bluuebunny/crossref_metadata_2025_split huggingface dataset:
An NS-segment exonic splicing enhancer regulates influenza A virus replication in mammalian cells
Authors: Huang Xiaofeng , Zheng Min , Wang Pui , Mok Bobo Wing-Yee , Liu Siwen , Lau Siu-Ying , Chen Pin , Liu Yen-Chin , Liu Honglian , Chen Yixin , Song Wenjun , Yuen Kwok-Yung , Chen Honglin 
Published: March 2017

AbstractInfluenza virus utilizes host splicing machinery to process viral mRNAs expressed from both M and NS segments. Through genetic analysis and functional characterization, we here show that the NS segment of H7N9 virus contains a unique G540A substitution, located within a previously undefined exonic splicing enhancer (ESE) motif present in the NEP mRNA of influenza A viruses. G540A supports virus replication in mammalian cells while retaining replication ability in avian cells. Host splicing regulator, SF2, interacts with this ESE to regulate splicing of NEP/NS1 mRNA and G540A substitution affects SF2–ESE interaction. The NS1 protein directly interacts with SF2 in the nucleus and modulates splicing of NS mRNAs during virus replication. We demonstrate that splicing of NEP/NS1 mRNA is regulated through a cis NEP-ESE motif and suggest a unique NEP-ESE may contribute to provide H7N9 virus with the ability to both circulate efficiently in avian hosts and replicate in mammalian cells.
Remineralization of particulate organic carbon in an ocean oxygen minimum zone
Authors: Cavan E. L. , Trimmer M. , Shelley F. , Sanders R. 
Published: March 2017

AbstractBiological oceanic processes, principally the surface production, sinking and interior remineralization of organic particles, keep atmospheric CO2 lower than if the ocean was abiotic. The remineralization length scale (RLS, the vertical distance over which organic particle flux declines by 63%, affected by particle respiration, fragmentation and sinking rates) controls the size of this effect and is anomalously high in oxygen minimum zones (OMZ). Here we show in the Eastern Tropical North Pacific OMZ 70% of POC remineralization is due to microbial respiration, indicating that the high RLS is the result of lower particle fragmentation by zooplankton, likely due to the almost complete absence of zooplankton particle interactions in OMZ waters. Hence, the sensitivity of zooplankton to ocean oxygen concentrations can have direct implications for atmospheric carbon sequestration. Future expansion of OMZs is likely to increase biological ocean carbon storage and act as a negative feedback on climate change.
LRRK2 levels in immune cells are increased in Parkinson’s disease
Authors: Cook D. A. , Kannarkat G. T. , Cintron A. F. , Butkovich Laura M. , Fraser Kyle B. , Chang J. , Grigoryan N. , Factor S. A. , West Andrew B. , Boss J. M. , Tansey M. G. 
Published: March 2017

AbstractMutations associated with leucine-rich repeat kinase 2 are the most common known cause of Parkinson’s disease. The known expression of leucine-rich repeat kinase 2 in immune cells and its negative regulatory function of nuclear factor of activated T cells implicates leucine-rich repeat kinase 2 in the development of the inflammatory environment characteristic of Parkinson’s disease. The aim of this study was to determine the expression pattern of leucine-rich repeat kinase 2 in immune cell subsets and correlate it with the immunophenotype of cells from Parkinson’s disease and healthy subjects. For immunophenotyping, blood cells from 40 Parkinson’s disease patients and 32 age and environment matched-healthy control subjects were analyzed by flow cytometry. Multiplexed immunoassays were used to measure cytokine output of stimulated cells. Leucine-rich repeat kinase 2 expression was increased in B cells (p = 0.0095), T cells (p = 0.029), and CD16+ monocytes (p = 0.01) of Parkinson’s disease patients compared to healthy controls. Leucine-rich repeat kinase 2 induction was also increased in monocytes and dividing T cells in Parkinson’s disease patients compared to healthy controls. In addition, Parkinson’s disease patient monocytes secreted more inflammatory cytokines compared to healthy control, and cytokine expression positively correlated with leucine-rich repeat kinase 2 expression in T cells from Parkinson’s disease but not healthy controls. Finally, the regulatory surface protein that limits T-cell activation signals, CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), was decreased in Parkinson’s disease compared to HC in T cells (p = 0.029). In sum, these findings suggest that leucine-rich repeat kinase 2 has a regulatory role in immune cells and Parkinson’s disease. Functionally, the positive correlations between leucine-rich repeat kinase 2 expression levels in T-cell subsets, cytokine expression and secretion, and T-cell activation states suggest that targeting leucine-rich repeat kinase 2 with therapeutic interventions could have direct effects on immune cell function.
Cooperation and competition shape ecological resistance during periodic spatial disturbance of engineered bacteria
Authors: Wilson Cortney E. , Lopatkin Allison J. , Craddock Travis J. A. , Driscoll William W. , Eldakar Omar Tonsi , Lopez Jose V. , Smith Robert P. 
Published: March 2017

AbstractCooperation is fundamental to the survival of many bacterial species. Previous studies have shown that spatial structure can both promote and suppress cooperation. Most environments where bacteria are found are periodically disturbed, which can affect the spatial structure of the population. Despite the important role that spatial disturbances play in maintaining ecological relationships, it remains unclear as to how periodic spatial disturbances affect bacteria dependent on cooperation for survival. Here, we use bacteria engineered with a strong Allee effect to investigate how the frequency of periodic spatial disturbances affects cooperation. We show that at intermediate frequencies of spatial disturbance, the ability of the bacterial population to cooperate is perturbed. A mathematical model demonstrates that periodic spatial disturbance leads to a tradeoff between accessing an autoinducer and accessing nutrients, which determines the ability of the bacteria to cooperate. Based on this relationship, we alter the ability of the bacteria to access an autoinducer. We show that increased access to an autoinducer can enhance cooperation, but can also reduce ecological resistance, defined as the ability of a population to resist changes due to disturbance. Our results may have implications in maintaining stability of microbial communities and in the treatment of infectious diseases.
Potential role of fecal microbiota from patients with slow transit constipation in the regulation of gastrointestinal motility
Authors: Ge Xiaolong , Zhao Wei , Ding Chao , Tian Hongliang , Xu Lizhi , Wang Hongkan , Ni Ling , Jiang Jun , Gong Jianfeng , Zhu Weiming , Zhu Minsheng , Li Ning 
Published: March 2017

AbstractThe gut microbiota is involved in various physiological functions, and disturbances in the host-microbiome have been proven to contribute to the dysfunction of gut; however, whether microbiota participates in the pathogenesis of constipation remains unclear. In this study, we extracted and analyzed microbiota in feces from constipated donors who had undergone effective therapy with fecal microbiota transplantation, transplanted microbiota into pseudo-germ-free mice, and measured gut motility. These mice presented with lower pellet frequency and water percentage, smaller pellet size, delayed gastrointestinal transit time, and weaker spontaneous contractions of colonic smooth muscle. To determine the mechanism underlying delayed gut motility, microbial metabolites were measured. Short chain fatty acids and secondary bile acids were decreased in mice receiving microbiota from constipated donors. Moreover, the compositional changes of gut microbiota in constipated patients were identified, including the operational taxonomic unit, and the species richness and α diversity were much greater than those in healthy volunteers. These findings suggest that alterations of the microbiome might affect gut motility via altered microbial-derived metabolites in the development of constipation, and the restoration of disturbed microbiota might improve the clinical phenotype. This study indicates that regulating the intestinal environment may be a novel therapy strategy for constipation.
Alix is required during development for normal growth of the mouse brain
Authors: Laporte Marine H. , Chatellard Christine , Vauchez Victoria , Hemming Fiona J. , Deloulme Jean-Christophe , Vossier Frédérique , Blot Béatrice , Fraboulet Sandrine , Sadoul Rémy 
Published: March 2017

AbstractAlix (ALG-2 interacting protein X) drives deformation and fission of endosomal and cell surface membranes and thereby intervenes in diverse biological processes including cell proliferation and apoptosis. Using embryonic fibroblasts of Alix knock-out mice, we recently demonstrated that Alix is required for clathrin-independent endocytosis. Here we show that mice lacking Alix suffer from severe reduction in the volume of the brain which affects equally all regions examined. The cerebral cortex of adult animals shows normal layering but is reduced in both medio-lateral length and thickness. Alix controls brain size by regulating its expansion during two distinct developmental stages. Indeed, embryonic surface expansion of the Alix ko cortex is reduced because of the loss of neural progenitors during a transient phase of apoptosis occurring between E11.5 and E12.5. Subsequent development of the Alix ko cortex occurs normally until birth, when Alix is again required for the post-natal radial expansion of the cortex through its capacity to allow proper neurite outgrowth. The need of Alix for both survival of neural progenitor cells and neurite outgrowth is correlated with its role in clathrin-independent endocytosis in neural progenitors and at growth cones. Thus Alix-dependent, clathrin independent endocytosis is essential for controlling brain size.
The protective effects of shikonin on hepatic ischemia/reperfusion injury are mediated by the activation of the PI3K/Akt pathway
Authors: Liu Tong , Zhang QingHui , Mo Wenhui , Yu Qiang , Xu Shizan , Li Jingjing , Li Sainan , Feng Jiao , Wu Liwei , Lu Xiya , Zhang Rong , Li Linqiang , Cheng Keran , Zhou Yuqing , Zhou Shunfeng , Kong Rui , Wang Fan , Dai Weiqi , Chen Kan , Xia Yujing , Lu Jie , Zhou Yingqun , Zhao Yan , Guo Chuanyong 
Published: March 2017

AbstractHepatic ischemia/reperfusion (I/R) injury, which can result in severe liver injury and dysfunction, occurs in a variety of conditions such as liver transplantation, shock, and trauma. Cell death in hepatic I/R injury has been linked to apoptosis and autophagy. Shikonin plays a significant protective role in ischemia/reperfusion injury. The purpose of the present study was to investigate the protective effect of shikonin on hepatic I/R injury and explore the underlying mechanism. Mice were subjected to segmental (70%) hepatic warm ischemia to induce hepatic I/R injury. Two doses of shikonin (7.5 and 12.5 mg/kg) were administered 2 h before surgery. Balb/c mice were randomly divided into four groups: normal control, I/R, and shikonin preconditioning at two doses (7.5 and 12.5 mg/kg). The serum and liver tissues were collected at three time points (3, 6, and 24 h). Shikonin significantly reduced serum AST and ALT levels and improved pathological features. Shikonin affected the expression of Bcl-2, Bax, caspase 3, caspase 9, Beclin-1, and LC3, and upregulated PI3K and p-Akt compared with the levels in the I/R group. Shikonin attenuated hepatic I/R injury by inhibiting apoptosis and autophagy through a mechanism involving the activation of PI3K/Akt signaling.
H2S regulates endothelial nitric oxide synthase protein stability by promoting microRNA-455-3p expression
Authors: Li Xing-Hui , Xue Wen-Long , Wang Ming-Jie , Zhou Yu , Zhang Cai-Cai , Sun Chen , Zhu Lei , Liang Kun , Chen Ying , Tao Bei-Bei , Tan Bo , Yu Bo , Zhu Yi-Chun 
Published: March 2017

AbstractThe aims of the present study are to determine whether hydrogen sulfide (H2S) is involved in the expression of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) production, and to identify the role of microRNA-455-3p (miR-455-3p) during those processes. In cultured human umbilical vein endothelial cells (HUVECs), the expression of miR-455-3p, eNOS protein and the NO production was detected after administration with 50 μM NaHS. The results indicated that H2S could augment the expression of miR-455-3p and eNOS protein, leading to the increase of NO level. We also found that overexpression of miR-455-3p in HUVECs increased the protein levels of eNOS whereas inhibition of miR-455-3p decreased it. Moreover, H2S and miR-455-3p could no longer increase the protein level of eNOS in the presence of proteasome inhibitor, MG-132. In vivo, miR-455-3p and eNOS expression were considerably increased in C57BL/6 mouse aorta, muscle and heart after administration with 50 μmol/kg/day NaHS for 7 days. We also identified that H2S levels and miR-455-3p expression increased in human atherosclerosis plaque while H2S levels decreased in plasma of atherosclerosis patients. Our data suggest that the stability of eNOS protein and the NO production could be regulated by H2S through miR-455-3p.
Stk38 Modulates Rbm24 Protein Stability to Regulate Sarcomere Assembly in Cardiomyocytes
Authors: Liu Jing , Kong Xu , Lee Yew Mun , Zhang Meng Kai , Guo Li Yan , Lin Yu , Lim Teck Kwang , Lin Qingsong , Xu Xiu Qin 
Published: March 2017

AbstractRNA-binding protein Rbm24 is a key regulator of heart development and required for sarcomere assembly and heart contractility. Yet, its underlying mechanism remains unclear. Here, we link serine/threonine kinase 38 (Stk38) signaling to the regulation of Rbm24 by showing that Rbm24 phosphorylation and its function could be modulated by Stk38. Using co-immunoprecipitation coupled with mass spectrometry technique, we identified Stk38 as an endogenous binding partner of Rbm24. Stk38 knockdown resulted in decreased Rbm24 protein level in cardiomyocytes. Further studies using Stk38 kinase inhibitor or activator showed that Rbm24 protein stability was regulated in a kinase activity-dependent manner. Deficiency of Stk38 caused reduction of sarcomere proteins and disarrangement of sarcomere, suggesting that Stk38 is essential for Rbm24 to regulate sarcomere assembly. Our results revealed that Stk38 kinase catalyzes the phosphorylation of Rbm24 during sarcomerogensis and this orchestrates accurate sarcomere alignment. This furthers our understanding of the regulatory mechanism of cardiac sarcomere assembly in both physiologic and pathologic contexts, and uncovers a potential novel pathway to cardiomyopathy through modulating the Stk38/Rbm24 protein activity.
Hormone therapy at early post-menopause increases cognitive control-related prefrontal activity
Authors: Girard Romuald , Météreau Elise , Thomas Julie , Pugeat Michel , Qu Chen , Dreher Jean-Claude 
Published: March 2017

AbstractClinical data have been equivocal and controversial as to the benefits to the brain and cognition of hormone therapy (HT) in postmenopausal women. Recent reevaluation of the role of estrogens proposed that HT may effectively prevent the deleterious effects of aging on cognition, and reduces the risks of dementia, including Alzheimer’s disease, if initiated early at the beginning of menopause. Yet, little is known about the effects of HT on brain activation related to cognitive control, the ability to make flexible decisions in relation to internal goals. Here, we used fMRI to directly test for a modulation of sequential 17β estradiol (2 mg/day) plus oral progesterone (100 mg/day) on task switching-related brain activity in women at early postmenopause. The results showed that HT enhanced dorsolateral prefrontal cortex recruitment during task switching. Between-subjects correlation analyses revealed that women who engaged more the dorsolateral prefrontal cortex showed higher task switching performance after HT administration. These results suggest that HT, when taken early at the beginning of postmenopause, may have beneficial effect on cognitive control prefrontal mechanisms. Together, these findings demonstrate that HT can prevent the appearance of reduced prefrontal cortex activity, a neurophysiological measure observed both in healthy aging and early dementia.
Bio-inspired colorimetric film based on hygroscopic coloration of longhorn beetles (Tmesisternus isabellae)
Authors: Seo Han-bok , Lee Seung-Yop 
Published: March 2017

AbstractStructure-dependent colour is caused by the interaction of light with photonic crystal structures rather than pigments. The elytra of longhorn beetles Tmesisternus isabellae appear to be iridescent green in a dry state and turn to red when exposed to humidity. Based on the hygroscopic colouration of the longhorn beetle, we have developed centimeter-scale colorimetric opal films using a novel self-assembly method. The micro-channel assisted assembly technique adopts both natural evaporation and rotational forced drying, enhancing the surface binding of silica particles and the packing density by reducing the lattice constant and structural defects. The fabricated large-scale photonic film changes its structural colour from green to red when exposed to water vapour, similarly to the colorimetric feature of the longhorn beetle. The humidity-dependent colour change of the opal film is shown to be reversible and durable over five-hundred cycles of wetting and drying.
Mechanistic Insights into the Anti-angiogenic Activity of Trypanosoma cruzi Protein 21 and its Potential Impact on the Onset of Chagasic Cardiomyopathy
Authors: Teixeira Samuel Cota , Lopes Daiana Silva , Gimenes Sarah Natalie Cirilo , Teixeira Thaise Lara , da Silva Marcelo Santos , Brígido Rebecca Tavares e Silva , da Luz Felipe Andrés Cordero , da Silva Aline Alves , Silva Makswell Almeida , Florentino Pilar Veras , Tavares Paula Cristina Brígido , dos Santos Marlus Alves , Ávila Veridiana de Melo Rodrigues , Silva Marcelo José Barbosa , Elias Maria Carolina , Mortara Renato Arruda , da Silva Claudio Vieira 
Published: March 2017

AbstractChronic chagasic cardiomyopathy (CCC) is arguably the most important form of the Chagas Disease, caused by the intracellular protozoanTrypanosoma cruzi; it is estimated that 10–30% of chronic patients develop this clinical manifestation. The most common and severe form of CCC can be related to ventricular abnormalities, such as heart failure, arrhythmias, heart blocks, thromboembolic events and sudden death. Therefore, in this study, we proposed to evaluate the anti-angiogenic activity of a recombinant protein fromT. cruzinamed P21 (rP21) and the potential impact of the native protein on CCC. Our data suggest that the anti-angiogenic activity of rP21 depends on the protein’s direct interaction with the CXCR4 receptor. This capacity is likely related to the modulation of the expression of actin and angiogenesis-associated genes. Thus, our results indicate thatT. cruziP21 is an attractive target for the development of innovative therapeutic agents against CCC.
Sedation of mechanically ventilated adults in intensive care unit: a network meta-analysis
Authors: Zhang Zhongheng , Chen Kun , Ni Hongying , Zhang Xiaoling , Fan Haozhe 
Published: March 2017

AbstractSedatives are commonly used for mechanically ventilated patients in intensive care units (ICU). However, a variety of sedatives are available and their efficacy and safety have been compared in numerous trials with inconsistent results. To resolve uncertainties regarding usefulness of these sedatives, we performed a systematic review and network meta-analysis. Randomized controlled trials comparing sedatives in mechanically ventilated ICU patients were included. Graph-theoretical methods were employed for network meta-analysis. A total of 51 citations comprising 52 RCTs were included in our analysis. Dexmedetomidine showed shorter MV duration than lorazepam (mean difference (MD): 68.7; 95% CI: 18.2–119.3 hours), midazolam (MD: 10.2; 95% CI: 7.7–12.7 hours) and propofol (MD: 3.4; 95% CI: 0.9–5.9 hours). Compared with dexmedetomidine, midazolam was associated with significantly increased risk of delirium (OR: 2.47; 95% CI: 1.17–5.19). Our study shows that dexmedetomidine has potential benefits in reducing duration of MV and lowering the risk of delirium.
Flexible wire-shaped strain sensor from cotton thread for human health and motion detection
Authors: Li Yuan-Qing , Huang Pei , Zhu Wei-Bin , Fu Shao-Yun , Hu Ning , Liao Kin 
Published: March 2017

AbstractIn this work, a wire-shaped flexible strain sensor was fabricated by encapsulating conductive carbon thread (CT) with polydimethylsiloxane (PDMS) elastomer. The key strain sensitive material, CT, was prepared by pyrolysing cotton thread in N2 atmosphere. The CT/PDMS composite wire shows a typical piezo-resistive behavior with high strain sensitivity. The gauge factors (GF) calculated at low strain of 0–4% and high strain of 8–10% are 8.7 and 18.5, respectively, which are much higher than that of the traditional metallic strain sensor (GF around 2). The wire-shaped CT/PDMS composite sensor shows excellent response to cyclic tensile loading within the strain range of 0–10%, the frequency range of 0.01–10 Hz, to up to 2000 cycles. The potential of the wire senor as wearable strain sensor is demonstrated by the finger motion and blood pulse monitoring. Featured by the low costs of cotton wire and PDMS resin, the simple structure and fabrication technique, as well as high performance with miniaturized size, the wire-shaped sensor based on CT/PDMS composite is believed to have a great potential for application in wearable electronics for human health and motion monitoring.
“Breakthrough” osmosis and unusually high power densities in Pressure-Retarded Osmosis in non-ideally semi-permeable supported membranes
Authors: Yaroshchuk Andriy 
Published: March 2017

AbstractOsmosis is the movement of solvent across a membrane induced by a solute-concentration gradient. It is very important for cell biology. Recently, it has started finding technological applications in the emerging processes of Forward Osmosis and Pressure-Retarded Osmosis. They use ultrathin and dense membranes supported mechanically by much thicker porous layers. Until now, these processes have been modelled by assuming the membrane to be ideally-semipermeable. We show theoretically that allowing for even minor deviations from ideal semipermeability to solvent can give rise to a previously overlooked mode of “breakthrough” osmosis. Here the rate of osmosis is very large (compared to the conventional mode) and practically unaffected by the so-called Internal Concentration Polarization. In Pressure-Retarded Osmosis, the power densities can easily exceed the conventional mode by one order of magnitude. Much more robust support layers can be used, which is an important technical advantage (reduced membrane damage) in Pressure-Retarded Osmosis.