bluuebunny/crossref_metadata_2025 huggingface dataset:
Corruption, Anticorruption, and the Transformation of Political Culture in Contemporary China
Authors: Keliher Macabe , Wu Hsinchao
Published: January 2016

Since its inception three years ago, Xi Jinping's anticorruption campaign has targeted some of China's biggest political and military figures and implicated tens of thousands of cadres. This article argues that the current campaign can be distinguished from the many others over the past thirty years not on account of its extensiveness, but rather in its systematic coupling with two other key moves: administrative reform and disciplinary regulation. Together, these three initiatives aim not only to clean up the malfeasance, graft, and bribery pervasive in Chinese political life today, but also to change the political culture. We demonstrate that the current leadership is forcing a shift in political norms and behaviors, and changing the shared assumptions and practices that inform the political dealings of the society, from the approval of permits to the promotion of judges.
Sarcopenia and cachexia in the era of obesity: clinical and nutritional impact
Authors: Prado C. M. , Cushen S. J. , Orsso C. E. , Ryan A. M.
Published: January 2016

Our understanding of body composition (BC) variability in contemporary populations has significantly increased with the use of imaging techniques. Abnormal BC such as sarcopenia (low muscle mass) and obesity (excess adipose tissue) are predictors of poorer prognosis in a variety of conditions or clinical situations. As a catabolic illness, a defining feature of cancer is muscle loss. Although the conceptual model of wasting in cancer is typically conceived as involuntary weight loss leading to low body weight, recent studies have shown that both sarcopenia and cachexia can be present with obesity. The combination of low muscle and high adipose tissue (sarcopenic obesity) is an emerging abnormal BC phenotype prevalent across the body weight, and hence BMI spectra. Sarcopenia and sarcopenic obesity in cancer are in most instances occult conditions, which have been independently associated with higher incidence of chemotherapy toxicity, shorter time to tumour progression, poorer outcomes of surgery, physical impairment and shorter survival. Although the mechanisms are yet to be fully understood, the associations with poorer clinical outcomes emphasise the value of nutritional assessment as well as the need to develop appropriate interventions to countermeasure abnormal BC. Sarcopenia and sarcopenic obesity create diverse nutritional requirements, highlighting the compelling need for a more comprehensive and differentiated understanding of energy and protein requirements in this heterogeneous population.
Examining cellular immune responses to inform development of a blood-stage malaria vaccine
Authors: STANISIC DANIELLE I. , GOOD MICHAEL F.
Published: January 2016

Naturally acquired immunity to the blood-stage of the malaria parasite develops slowly in areas of high endemicity, but is not sterilizing. It manifests as a reduction in parasite density and clinical symptoms. Immunity as a result of blood-stage vaccination has not yet been achieved in humans, although there are many animal models where vaccination has been successful. The development of a blood-stage vaccine has been complicated by a number of factors including limited knowledge of human-parasite interactions and which antigens and immune responses are critical for protection. Opinion is divided as to whether this vaccine should aim to accelerate the acquisition of responses acquired following natural exposure, or whether it should induce a different response. Animal and experimental human models suggest that cell-mediated immune responses can control parasite growth, but these responses can also contribute to significant immunopathology if unregulated. They are largely ignored in most blood-stage malaria vaccine development strategies. Here, we discuss key observations relating to cell-mediated immune responses in the context of experimental human systems and field studies involving naturally exposed individuals and how this may inform the development of a blood-stage malaria vaccine.
Naturally acquired immunity to sexual stageP. falciparumparasites
Authors: STONE WILL J. R. , DANTZLER KATHLEEN W. , NILSSON SANDRA K. , DRAKELEY CHRIS J. , MARTI MATTHIAS , BOUSEMA TEUN , RIJPMA SANNA R.
Published: January 2016

Gametocytes are the specialized form ofPlasmodiumparasites that are responsible for human-to-mosquito transmission of malaria. Transmission of gametocytes is highly effective, but represents a biomass bottleneck for the parasite that has stimulated interest in strategies targeting the transmission stages separately from those responsible for clinical disease. Studying targets of naturally acquired immunity against transmission-stage parasites may reveal opportunities for novel transmission reducing interventions, particularly the development of a transmission blocking vaccine (TBV). In this review, we summarize the current knowledge on immunity against the transmission stages ofPlasmodium. This includes immune responses against epitopes on the gametocyte-infected erythrocyte surface during gametocyte development, as well as epitopes present upon gametocyte activation in the mosquito midgut. We present an analysis of historical data on transmission reducing immunity (TRI), as analysed in mosquito feeding assays, and its correlation with natural recognition of sexual stage specific proteins Pfs48/45 and Pfs230. Although high antibody titres towards either one of these proteins is associated with TRI, the presence of additional, novel targets is anticipated. In conclusion, the identification of novel gametocyte-specific targets of naturally acquired immunity against different gametocyte stages could aid in the development of potential TBV targets and ultimately an effective transmission blocking approach.
Immunological processes underlying the slow acquisition of humoral immunity to malaria
Authors: RYG-CORNEJO VICTORIA , LY ANN , HANSEN DIANA S.
Published: January 2016

Malaria is one of the most serious infectious diseases with ~250 million clinical cases annually. Most cases of severe disease are caused byPlasmodium falciparum. The blood stage ofPlasmodiumparasite is entirely responsible for malaria-associated pathology. Disease syndromes range from fever to more severe complications, including respiratory distress, metabolic acidosis, renal failure, pulmonary oedema and cerebral malaria. The most susceptible population to severe malaria is children under the age of 5, with low levels of immunity. It is only after many years of repeated exposure, that individuals living in endemic areas develop clinical immunity. This form of protection does not result in sterilizing immunity but prevents clinical episodes by substantially reducing parasite burden. Naturally acquired immunity predominantly targets blood-stage parasites and it is known to require antibody responses. A large body of epidemiological evidence suggests that antibodies toPlasmodiumantigens are inefficiently generated and rapidly lost in the absence of ongoing exposure, which suggests a defect in the development of B cell immunological memory. This review summarizes the main findings to date contributing to our understanding on cellular processes underlying the slow acquisition of humoral immunity to malaria. Some of the key outstanding questions in the field are discussed.
Multilocus sequence typing of 102 Burkholderia pseudomallei strains isolated from China
Authors: FANG Y. , ZHU P. , LI Q. , CHEN H. , LI Y. , REN C. , HU Y. , TAN Z. , GU J. , MAO X.
Published: January 2016

The phylogenetic and epidemiological relationships of 102 Burkholderia pseudomallei clinical isolates from different geographical and population sources in China were investigated by multilocus sequence typing (MLST). The MLST data were analysed using the e-BURST algorithm, and an unweighted pair-group method with arithmetic mean dendrogram was constructed based on the pair-wise differences in the allelic profiles of the strains. Forty-one sequence types (STs) were identified, of which eight were novel (ST1341, ST1345, ST1346, ST1347, ST1348, ST1349, ST1350, ST1351). No geographical-specific or host population-specific phylogenetic lineages were identified. ST46, ST50, ST55, ST58, ST70 and ST1095 predominated, but ~44% of isolates were assigned to 45 STs illustrating high genetic diversity in the strain collection. Additionally, the phylogenetic relationships of the dominant STs in China showed significant linkeage with B. pseudomallei isolates from Thailand. Analysis of the gmhD allele suggests high genetic variation in B. pseudomallei in China.
Introduction and prolonged circulation of G12 rotaviruses in Sicily
Authors: GIAMMANCO G. M. , BONURA F. , DI BERNARDO F. , CASCIO A. , FERRERA G. , DONES P. , SAPORITO L. , COLLURA A. , TERRANOVA D. M. , VALENZISE M. , ALLÙ M. T. , CASUCCIO N. , PALERMO M. , BÁNYAI K. , MARTELLA V. , DE GRAZIA S.
Published: January 2016

Genotype G12 strains are now considered to be the sixth most prevalent human rotaviruses worldwide. In two Sicilian cities, Palermo and Messina, surveillance of rotavirus circulation performed since 1985 and 2009, respectively, did not detect G12 strains until 2012. From 2012 to 2014 rotavirus infection was detected in 29·7% of 1647 stool samples collected from children admitted for acute gastroenteritis to three Sicilian hospitals in Palermo, Messina and Ragusa. In 2012, G12P[8] was first detected in Palermo and then in Messina where it represented the second most frequent genotype (20% prevalence) after G1P[8]. Thereafter, G12 strains continued to circulate in Sicily, showing a marked prevalence in Ragusa (27·8%) in 2013 and in Palermo (21%) and Messina (16·6%) in 2014. All but one of the Sicilian G12 strains carried a P[8] VP4 genotype, whereas the single non-P[8] rotavirus strain was genotyped as G12P[9]. Phylogenetic analysis of the VP7 and VP4 sequences allowed distinction of several genetic lineages and separation of the G12P[8] strains into three cluster combinations. These findings indicate independent introductions of G12 rotavirus strains in Sicily in recent years.
Comparison of fundamental physical properties of the model cells (protocells) and the living cells reveals the need in protophysiology
Authors: Matveev V.V.
Published: January 2016

A hypothesis is proposed about potassium ponds being the cradles of life enriches the gamut of ideas about the possible conditions of pre-biological evolution on the primeval Earth, but does not bring us closer to solving the real problem of the origin of life. The gist of the matter lies in the mechanism of making a delimitation between two environments – the intracellular environment and the habitat of protocells. Since the sodium–potassium pump (Na+/K+-ATPase) was discovered, no molecular model has been proposed for a predecessor of the modern sodium pump. This has brought into life the idea of the potassium pond, wherein protocells would not need a sodium pump. However, current notions of the operation of living cells come into conflict with even physical laws when trying to use them to explain the origin and functioning of protocells. Thus, habitual explanations of the physical properties of living cells have become inapplicable to explain the corresponding properties of Sidney Fox's microspheres. Likewise, existing approaches to solving the problem of the origin of life do not see the need for the comparative study of living cells and cell models, assemblies of biological and artificial small molecules and macromolecules under physical conditions conducive to the origin of life. The time has come to conduct comprehensive research into the fundamental physical properties of protocells and create a new discipline – protocell physiology or protophysiology – which should bring us much closer to solving the problem of the origin of life.
A matter of principle(s): The legal effect of impartiality and neutrality on States as humanitarian actors
Authors: Mačák Kubo
Published: January 2016

This article examines the legal nature of the principles of impartiality and neutrality of humanitarian action, focusing on States as humanitarian actors. It argues that international law does not provide a general legal basis for the universal applicability of these principles, contrary to a common interpretation of the International Court of Justice's 1986 judgment in theNicaraguacase. Nevertheless, impartiality and neutrality may have a significant legal effect on the conduct of States. They may be directly binding on States through the operation of Security Council resolutions drafted in mandatory language. In addition, they may have indirect effect due to the States’ obligation to respect humanitarian organizations’ adherence to the principles. On the basis of this argument, the article pleads for increased conceptual clarity and, in turn, effectiveness of humanitarian action.
The future of mental health care: peer-to-peer support and social media
Authors: Naslund J. A. , Aschbrenner K. A. , Marsch L. A. , Bartels S. J.
Published: January 2016

Aims:

People with serious mental illness are increasingly turning to popular social media, including Facebook, Twitter or YouTube, to share their illness experiences or seek advice from others with similar health conditions. This emerging form of unsolicited communication among self-forming online communities of patients and individuals with diverse health concerns is referred to as peer-to-peer support. We offer a perspective on how online peer-to-peer connections among people with serious mental illness could advance efforts to promote mental and physical wellbeing in this group.

Methods:

In this commentary, we take the perspective that when an individual with serious mental illness decides to connect with similar others online it represents a critical point in their illness experience. We propose a conceptual model to illustrate how online peer-to-peer connections may afford opportunities for individuals with serious mental illness to challenge stigma, increase consumer activation and access online interventions for mental and physical wellbeing.

Results:

People with serious mental illness report benefits from interacting with peers online from greater social connectedness, feelings of group belonging and by sharing personal stories and strategies for coping with day-to-day challenges of living with a mental illness. Within online communities, individuals with serious mental illness could challenge stigma through personal empowerment and providing hope. By learning from peers online, these individuals may gain insight about important health care decisions, which could promote mental health care seeking behaviours. These individuals could also access interventions for mental and physical wellbeing delivered through social media that could incorporate mutual support between peers, help promote treatment engagement and reach a wider demographic. Unforeseen risks may include exposure to misleading information, facing hostile or derogatory comments from others, or feeling more uncertain about one's health condition. However, given the evidence to date, the benefits of online peer-to-peer support appear to outweigh the potential risks.

Conclusion:

Future research must explore these opportunities to support and empower people with serious mental illness through online peer networks while carefully considering potential risks that may arise from online peer-to-peer interactions. Efforts will also need to address methodological challenges in the form of evaluating interventions delivered through social media and collecting objective mental and physical health outcome measures online. A key challenge will be to determine whether skills learned from peers in online networks translate into tangible and meaningful improvements in recovery, employment, or mental and physical wellbeing in the offline world.
Differentiation of human monocytes and derived subsets of macrophages and dendritic cells by the HLDA10 monoclonal antibody panel
Authors: Ohradanova‐Repic Anna , Machacek Christian , Fischer Michael B , Stockinger Hannes
Published: January 2016

The mononuclear phagocyte system, consisting of monocytes, macrophages and dendritic cells (DCs), has an important role in tissue homeostasis as well as in eliciting immune responses against invading pathogens. Blood monocytes have been viewed for decades as precursors of tissue macrophages. Although the newest data show that in the steady state resident macrophages of many organs are monocyte independent, blood monocytes critically contribute to tissue macrophage and DC pools upon inflammation. To better understand the relationship between these populations and their phenotype, we isolated and differentiated human blood CD14+ monocytes in vitro into immature and mature monocyte‐derived dendritic cells (MoDCs) as well as into seven different monocyte‐derived macrophage subsets. We used the panel of 70 monoclonal antibodies (mAbs) submitted to the 10th Human Leukocyte Differentiation Antigen Workshop to determine the expression profiles of these 10 populations by flow cytometry. We now can compile subpanels of mAbs to differentiate the 10 monocyte/macrophage/MoDC subsets, providing the basis for novel diagnostic and therapeutic tools.
Ciliated neurons lining the central canal sense both fluid movement and pH through ASIC3
Authors: Jalalvand Elham , Robertson Brita , Wallén Peter , Grillner Sten
Published: January 2016

Cerebrospinal fluid-contacting (CSF-c) cells are found in all vertebrates but their function has remained elusive. We recently identified one type of laterally projecting CSF-c cell in lamprey spinal cord with neuronal properties that expresses GABA and somatostatin. We show here that these CSF-c neurons respond to both mechanical stimulation and to lowered pH. These effects are most likely mediated by ASIC3-channels, since APETx2, a specific antagonist of ASIC3, blocks them both. Furthermore, lowering of pH as well as application of somatostatin will reduce the locomotor burst rate. The somatostatin receptor antagonist counteracts the effects of both a decrease in pH and of somatostatin. Lateral bending movement imposed on the spinal cord, as would occur during natural swimming, activates CSF-c neurons. Taken together, we show that CSF-c neurons act both as mechanoreceptors and as chemoreceptors through ASIC3 channels, and their action may protect against pH-changes resulting from excessive neuronal activity.
Electromechanical control of nitrogen-vacancy defect emission using graphene NEMS
Authors: Reserbat-Plantey Antoine , Schädler Kevin G. , Gaudreau Louis , Navickaite Gabriele , Güttinger Johannes , Chang Darrick , Toninelli Costanza , Bachtold Adrian , Koppens Frank H. L.
Published: January 2016

Despite recent progress in nano-optomechanics, active control of optical fields at the nanoscale has not been achieved with an on-chip nano-electromechanical system (NEMS) thus far. Here we present a new type of hybrid system, consisting of an on-chip graphene NEMS suspended a few tens of nanometres above nitrogen-vacancy centres (NVCs), which are stable single-photon emitters embedded in nanodiamonds. Electromechanical control of the photons emitted by the NVC is provided by electrostatic tuning of the graphene NEMS position, which is transduced to a modulation of NVC emission intensity. The optomechanical coupling between the graphene displacement and the NVC emission is based on near-field dipole–dipole interaction. This class of optomechanical coupling increases strongly for smaller distances, making it suitable for nanoscale devices. These achievements hold promise for selective control of emitter arrays on-chip, optical spectroscopy of individual nano-objects, integrated optomechanical information processing and open new avenues towards quantum optomechanics.
Making hybrid [n]-rotaxanes as supramolecular arrays of molecular electron spin qubits
Authors: Fernandez Antonio , Ferrando-Soria Jesus , Pineda Eufemio Moreno , Tuna Floriana , Vitorica-Yrezabal Iñigo J. , Knappke Christiane , Ujma Jakub , Muryn Christopher A. , Timco Grigore A. , Barran Perdita E. , Ardavan Arzhang , Winpenny Richard E.P.
Published: January 2016

Quantum information processing (QIP) would require that the individual units involved—qubits—communicate to other qubits while retaining their identity. In many ways this resembles the way supramolecular chemistry brings together individual molecules into interlocked structures, where the assembly has one identity but where the individual components are still recognizable. Here a fully modular supramolecular strategy has been to link hybrid organic–inorganic [2]- and [3]-rotaxanes into still larger [4]-, [5]- and [7]-rotaxanes. The ring components are heterometallic octanuclear [Cr7NiF8(O2CtBu)16]– coordination cages and the thread components template the formation of the ring about the organic axle, and are further functionalized to act as a ligand, which leads to large supramolecular arrays of these heterometallic rings. As the rings have been proposed as qubits for QIP, the strategy provides a possible route towards scalable molecular electron spin devices for QIP. Double electron–electron resonance experiments demonstrate inter-qubit interactions suitable for mediating two-qubit quantum logic gates.
IL-7 signalling represses Bcl-6 and the TFH gene program
Authors: McDonald Paul W. , Read Kaitlin A. , Baker Chandra E. , Anderson Ashlyn E. , Powell Michael D. , Ballesteros-Tato André , Oestreich Kenneth J.
Published: January 2016

The transcriptional repressor Bcl-6 is linked to the development of both CD4+ T follicular helper (TFH) and central memory T (TCM) cells. Here, we demonstrate that in response to decreased IL-2 signalling, T helper 1 (TH1) cells upregulate Bcl-6 and co-initiate TFH- and TCM-like gene programs, including expression of the cytokine receptors IL-6Rα and IL-7R. Exposure of this potentially bi-potent cell population to IL-6 favours the TFH gene program, whereas IL-7 signalling represses TFH-associated genes including Bcl6 and Cxcr5, but not the TCM-related genes Klf2 and Sell. Mechanistically, IL-7-dependent activation of STAT5 contributes to Bcl-6 repression. Importantly, antigen-specific IL-6Rα+IL-7R+ CD4+ T cells emerge from the effector population at late time points post influenza infection. These data support a novel role for IL-7 in the repression of the TFH gene program and evoke a divergent regulatory mechanism by which post-effector TH1 cells may contribute to long-term cell-mediated and humoral immunity.
Implementation of meiosis prophase I programme requires a conserved retinoid-independent stabilizer of meiotic transcripts
Authors: Abby Emilie , Tourpin Sophie , Ribeiro Jonathan , Daniel Katrin , Messiaen Sébastien , Moison Delphine , Guerquin Justine , Gaillard Jean-Charles , Armengaud Jean , Langa Francina , Toth Attila , Martini Emmanuelle , Livera Gabriel
Published: January 2016

Sexual reproduction is crucially dependent on meiosis, a conserved, specialized cell division programme that is essential for the production of haploid gametes. Here we demonstrate that fertility and the implementation of the meiotic programme require a previously uncharacterized meiosis-specific protein, MEIOC.Meiocinvalidation in mice induces early and pleiotropic meiotic defects in males and females. MEIOC prevents meiotic transcript degradation and interacts with an RNA helicase that binds numerous meiotic mRNAs. Our results indicate that proper engagement into meiosis necessitates the specific stabilization of meiotic transcripts, a previously little-appreciated feature in mammals. Remarkably, the upregulation of MEIOC at the onset of meiosis does not require retinoic acid and STRA8 signalling. Thus, we propose that the complete induction of the meiotic programme requires both retinoic acid-dependent and -independent mechanisms. The latter process involving post-transcriptional regulation likely represents an ancestral mechanism, given that MEIOC homologues are conserved throughout multicellular animals.
“Click on the bidirectional switch”: the aptasensor for simultaneous detection of lysozyme and ATP with high sensitivity and high selectivity
Authors: Chen Feng , Cai Changqun , Chen Xiaoming , Chen Chunyan
Published: January 2016

A bifunctional and simple aptasensor was designed to one-spot simultaneously detect two analytes, lysozyme and ATP. The aptasensor was obtained by the electronic interaction between methyl violet (MV) and dsDNA. The dsDNA was obtained by hybridization of ATP aptamer and lysozyme aptamer. And we used the resonance light scattering (RLS) technique to detect the concentration of lysozyme and ATP. During the procedure of detection, the aptasensor works like a bidirectional switch, the corresponding side of the dsDNA will open when the target (lysozyme or ATP) “click” the aptamer, which results in corresponding RLS signal change. By the combination of the RLS technique, it is found that the changed RLS intensity was proportional to the concentration of lysozyme and ATP. The mixtures of ATP and lysozyme also met two binary function relations. The results indicated that the aptasensor could achieve simultaneous detection of ATP and lysozyme, the detection limits of ATP and lysozyme could reach 10−11 M and 10−12 M, respectively. The aptasensor shows potential application for small molecule and protein detection by RLS, it could extend the application of RLS technique.
In situ genetic correction of F8 intron 22 inversion in hemophilia A patient-specific iPSCs
Authors: Wu Yong , Hu Zhiqing , Li Zhuo , Pang Jialun , Feng Mai , Hu Xuyun , Wang Xiaolin , Lin-Peng Siyuan , Liu Bo , Chen Fangping , Wu Lingqian , Liang Desheng
Published: January 2016

Nearly half of severe Hemophilia A (HA) cases are caused by F8 intron 22 inversion (Inv22). This 0.6-Mb inversion splits the 186-kb F8 into two parts with opposite transcription directions. The inverted 5′ part (141 kb) preserves the first 22 exons that are driven by the intrinsic F8 promoter, leading to a truncated F8 transcript due to the lack of the last 627 bp coding sequence of exons 23–26. Here we describe an in situ genetic correction of Inv22 in patient-specific induced pluripotent stem cells (iPSCs). By using TALENs, the 627 bp sequence plus a polyA signal was precisely targeted at the junction of exon 22 and intron 22 via homologous recombination (HR) with high targeting efficiencies of 62.5% and 52.9%. The gene-corrected iPSCs retained a normal karyotype following removal of drug selection cassette using a Cre-LoxP system. Importantly, both F8 transcription and FVIII secretion were rescued in the candidate cell types for HA gene therapy including endothelial cells (ECs) and mesenchymal stem cells (MSCs) derived from the gene-corrected iPSCs. This is the first report of an efficient in situ genetic correction of the large inversion mutation using a strategy of targeted gene addition.
A highly selective and sensitive near-infrared fluorescent probe for imaging of hydrogen sulphide in living cells and mice
Authors: Zhang Ling , Zheng Xi Emily , Zou Fang , Shang Yanguo , Meng Wenqi , Lai En , Xu Zhichen , Liu Yi , Zhao Jing
Published: January 2016

Hydrogen sulphide (H2S), the third endogenous gaseous signalling molecule, has attracted attention in biochemical research. The selective detection of H2S in living systems is essential for studying its functions. Fluorescence detection methods have become useful tools to explore the physiological roles of H2S because of their real-time and non-destructive characteristics. Herein we report a near-infrared fluorescent probe, NIR-HS, capable of tracking H2S in living organisms. With high sensitivity, good selectivity and low cytotoxicity, NIR-HS was able to recognize both the exogenous and endogenous H2S in living cells. More importantly, it realized the visualization of endogenous H2S generated in cells overexpressing cystathionine β-synthase (CBS), one of the enzymes responsible for producing endogenous H2S. The probe was also successfully applied to detect both the exogenous and endogenous H2S in living mice. The superior sensing properties of the probe render it a valuable research tool in the H2S-related medical research.
Extraction, purification and anti-fatigue activity of γ-aminobutyric acid from mulberry (Morus alba L.) leaves
Authors: Chen Hengwen , He Xuanhui , Liu Yan , Li Jun , He Qingyong , Zhang Cuiying , Wei Benjun , Zhang Ye , Wang Jie
Published: January 2016

Mulberry (Morus alba L.) is a tree species of Moraceae widely distributed in Southern China. In the present study, the white crystal of γ-aminobutyric acid (GABA) was purified from mulberry leaves and its bioactivity was also investigated. The main results were as follows: first, the crude GABA was extracted from mulberry leaves by using biochemical methods. Then, the crude was purified by chromatography over an S-8 macroporous resin, Sephadex G-10 and 732 cation exchange resin to yield a white crystal. Lavage administration and exposure of GABA to male NIH mice showed no adverse effects on their growth and development. In an endurance capacity test, the average loaded-swimming time of medium dose was 111.60% longer than the control (P < 0.01). Further investigations showed that relative to that of model control, the respective blood lactate (BL) concentrations of low- and medium-dose were 28.52% and 28.81% lower (P < 0.05), whereas the levels of blood urea nitrogen (BUN) were 36.83% and 40.54% lower (P < 0.05) and that of liver glycogen (LG) levels were 12.81% and 17.22% lower (P < 0.05). The results indicated that GABA has an advantage over taurine of anti-fatigue effect. These findings were indicative of the anti-fatigue activity of GABA.
A Generic Platform for Cellular Screening Against Ubiquitin Ligases
Authors: Maculins Timurs , Carter Nikki , Dorval Thierry , Hudson Kevin , Nissink J. Willem M. , Hay Ronald T. , Alwan Husam
Published: January 2016

Ubiquitin signalling regulates most aspects of cellular life, thus deregulation of ubiquitylation has been linked with a number of diseases. E3 ubiquitin ligases provide substrate selectivity in ubiquitylation cascades and are therefore considered to be attractive targets for developing therapeutic molecules. In contrast to established drug target classes, such as protein kinases, GPCRs, hormone receptors and ion channels, ubiquitin drug discovery is in its early stages. This is, in part, due to the complexity of the ubiquitylation pathways and the lack of robust quantitative technologies that allow high-throughput screening of inhibitors. Here we report the development of a Ubiquitin Ligase Profiling system, which is a novel and generic cellular technology designed to facilitate identification of selective inhibitors against RING type E3 ubiquitin ligases. Utilization of this system requires a single co-transfection of cells with assay vectors, thereby enabling readout of E3 ubiquitin ligase catalytic activity within the cellular environment. Therefore, our robust high-throughput screening platform offers novel opportunities for the development of inhibitors against this difficult-to-target E3 ligase enzyme class.
Assessing the impact of humidex on HFMD in Guangdong Province and its variability across social-economic status and age groups
Authors: Zhang Wangjian , Du Zhicheng , Zhang Dingmei , Yu Shicheng , Huang Yong , Hao Yuantao
Published: January 2016

Humidex is a meteorological index that combines the impacts of temperature and humidity and is directly comparable with dry temperature in degrees Celsius. However, to date, no research has focused on the effect of humidex on hand, foot and mouth disease (HFMD). The current study was designed to address this research need. Case-based HFMD surveillance data and daily meteorological data collected between 2010 and 2012 was obtained from the China CDC and the National Meteorological Information Center, respectively. Distributed lag nonlinear models were applied to assess the impact of humidex on HFMD among children under 15 years oldin Guangdong and its variability across social-economic status and age groups. We found that relative risk (RR) largely increased with humidex. Lag-specific and cumulative humidex-RR curves for children from the Pearl-River Delta Region as well as older children were more likely to show two-peak distribution patterns. One RR peak occurred at a humidex of between 15 and 20 and the other occurred between 30 and 35. This study provides a comprehensive picture of the impact of humidex on HFMD incidence in Guangdong Province. Results from the present study should be important in the development of area-and-age-targeted control programs.
Structural brain alterations in primary open angle glaucoma: a 3T MRI study
Authors: Wang Jieqiong , Li Ting , Sabel Bernhard A. , Chen Zhiqiang , Wen Hongwei , Li Jianhong , Xie Xiaobin , Yang Diya , Chen Weiwei , Wang Ningli , Xian Junfang , He Huiguang
Published: January 2016

Glaucoma is not only an eye disease but is also associated with degeneration of brain structures. We now investigated the pattern of visual and non-visual brain structural changes in 25 primary open angle glaucoma (POAG) patients and 25 age-gender-matched normal controls using T1-weighted imaging. MRI images were subjected to volume-based analysis (VBA) and surface-based analysis (SBA) in the whole brain as well as ROI-based analysis of the lateral geniculate nucleus (LGN), visual cortex (V1/2), amygdala and hippocampus. While VBA showed no significant differences in the gray matter volumes of patients, SBA revealed significantly reduced cortical thickness in the right frontal pole and ROI-based analysis volume shrinkage in LGN bilaterally, right V1 and left amygdala. Structural abnormalities were correlated with clinical parameters in a subset of the patients revealing that the left LGN volume was negatively correlated with bilateral cup-to-disk ratio (CDR), the right LGN volume was positively correlated with the mean deviation of the right visual hemifield and the right V1 cortical thickness was negatively correlated with the right CDR in glaucoma. These results demonstrate that POAG affects both vision-related structures and non-visual cortical regions. Moreover, alterations of the brain visual structures reflect the clinical severity of glaucoma.
Comparative transcriptomic analysis uncovers the complex genetic network for resistance to Sclerotinia sclerotiorum in Brassica napus
Authors: Wu Jian , Zhao Qing , Yang Qingyong , Liu Han , Li Qingyuan , Yi Xinqi , Cheng Yan , Guo Liang , Fan Chuchuan , Zhou Yongming
Published: January 2016

Sclerotinia stem rot caused by Sclerotinia sclerotiorum is one of the most devastating diseases in many important crops including Brassica napus worldwide. Quantitative resistance is the only source for genetic improvement of Sclerotinia-resistance in B. napus, but the molecular basis for such a resistance is largely unknown. Here, we performed dynamic transcriptomic analyses to understand the differential defense response to S. sclerotiorum in a resistant line (R-line) and a susceptible line (S-line) of B. napus at 24, 48 and 96 h post-inoculation. Both the numbers of and fold changes in differentially expressed genes in the R-line were larger than those in the S-line. We identified 9001 relative differentially expressed genes in the R-line compared with the S-line. The differences between susceptibility and resistance were associated with the magnitude of expression changes in a set of genes involved in pathogen recognition, MAPK signaling cascade, WRKY transcription regulation, jasmonic acid/ethylene signaling pathways and biosynthesis of defense-related protein and indolic glucosinolate. The results were supported by quantitation of defense-related enzyme activity and glucosinolate contents. Our results provide insights into the complex molecular mechanism of the defense response to S. sclerotiorum in B. napus and for development of effective strategies in Sclerotinia-resistance breeding.
Evidence for genetic regulation of mRNA expression of the dosage-sensitive gene retinoic acid induced-1 (RAI1) in human brain
Authors: Chen Li , Tao Yu , Song Fan , Yuan Xi , Wang Jian , Saffen David
Published: January 2016

RAI1 (retinoic acid induced-1) is a dosage-sensitive gene that causes Smith-Magenis syndrome (SMS) when mutated or deleted and Potocki-Lupski Syndrome (PTLS) when duplicated, with psychiatric features commonly observed in both syndromes. How common genetic variants regulate this gene, however, is unknown. In this study, we found that RAI1 mRNA expression in Chinese prefrontal and temporal cortex correlate with genotypes of common single nucleotide polymorphisms (SNPs) located in the RAI1 5′-upstream region. Using genotype imputation, “R2-Δ2” analysis and data from the RegulomeDB database, we identified SNPs rs4925102 and rs9907986 as possible regulatory variants, accounting for approximately 30–40% of the variance in RAI1 mRNA expression in both brain regions. Specifically, rs4925102 and rs9907986 are predicted to disrupt the binding of retinoic acid RXR-RAR receptors and the transcription factor DEAF1 (Deformed epidermal autoregulatory factor-1), respectively. Consistent with these predictions, we observed binding of RXRα and RARα to the predicted RAI1 target in chromatin immunoprecipitation assays. Retinoic acid is crucial for early development of the central neural system and DEAF1 is associated with intellectual disability. The observation that a significant portion of RAI1 mRNA expression is genetically controlled raises the possibility that common RAI1 5′-region regulatory variants contribute more generally to psychiatric disorders.
Route towards Localization for Quantum Anomalous Hall Systems with Chern Number 2
Authors: Song Zhi-Gang , Zhang Yan-Yang , Song Jun-Tao , Li Shu-Shen
Published: January 2016

The quantum anomalous Hall system with Chern number 2 can be destroyed by sufficiently strong disorder. During its process towards localization, it was found that the electronic states will be directly localized to an Anderson insulator (with Chern number 0), without an intermediate Hall plateau with Chern number 1. Here we investigate the topological origin of this phenomenon, by calculating the band structures and Chern numbers for disordered supercells. We find that on the route towards localization, there exists a hidden state with Chern number 1, but it is too short and too fluctuating to be practically observable. This intermediate state cannot be stabilized even after some “smart design” of the model and this should be a universal phenomena for insulators with high Chern numbers. By performing numerical scaling of conductances, we also plot the renormalization group flows for this transition, with Chern number 1 state as an unstable fixed point. This is distinct from known results and can be tested by experiments and further theoretical analysis.
Remarkably high mobility ultra-thin-film metal-oxide transistor with strongly overlapped orbitals
Authors: Wei Shih Chen , Chin Albert , Fu Lu Chun , Fang Su Wei
Published: January 2016

High mobility channel thin-film-transistor (TFT) is crucial for both display and future generation integrated circuit. We report a new metal-oxide TFT that has an ultra-thin 4.5 nm SnO2 thickness for both active channel and source-drain regions, very high 147 cm2/Vs field-effect mobility, high ION/IOFF of 2.3 × 107, small 110 mV/dec sub-threshold slope and a low VD of 2.5 V for low power operation. This mobility is already better than chemical-vapor-deposition grown multi-layers MoS2 TFT. From first principle quantum-mechanical calculation, the high mobility TFT is due to strongly overlapped orbitals.
Genome-wide association study identifies three key loci for high mesocarp oil content in perennial crop oil palm
Authors: Teh Chee-Keng , Ong Ai-Ling , Kwong Qi-Bin , Apparow Sukganah , Chew Fook-Tim , Mayes Sean , Mohamed Mohaimi , Appleton David , Kulaveerasingam Harikrishna
Published: January 2016

GWAS in out-crossing perennial crops is typically limited by insufficient marker density to account for population diversity and effects of population structure resulting in high false positive rates. The perennial crop oil palm is the most productive oil crop. We performed GWAS for oil-to-dry-mesocarp content (O/DM) on 2,045 genotyped tenera palms using 200K SNPs that were selected based on the short-range linkage disequilibrium distance, which is inherent with long breeding cycles and heterogeneous breeding populations. Eighty loci were significantly associated with O/DM (p ≤ 10−4) and three key signals were found. We then evaluated the progeny of a Deli x AVROS breeding trial and a 4% higher O/DM was observed amongst those having the beneficial genotypes at two of the three key loci (p < 0.05). We have initiated MAS and large-scale planting of elite dura and pisifera parents to generate the new commercial tenera palms with higher O/DM potential.
Associations of gut-flora-dependent metabolite trimethylamine-N-oxide, betaine and choline with non-alcoholic fatty liver disease in adults
Authors: Chen Yu-ming , Liu Yan , Zhou Rui-fen , Chen Xiao-ling , Wang Cheng , Tan Xu-ying , Wang Li-jun , Zheng Rui-dan , Zhang Hong-wei , Ling Wen-hua , Zhu Hui-lian
Published: January 2016

Many studies suggest that trimethylamine-N-oxide (TMAO), a gut-flora-dependent metabolite of choline, contributes to the risk of cardiovascular diseases, but little is known for non-alcoholic fatty liver disease (NAFLD). We examined the association of circulating TMAO, choline and betaine with the presence and severity of NAFLD in Chinese adults. We performed a hospital-based case-control study (CCS) and a cross-sectional study (CSS). In the CCS, we recruited 60 biopsy-proven NAFLD cases and 35 controls (18–60 years) and determined serum concentrations of TMAO, choline and betaine by HPLC-MS/MS. For the CSS, 1,628 community-based adults (40-75 years) completed the blood tests and ultrasonographic NAFLD evaluation. In the CCS, analyses of covariance showed adverse associations of ln-transformed serum levels of TMAO, choline and betaine/choline ratio with the scores of steatosis and total NAFLD activity (NAS) (all P-trend <0.05). The CSS revealed that a greater severity of NAFLD was independently correlated with higher TMAO but lower betaine and betaine/choline ratio (all P-trend <0.05). No significant choline-NAFLD association was observed. Our findings showed adverse associations between the circulating TMAO level and the presence and severity of NAFLD in hospital- and community-based Chinese adults and a favorable betaine-NAFLD relationship in the community-based participants.
Maternal immune activation produces neonatal excitability defects in offspring hippocampal neurons from pregnant rats treated with poly I:C
Authors: Patrich Eti , Piontkewitz Yael , Peretz Asher , Weiner Ina , Attali Bernard
Published: January 2016

Maternal immune activation (MIA) resulting from prenatal exposure to infectious pathogens or inflammatory stimuli is increasingly recognized to play an important etiological role in neuropsychiatric disorders with neurodevelopmental features. MIA in pregnant rodents induced by injection of the synthetic double-stranded RNA, Poly I:C, a mimic of viral infection, leads to a wide spectrum of behavioral abnormalities as well as structural and functional defects in the brain. Previous MIA studies using poly I:C prenatal treatment suggested that neurophysiological alterations occur in the hippocampus. However, these investigations used only juvenile or adult animals. We postulated that MIA-induced alterations could occur earlier at neonatal/early postnatal stages. Here we examined the neurophysiological properties of cultured pyramidal-like hippocampal neurons prepared from neonatal (P0-P2) offspring of pregnant rats injected with poly I:C. Offspring neurons from poly I:C-treated mothers exhibited significantly lower intrinsic excitability and stronger spike frequency adaptation, compared to saline. A similar lower intrinsic excitability was observed in CA1 pyramidal neurons from hippocampal slices of two weeks-old poly I:C offspring. Cultured hippocampal neurons also displayed lower frequency of spontaneous firing, higher charge transfer of IPSCs and larger amplitude of miniature IPSCs. Thus, maternal immune activation leads to strikingly early neurophysiological abnormalities in hippocampal neurons.
Enhanced engraftment, proliferation and therapeutic potential in heart using optimized human iPSC-derived cardiomyocytes
Authors: Funakoshi Shunsuke , Miki Kenji , Takaki Tadashi , Okubo Chikako , Hatani Takeshi , Chonabayashi Kazuhisa , Nishikawa Misato , Takei Ikue , Oishi Akiko , Narita Megumi , Hoshijima Masahiko , Kimura Takeshi , Yamanaka Shinya , Yoshida Yoshinori
Published: January 2016

Human pluripotent stem cell-derived cardiomyocytes (CMs) are a promising tool for cardiac cell therapy. Although transplantation of induced pluripotent stem cell (iPSC)-derived CMs have been reported in several animal models, the treatment effect was limited, probably due to poor optimization of the injected cells. To optimize graft cells for cardiac reconstruction, we compared the engraftment efficiency of intramyocardially-injected undifferentiated-iPSCs, day4 mesodermal cells and day8, day20 and day30 purified iPSC-CMs after initial differentiation by tracing the engraftment ratio (ER) using in vivo bioluminescence imaging. This analysis revealed the ER of day20 CMs was significantly higher compared to other cells. Transplantation of day20 CMs into the infarcted hearts of immunodeficient mice showed good engraftment and echocardiography showed significant functional improvement by cell therapy. Moreover, the imaging signal and ratio of Ki67-positive CMs at 3 months post injection indicated engrafted CMs proliferated in the host heart. Although this graft growth reached a plateau at 3 months, histological analysis confirmed progressive maturation from 3 to 6 months. These results suggested that day20 CMs had very high engraftment, proliferation and therapeutic potential in host mouse hearts. They also demonstrate this model can be used to track the fate of transplanted cells over a long time.
Development of a self-administered web-based test for longitudinal cognitive assessment
Authors: Ruano Luis , Sousa Andreia , Severo Milton , Alves Ivânia , Colunas Márcio , Barreto Rui , Mateus Cátia , Moreira Sandra , Conde Eduardo , Bento Virgílio , Lunet Nuno , Pais Joana , Tedim Cruz Vítor
Published: January 2016

Sequential testing with brief cognitive tools has been recommended to improve cognitive screening and monitoring, however the few available tools still depend on an external evaluator and periodic visits. We developed a self-administered computerized test intended for longitudinal cognitive testing (Brain on Track). The test can be performed from a home computer and is composed of several subtests, expected to evaluate different cognitive domains, all including random elements to minimize learning effects. An initial (A) and a refined version of the test (B) were applied to patients with mild cognitive impairment or early dementia (n = 88) and age and education-matched controls. A subsample of a population-based cohort (n = 113) performed the test at home every three months to evaluate test-retest reliability. The test’s final version Cronbach’s alpha was 0.90, test scores were significantly different between patients and controls (p = 0.001), the area under the receiver operating characteristic curve was 0.75 and the smallest real difference (43.04) was lower than the clinical relevant difference (56.82). In the test-retest reliability analysis 9/10 subtests showed two-way mixed single intraclass consistency correlation coefficient >0.70. These results imply good internal consistency, discriminative ability and reliability when performed at home, encouraging further longitudinal clinical and population-based studies.