotic Plaque Induced Vascular Smooth Muscle Cell Senescence
Authors: Sanada Fumihiro , Muratsu Jun , Otsu Rei , Shimizu Hideo , Koibuchi Nobutaka , Uchida Kazutaka , Taniyama Yoshiaki , Yoshimura Shinichi , Rakugi Hiromi , Morishita Ryuichi 
Published: December 2017

AbstractOur previous study demonstrated that coagulation factor Xa (FXa) induced endothelial cell senescence, resulting in inflammation and impaired angiogenesis. This mechanism is dictated through protease-activated receptors, PARs, insulin-like growth factor-binding protein 5 (IGFBP-5), and p53. Activation of PARs contributes to the pathophysiology of several chronic inflammatory diseases, including atherosclerosis. Thus, we speculated that similar mechanism might participate in the progression of atherosclerotic plaques. In the present study, we successfully identified the cells that produced FX/Xa in atherosclerosis using human atherosclerotic plaques obtained from carotid endarterectomy. In situ hybridization for FX revealed that FX was generated in vascular smooth muscle cells (VSMC), inflammatory cells, and endothelial cells. Then, we examined the effects of FXa on the growth of VSMC in vitro. The present study revealed that chronic FXa stimulation significantly induced the senescence of VSMC with concomitant upregulation of IGFBP-5 and p53. Inhibition of FXa signaling with rivaroxaban or knock down of IGFBP-5 significantly reduced FXa-induced VSMC senescence and inflammatory cytokine production. Finally, we confirmed that FXa and IGFBP-5 are co-distributed in atherosclerotic plaques. In conclusion, induction of senescence of VSMC induced by locally produced FX/Xa may contribute to the progression of atherosclerosis.
Energy curtailment of DC series–parallel connected offshore wind farms
Authors: Lakshmanan Padmavathi , Guo Jingli , Liang Jun 
Published: December 2017

This study presents an analysis of the energy curtailment caused by the DC series–parallel collection systems of HVDC connected offshore wind farms. Wind speed differences between the series connected wind turbines cause unequal voltages at the DC output of the wind turbines. This can lead to unacceptable over‐voltage or under‐voltage conditions. The over‐voltage and under‐voltage conditions on the turbine DC outputs can be avoided by curtailing the power outputs of the wind turbines, which will result in loss of wind power. The annual energy curtailment due to the over‐voltage limits of turbine DC–DC converters is analysed for a 200 MW DC series–parallel wind farm. The impact of wake effects on the energy curtailment losses is quantified and demonstrated with a case study.
Transcatheter Aortic Valve Replacement in Female Patients—Present Scenario
Authors: Itzhaki Ben Zadok Osnat , Orvin Katia , Kornowski Ran 
Published: December 2017

AbstractSince the publication of the pivotal PARTNER study, the transcatheter aortic valve replacement (TAVR) procedure has been established as a noninferior alternative to the traditional aortic valve replacement surgery in severe aortic stenosis (AS) patients with high-surgical risk. Approximately 50% of patients undergoing TAVR are females, and cumulative findings from various worldwide cohorts have shown sex-related differences in short- and long-term morbidity and mortality. Notably, most data indicate improved long-term mortality in female patients. These differences are partly the results of distinct anatomical and physiologic characteristics in female patients, compared with male patients. Nevertheless, recent data from intermediate-surgical risk cohorts have demonstrated that sex-related mortality differences are less apparent. Here, we review the latest literature on the influence of patient's sex on TAVR morbidity and mortality and discuss possible explanations for the outcomes presented.
Prophylactic Measures to Prevent Soft Tissue Abnormalities after Trauma
Authors: Sokoya Mofiyinfolu , Ducic Yadranko , Sawhney Raja 
Published: December 2017

AbstractThe goal of any reconstructive procedure is a complete return to premorbid form and function. Unfortunately, a return of pretraumatic form is routinely not considered during surgical planning. This leads to uncontrolled contracture of the soft tissue elements and permanent disfigurement. The goal of this article is to review interventions that improve soft tissue healing and long-term outcomes.
Repair of the Malpositioned Lower Lid
Authors: Chan David , Sokoya Mofiyinfolu , Ducic Yadranko 
Published: December 2017

AbstractComplications from surgical approaches to the orbit can be associated with debilitating morbidity and negative surgical outcomes. The surgeon must be familiar with the different factors that predispose a patient to these complications and be facile with techniques to avoid them. In this article, the authors discuss the surgical anatomy of the lower eyelid, as well as various complications that result from eyelid surgery, including lower lid retraction, ectropion, entropion, canthal malposition, and midface descent. They also discuss various management techniques that are employed in addressing these complications.
Complications of Facial Trauma of the Fronto-orbital Region
Authors: Cleveland Patrick , Smith Jesse 
Published: December 2017

AbstractTraumatic injuries to the orbitofrontal region place some of the most important structures of the face at risk: the eyes, frontal skull, and brain. A thorough knowledge of complications from resultant trauma, and from attempted surgical corrections, is necessary to offer patients the best outcomes, ensuring proper healing with excellent long-term results.