bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of the unusual threonine string in the conversion of prion protein
Authors: Abskharon Romany , Wang Fei , Vander Stel Kayla J. , Sinniah Kumar , Ma Jiyan 
Published: December 2016

AbstractThe conversion of normal prion protein (PrP) into pathogenic PrP conformers is central to prion disease, but the mechanism remains unclear. The α-helix 2 of PrP contains a string of four threonines, which is unusual due to the high propensity of threonine to form β-sheets. This structural feature was proposed as the basis for initiating PrP conversion, but experimental results have been conflicting. We studied the role of the threonine string on PrP conversion by analyzing mouse Prnpa and Prnpb polymorphism that contains a polymorphic residue at the beginning of the threonine string, and PrP mutants in which threonine 191 was replaced by valine, alanine, or proline. The PMCA (protein misfolding cyclic amplification) assay was able to recapitulate the in vivo transmission barrier between PrPa and PrPb. Relative to PMCA, the amyloid fibril growth assay is less restrictive, but it did reflect certain properties of in vivo prion transmission. Our results suggest a plausible theory explaining the apparently contradictory results in the role of the threonine string in PrP conversion and provide novel insights into the complicated relationship among PrP stability, seeded conformational change, and prion structure, which is critical for understanding the molecular basis of prion infectivity.
Shared and unique patterns of phenotypic diversification along a stream gradient in two congeneric species
Authors: Jourdan Jonas , Krause Sarah T. , Lazar V. Max , Zimmer Claudia , Sommer-Trembo Carolin , Arias-Rodriguez Lenin , Klaus Sebastian , Riesch Rüdiger , Plath Martin 
Published: December 2016

AbstractStream ecosystems show gradual variation of various selection factors, which can result in a zonation of species distributions and gradient evolution of morphological and life-history traits within species. Identifying the selective agents underlying such phenotypic evolution is challenging as different species could show shared and/or unique (species-specific) responses to components of the river gradient. We studied a stream gradient inhabited by two mosquitofishes (genus Gambusia) in the Río Grijalva basin in southern Mexico and found a patchy distribution pattern of both congeners along a stretch of 100 km, whereby one species was usually dominant at a given site. We uncovered both shared and unique patterns of diversification: some components of the stream gradient, including differences in piscine predation pressure, drove shared patterns of phenotypic divergence, especially in females. Other components of the gradient, particularly abiotic factors (max. annual temperature and temperature range) resulted in unique patterns of divergence, especially in males. Our study highlights the complexity of selective regimes in stream ecosystems. It exemplifies that even closely related, congeneric species can respond in unique ways to the same components of the river gradient and shows how both sexes can exhibit quite different patterns of divergence in multivariate phenotypic character suites.
Novel inhibitors of Mycobacterium tuberculosis GuaB2 identified by a target based high-throughput phenotypic screen
Authors: Cox Jonathan A. G. , Mugumbate Grace , Del Peral Laura Vela-Glez , Jankute Monika , Abrahams Katherine A. , Jervis Peter , Jackenkroll Stefan , Perez Arancha , Alemparte Carlos , Esquivias Jorge , Lelièvre Joël , Ramon Fernando , Barros David , Ballell Lluis , Besra Gurdyal S. 
Published: December 2016

AbstractHigh-throughput phenotypic screens have re-emerged as screening tools in antibiotic discovery. The advent of such technologies has rapidly accelerated the identification of ‘hit’ compounds. A pre-requisite to medicinal chemistry optimisation programmes required to improve the drug-like properties of a ‘hit’ molecule is identification of its mode of action. Herein, we have combined phenotypic screening with a biased target-specific screen. The inosine monophosphate dehydrogenase (IMPDH) protein GuaB2 has been identified as a drugable target in Mycobacterium tuberculosis, however previously identified compounds lack the desired characteristics necessary for further development into lead-like molecules. This study has identified 7 new chemical series from a high-throughput resistance-based phenotypic screen using Mycobacterium bovis BCG over-expressing GuaB2. Hit compounds were identified in a single shot high-throughput screen, validated by dose response and subjected to further biochemical analysis. The compounds were also assessed using molecular docking experiments, providing a platform for their further optimisation using medicinal chemistry. This work demonstrates the versatility and potential of GuaB2 as an anti-tubercular drug target.
Changes in mitochondrial homeostasis and redox status in astronauts following long stays in space
Authors: Indo Hiroko P. , Majima Hideyuki J. , Terada Masahiro , Suenaga Shigeaki , Tomita Kazuo , Yamada Shin , Higashibata Akira , Ishioka Noriaki , Kanekura Takuro , Nonaka Ikuya , Hawkins Clare L. , Davies Michael J. , Clair Daret K. St , Mukai Chiaki 
Published: December 2016

AbstractThe effects of long-term exposure to extreme space conditions on astronauts were investigated by analyzing hair samples from ten astronauts who had spent six months on the International Space Station (ISS). Two samples were collected before, during and after their stays in the ISS; hereafter, referred to as Preflight, Inflight and Postflight, respectively. The ratios of mitochondrial (mt) to nuclear (n) DNA and mtRNA to nRNA were analyzed via quantitative PCR. The combined data of Preflight, Inflight and Postflight show a significant reduction in the mtDNA/nDNA in Inflight, and significant reductions in the mtRNA/nRNA ratios in both the Inflight and Postflight samples. The mtRNA/mtDNA ratios were relatively constant, except in the Postflight samples. Using the same samples, the expression of redox and signal transduction related genes, MnSOD, CuZnSOD, Nrf2, Keap1, GPx4 and Catalase was also examined. The results of the combined data from Preflight, Inflight and Postflight show a significant decrease in the expression of all of the redox-related genes in the samples collected Postflight, with the exception of Catalase, which show no change. This decreased expression may contribute to increased oxidative stress Inflight resulting in the mitochondrial damage that is apparent Postflight.
The Management and Prognostic Prediction of Adenocarcinoma of Appendix
Authors: Xie Xin , Zhou Zhangjian , Song Yongchun , Li Wenhan , Diao Dongmei , Dang Chengxue , Zhang Hao 
Published: December 2016

AbstractMalignant tumours of the appendix are quite rare, especially appendiceal adenocarcinomas, which may be difficult to detect preoperatively or intraoperatively. We collected data for 1404 patients with adenocarcinoma of the appendix from the Surveillance, Epidemiology, and End Results Program (SEER) database to explore the potential associations between clinicopathological factors and overall survival. Furthermore, a novel nomogram for predicting prognosis was developed based on our analysis of the SEER data. The nomogram prediction model included seven prognostic factors derived based on different clinical estimates. When compared with the traditional tumour-node-metastasis (TNM) staging system, the nomogram prediction model showed superior discriminatory power (Harrell’s C-index, 0.741 vs. 0.686) and a greater degree of similarity to actual 5-year overall survival after calibration (Akaike Information Criterion index, 5270.781 vs. 5430.141). Finally, we provide recommendations for the management of patients with adenocarcinoma of the appendix. Notably, we found the depth of adenocarcinoma invasion may be used as an indicator to determine the optimal surgical approach. For mucinous adenocarcinomas of the appendix, because these tumours are characterized by unique biological behaviour, intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) is recommended. However, whether systematic chemotherapy should be administered to patients with adenocarcinoma of the appendix requires further investigation.
Multicenter evaluation of crystal violet decolorization assay (CVDA) for rapid detection of isoniazid and rifampicin resistance in Mycobacterium tuberculosis
Authors: Coban Ahmet Yilmaz , Akbal Ahmet Ugur , Bicmen Can , Albay Ali , Sig Ali Korhan , Uzun Meltem , Selale Deniz Sertel , Ozkutuk Nuri , Surucuoglu Suheyla , Albayrak Nurhan , Ucarman Nilay , Ozkutuk Aydan , Esen Nuran , Ceyhan Ismail , Ozyurt Mustafa , Bektore Bayhan , Aslan Gonul , Delialioğlu Nuran , Alp Alpaslan 
Published: December 2016

AbstractThe aim of this multicenter study was to evaluate the performance of the crystal violet decolorization assay (CVDA) for detection of multidrug resistant tuberculosis (MDR-TB). This study was performed in 11 centers in two phases. A total of 156 isolates were tested for INH and RIF resistance. In the phase I, 106 clinical isolates were tested in the Center 1–7. In the phase 2, 156 clinical isolates were tested in the center 1–6, center 8–11. Eighty six of 156 tested isolates were the same in phase I. Agreements were 96.2–96.8% for INH and 98.1–98.7% for RIF in the phase I-II, respectively. Mean time to obtain the results in the phase I was 14.3 ± 5.4 days. In the phase II, mean time to obtain the results was 11.6 ± 3.5 days. Test results were obtained within 14days for 62.3% (66/106) of isolates in the phase I and 81.4% (127/156) of isolates in the phase II. In conclusion, CVDA is rapid, reliable, inexpensive, and easy to perform for rapid detection of MDR-TB isolates. In addition, it could be adapted for drug susceptibility testing with all drugs both in developed and developing countries.
New cell motility model observed in parasitic cnidarian Sphaerospora molnari (Myxozoa:Myxosporea) blood stages in fish
Authors: Hartigan A. , Estensoro I. , Vancová M. , Bílý T. , Patra S. , Eszterbauer E. , Holzer A. S. 
Published: December 2016

AbstractCellular motility is essential for microscopic parasites, it is used to reach the host, migrate through tissues, or evade host immune reactions. Many cells employ an evolutionary conserved motor protein– actin, to crawl or glide along a substrate. We describe the peculiar movement of Sphaerospora molnari, a myxozoan parasite with proliferating blood stages in its host, common carp. Myxozoa are highly adapted parasitic cnidarians alternately infecting vertebrates and invertebrates. S. molnari blood stages (SMBS) have developed a unique “dancing” behaviour, using the external membrane as a motility effector to rotate and move the cell. SMBS movement is exceptionally fast compared to other myxozoans, non-directional and constant. The movement is based on two cytoplasmic actins that are highly divergent from those of other metazoans. We produced a specific polyclonal actin antibody for the staining and immunolabelling of S. molnari’s microfilaments since we found that neither commercial antibodies nor phalloidin recognised the protein or microfilaments. We show the in situ localization of this actin in the parasite and discuss the importance of this motility for evasion from the cellular host immune response in vitro. This new type of motility holds key insights into the evolution of cellular motility and associated proteins.
Brusatol inhibits HIF-1 signaling pathway and suppresses glucose uptake under hypoxic conditions in HCT116 cells
Authors: Lu Yapeng , Wang Bo , Shi Qian , Wang Xueting , Wang Dang , Zhu Li 
Published: December 2016

AbstractHypoxia-inducible factor-1 (HIF-1) is an important transcription factor that induces adaptive responses upon low oxygen conditions in human cancers and triggers off a poor prognostic outcome of conventional treatments. In this study, we discovered for the first time that brusatol (BRU), a quassinoid extracted from Brucea Esters, has the capability to inhibit HIF-1 signaling pathway. We found that BRU concentration-dependently down-regulated HIF-1α protein levels under hypoxia or CoCl2-induced mimic hypoxia in HCT116 cells without causing significant cytotoxicity. Besides, the transactivation activity of HIF-1 was suppressed by BRU under hypoxic conditions, as well as the expression of HIF-1 target genes, including VEGF, GLUT1, HK2 and LDHA. In addition, BRU can also decrease glucose consumption under hypoxia through inhibition of HIF-1 signaling pathway. Further studies revealed that the inhibitory effect of BRU on HIF-1 signaling pathway might be attributed to promoting degradation of HIF-1α. Interestingly, intracellular reactive oxygen species (ROS) levels and mitochondrial ROS level were both decreased by BRU treatment, indicating the involvment of mitochondrial ROS regulation in the action of BRU. Taken together, these results provided clear evidence for BRU-mediated HIF-1α regulation and suggested its therapeutic potential in colon tumors.
Declining Prevalence of Disease Vectors Under Climate Change
Authors: Escobar Luis E. , Romero-Alvarez Daniel , Leon Renato , Lepe-Lopez Manuel A. , Craft Meggan E. , Borbor-Cordova Mercy J. , Svenning Jens-Christian 
Published: December 2016

AbstractMore than half of the world population is at risk of vector-borne diseases including dengue fever, chikungunya, zika, yellow fever, leishmaniasis, chagas disease, and malaria, with highest incidences in tropical regions. In Ecuador, vector-borne diseases are present from coastal and Amazonian regions to the Andes Mountains; however, a detailed characterization of the distribution of their vectors has never been carried out. We estimate the distribution of 14 vectors of the above vector-borne diseases under present-day and future climates. Our results consistently suggest that climate warming is likely threatening some vector species with extinction, locally or completely. These results suggest that climate change could reduce the burden of specific vector species. Other vector species are likely to shift and constrain their geographic range to the highlands in Ecuador potentially affecting novel areas and populations. These forecasts show the need for development of early prevention strategies for vector species currently absent in areas projected as suitable under future climate conditions. Informed interventions could reduce the risk of human exposure to vector species with distributional shifts, in response to current and future climate changes. Based on the mixed effects of future climate on human exposure to disease vectors, we argue that research on vector-borne diseases should be cross-scale and include climatic, demographic, and landscape factors, as well as forces facilitating disease transmission at fine scales.
Enhanced Conversion Efficiency of III–V Triple-junction Solar Cells with Graphene Quantum Dots
Authors: Lin Tzu-Neng , Santiago Svette Reina Merden S. , Zheng Jie-An , Chao Yu-Chiang , Yuan Chi-Tsu , Shen Ji-Lin , Wu Chih-Hung , Lin Cheng- An J. , Liu Wei-Ren , Cheng Ming-Chiang , Chou Wu-Ching 
Published: December 2016

AbstractGraphene has been used to synthesize graphene quantum dots (GQDs) via pulsed laser ablation. By depositing the synthesized GQDs on the surface of InGaP/InGaAs/Ge triple-junction solar cells, the short-circuit current, fill factor, and conversion efficiency were enhanced remarkably. As the GQD concentration is increased, the conversion efficiency in the solar cell increases accordingly. A conversion efficiency of 33.2% for InGaP/InGaAs/Ge triple-junction solar cells has been achieved at the GQD concentration of 1.2 mg/ml, corresponding to a 35% enhancement compared to the cell without GQDs. On the basis of time-resolved photoluminescence, external quantum efficiency, and work-function measurements, we suggest that the efficiency enhancement in the InGaP/InGaAs/Ge triple-junction solar cells is primarily caused by the carrier injection from GQDs to the InGaP top subcell.
The involvement of dityrosine crosslinking in α-synuclein assembly and deposition in Lewy Bodies in Parkinson’s disease
Authors: Al-Hilaly Youssra K. , Biasetti Luca , Blakeman Ben J. F. , Pollack Saskia J. , Zibaee Shahin , Abdul-Sada Alaa , Thorpe Julian R. , Xue Wei-Feng , Serpell Louise C. 
Published: December 2016

AbstractParkinson’s disease (PD) is characterized by intracellular, insoluble Lewy bodies composed of highly stable α-synuclein (α-syn) amyloid fibrils. α-synuclein is an intrinsically disordered protein that has the capacity to assemble to form β-sheet rich fibrils. Oxidiative stress and metal rich environments have been implicated in triggering assembly. Here, we have explored the composition of Lewy bodies in post-mortem tissue using electron microscopy and immunogold labeling and revealed dityrosine crosslinks in Lewy bodies in brain tissue from PD patients. In vitro, we show that dityrosine cross-links in α-syn are formed by covalent ortho-ortho coupling of two tyrosine residues under conditions of oxidative stress by fluorescence and confirmed using mass-spectrometry. A covalently cross-linked dimer isolated by SDS-PAGE and mass analysis showed that dityrosine dimer was formed via the coupling of Y39-Y39 to give a homo dimer peptide that may play a key role in formation of oligomeric and seeds for fibril formation. Atomic force microscopy analysis reveals that the covalent dityrosine contributes to the stabilization of α-syn assemblies. Thus, the presence of oxidative stress induced dityrosine could play an important role in assembly and toxicity of α-syn in PD.
CREB3L3 controls fatty acid oxidation and ketogenesis in synergy with PPARα
Authors: Nakagawa Yoshimi , Satoh Aoi , Tezuka Hitomi , Han Song-iee , Takei Kenta , Iwasaki Hitoshi , Yatoh Shigeru , Yahagi Naoya , Suzuki Hiroaki , Iwasaki Yasumasa , Sone Hirohito , Matsuzaka Takashi , Yamada Nobuhiro , Shimano Hitoshi 
Published: December 2016

AbstractCREB3L3 is involved in fatty acid oxidation and ketogenesis in a mutual manner with PPARα. To evaluate relative contribution, a combination of knockout and transgenic mice was investigated. On a ketogenic-diet (KD) that highlights capability of hepatic ketogenesis, Creb3l3−/− mice exhibited reduction of expression of genes for fatty oxidation and ketogenesis comparable to Ppara−/− mice. Most of the genes were further suppressed in double knockout mice indicating independent contribution of hepatic CREB3L3. During fasting, dependency of ketogenesis on CREB3L3 is lesser extents than Ppara−/− mice suggesting importance of adipose PPARα for supply of FFA and hyperlipidemia in Creb3l3−/− mice. In conclusion CREB3L3 plays a crucial role in hepatic adaptation to energy starvation via two pathways: direct related gene regulation and an auto-loop activation of PPARα. Furthermore, as KD-fed Creb3l3−/− mice exhibited severe fatty liver, activating inflammation, CREB3L3 could be a therapeutic target for NAFLD.
Sensitive and accurate quantification of human malaria parasites using droplet digital PCR (ddPCR)
Authors: Koepfli Cristian , Nguitragool Wang , Hofmann Natalie E. , Robinson Leanne J. , Ome-Kaius Maria , Sattabongkot Jetsumon , Felger Ingrid , Mueller Ivo 
Published: December 2016

AbstractAccurate quantification of parasite density in the human host is essential for understanding the biology and pathology of malaria. Semi-quantitative molecular methods are widely applied, but the need for an external standard curve makes it difficult to compare parasite density estimates across studies. Droplet digital PCR (ddPCR) allows direct quantification without the need for a standard curve. ddPCR was used to diagnose and quantify P. falciparum and P. vivax in clinical patients as well as in asymptomatic samples. ddPCR yielded highly reproducible measurements across the range of parasite densities observed in humans, and showed higher sensitivity than qPCR to diagnose P. falciparum, and equal sensitivity for P. vivax. Correspondence in quantification was very high (>0.95) between qPCR and ddPCR. Quantification between technical replicates by ddPCR differed 1.5–1.7-fold, compared to 2.4–6.2-fold by qPCR. ddPCR facilitates parasite quantification for studies where absolute densities are required, and will increase comparability of results reported from different laboratories.
Establishment of the cytoplasmic incompatibility-inducing Wolbachia strain wMel in an important agricultural pest insect
Authors: Zhou Xiao-Fei , Li Zheng-Xi 
Published: December 2016

AbstractThewMelWolbachiastrain was known for cytoplasmic incompatibility (CI)-induction and blocking the transmission of dengue. However, it is unknown whether it can establish and induce CI in a non-dipteran host insect. Here we artificially transferredwMel fromDrosophila melanogasterinto the whiteflyBemisia tabaci. Fluorescencein situhybridisation demonstrated thatwMel had successfully transfected the new host. Reciprocal crossing was conducted withwMel-transfected and wild-type isofemale lines, indicating thatwMel could induce a strong CI without imposing significant cost on host fecundity. We then determined the maternal transmission efficiency ofwMel in the offspring generations, showing a fluctuating trend over a period of 12 generations. We thus detected the titre ofwMel during different developmental stages and in different generations by using real-time quantitative PCR, revealing a similar fluctuating mode, but it was not significantly correlated with the dynamics of transmission efficiency. These results suggest thatwMel can be established inB.tabaci, a distantly related pest insect of agricultural importance; moreover, it can induce a strong CI phenotype in the recipient host insect, suggesting a potential for its use in biological control ofB. tabaci.
Interplay of multiple synaptic plasticity features in filamentary memristive devices for neuromorphic computing
Authors: La Barbera Selina , Vincent Adrien F. , Vuillaume Dominique , Querlioz Damien , Alibart Fabien 
Published: December 2016

AbstractBio-inspired computing represents today a major challenge at different levels ranging from material science for the design of innovative devices and circuits to computer science for the understanding of the key features required for processing of natural data. In this paper, we propose a detail analysis of resistive switching dynamics in electrochemical metallization cells for synaptic plasticity implementation. We show how filament stability associated to joule effect during switching can be used to emulate key synaptic features such as short term to long term plasticity transition and spike timing dependent plasticity. Furthermore, an interplay between these different synaptic features is demonstrated for object motion detection in a spike-based neuromorphic circuit. System level simulation presents robust learning and promising synaptic operation paving the way to complex bio-inspired computing systems composed of innovative memory devices.