bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optogenetically stimulating intact rat corticospinal tract post-stroke restores motor control through regionalized functional circuit formation
Authors: Wahl A. S. , Büchler U. , Brändli A. , Brattoli B. , Musall S. , Kasper H. , Ineichen B. V. , Helmchen F. , Ommer B. , Schwab M. E. 
Published: October 2017

AbstractCurrent neuromodulatory strategies to enhance motor recovery after stroke often target large brain areas non-specifically and without sufficient understanding of their interaction with internal repair mechanisms. Here we developed a novel therapeutic approach by specifically activating corticospinal circuitry using optogenetics after large strokes in rats. Similar to a neuronal growth-promoting immunotherapy, optogenetic stimulation together with intense, scheduled rehabilitation leads to the restoration of lost movement patterns rather than induced compensatory actions, as revealed by a computer vision-based automatic behavior analysis. Optogenetically activated corticospinal neurons promote axonal sprouting from the intact to the denervated cervical hemi-cord. Conversely, optogenetically silencing subsets of corticospinal neurons in recovered animals, results in mistargeting of the restored grasping function, thus identifying the reestablishment of specific and anatomically localized cortical microcircuits. These results provide a conceptual framework to improve established clinical techniques such as transcranial magnetic or transcranial direct current stimulation in stroke patients.
Sortilin limits EGFR signaling by promoting its internalization in lung cancer
Authors: Al-Akhrass Hussein , Naves Thomas , Vincent François , Magnaudeix Amandine , Durand Karine , Bertin François , Melloni Boris , Jauberteau Marie-Odile , Lalloué Fabrice 
Published: October 2017

AbstractTyrosine kinase receptors such as the epidermal growth factor receptor (EGFR) transduce information from the microenvironment into the cell and activate homeostatic signaling pathways. Internalization and degradation of EGFR after ligand binding limits the intensity of proliferative signaling, thereby helping to maintain cell integrity. In cancer cells, deregulation of EGFR trafficking has a variety of effects on tumor progression. Here we report that sortilin is a key regulator of EGFR internalization. Loss of sortilin in tumor cells promoted cell proliferation by sustaining EGFR signaling at the cell surface, ultimately accelerating tumor growth. In lung cancer patients, sortilin expression decreased with increased pathologic grade, and expression of sortilin was strongly correlated with survival, especially in patients with high EGFR expression. Sortilin is therefore a regulator of EGFR intracellular trafficking that promotes receptor internalization and limits signaling, which in turn impacts tumor growth.
Structural and mechanistic insights into ATRX-dependent and -independent functions of the histone chaperone DAXX
Authors: Hoelper Dominik , Huang Hongda , Jain Aayushi Y. , Patel Dinshaw J. , Lewis Peter W. 
Published: October 2017

AbstractThe ATRX–DAXX histone chaperone complex incorporates the histone variant H3.3 at heterochromatic regions in a replication-independent manner. Here, we present a high-resolution x-ray crystal structure of an interaction surface between ATRX and DAXX. We use single amino acid substitutions in DAXX that abrogate formation of the complex to explore ATRX-dependent and ATRX-independent functions of DAXX. We find that the repression of specific murine endogenous retroviruses is dependent on DAXX, but not on ATRX. In support, we reveal the existence of two biochemically distinct DAXX-containing complexes: the ATRX–DAXX complex involved in gene repression and telomere chromatin structure, and a DAXX–SETDB1–KAP1–HDAC1 complex that represses endogenous retroviruses independently of ATRX and H3.3 incorporation into chromatin. We find that histone H3.3 stabilizes DAXX protein levels and can affect DAXX-regulated gene expression without incorporation into nucleosomes. Our study demonstrates a nucleosome-independent function for the H3.3 histone variant.
Structure-based insights into self-cleavage by a four-way junctional twister-sister ribozyme
Authors: Zheng Luqian , Mairhofer Elisabeth , Teplova Marianna , Zhang Ye , Ma Jinbiao , Patel Dinshaw J. , Micura Ronald , Ren Aiming 
Published: October 2017

AbstractHere we report on the crystal structure and cleavage assays of a four-way junctional twister-sister self-cleaving ribozyme. Notably, 11 conserved spatially separated loop nucleotides are brought into close proximity at the ribozyme core through long-range interactions mediated by hydrated Mg2+ cations. The C62–A63 step at the cleavage site adopts a splayed-apart orientation, with flexible C62 directed outwards, whereas A63 is directed inwards and anchored by stacking and hydrogen-bonding interactions. Structure-guided studies of key base, sugar, and phosphate mutations in the twister-sister ribozyme, suggest contributions to the cleavage chemistry from interactions between a guanine at the active site and the non-bridging oxygen of the scissile phosphate, a feature found previously also for the related twister ribozyme. Our four-way junctional pre-catalytic structure differs significantly in the alignment at the cleavage step (splayed-apart vs. base-stacked) and surrounding residues and hydrated Mg2+ ions relative to a reported three-way junctional pre-catalytic structure of the twister-sister ribozyme.
Design rules for light-emitting electrochemical cells delivering bright luminance at 27.5 percent external quantum efficiency
Authors: Tang Shi , Sandström Andreas , Lundberg Petter , Lanz Thomas , Larsen Christian , van Reenen Stephan , Kemerink Martijn , Edman Ludvig 
Published: October 2017

AbstractThe light-emitting electrochemical cell promises cost-efficient, large-area emissive applications, as its characteristic in-situ doping enables use of air-stabile electrodes and a solution-processed single-layer active material. However, mutual exclusion of high efficiency and high brightness has proven a seemingly fundamental problem. Here we present a generic approach that overcomes this critical issue, and report on devices equipped with air-stabile electrodes and outcoupling structure that deliver a record-high efficiency of 99.2 cd A−1 at a bright luminance of 1910 cd m−2. This device significantly outperforms the corresponding optimized organic light-emitting diode despite the latter employing calcium as the cathode. The key to this achievement is the design of the host–guest active material, in which tailored traps suppress exciton diffusion and quenching in the central recombination zone, allowing efficient triplet emission. Simultaneously, the traps do not significantly hamper electron and hole transport, as essentially all traps in the transport regions are filled by doping.
Blood Pressure Management for Acute Intracerebral Hemorrhage: A Meta-Analysis
Authors: Shi Ligen , Xu Shenbin , Zheng Jingwei , Xu Jing , Zhang Jianmin 
Published: October 2017

AbstractInconsistent data from the randomized trials ignites controversy on intensive blood pressure (BP) reduction for acute intracerebral hemorrhage (ICH). This study aims to examine the association between BP lowering and clinical outcomes among patients with acute ICH. We conducted this meta-analysis based on the published randomized controlled trials (RCTs). Data were included from 6 RCTs involving 4412 patients. No significant improvements were observed in hematoma growth at 24 hours, neurologic improvement at 24 hours, hypotension at 72 hours, death or dependency at 90 days, mortality at 90 days, and serious adverse events at 90 days between intensive and conservative BP lowering groups. High heterogeneity was observed between estimates in hematoma growth (I2 = 49). Univariate meta-regression and subgroup analysis showed that intensive BP lowering showed a significant decrease in hematoma growth in age ≤62 years, time from symptoms onset to treatment ≤6 hours, baseline hematoma volume ≤15 mL, and combined intraventricular hemorrhage ≤25% subgroups. In conclusion, intensive BP management in patients with ICH is safe. Intensive BP lowering could reduce hematoma growth in those patients (≤62 years old) with ICH volume less than 15 mL receiving BP management within 6 hours after randomization.
Comparative metabolomics study on therapeutic mechanism of electro-acupuncture and moxibustion on rats with chronic atrophic gastritis (CAG)
Authors: Liu Cai-chun , Chen Jiao-long , Chang Xiao-rong , He Qi-da , Shen Jia-cheng , Lian Lin-yu , Wang Ya-dong , Zhang Yuan , Ma Fu-qiang , Huang Hui-ying , Yang Zong-bao 
Published: October 2017

AbstractSome studies have proved that both acupuncture and moxibustion are very effective for the treatment of CAG. However, little is known about therapeutic mechanism of electro-acupuncture and moxibustion on CAG as well as the difference between them. On the other hand, metabolomics is a ‘top-down’ approach to understand metabolic changes of organisms caused by disease or interventions in holistic context, which consists with the holistic thinking of electro-acupuncture and moxibustion treatment. In this study, the difference of therapeutic mechanism between electro-acupuncture and moxibustion on CAG rats was investigated by a1H NMR-based metabolomics analysis of multiple biological samples (serum, stomach, cerebral cortex and medulla) coupled with pathological examination and molecular biological assay. For all sample types, both electro-acupuncture and moxibustion intervention showed beneficial effects by restoring many CAG-induced metabolic changes involved in membrane metabolism, energy metabolism and function of neurotransmitters. Notably, the moxibustion played an important role in CAG treatment mainly by regulating energy metabolism in serum, while main acting site of electro-acupuncture treatment was nervous system in stomach and brain. These findings are helpful to facilitate the therapeutic mechanism elucidating of electro-acupuncture and moxibustion on CAG rats. Metabolomics is promising in mechanisms study for traditional Chinese medicine (TCM).
Mir-21 Mediates the Inhibitory Effect of Ang (1–7) on AngII-induced NLRP3 Inflammasome Activation by Targeting Spry1 in lung fibroblasts
Authors: Sun Na-Na , Yu Chang-Hui , Pan Miao-Xia , Zhang Yue , Zheng Bo-Jun , Yang Qian-Jie , Zheng Ze-Mao , Meng Ying 
Published: October 2017

AbstractMicroRNA-21 (mir-21) induced by angiotensin II (AngII) plays a vital role in the development of pulmonary fibrosis, and the NLRP3 inflammasome is known to be involved in fibrogenesis. However, whether there is a link between mir-21 and the NLRP3 inflammasome in pulmonary fibrosis is unknown. Angiotensin-converting enzyme 2/angiotensin(1–7) [ACE2/Ang(1–7)] has been shown to attenuate AngII-induced pulmonary fibrosis, but it is not clear whether ACE2/Ang(1–7) protects against pulmonary fibrosis by inhibiting AngII-induced mir-21 expression. This study’s aim was to investigate whether mir-21 activates the NLRP3 inflammasome and mediates the different effects of AngII and ACE2/Ang(1–7) on lung fibroblast apoptosis and collagen synthesis. In vivo, AngII exacerbated bleomycin (BLM)-induced lung fibrosis in rats, and elevated mir-21 and the NLRP3 inflammasome. In contrast, ACE2/Ang(1–7) attenuated BLM-induced lung fibrosis, and decreased mir-21 and the NLRP3 inflammasome. In vitro, AngII activated the NLRP3 inflammasome by up-regulating mir-21, and ACE2/Ang(1–7) inhibited NLRP3 inflammasome activation by down-regulating AngII-induced mir-21. Over-expression of mir-21 activated the NLRP3 inflammasome via the ERK/NF-κB pathway by targeting Spry1, resulting in apoptosis resistance and collagen synthesis in lung fibroblasts. These results indicate that mir-21 mediates the inhibitory effect of ACE2/Ang(1–7) on AngII-induced activation of the NLRP3 inflammasome by targeting Spry1 in lung fibroblasts.
IP-10 Kinetics in the First Week of Therapy are Strongly Associated with Bacteriological Confirmation of Tuberculosis Diagnosis in HIV-Infected Patients
Authors: García-Basteiro Alberto L. , Mambuque Edson , den Hertog Alice , Saavedra Belén , Cuamba Inocencia , Oliveras Laura , Blanco Silvia , Bulo Helder , Brew Joe , Cuevas Luis E. , Cobelens Frank , Nhabomba Augusto , Anthony Richard 
Published: October 2017

AbstractSimple effective tools to monitor the long treatment of tuberculosis (TB) are lacking. Easily measured host derived biomarkers have been identified but need to be validated in larger studies and different population groups. Here we investigate the early response in IP-10 levels (between day 0 and day 7 of TB therapy) to identify bacteriological status at diagnosis among 127 HIV-infected patients starting TB treatment. All participants were then classified as responding or not responding to treatment blindly using a previously described IP-10 kinetic algorithm. There were 77 bacteriologically confirmed cases and 41 Xpert MTB/RIF® and culture negative cases. Most participants had a measurable decline in IP-10 during the first 7 days of therapy. Bacteriologically confirmed cases were more likely to have high IP-10 levels at D0 and had a steeper decline than clinically diagnosed cases (mean decline difference 2231 pg/dl, 95% CI: 897–3566, p = 0.0013). Bacteriologically confirmed cases were more likely to have a measurable decline in IP-10 at day 7 than clinically diagnosed cases (48/77 (62.3%) vs 13/41 (31.7%), p < 0.001). This study confirms the association between a decrease in IP-10 levels during the first week of treatment and a bacteriological confirmation at diagnosis in a large cohort of HIV positive patients.
In-silico gene essentiality analysis of polyamine biosynthesis reveals APRT as a potential target in cancer
Authors: Pey Jon , San José-Eneriz Edurne , Ochoa María Carmen , Apaolaza Iñigo , de Atauri Pedro , Rubio Angel , Cendoya Xabier , Miranda Estíbaliz , Garate Leire , Cascante Marta , Carracedo Arkaitz , Agirre Xabier , Prosper Felipe , Planes Francisco J. 
Published: October 2017

AbstractConstraint-based modeling for genome-scale metabolic networks has emerged in the last years as a promising approach to elucidate drug targets in cancer. Beyond the canonical biosynthetic routes to produce biomass, it is of key importance to focus on metabolic routes that sustain the proliferative capacity through the regulation of other biological means in order to improve in-silico gene essentiality analyses. Polyamines are polycations with central roles in cancer cell proliferation, through the regulation of transcription and translation among other things, but are typically neglected in in silico cancer metabolic models. In this study, we analysed essential genes for the biosynthesis of polyamines. Our analysis corroborates the importance of previously known regulators of the pathway, such as Adenosylmethionine Decarboxylase 1 (AMD1) and uncovers novel enzymes predicted to be relevant for polyamine homeostasis. We focused on Adenine Phosphoribosyltransferase (APRT) and demonstrated the detrimental consequence of APRT gene silencing on different leukaemia cell lines. Our results highlight the importance of revisiting the metabolic models used for in-silico gene essentiality analyses in order to maximize the potential for drug target identification in cancer.
Exosomal microRNA signatures in multiple sclerosis reflect disease status
Authors: Ebrahimkhani Saeideh , Vafaee Fatemeh , Young Paul E. , Hur Suzy S. J. , Hawke Simon , Devenney Emma , Beadnall Heidi , Barnett Michael H. , Suter Catherine M. , Buckland Michael E. 
Published: October 2017

AbstractMultiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). There is currently no single definitive test for MS. Circulating exosomes represent promising candidate biomarkers for a host of human diseases. Exosomes contain RNA, DNA, and proteins, can cross the blood-brain barrier, and are secreted from almost all cell types including cells of the CNS. We hypothesized that serum exosomal miRNAs could present a useful blood-based assay for MS disease detection and monitoring. Exosome-associated microRNAs in serum samples from MS patients (n = 25) and matched healthy controls (n = 11) were profiled using small RNA next generation sequencing. We identified differentially expressed exosomal miRNAs in both relapsing-remitting MS (RRMS) (miR-15b-5p, miR-451a, miR-30b-5p, miR-342-3p) and progressive MS patient sera (miR-127-3p, miR-370-3p, miR-409-3p, miR-432-5p) in relation to controls. Critically, we identified a group of nine miRNAs (miR-15b-5p, miR-23a-3p, miR-223-3p, miR-374a-5p, miR-30b-5p, miR-433-3p, miR-485-3p, miR-342-3p, miR-432-5p) that distinguished relapsing-remitting from progressive disease. Eight out of nine miRNAs were validated in an independent group (n = 11) of progressive MS cases. This is the first demonstration that microRNAs associated with circulating exosomes are informative biomarkers not only for the diagnosis of MS, but in predicting disease subtype with a high degree of accuracy.
The Effects of Serum Proteins on Magnesium Alloy Degradation in Vitro
Authors: Johnson Ian , Jiang Wensen , Liu Huinan 
Published: October 2017

AbstractMagnesium (Mg) alloys are promising materials for biodegradable implants, but their clinical translation requires improved control over their degradation rates. Proteins may be a major contributing factor to Mg alloy degradation, but are not yet fully understood. This article reports the effects of fetal bovine serum (FBS), a physiologically relevant mixture of proteins, on Mg and Mg alloy degradation. FBS had little impact on mass loss of pure Mg during immersion degradation, regardless of whether or not a native oxide layer was present on the sample surface. FBS reduced the mass loss of Mg-Yttrium (MgY) alloy with an oxidized surface during immersion degradation, but increased the mass loss for the same alloy with a metallic surface (surface oxides were removed). FBS also influenced the mode of degradation by limiting the depth of pit formation during degradation processes on commercially pure Mg with metallic or oxidized surfaces and on MgY alloy with oxidized surfaces. The results demonstrated that serum proteins had significant interactions with Mg-based biodegradable metals, and these interactions may be modified by alloy composition and processing. Therefore, proteins should be taken into account when designing experiments to assess degradation of Mg-based implants.
NADPH oxidase 4 modulates hepatic responses to lipopolysaccharide mediated by Toll-like receptor-4
Authors: Singh Anand , Koduru Bhargav , Carlisle Cameron , Akhter Hasina , Liu Rui-Ming , Schroder Katrin , Brandes Ralf P. , Ojcius David M. 
Published: October 2017

AbstractChronic inflammation plays a key role in development of many liver diseases. Stimulation of Toll-like receptor 4 (TLR4) by bacterial lipopolysaccharide (LPS) initiates inflammation and promotes development of hepatocellular carcinoma and other liver diseases. NADPH oxidases contribute to LPS-induced reactive oxygen species (ROS) production and modulate TLR responses, but whether these enzymes function in TLR4 responses of hepatocytes is unknown. In the present work, we examined the role of NADPH oxidase 4 (Nox4) in LPS-induced TLR4 responses in human hepatoma cells and wildtype and Nox4-deficient mice. We found that LPS increased expression of Nox4, TNF-α, and proliferating cell nuclear antigen (PCNA). Nox4 silencing suppressed LPS-induced TNF-α and PCNA increases in human cells. The LPS-induced TNF-α increases were MyD88-dependent, and were attenuated in primary hepatocytes isolated from Nox4-deficient mice. We found that Nox4 mediated LPS-TLR4 signaling in hepatocytes via NF-ĸB and AP-1 pathways. Moreover, the effect of Nox4 depletion was time-dependent; following six weeks of repeated LPS stimulationin vivo, hepatic TNF-α and PCNA responses subsided in Nox4-deficient mice compared with wildtype mice. Therefore, our data suggest that Nox4 mediates LPS-TLR4 signaling in human hepatoma cells and murine hepatocytes and may contribute to the ability of LPS to stimulate liver pathology.
Effects of gas sorption-induced swelling/shrinkage on the cleat compressibility of coal under different bedding directions
Authors: Peng Shoujian , Fang Zhiming , Shen Jian , Xu Jiang , Wang Geoff 
Published: October 2017

AbstractThe cleat compressibility of coal is a key parameter that is extensively used in modeling the coal reservoir permeability for Coal Bed Methane (CBM) recovery. Cleat compressibility is often determined from the permeability measurement made at different confining pressures but with a constant pore pressure. Hence, this parameter ignores the sorption strain effects on the cleat compressibility. By using the transient pulse decay (TPD) technique, this study presents the results from a laboratory characterization program using coal core drilled from different bedding directions to estimate gas permeability and coal cleat compressibility under different pore pressures while maintaining effective stress constant. Cleat compressibility was determined from permeability and sorption strain measurements that are made at different pore pressures under an effective stress constant. Results show that the cleat compressibility of coal increases slightly with the increase of pore pressure. Moreover, the cleat compressibility of Sample P (representing the face cleats in coal) is larger than that of Sample C (representing the butt cleats in coal). This result suggests that cleat compressibility should not be regarded as constant in the modeling of the CBM recovery. Furthermore, the compressibility of face cleats is considerably sensitive to the sorption-induced swelling/shrinkage and offers significant effects on the coal permeability.
Learning an unknown transformation via a genetic approach
Authors: Spagnolo Nicolò , Maiorino Enrico , Vitelli Chiara , Bentivegna Marco , Crespi Andrea , Ramponi Roberta , Mataloni Paolo , Osellame Roberto , Sciarrino Fabio 
Published: October 2017

AbstractRecent developments in integrated photonics technology are opening the way to the fabrication of complex linear optical interferometers. The application of this platform is ubiquitous in quantum information science, from quantum simulation to quantum metrology, including the quest for quantum supremacy via the boson sampling problem. Within these contexts, the capability to learn efficiently the unitary operation of the implemented interferometers becomes a crucial requirement. In this letter we develop a reconstruction algorithm based on a genetic approach, which can be adopted as a tool to characterize an unknown linear optical network. We report an experimental test of the described method by performing the reconstruction of a 7-mode interferometer implemented via the femtosecond laser writing technique. Further applications of genetic approaches can be found in other contexts, such as quantum metrology or learning unknown general Hamiltonian evolutions.