bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transporter protein and drug-conjugated gold nanoparticles capable of bypassing the blood-brain barrier
Authors: Zhang Yanhua , Walker Janelle Buttry , Minic Zeljka , Liu Fangchao , Goshgarian Harry , Mao Guangzhao 
Published: May 2016

AbstractDrug delivery to the central nervous system (CNS) is challenging due to the inability of many drugs to cross the blood-brain barrier (BBB). Here, we show that wheat germ agglutinin horse radish peroxidase (WGA-HRP) chemically conjugated to gold nanoparticles (AuNPs) can be transported to the spinal cord and brainstem following intramuscular injection into the diaphragm of rats. We synthesized and determined the size and chemical composition of a three-part nanoconjugate consisting of WGA-HRP, AuNPs and drugs for the treatment of diaphragm paralysis associated with high cervical spinal cord injury (SCI). Upon injection into the diaphragm muscle of rats, we show that the nanoconjugate is capable of delivering the drug at a much lower dose than the unconjugated drug injected systemically to effectively induce respiratory recovery in rats following SCI. This study not only demonstrates a promising strategy to deliver drugs to the CNS bypassing the BBB but also contributes a potential nanotherapy for the treatment of respiratory muscle paralysis resulted from cervical SCI.
Confined SnO2 quantum-dot clusters in graphene sheets as high-performance anodes for lithium-ion batteries
Authors: Zhu Chengling , Zhu Shenmin , Zhang Kai , Hui Zeyu , Pan Hui , Chen Zhixin , Li Yao , Zhang Di , Wang Da-Wei 
Published: May 2016

AbstractConstruction of metal oxide nanoparticles as anodes is of special interest for next-generation lithium-ion batteries. The main challenge lies in their rapid capacity fading caused by the structural degradation and instability of solid-electrolyte interphase (SEI) layer during charge/discharge process. Herein, we address these problems by constructing a novel-structured SnO2-based anode. The novel structure consists of mesoporous clusters of SnO2 quantum dots (SnO2 QDs), which are wrapped with reduced graphene oxide (RGO) sheets. The mesopores inside the clusters provide enough room for the expansion and contraction of SnO2 QDs during charge/discharge process while the integral structure of the clusters can be maintained. The wrapping RGO sheets act as electrolyte barrier and conductive reinforcement. When used as an anode, the resultant composite (MQDC-SnO2/RGO) shows an extremely high reversible capacity of 924 mAh g−1 after 200 cycles at 100 mA g−1, superior capacity retention (96%), and outstanding rate performance (505 mAh g−1 after 1000 cycles at 1000 mA g−1). Importantly, the materials can be easily scaled up under mild conditions. Our findings pave a new way for the development of metal oxide towards enhanced lithium storage performance.
Phosphoprotein network analysis of white adipose tissues unveils deregulated pathways in response to high-fat diet
Authors: Alli Shaik Asfa , Qiu Beiying , Wee Sheena , Choi Hyungwon , Gunaratne Jayantha , Tergaonkar Vinay 
Published: May 2016

AbstractDespite efforts in the last decade, signaling aberrations associated with obesity remain poorly understood. To dissect molecular mechanisms that define this complex metabolic disorder, we carried out global phosphoproteomic analysis of white adipose tissue (WAT) from mice fed on low-fat diet (LFD) and high-fat diet (HFD). We quantified phosphorylation levels on 7696 peptides, and found significant differential phosphorylation levels in 282 phosphosites from 191 proteins, including various insulin-responsive proteins and metabolic enzymes involved in lipid homeostasis in response to high-fat feeding. Kinase-substrate prediction and integrated network analysis of the altered phosphoproteins revealed underlying signaling modulations during HFD-induced obesity, and suggested deregulation of lipogenic and lipolytic pathways. Mutation of the differentially-regulated novel phosphosite on cytoplasmic acetyl-coA forming enzyme ACSS2 (S263A) upon HFD-induced obesity led to accumulation of serum triglycerides and reduced insulin-responsive AKT phosphorylation as compared to wild type ACSS2, thus highlighting its role in obesity. Altogether, our study presents a comprehensive map of adipose tissue phosphoproteome in obesity and reveals many previously unknown candidate phosphorylation sites for future functional investigation.
Targeting multiple response regulators of Mycobacterium tuberculosis augments the host immune response to infection
Authors: Banerjee Srijon Kaushik , Kumar Manish , Alokam Reshma , Sharma Arun Kumar , Chatterjee Ayan , Kumar Ranjeet , Sahu Sanjaya Kumar , Jana Kuladip , Singh Ramandeep , Yogeeswari Perumal , Sriram Dharmarajan , Basu Joyoti , Kundu Manikuntala 
Published: May 2016

AbstractThe genome of M. tuberculosis (Mtb) encodes eleven paired two component systems (TCSs) consisting of a sensor kinase (SK) and a response regulator (RR). The SKs sense environmental signals triggering RR-dependent gene expression pathways that enable the bacterium to adapt in the host milieu. We demonstrate that a conserved motif present in the C-terminal domain regulates the DNA binding functions of the OmpR family of Mtb RRs. Molecular docking studies against this motif helped to identify two molecules with a thiazolidine scaffold capable of targeting multiple RRs and modulating their regulons to attenuate bacterial replication in macrophages. The changes in the bacterial transcriptome extended to an altered immune response with increased autophagy and NO production, leading to compromised survival of Mtb in macrophages. Our findings underscore the promise of targeting multiple RRs as a novel yet unexplored approach for development of new anti-mycobacterial agents particularly against drug-resistant Mtb.
A single exercise bout enhances the manufacture of viral-specific T-cells from healthy donors: implications for allogeneic adoptive transfer immunotherapy
Authors: Spielmann Guillaume , Bollard Catherine M. , Kunz Hawley , Hanley Patrick J. , Simpson Richard J. 
Published: May 2016

AbstractCytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections remain a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The adoptive transfer of donor-derived viral-specific cytotoxic T-cells (VSTs) is an effective treatment for controlling CMV and EBV infections after HSCT; however, new practical methods are required to augment the ex vivo manufacture of multi-VSTs from healthy donors. This study investigated the effects of a single exercise bout on the ex vivo manufacture of multi-VSTs. PBMCs isolated from healthy CMV/EBV seropositive participants before (PRE) and immediately after (POST) 30-minutes of cycling exercise were stimulated with CMV (pp65 and IE1) and EBV (LMP2A and BMLF1) peptides and expanded over 8 days. The number (fold difference from PRE) of T-cells specific for CMV pp65 (2.6), EBV LMP2A (2.5) and EBV BMLF1 (4.4) was greater among the VSTs expanded POST. VSTs expanded PRE and POST had similar phenotype characteristics and were equally capable of MHC-restricted killing of autologous target cells. We conclude that a single exercise bout enhances the manufacture of multi-VSTs from healthy donors without altering their phenotype or function and may serve as a simple and economical adjuvant to boost the production of multi-VSTs for allogeneic adoptive transfer immunotherapy.
Potent neutralizing monoclonal antibodies against Ebola virus infection
Authors: Zhang Qi , Gui Miao , Niu Xuefeng , He Shihua , Wang Ruoke , Feng Yupeng , Kroeker Andrea , Zuo Yanan , Wang Hua , Wang Ying , Li Jiade , Li Chufang , Shi Yi , Shi Xuanling , Gao George F. , Xiang Ye , Qiu Xiangguo , Chen Ling , Zhang Linqi 
Published: May 2016

AbstractEbola virus infections cause a deadly hemorrhagic disease for which no vaccines or therapeutics has received regulatory approval. Here we show isolation of three (Q206, Q314 and Q411) neutralizing monoclonal antibodies (mAbs) against the surface glycoprotein (GP) of Ebola virus identified in West Africa in 2014 through sequential immunization of Chinese rhesus macaques and antigen-specific single B cell sorting. These mAbs demonstrated potent neutralizing activities against both pseudo and live Ebola virus independent of complement. Biochemical, single particle EM, and mutagenesis analysis suggested Q206 and Q411 recognized novel epitopes in the head while Q314 targeted the glycan cap in the GP1 subunit. Q206 and Q411 appeared to influence GP binding to its receptor NPC1. Treatment with these mAbs provided partial but significant protection against disease in a mouse model of Ebola virus infection. These novel mAbs could serve as promising candidates for prophylactic and therapeutic interventions against Ebola virus infection.
Effects of ADMA on gene expression and metabolism in serum-starved LoVo cells
Authors: Zheng Ningning , Wang Ke , He Jiaojiao , Qiu Yunping , Xie Guoxiang , Su Mingming , Jia Wei , Li Houkai 
Published: May 2016

AbstractSerum starvation is a typical way for inducing tumor cell apoptosis and stress. Asymmetric dimethylarginine (ADMA) is an endogenous metabolite. Our previous study reveals the plasma ADMA level is elevated in colon cancer patients, which can attenuate serum starvation-induced apoptosis in LoVo cells. In current study, we evaluated the effects of ADMA on gene expression and metabolism in serum-starved LoVo cells with gene microarray and metabolomic approaches. Our results indicated that 96 h serum starvation induced comprehensive alterations at transcriptional level, and most of them were restored by ADMA. The main signaling pathways induced by serum starvation included cancers-related pathways, pathways in cell death, apoptosis, and cell cycle etc. Meanwhile, the metabolomic data showed serum-starved cells were clearly separated with control cells, but not with ADMA-treated cells in PCA model. The identified differential metabolites indicated serum starvation significantly suppressed TCA cycle, altered glucose and fatty acids metabolism, as well as nucleic acids metabolism. However, very few differential metabolites were identified between ADMA and serum-starved cells. In summary, our current results indicated serum starvation profoundly altered the gene expression and metabolism of LoVo cells, whereas ADMA could restore most of the changes at transcriptional level, but not at metabolic level.
Dynamic allocation and transfer of non-structural carbohydrates, a possible mechanism for the explosive growth of Moso bamboo (Phyllostachys heterocycla)
Authors: Song Xinzhang , Peng Changhui , Zhou Guomo , Gu Honghao , Li Quan , Zhang Chao 
Published: May 2016

AbstractMoso bamboo can rapidly complete its growth in both height and diameter within only 35–40 days after shoot emergence. However, the underlying mechanism for this “explosive growth” remains poorly understood. We investigated the dynamics of non-structural carbohydrates (NSCs) in shoots and attached mature bamboos over a 20-month period. The results showed that Moso bamboos rapidly completed their height and diameter growth within 38 days. At the same time, attached mature bamboos transferred almost all the NSCs of their leaves, branches and especially trunks and rhizomes to the “explosively growing” shoots via underground rhizomes for the structural growth and metabolism of shoots. Approximately 4 months after shoot emergence, this transfer stopped when the leaves of the young bamboos could independently provide enough photoassimilates to meet the carbon demands of the young bamboos. During this period, the NSC content of the leaves, branches, trunks and rhizomes of mature bamboos declined by 1.5, 23, 28 and 5 fold, respectively. The trunk contributed the most NSCs to the shoots. Our findings provide new insight and a possible rational mechanism explaining the “explosive growth” of Moso bamboo and shed new light on understanding the role of NSCs in the rapid growth of Moso bamboo.
Revealing the role of oxidation state in interaction between nitro/amino-derived particulate matter and blood proteins
Authors: Liu Zhen , Li Ping , Bian Weiwei , Yu Jingkai , Zhan Jinhua 
Published: May 2016

AbstractSurface oxidation states of ultrafine particulate matter can influence the proinflammatory responses and reactive oxygen species levels in tissue. Surface active species of vehicle-emission soot can serve as electron transfer-mediators in mitochondrion. Revealing the role of surface oxidation state in particles-proteins interaction will promote the understanding on metabolism and toxicity. Here, the surface oxidation state was modeled by nitro/amino ligands on nanoparticles, the interaction with blood proteins were evaluated by capillary electrophoresis quantitatively. The nitro shown larger affinity than amino. On the other hand, the affinity to hemoglobin is 103 times larger than that to BSA. Further, molecular docking indicated the difference of binding intensity were mainly determined by hydrophobic forces and hydrogen bonds. These will deepen the quantitative understanding of protein-nanoparticles interaction from the perspective of surface chemical state.
Task modulation of disyllabic spoken word recognition in Mandarin Chinese: a unimodal ERP study
Authors: Huang Xianjun , Yang Jin-Chen , Chang Ruohan , Guo Chunyan 
Published: May 2016

AbstractUsing unimodal auditory tasks of word-matching and meaning-matching, this study investigated how the phonological and semantic processes in Chinese disyllabic spoken word recognition are modulated by top-down mechanism induced by experimental tasks. Both semantic similarity and word-initial phonological similarity between the primes and targets were manipulated. Results showed that at early stage of recognition (~150–250 ms), an enhanced P2 was elicited by the word-initial phonological mismatch in both tasks. In ~300–500 ms, a fronto-central negative component was elicited by word-initial phonological similarities in the word-matching task, while a parietal negativity was elicited by semantically unrelated primes in the meaning-matching task, indicating that both the semantic and phonological processes can be involved in this time window, depending on the task requirements. In the late stage (~500–700 ms), a centro-parietal Late N400 was elicited in both tasks, but with a larger effect in the meaning-matching task than in the word-matching task. This finding suggests that the semantic representation of the spoken words can be activated automatically in the late stage of recognition, even when semantic processing is not required. However, the magnitude of the semantic activation is modulated by task requirements.
Management of bipolar disorder in the intercontinental region: an international, multicenter, non-interventional, cross-sectional study in real-life conditions
Authors: Samalin Ludovic , Vieta Eduard , Okasha Tarek Ahmed , Uddin MM. Jalal , Ahmadi Abhari Seyed Ali , Nacef Fethi , Mishyiev Vyacheslav , Aizenberg Dovi , Ratner Yaël , Melas-Melt Lydie , Sedeki Idir , Llorca Pierre Michel 
Published: May 2016

AbstractMost of the existing data on real-life management of bipolar disorder are from studies conducted in western countries (mostly United States and Europe). This multinational, observational cohort study aimed to describe the management and clinical outcomes of bipolar patients in real-life conditions across various intercontinental countries (Bangladesh, Egypt, Iran, Israel, Tunisia, and Ukraine). Data on socio-demographic and disease characteristics, current symptomatology, and pharmacological treatment were collected. Comparisons between groups were performed using standard statistical tests. Overall, 1180 patients were included. The median time from initial diagnosis was 80 months. Major depressive disorder was the most common initial diagnosis. Mood stabilizers and antipsychotics were the most common drugs being prescribed at the time of the study. Antidepressants (mainly selective serotonin uptake inhibitors [SSRIs]) were administered to 36.1% of patients. Patients with bipolar I disorder received higher number of antipsychotics and anxiolytics than those with bipolar II disorder (p < 0.001). Presence of depressive symptoms was associated with an increase in antidepressant use (p < 0.001). Bipolar disorder real-life management practice, irrespective of region, shows a delay in diagnosis and an overuse of antidepressants. Clinical decision-making appears to be based on a multidimensional approach related to current symptomatology and type of bipolar disorder.
Self-cleaning and antibiofouling enamel surface by slippery liquid-infused technique
Authors: Yin JiaLi , Mei May Lei , Li QuanLi , Xia Rong , Zhang ZhiHong , Chu Chun Hung 
Published: May 2016

AbstractWe aimed to create a slippery liquid-infused enamel surface with antibiofouling property to prevent dental biofilm/plaque formation. First, a micro/nanoporous enamel surface was obtained by 37% phosphoric acid etching. The surface was then functionalized by hydrophobic low-surface energy heptadecafluoro-1,1,2,2-tetra- hydrodecyltrichlorosilane. Subsequent infusion of fluorocarbon lubricants (Fluorinert FC-70) into the polyfluoroalkyl-silanized rough surface resulted in an enamel surface with slippery liquid-infused porous surface (SLIPS). The results of water contact angle measurement, diffuse-reflectance Fourier transform infrared spectroscopy and atomic force microscope confirmed that the SLIPS was successfully constructed on the enamel surface. The antibiofouling property of the SLIPS was evaluated by the adsorption of salivary protein of mucin and Streptococcus mutans in vitro, as well as dental biofilm formation using a rabbit model in vivo. The results showed that the SLIPS on the enamel surface significantly inhibited mucin adhesion and S. mutans biofilm formation in vitro and inhibited dental plaque formation in vivo.
Molecular Mechanism for Conformational Dynamics of Ras·GTP Elucidated from In-Situ Structural Transition in Crystal
Authors: Matsumoto Shigeyuki , Miyano Nao , Baba Seiki , Liao Jingling , Kawamura Takashi , Tsuda Chiemi , Takeda Azusa , Yamamoto Masaki , Kumasaka Takashi , Kataoka Tohru , Shima Fumi 
Published: May 2016

AbstractRas•GTP adopts two interconverting conformational states, state 1 and state 2, corresponding to inactive and active forms, respectively. However, analysis of the mechanism for state transition was hampered by the lack of the structural information on wild-type Ras state 1 despite its fundamental nature conserved in the Ras superfamily. Here we solve two new crystal structures of wild-type H-Ras, corresponding to state 1 and state 2. The state 2 structure seems to represent an intermediate of state transition and, intriguingly, the state 1 crystal is successfully derived from this state 2 crystal by regulating the surrounding humidity. Structural comparison enables us to infer the molecular mechanism for state transition, during which a wide range of hydrogen-bonding networks across Switch I, Switch II and the α3-helix interdependently undergo gross rearrangements, where fluctuation of Tyr32, translocation of Gln61, loss of the functional water molecules and positional shift of GTP play major roles. The NMR-based hydrogen/deuterium exchange experiments also support this transition mechanism. Moreover, the unveiled structural features together with the results of the biochemical study provide a new insight into the physiological role of state 1 as a stable pool of Ras•GTP in the GDP/GTP cycle of Ras.
Circulating Zinc-α2-glycoprotein levels and Insulin Resistance in Polycystic Ovary Syndrome
Authors: Lai Yerui , Chen Jinhua , Li Ling , Yin Jingxia , He Junying , Yang Mengliu , Jia Yanjun , Liu Dongfang , Liu Hua , Liao Yong , Yang Gangyi 
Published: May 2016

AbstractThe aim of study was to assess the relationship between zinc-α2-glycoprotein (ZAG) and androgen excess with insulin resistance in polycystic ovary syndrome (PCOS) women. 99 PCOS women and 100 healthy controls were recruited. Euglycemic-hyperinsulinemic clamp (EHC) was preformed to assess their insulin sensitivity. Circulating ZAG was determined with an ELISA kit. In healthy subjects, circulating ZAG levels exhibited a characteristic diurnal rhythm in humans, with a major nocturnal rise occurring between midnight and early morning. Circulating ZAG and M-value were much lower in PCOS women than in the controls. In all population, overweight/obese subjects had significantly lower circulating ZAG levels than lean individuals. Multiple linear regression analysis revealed that only M-value and the area under the curve for glucose were independently related factors to circulating ZAG in PCOS women. Multivariate logistic regression analysis showed that circulating ZAG was significantly associated with PCOS even after controlling for anthropometric variables, blood pressure, lipid profile and hormone levels. The PCOS women with high ZAG had fewer MetS, IGT and polycystic ovaries as compared with the low ZAG PCOS women. Taken together, circulating ZAG levels are reduced in women with PCOS and ZAG may be a cytokine associated with insulin resistance in PCOS women.
Improving classification of mature microRNA by solving class imbalance problem
Authors: Wang Ying , Li Xiaoye , Tao Bairui 
Published: May 2016

AbstractMicroRNAs (miRNAs) are ~20–25 nucleotides non-coding RNAs, which regulated gene expression in the post-transcriptional level. The accurate rate of identifying the start sit of mature miRNA from a given pre-miRNA remains lower. It is noting that the mature miRNA prediction is a class-imbalanced problem which also leads to the unsatisfactory performance of these methods. We improved the prediction accuracy of classifier using balanced datasets and presented MatFind which is used for identifying 5′ mature miRNAs candidates from their pre-miRNA based on ensemble SVM classifiers with idea of adaboost. Firstly, the balanced-dataset was extract based on K-nearest neighbor algorithm. Secondly, the multiple SVM classifiers were trained in orderly using the balance datasets base on represented features. At last, all SVM classifiers were combined together to form the ensemble classifier. Our results on independent testing dataset show that the proposed method is more efficient than one without treating class imbalance problem. Moreover, MatFind achieves much higher classification accuracy than other three approaches. The ensemble SVM classifiers and balanced-datasets can solve the class-imbalanced problem, as well as improve performance of classifier for mature miRNA identification. MatFind is an accurate and fast method for 5′ mature miRNA identification.