bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure of Turnip mosaic virus and its viral-like particles
Authors: Cuesta Rebeca , Yuste-Calvo Carmen , Gil-Cartón David , Sánchez Flora , Ponz Fernando , Valle Mikel 
Published: October 2019

AbstractTurnip mosaic virus (TuMV), a potyvirus, is a flexible filamentous plant virus that displays a helical arrangement of coat protein copies (CPs) bound to the ssRNA genome. TuMV is a bona fide representative of the Potyvirus genus, one of most abundant groups of plant viruses, which displays a very wide host range. We have studied by cryoEM the structure of TuMV virions and its viral-like particles (VLPs) to explore the role of the interactions between proteins and RNA in the assembly of the virions. The results show that the CP-RNA interaction is needed for the correct orientation of the CP N-terminal arm, a region that plays as a molecular staple between CP subunits in the fully assembled virion.
A highly sensitive safrole sensor based on polyvinyl acetate (PVAc) nanofiber-coated QCM
Authors: Triyana Kuwat , Rianjanu Aditya , Nugroho Doni Bowo , As’ari Ahmad Hasan , Kusumaatmaja Ahmad , Roto Roto , Suryana Risa , Wasisto Hutomo Suryo 
Published: October 2019

AbstractA novel, highly sensitive and selective safrole sensor has been developed using quartz crystal microbalance (QCM) coated with polyvinyl acetate (PVAc) nanofibers. The nanofibers were collected on the QCM sensing surface using an electrospinning method with an average diameter ranging from 612 nm to 698 nm and relatively high Q–factors (rigid coating). Scanning electron microscopy (SEM) and atomic force microscopy (AFM) were used to analyze the PVAc nanofiber surface morphology, confirming its high surface area and roughness, which are beneficial in improving the sensor sensitivity compared to its thin-film counterpart. The as-spun PVAc nanofiber sensor could demonstrate a safrole limit of detection (LOD) of down to 0.7 ppm with a response time of 171 s and a sensitivity of 1.866 Hz/ppm. It also showed good reproducibility, rapid response time, and excellent recovery. Moreover, cross-interference of the QCM sensor response to non-target gases was investigated, yielding very low cross-sensitivity and high selectivity of the safrole sensor. Owing to its high robustness and low fabrication cost, this proposed sensing device is expected to be a promising alternative to classical instrumental analytical methods for monitoring safrole-based drug precursors.
Use of reliable contraceptives and its correlates among women participating in Simulated HIV vaccine efficacy trials in key-populations in Uganda
Authors: Abaasa Andrew , Todd Jim , Mayanja Yunia , Price Matt , Fast Patricia E. , Kaleebu Pontiano , Nash Stephen 
Published: October 2019

AbstractTo prevent pregnancy in trials, reliable contraceptive use is key. We investigated reliable contraceptive use at baseline and six months in key-populations in Uganda, during two Simulated HIV Vaccine Efficacy trials (SiVETs). SiVETs were nested within observational cohorts of Fisherfolk (2012–2014) and Female sex workers (2014–2017). Women in the observational cohorts were screened and enrolled into the SiVET. The trial administered a licensed Hepatitis B vaccine at 0, 1 and 6 months. Contraceptive use data were recorded at baseline and follow-up clinic visits. Reliable contraceptives (injectable Depot Medroxyprogesterone Acetate (DMPA), implant, pills, and intrauterine device (IUD)) were promoted and provided to women not using a reliable method at enrolment. Overall, 367 women were enrolled. At baseline 203 (55%) reported use of reliable contraceptive. Of the 164 women not using a reliable method at enrolment, 131 (80%) started using them during follow-up bringing the overall number to 334 (91%) at the end of follow-up. Young age (≤35 years) was an independent predictor of reliable contraceptive use at both time points while other factors varied. Promotion and provision of reliable contraceptives increased the proportion using them and could help reduce the risk of pregnancy in future HIV prevention trials.
Identification of novel targets for host-directed therapeutics against intracellular Staphylococcus aureus
Authors: Bravo-Santano Natalia , Capilla-Lasheras Pablo , Mateos Luis M. , Calle Yolanda , Behrends Volker , Letek Michal 
Published: October 2019

AbstractDuring patient colonization,Staphylococcus aureusis able to invade and proliferate within human cells to evade the immune system and last resort drugs such as vancomycin. Hijacking specific host molecular factors and/or pathways is necessary for pathogens to successfully establish an intracellular infection. In this study, we employed an unbiased shRNA screening coupled with ultra-fast sequencing to screen 16,000 human genes duringS. aureusinfection and we identified several host genes important for this intracellular pathogen. In addition, we interrogated our screening results to find novel host-targeted therapeutics against intracellularS. aureus. We found that silencing the human geneTRAM2resulted in a significant reduction of intracellular bacterial load while host cell viability was restored, showing its importance during intracellular infection. Furthermore, TRAM2 is an interactive partner of the endoplasmic reticulum SERCA pumps and treatment with the SERCA-inhibitor Thapsigargin halted intracellular MRSA survival. Our results suggest that Thapsigargin could be repurposed to tackleS. aureushost cell infection in combination with conventional antibiotics.
Biochemical and Structural Insights Concerning Triclosan Resistance in a Novel YX7K Type Enoyl-Acyl Carrier Protein Reductase from Soil Metagenome
Authors: Khan Raees , Zeb Amir , Choi Kihyuck , Lee Gihwan , Lee Keun Woo , Lee Seon-Woo 
Published: October 2019

AbstractEnoyl-acyl carrier protein reductase (ENR) catalyzes the last reduction step in the bacterial type II fatty acid biosynthesis cycle. ENRs include FabI, FabL, FabL2, FabK, and FabV. Previously, we reported a unique triclosan (TCL) resistant ENR homolog that was predominant in obligate intracellular pathogenic bacteria and Apicomplexa. Herein, we report the biochemical and structural basis of TCL resistance in this novel ENR. The purified protein revealed NADH-dependent ENR activity and shared similarity to prototypic FabI. Thus, this metagenome-derived ENR was designated FabI2. Unlike other prototypic bacterial ENRs with the YX6K type catalytic domain, FabI2 possessed a unique YX7K type catalytic domain. Computational modeling followed by site-directed mutagenesis revealed that mild resistance (20 µg/ml of minimum inhibitory concentration) of FabI2 to TCL was confined to the relatively less bulky side chain of A128. Substitution of A128 in FabI2 with bulky valine (V128) elevated TCL resistance. Phylogenetic analysis further suggested that the novel FabI2 and prototypical FabI evolved from a common short-chain dehydrogenase reductase family. To our best knowledge, FabI2 is the only known ENR shared by intracellular pathogenic prokaryotes, intracellular pathogenic lower eukaryotes, and a few higher eukaryotes. This suggests that the ENRs of prokaryotes and eukaryotes diverged from a common ancestral ENR of FabI2.
Synapsins are expressed at neuronal and non-neuronal locations in Octopus vulgaris
Authors: Maiole Federica , Tedeschi Giulia , Candiani Simona , Maragliano Luca , Benfenati Fabio , Zullo Letizia 
Published: October 2019

AbstractSynapsins are a family of phosphoproteins fundamental to the regulation of neurotransmitter release. They are typically neuron-specific, although recent evidence pointed to their expression in non-neuronal cells where they play a role in exocytosis and vesicle trafficking. In this work, we characterized synapsin transcripts in the invertebrate mollusk Octopus vulgaris and present evidence of their expression not only in the brain but also in male and female reproductive organs. We identified three synapsin isoforms phylogenetically correlated to that of other invertebrates and with a modular structure characteristic of mammalian synapsins with a central, highly conserved C domain, important for the protein functions, and less conserved A, B and E domains. Our molecular modeling analysis further provided a solid background for predicting synapsin functional binding to ATP, actin filaments and secretory vesicles. Interestingly, we found that synapsin expression in ovary and testis increased during sexual maturation in cells with a known secretory role, potentially matching the occurrence of a secretion process. This might indicate that its secretory role has evolved across animals according to cell activity in spite of cell identity. We believe that this study may yield insights into the convergent evolution of ubiquitously expressed proteins between vertebrates and invertebrates.
The effects of temporal pressure on obstacle negotiation and gaze behaviour in young adults with simulated vision loss
Authors: Zult Tjerk , Allsop Jonathan , Timmis Matthew A. , Pardhan Shahina 
Published: October 2019

AbstractIndividuals with vision loss adapt their locomotion and gaze behaviour to safely negotiate objects in temporally unconstrained situations. However, everyday activities are often performed under time-pressure. We investigated the effects of blur on anxiety, movement kinematics and gaze behaviour during the negotiation of a floor-based obstacle under three amounts of pressure: 1) no-pressure; 2) tonal-pressure: an intermittent tone was played at a constant frequency; 3) tonal + time pressure: the intermittent tone increased in frequency and participants had to walk 20% faster to reach the end of the lab. Irrespective of the amount of pressure, the blurred vs. normal vision group reported 32% more anxiety, lifted the lead foot 43% higher and 10% slower over the obstacle, and looked 6% longer and 6% more frequently ahead of the obstacle. In the tonal + time pressure vs. no-pressure condition, both groups were more anxious, showed adaptations in movement kinematics related to walking faster, and adopted a ‘checking strategy’ by shortening their fixation durations at the obstacle. These results show that irrespective of temporal pressure, the blurred vision group remained more cautious as to how the lead foot negotiated the obstacle, in order to reduce the chance of tripping during crossing.
Novel application of neural network modelling for multicomponent herbal medicine optimization
Authors: Ren Yong-Shen , Lei Lei , Deng Xin , Zheng Yao , Li Yan , Li Jun , Mei Zhi-Nan 
Published: October 2019

AbstractThe conventional method for effective or toxic chemical substance identification of multicomponent herbal medicine is based on single component separation, which is time-consuming, labor intensive, inefficient, and neglects the interaction and integrity among the components; therefore, it is necessary to find an alternative routine to evaluate the components more efficiently and scientifically. In this study, sodium aescinate injection (SAI), obtained from different manufacturers and prepared as “components knockout” samples, was chosen as the case study. The chemical fingerprints of SAI were obtained by high-performance liquid chromatography to provide the chemical information. The effectiveness and irritation of each sample were evaluated using anti-inflammatory and irritation tests, and then “Gray correlation” analysis (GCA) was applied to rank the effectiveness and irritability of each component to provide a preliminary judgment for product optimization. The prediction model of the proportions of the expected components was constructed using the artificial neural network. The results of the GCA showed that the irritation sorting of each SAI component was in the order of B > A > G > J > I > H > D > F > E > C and the effectiveness sorting of SAI components was in the order of D > C > B > A > F > E > H > I > G > J; the predictive proportion of SAI was optimized by the BP neural network as A: B: C: D: E: F = 0.7526: 0.5005: 5.4565: 1.4149: 0.8113: 1.0642. This study provided a scientific, accurate, reliable, and efficient approach for the proportion optimization of multicomponent drugs, which has a good prospect of popularization and application in product upgrading and development of herbal medicine.
Common features of F-18 FDG PET/CT findings in Scrub Typhus: prospective study before and after antibiotics therapy
Authors: Hwang Joo-Hee , Han Yeon-Hee , Choi Seung Hee , Jeon Mir , Kim Suhyun , Kim Yeon-Joon , Lee Chang-Seop , Lim Seok Tae 
Published: October 2019

AbstractScrub typhus is an acute febrile illness caused by obligate intracellular organism Orientia tsutsugamushi. While there have been many reports on the evaluation of disease activity and infectious diseases using F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), the clinical value of FDG PET/CT in scrub typhus has not been fully investigated. We enrolled 17 patients who were 18 years of age or older and clinically suspected of having scrub typhus with eschar. Clinical assessments, blood samples, and FDG PET/CT images were obtained at enrolment and again after 3 weeks. The median age of the patients was 65 years; 9 (52.9%) patients were male. On initial FDG PET/CT, the eschars showed markedly increased FDG uptake on PET imaging that improved after treatment. Generalized lymphadenopathy and splenomegaly with high FDG uptake were observed in all patients. On follow-up FDG PET/CT after appropriate therapy, FDG uptake and sizes of eschar, lymph nodes, and spleen were markedly decreased. As far as we are aware, this is the first investigation with multiple patients of FDG PET/CT in scrub typhus and the demonstration of clinical utility. FDG PET/CT imaging of scrub typhus could provide useful information about the clinical features before and after antibiotic treatment.
Early renal dysfunction and fibroblast growth factor-23 in patients with small vessel disease-related stroke
Authors: Fandler-Höfler Simon , Enzinger Christian , Kneihsl Markus , Pinter Daniela , Eppinger Sebastian , Obermayer-Pietsch Barbara , Goritschan Anna , Hafner-Giessauf Hildegard , Rosenkranz Alexander R. , Fazekas Franz , Gattringer Thomas 
Published: October 2019

AbstractInteractions between cerebral small vessel disease (CSVD) and renal dysfunction (RD) have been reported, but previous studies were mostly retrospective and limited to measurements of estimated glomerular filtration rate (eGFR). In this prospective, longitudinal study of patients with CSVD-related recent small subcortical infarcts (RSSI), we aimed at a comprehensive exploration of markers of early RD and their association with microvascular brain damage. We investigated 101 stroke patients (mean age: 60.2 ± 10.7 years) with an MRI-confirmed RSSI who underwent follow-up brain MRI 15 months post-stroke. Besides serum creatinine and eGFR, we assessed urinary Albumin-Creatinine Ratio and fibroblast growth factor-23 (FGF-23). RD was classified according to recent Kidney Disease: Improving Global Outcomes criteria. We identified 24 patients with RD, only six patients revealed an eGFR <60 mL/min/1.73 m². RSSI patients with RD more often had severe white matter hyperintensities (WMH, 58% vs. 36%, p = 0.04). CSVD progression was not dependent on RD. However, patients in the highest FGF-23 quartile more frequently had new microangiopathic lesions on follow-up MRI (50% vs. 21%, p = 0.03). Early RD was found in a quarter of RSSI patients and associated with WMH severity, but not CSVD progression. High FGF-23 indicates an increased risk for ongoing microvascular brain damage, warranting further studies.
Left-handedness is associated with greater fighting success in humans
Authors: Richardson Thomas , Gilman R. Tucker 
Published: October 2019

AbstractLeft-handedness is a costly, sexually dimorphic trait found at low frequencies in all human populations. How the handedness polymorphism is maintained is unclear. The fighting hypothesis argues that left-handed men have a negative frequency-dependent advantage in violent intrasexual competition giving them a selective advantage. In support of this, many studies have found that left-handed men are overrepresented among modern professional fighters, but studies typically find no difference in fighting success between left and right-handed fighters. We studied over 13,800 professional boxers and mixed martial artists of varying abilities in three of the largest samples to test this hypothesis to date, finding robust evidence that left-handed fighters have greater fighting success. This held for both male and female fighters, and for both percentage of fights won and an objective measure of fighting ability. We replicated previous results showing that left-handed fighters are strongly overrepresented in professional combat sports, but left-handed fighters did not show greater variance in fighting ability, a hypothesis suggested in previous studies. Overall we find strong evidence consistent with the fighting hypothesis.
Comparison of three different reduction methods of the ankle mortise in unstable syndesmotic injuries
Authors: Vetter Sven Yves , Beisemann Nils , Keil Holger , Schnetzke Marc , Swartman Benedict , Franke Jochen , Grützner Paul Alfred , Privalov Maxim 
Published: October 2019

AbstractIn order to achieve a clinically satisfying result and to prevent posttraumatic osteoarthritis in the treatment of unstable syndesmotic injuries, anatomically correct reduction is crucial. The objective of the study was to investigate three different reduction methods of the ankle mortise in unstable syndesmotic injuries. In a specimen model with 38 uninjured fresh-frozen lower legs, a complete syndesmotic dissection was performed. The ankle mortise was reduced with either a collinear reduction clamp, a conventional reduction forceps or manually with crossing K-wires. The reduction clamps and the K-wires were placed in a 0°-angle to the leg axis. The clamps were positioned on the posterolateral ridge of the fibula 20 mm proximal to the ankle joint line. A cone beam computed tomography was performed after dissection and after each reduction. Tibio-fibular distances and angles were determined. Despite significant differences in terms of overcompression (0.09–0.33 mm; p = 0.000–0.063) and the slight external rotation (0.29–0.47°; p = 0.014–0.07), the results show a satisfying reduction of the ankle mortise. There were no considerable differences between the reduction methods. It can therefore be concluded that the ankle mortise can be reduced with any of the methods used, but that the positioning and the contact pressure must be considered.
miR-365 inhibits duck myoblast proliferation by targeting IGF-I via PI3K/Akt pathway
Authors: Sun Wenqiang , Hu Shenqiang , Hu Jiwei , Yang Shuang , Hu Bo , Qiu Jiamin , Gan Xiang , Liu Hehe , Li Liang , Wang Jiwen 
Published: October 2019

Abstract
miR-365 is found to be involved in cancer cell proliferation and apoptosis. However, it remains unknown if and how miR-365 plays a role in myoblast proliferation. In the present study, we found that overexpression of miR-365 can inhibit duck myoblast proliferation. To uncover the mechanism by which miR-365 inhibits duck myoblast proliferation, we showed that miR-365 can down-regulate insulin-like growth factor-I (IGF-I) by directly targeting its 3′untranslated region (UTR). Moreover, enhanced miR-365 decreased the mRNA expression of PI3K, Akt, mTOR and S6K. Importantly, the enhanced PI3K, Akt, mTOR and S6K expression by miR-365 inhibitor (anti-miR-365) was abrogated by treatment with LY294002, a PI3K inhibitor. Together, our results indicated that miR-365 may target IGF-I to inhibit duck myoblast proliferation via PI3K/Akt pathway.
Thousand and one kinase 1 protects MCAO-induced cerebral ischemic stroke in rats by decreasing apoptosis and pro-inflammatory factors
Authors: Li Jiahui , Liu Zhijie , Wang Liling , Xu Haiyan , Wang Yulin 
Published: October 2019

Abstract
Background: Birth hypoxia causes neonatal mortality and morbidity. Hypoxia/ischemia can facilitate brain damage, causing various kinds of diseases, such as ischemic stroke. It is necessary to understand the potential underlying mechanisms of ischemic stroke. Previous studies revealed the involvement of thousand and one kinase 1 (TAOK1) in many cellular processes. Methods: Herein, middle cerebral artery (MCA) occlusion (MCAO) was performed in rats to establish ischemic stroke in the animal model, and cortical neural stem cells from rats were treated with oxygen-glucose deprivation (OGD) to induce ischemic stroke cell model. The animal model of ischemic stroke was validated by Bederson and Zea-Longa neurological deficit scores and rotarod test. TAOK1 expression was examined by quantitative real-time PCR (qRT-PCR), Western blot, and immunofluorescent staining both in vivo and in vitro. Result: Compared with sham animals, the MCAO rats showed a significant increase in the neurological scores, and obvious motor behavioral deficits. Meanwhile, there was increased apoptosis and inflammatory response in the model group. TAOK1 overexpression reversed the OGD-induced cell injury, while TAOK1 knockdown exhibited the opposing effects. On the mechanism, the OGD-induced suppression of PI3K/AKT, and activation of mitogen-activated protein kinase (MAPK) signaling pathways were abolished by TAOK1 overexpression, and aggravated by TAOK1 knockdown in vitro. Moreover, we proved that the inhibitory effect of TAOK1 on OGD-induced apoptosis was dependent on the intracellular kinase activity. Conclusion: TAOK1 protected MCAO-induced cerebral ischemic stroke by decreasing the pro-inflammatory factors and apoptosis via PI3K/AKT and MAPK signaling pathways.
Tumor-associated macrophage-derived exosomal microRNA-155-5p stimulates intracranial aneurysm formation and macrophage infiltration
Authors: Feng Zhengzhe , Zhang Xiaoxi , Li Li , Wang Chuanchuan , Feng Mingtao , Zhao Kaijun , Zhao Rui , Liu Jianmin , Fang Yibin 
Published: October 2019

AbstractTumor-associated macrophages (TAMs) play a regulatory role in inflammation and cancer. Exosomes derived from macrophages carrying microRNAs (miRNAs or miRs) are of great value for cancer therapy. Gremlin 1 (GREM1), a member of the antagonists of secreted bone morphogenetic protein, has been implicated in the pathophysiology of multiple diseases or cancers. Based on the predictions of miRNA–mRNA interaction, GREM1 was found to be a target gene of miR-155-5p. Here, the present study aims to explore the role of TAM-derived exosomal miR-155-5p by regulating GREM1 in intracranial aneurysm (IA). The collected results showed that GREM1 was down-regulated in IA, while miR-155-5p was up-regulated in TAM-derived exosomes. Smooth muscle cells (SMCs) were co-cultured with TAMs or exposed to exosomes derived from TAMs transfected with either miR-155-5p mimic or miR-155-5p inhibitor for exploring their roles in proliferation and migration of SMCs in vitro. Accordingly, in vitro experiments showed that TAM-derived exosomal miR-155-5p could promote proliferation and migration of SMCs by targeting GREM1. The effects of TAM-derived exosomal miR-155-5p on IA formation and TAM activation and infiltration by regulation of GREM1 in vivo were measured in IA rats injected with exosomes or those from TAMs transfected with miR-155-5p inhibitor. In vivo experimental results consistently confirmed that TAM-derived exosomes carrying miR-155-5p promoted IA formation and TAM activation and infiltration. In conclusion, TAM-derived exosomal miR-155-5p promotes IA formation via GREM1, which points to miR-155-5p as a possible therapeutic target for IA.