bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fragment-based de novo design of a cystathionine γ-lyase selective inhibitor blocking hydrogen sulfide production
Authors: Corvino Angela , Severino Beatrice , Fiorino Ferdinando , Frecentese Francesco , Magli Elisa , Perissutti Elisa , Santagada Vincenzo , Bucci Mariarosaria , Cirino Giuseppe , Kelly Geoff , Servillo Luigi , Popowicz Grzegorz , Pastore Annalisa , Caliendo Giuseppe 
Published: October 2016

AbstractHydrogen sulfide is an essential catabolite that intervenes in the pathophysiology of several diseases from hypertension to stroke, diabetes and pancreatitis. It is endogenously synthesized mainly by two pyridoxal-5′-phosphate-dependent enzymes involved in L-cysteine metabolism: cystathionine-ß-synthase (CBS) and cystathionine-γ-lyase (CSE). Research in this field is currently impaired by the lack of pharmacological tools such as selective enzymatic inhibitors that could target specifically only one of these pathways. We used a novel approach based on a hybrid method that includes drug design, synthetic biology, metabolomics and pharmacological assays to rationally design a new inhibitor selective for the CSE enzyme. The identification of this compound opens new frontiers towards a better understanding of the role of CSE over CBS in the pathophysiology of diseases where a role for the H2S pathway has been proposed and the development of new lead compounds that could target the CSE enzyme.
Replenishment of microRNA-188-5p restores the synaptic and cognitive deficits in 5XFAD Mouse Model of Alzheimer’s Disease
Authors: Lee Kihwan , Kim Hyunju , An Kyongman , Kwon Oh-Bin , Park Sungjun , Cha Jin Hee , Kim Myoung-Hwan , Lee Yoontae , Kim Joung-Hun , Cho Kwangwook , Kim Hye-Sun 
Published: October 2016

AbstractMicroRNAs have emerged as key factors in development, neurogenesis and synaptic functions in the central nervous system. In the present study, we investigated a pathophysiological significance of microRNA-188-5p (miR-188-5p) in Alzheimer’s disease (AD). We found that oligomeric Aβ1-42 treatment diminished miR-188-5p expression in primary hippocampal neuron cultures and that miR-188-5p rescued the Aβ1-42-mediated synapse elimination and synaptic dysfunctions. Moreover, the impairments in cognitive function and synaptic transmission observed in 7-month-old five familial AD (5XFAD) transgenic mice, were ameliorated via viral-mediated expression of miR-188-5p. miR-188-5p expression was down-regulated in the brain tissues from AD patients and 5XFAD mice. The addition of miR-188-5p rescued the reduction in dendritic spine density in the primary hippocampal neurons treated with oligomeric Aβ1-42 and cultured from 5XFAD mice. The reduction in the frequency of mEPSCs was also restored by addition of miR-188-5p. The impairments in basal fEPSPs and cognition observed in 7-month-old 5XFAD mice were ameliorated via the viral-mediated expression of miR-188-5p in the hippocampus. Furthermore, we found that miR-188 expression is CREB-dependent. Taken together, our results suggest that dysregulation of miR-188-5p expression contributes to the pathogenesis of AD by inducing synaptic dysfunction and cognitive deficits associated with Aβ-mediated pathophysiology in the disease.
Exposure to the Functional Bacterial Amyloid Protein Curli Enhances Alpha-Synuclein Aggregation in Aged Fischer 344 Rats and Caenorhabditis elegans
Authors: Chen Shu G. , Stribinskis Vilius , Rane Madhavi J. , Demuth Donald R. , Gozal Evelyne , Roberts Andrew M. , Jagadapillai Rekha , Liu Ruolan , Choe Kyonghwan , Shivakumar Bhooma , Son Francheska , Jin Shunying , Kerber Richard , Adame Anthony , Masliah Eliezer , Friedland Robert P. 
Published: October 2016

AbstractMisfolded alpha-synuclein (AS) and other neurodegenerative disorder proteins display prion-like transmission of protein aggregation. Factors responsible for the initiation of AS aggregation are unknown. To evaluate the role of amyloid proteins made by the microbiota we exposed aged rats and transgenicC.eleganstoE.coliproducing the extracellular bacterial amyloid protein curli. Rats exposed to curli-producing bacteria displayed increased neuronal AS deposition in both gut and brain and enhanced microgliosis and astrogliosis compared to rats exposed to either mutant bacteria unable to synthesize curli, or to vehicle alone. Animals exposed to curli producing bacteria also had more expression of TLR2, IL-6 and TNF in the brain than the other two groups. There were no differences among the rat groups in survival, body weight, inflammation in the mouth, retina, kidneys or gut epithelia, and circulating cytokine levels. AS-expressingC.elegansfed on curli-producing bacteria also had enhanced AS aggregation. These results suggest that bacterial amyloid functions as a trigger to initiate AS aggregation through cross-seeding and also primes responses of the innate immune system.
Plasticity mechanisms in HfN at elevated and room temperature
Authors: Vinson Katherine , Yu Xiao-Xiang , De Leon Nicholas , Weinberger Christopher R. , Thompson Gregory B. 
Published: October 2016

AbstractHfN specimens deformed via four-point bend tests at room temperature and at 2300 °C (~0.7 Tm) showed increased plasticity response with temperature. Dynamic diffraction via transmission electron microscopy (TEM) revealed ⟨110⟩{111} as the primary slip system in both temperature regimes and ⟨110⟩{110} to be a secondary slip system activated at elevated temperature. Dislocation line lengths changed from a primarily linear to a curved morphology with increasing temperature suggestive of increased dislocation mobility being responsible for the brittle to ductile temperature transition. First principle generalized stacking fault energy calculations revealed an intrinsic stacking fault (ISF) along ⟨112⟩{111}, which is the partial dislocation direction for slip on these close packed planes. Though B1 structures, such as NaCl and HfC predominately slip on ⟨110⟩{110}, the ISF here is believed to facilitate slip on the {111} planes for this B1 HfN phase.
Structure-based discovery of potentially active semiochemicals for Cydia pomonella (L.)
Authors: Liu Jiyuan , Tian Zhen , Zhang Yalin 
Published: October 2016

AbstractThe development of physiologically active semiochemicals is largely limited by the labor-consuming searching process. How to screen active semiochemicals efficiently is of significance to the extension of behavior regulation in pest control. Here pharmacophore modeling and shape-based virtual screening were combined to predict candidate ligands for Cydia pomonella pheromone binding protein 1 (CpomPBP1). Out of the predicted compounds, ETrME displayed the highest affinity to CpomPBP1. Further studies on the interaction between CpomPBP1 and ETrME, not only depicted the binding mode, but also revealed residues providing negative and positive contributions to the ETrME binding. Moreover, key residues involved in interacting with ETrME of CpomPBP1 were determined as well. These findings were significant to providing insights for the future searching and optimization of active semiochemicals.
Cystathionine γ-lyase is expressed in human atherosclerotic plaque microvessels and is involved in micro-angiogenesis
Authors: van den Born J. C. , Mencke R. , Conroy S. , Zeebregts C. J. , van Goor H. , Hillebrands J. L. 
Published: October 2016

AbstractAtherosclerotic plaques are classically divided into stable and vulnerable plaques. Vulnerable plaques are prone to rupture with a risk for infarction. High intraplaque microvessel density predisposes to plaque vulnerability. Hydrogen sulfide (H2S) is a proangiogenic gasotransmitter which is endogenously produced by cystathionine γ-lyase (CSE), and is believed to have vasculoprotective effects. However, due to its proangiogenic effects, H2S may result in pathological angiogenesis in atherosclerotic plaques, thereby increasing plaque vulnerability. The aim of this study was to determine CSE expression pattern in atherosclerotic plaques, and investigate whether CSE is involved in micro-angiogenesis in vitro. Endarterectomy plaques were studied for CSE expression, and the role of CSE in micro-angiogenesis was studied in vitro. CSE is expressed in plaques with similar levels in both stable and vulnerable plaques. CSE co-localized with von Willebrand Factor-positive microvessel endothelial cells and alpha-smooth-muscle actin-positive SMCs. In vitro, inhibition of CSE in HMEC-1 reduced tube formation, cell viability/proliferation, and migration which was restored after culture in the presence of H2S donor GYY4137. CSE is expressed in intraplaque microvessels, and H2S is a stimulator of micro-angiogenesis in vitro. Due to this pro-angiogenic effect, high levels of CSE in atherosclerotic plaques may be a potential risk for plaque vulnerability.
Aromatic and proteomic analyses corroborate the distinction between Mediterranean landraces and modern varieties of durum wheat
Authors: Vita Federico , Taiti Cosimo , Pompeiano Antonio , Gu Zuguang , Lo Presti Emilio , Whitney Larisa , Monti Michele , Di Miceli Giuseppe , Giambalvo Dario , Ruisi Paolo , Guglielminetti Lorenzo , Mancuso Stefano 
Published: October 2016

AbstractIn this paper volatile organic compounds (VOCs) from durum wheat cultivars and landraces were analyzed using PTR-TOF-MS. The aim was to characterize the VOC’s profile of the wholemeal flour and of the kernel to find out if any VOCs were specific to varieties and sample matrices. The VOC data is accompanied by SDS-PAGE analyses of the storage proteins (gliadins and glutenins). Statistical analyses was carried out both on the signals obtained by MS and on the protein profiles. The difference between the VOC profile of two cultivars or two preparations of the same sample - matrices, in this case kernel vs wholemeal flour - can be very subtle; the high resolution of PTR-TOF-MS - down to levels as low as pptv - made it possible to recognize these differences. The effects of grinding on the VOC profiles were analyzed using SIMPER and Tanglegram statistical methods. Our results show that it is possible describe samples using VOC profiles and protein data.
Grain Boundary Specific Segregation in Nanocrystalline Fe(Cr)
Authors: Zhou Xuyang , Yu Xiao-xiang , Kaub Tyler , Martens Richard L. , Thompson Gregory B. 
Published: October 2016

AbstractA cross-correlative precession electron diffraction – atom probe tomography investigation of Cr segregation in a Fe(Cr) nanocrystalline alloy was undertaken. Solute segregation was found to be dependent on grain boundary type. The results of which were compared to a hybrid Molecular Dynamics and Monte Carlo simulation that predicted the segregation for special character, low angle, and high angle grain boundaries, as well as the angle of inclination of the grain boundary. It was found that the highest segregation concentration was for the high angle grain boundaries and is explained in terms of clustering driven by the onset of phase separation. For special character boundaries, the highest Gibbsain interfacial excess was predicted at the incoherent ∑3 followed by ∑9 and ∑11 boundaries with negligible segregation to the twin and ∑5 boundaries. In addition, the low angle grain boundaries predicted negligible segregation. All of these trends matched well with the experiment. This solute-boundary segregation dependency for the special character grain boundaries is explained in terms of excess volume and the energetic distribution of the solute in the boundary.
Low Complexity Compression and Speed Enhancement for Optical Scanning Holography
Authors: Tsang P. W. M. , Poon T.-C. , Liu J.-P. , Kim T. , Kim Y. S. 
Published: October 2016

AbstractIn this paper we report a low complexity compression method that is suitable for compact optical scanning holography (OSH) systems with different optical settings. Our proposed method can be divided into 2 major parts. First, an automatic decision maker is applied to select the rows of holographic pixels to be scanned. This process enhances the speed of acquiring a hologram, and also lowers the data rate. Second, each row of down-sampled pixels is converted into a one-bit representation with delta modulation (DM). Existing DM-based hologram compression techniques suffers from the disadvantage that a core parameter, commonly known as the step size, has to be determined in advance. However, the correct value of the step size for compressing each row of hologram is dependent on the dynamic range of the pixels, which could deviate significantly with the object scene, as well as OSH systems with different opical settings. We have overcome this problem by incorporating a dynamic step-size adjustment scheme. The proposed method is applied in the compression of holograms that are acquired with 2 different OSH systems, demonstrating a compression ratio of over two orders of magnitude, while preserving favorable fidelity on the reconstructed images.
Infant-specific gaze patterns in response to radial optic flow
Authors: Shirai Nobu , Imura Tomoko 
Published: October 2016

AbstractThe focus of a radial optic flow is a valid visual cue used to perceive and control the heading direction of animals. Gaze patterns in response to the focus of radial optic flow were measured in human infants (N = 100, 4–18 months) and in adults (N = 20) using an eye-tracking technique. Overall, although the adults showed an advantage in detecting the focus of an expansion flow (representing forward locomotion) against that of a contraction flow (representing backward locomotion), infants younger than 1 year showed an advantage in detecting the focus of a contraction flow. Infants aged between 13 and 18 months showed no significant advantage in detecting the focus in either the expansion or in the contraction flow. The uniqueness of the gaze patterns in response to the focus of radial optic flow in infants shows that the visual information necessary to perceive heading direction potentially differs between younger and mature individuals.
Genetic and clinical characterization of Pakistani families with Bardet-Biedl syndrome extends the genetic and phenotypic spectrum
Authors: Maria Maleeha , Lamers Ideke J. C. , Schmidts Miriam , Ajmal Muhammad , Jaffar Sulman , Ullah Ehsan , Mustafa Bilal , Ahmad Shakeel , Nazmutdinova Katia , Hoskins Bethan , van Wijk Erwin , Koster-Kamphuis Linda , Khan Muhammad Imran , Beales Phil L. , Cremers Frans P. M. , Roepman Ronald , Azam Maleeha , Arts Heleen H. , Qamar Raheel 
Published: October 2016

AbstractBardet-Biedl syndrome (BBS) is an autosomal recessive disorder that is both genetically and clinically heterogeneous. To date 19 genes have been associated with BBS, which encode proteins active at the primary cilium, an antenna-like organelle that acts as the cell’s signaling hub. In the current study, a combination of mutation screening, targeted sequencing of ciliopathy genes associated with BBS, and whole-exome sequencing was used for the genetic characterization of five families including four with classic BBS symptoms and one BBS-like syndrome. This resulted in the identification of novel mutations in BBS genes ARL6 and BBS5, and recurrent mutations in BBS9 and CEP164. In the case of CEP164, this is the first report of two siblings with a BBS-like syndrome with mutations in this gene. Mutations in this gene were previously associated with nephronophthisis 15, thus the current results expand the CEP164-associated phenotypic spectrum. The clinical and genetic spectrum of BBS and BBS-like phenotypes is not fully defined in Pakistan. Therefore, genetic studies are needed to gain insights into genotype-phenotype correlations, which will in turn improve the clinician’s ability to make an early and accurate diagnosis, and facilitate genetic counseling, leading to directly benefiting families with affected individuals.
Single cell dynamic phenotyping
Authors: Patsch Katherin , Chiu Chi-Li , Engeln Mark , Agus David B. , Mallick Parag , Mumenthaler Shannon M. , Ruderman Daniel 
Published: October 2016

AbstractLive cell imaging has improved our ability to measure phenotypic heterogeneity. However, bottlenecks in imaging and image processing often make it difficult to differentiate interesting biological behavior from technical artifact. Thus there is a need for new methods that improve data quality without sacrificing throughput. Here we present a 3-step workflow to improve dynamic phenotype measurements of heterogeneous cell populations. We provide guidelines for image acquisition, phenotype tracking, and data filtering to remove erroneous cell tracks using the novel Tracking Aberration Measure (TrAM). Our workflow is broadly applicable across imaging platforms and analysis software. By applying this workflow to cancer cell assays, we reduced aberrant cell track prevalence from 17% to 2%. The cost of this improvement was removing 15% of the well-tracked cells. This enabled detection of significant motility differences between cell lines. Similarly, we avoided detecting a false change in translocation kinetics by eliminating the true cause: varied proportions of unresponsive cells. Finally, by systematically seeking heterogeneous behaviors, we detected subpopulations that otherwise could have been missed, including early apoptotic events and pre-mitotic cells. We provide optimized protocols for specific applications and step-by-step guidelines for adapting them to a variety of biological systems.
GSF2 deletion increases lactic acid production by alleviating glucose repression in Saccharomyces cerevisiae
Authors: Baek Seung-Ho , Kwon Eunice Y. , Kim Seon-Young , Hahn Ji-Sook 
Published: October 2016

AbstractImproving lactic acid (LA) tolerance is important for cost-effective microbial production of LA under acidic fermentation conditions. Previously, we generated LA-tolerant D-LA-producing S. cerevisiae strain JHY5310 by laboratory adaptive evolution of JHY5210. In this study, we performed whole genome sequencing of JHY5310, identifying four loss-of-function mutations in GSF2, SYN8, STM1, and SIF2 genes, which are responsible for the LA tolerance of JHY5310. Among the mutations, a nonsense mutation in GSF2 was identified as the major contributor to the improved LA tolerance and LA production in JHY5310. Deletion of GSF2 in the parental strain JHY5210 significantly improved glucose uptake and D-LA production levels, while derepressing glucose-repressed genes including genes involved in the respiratory pathway. Therefore, more efficient generation of ATP and NAD+ via respiration might rescue the growth defects of the LA-producing strain, where ATP depletion through extensive export of lactate and proton is one of major reasons for the impaired growth. Accordingly, alleviation of glucose repression by deleting MIG1 or HXK2 in JHY5210 also improved D-LA production. GSF2 deletion could be applied to various bioprocesses where increasing biomass yield or respiratory flux is desirable.
Clinical Relevance and Molecular Phenotypes in Gastric Cancer, of TP53 Mutations and Gene Expressions, in Combination With Other Gene Mutations
Authors: Park Sungjin , Lee Jinhyuk , Kim Yon Hui , Park Jaheun , Shin Jung-Woog , Nam Seungyoon 
Published: October 2016

AbstractWhile altered TP53 is the most frequent mutation in gastric cancer (GC), its association with molecular or clinical phenotypes (e.g., overall survival, disease-free survival) remains little known. To that end, we can use genome-wide approaches to identify altered genes significantly related to mutated TP53. Here, we identified significant differences in clinical outcomes, as well as in molecular phenotypes, across specific GC tumor subpopulations, when combining TP53 with other signaling networks, including WNT and its related genes NRXN1, CTNNB1, SLITRK5, NCOR2, RYR1, GPR112, MLL3, MTUS2, and MYH6. Moreover, specific GC subpopulations indicated by dual mutation of NRXN1 and TP53 suggest different drug responses, according to the Connectivity Map, a pharmacological drug-gene association tool. Overall, TP53 mutation status in GC is significantly relevant to clinical or molecular categories. Thus, our approach can potentially provide a patient stratification strategy by dissecting previously unknown multiple TP53-mutated patient groups.
Hypothalamic sensing of ketone bodies after prolonged cerebral exposure leads to metabolic control dysregulation
Authors: Carneiro Lionel , Geller Sarah , Hébert Audrey , Repond Cendrine , Fioramonti Xavier , Leloup Corinne , Pellerin Luc 
Published: October 2016

AbstractKetone bodies have been shown to transiently stimulate food intake and modify energy homeostasis regulatory systems following cerebral infusion for a moderate period of time (<6 hours). As ketone bodies are usually enhanced during episodes of fasting, this effect might correspond to a physiological regulation. In contrast, ketone bodies levels remain elevated for prolonged periods during obesity, and thus could play an important role in the development of this pathology. In order to understand this transition, ketone bodies were infused through a catheter inserted in the carotid to directly stimulate the brain for a period of 24 hours. Food ingested and blood circulating parameters involved in metabolic control as well as glucose homeostasis were determined. Results show that ketone bodies infusion for 24 hours increased food intake associated with a stimulation of hypothalamic orexigenic neuropeptides. Moreover, insulinemia was increased and caused a decrease in glucose production despite an increased resistance to insulin. The present study confirms that ketone bodies reaching the brain stimulates food intake. Moreover, we provide evidence that a prolonged hyperketonemia leads to a dysregulation of energy homeostasis control mechanisms. Finally, this study shows that brain exposure to ketone bodies alters insulin signaling and consequently glucose homeostasis.
Effects of porcine MyD88 knockdown on the expression of TLR4 pathway-related genes and proinflammatory cytokines
Authors: Dai Chaohui , Sun Li , Yu Lihuai , Zhu Guoqiang , Wu Shenglong , Bao Wenbin 
Published: October 2016

As a critical adapter protein in Toll-like receptor (TLR)/Interleukin (IL)-1R signalling pathway, myeloid differentiation protein 88 (MyD88) plays an important role in immune responses and host defence against pathogens. The present study was designed to provide a foundation and an important reagent for the mechanistic study of MyD88 and its role TLR/IL-1R signalling pathways in porcine immunity. Lentivirus-mediated RNAi was used to generate a porcine PK15 cell line with a silenced MyD88 gene and quantitative real-time PCR (qPCR) and Western blotting were used to detect changes in the expression of critical genes in the Toll-like receptor 4 (TLR4) signalling pathway. ELISA was used to measure the levels of seven proinflammatory cytokines–interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), IL-6, IL-8, IL-12, macrophage inflammatory protein (MIP)-1α and MIP-1β–in cell culture supernatants after MyD88 silencing. We successfully obtained a PK15 cell line with 61% MyD88 mRNA transcript down-regulated. In PK15 cells with MyD88 silencing, the transcript levels of TLR4 and IL-1β were significantly reduced, whereas there were no significant changes in the expression levels of cluster of differentiation antigen 14 (CD14), interferon-α (IFN-α) or TNF-α. The ELISA results showed that the levels of most cytokines were not significantly changed apart from IL-8 without stimulation, which was significantly up-regulated. When cells were induced by lipopolysaccharide (LPS) (0.1 μg/ml) for 6 h, the global level of seven proinflammatory cytokines up-regulated and the level of IL-1β, TNF-α, IL-6, IL-8 and IL-12 of Blank and negative control (NC) group up-regulated more significantly than RNAi group (P&lt;0.05), which revealed that the MyD88 silencing could reduce the TLR4 signal transduction which inhibited the release of proinflammatory cytokines and finally leaded to immunosuppression.