bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of cell death by the novel proteasome inhibitor marizomib in glioblastoma in vitro and in vivo
Authors: Manton Christa A. , Johnson Blake , Singh Melissa , Bailey Cavan P. , Bouchier-Hayes Lisa , Chandra Joya 
Published: January 2016

AbstractNew therapies for glioblastoma (GBM) are needed, as five-year survival is <10%. The proteasome inhibitor marizomib (MRZ) has inhibitory and death-inducing properties unique from previous inhibitors such as bortezomib (BTZ) and has not been well examined in GBM. We evaluated the mechanism of death and in vivo properties of MRZ in GBM. The activation kinetics of initiator caspases 2, 8 and 9 were assessed using chemical and knockdown strategies to determine their contribution to cell death. Blood brain barrier permeance and proteasome inhibition by MRZ and BTZ were examined in an orthotopic GBM model. Blockade of caspase 9, relative to other caspases, was most protective against both MRZ and BTZ. Only MRZ increased the proteasome substrate p27 in orthotopic brain tumors after a single injection, while both MRZ and BTZ increased p21 levels after multiple treatments. Cleavage of caspase substrate lamin A was increased in orthotopic brain tumors from mice treated with MRZ or BTZ and the histone deacetylase inhibitor vorinostat. Our data indicate that MRZ induces caspase 9-dependent death in GBM, suggesting drug efficacy biomarkers and possible resistance mechanisms. MRZ reaches orthotopic brain tumors where it inhibits proteasome function and increases death in combination with vorinostat.
Sexual Conspecific Aggressive Response (SCAR): A Model of Sexual Trauma that Disrupts Maternal Learning and Plasticity in the Female Brain
Authors: Shors Tracey J. , Tobόn Krishna , DiFeo Gina , Durham Demetrius M. , Chang Han Yan M. 
Published: January 2016

AbstractSexual aggression can disrupt processes related to learning as females emerge from puberty into young adulthood. To model these experiences in laboratory studies, we developed SCAR, which stands for Sexual Conspecific Aggressive Response. During puberty, a rodent female is paired daily for 30-min with a sexually-experienced adult male. During the SCAR experience, the male tracks the anogenital region of the female as she escapes from pins. Concentrations of the stress hormone corticosterone were significantly elevated during and after the experience. Moreover, females that were exposed to the adult male throughout puberty did not perform well during training with an associative learning task nor did they learn well to express maternal behaviors during maternal sensitization. Most females that were exposed to the adult male did not learn to care for offspring over the course of 17 days. Finally, females that did not express maternal behaviors retained fewer newly-generated cells in their hippocampus whereas those that did express maternal behaviors retained more cells, most of which would differentiate into neurons within weeks. Together these data support SCAR as a useful laboratory model for studying the potential consequences of sexual aggression and trauma for the female brain during puberty and young adulthood.
The Regulation of Exosporium-Related Genes in Bacillus thuringiensis
Authors: Peng Qi , Kao Guiwei , Qu Ning , Zhang Jie , Li Jie , Song Fuping 
Published: January 2016

AbstractBacillus anthracis, Bacillus cereus and Bacillus thuringiensis (Bt) are spore-forming members of the Bacillus cereus group. Spores of B. cereus group species are encircled by exosporium, which is composed of an external hair-like nap and a paracrystalline basal layer. Despite the extensive studies on the structure of the exosporium-related proteins, little is known about the transcription and regulation of exosporium gene expression in the B. cereus group. Herein, we studied the regulation of several exosporium-related genes in Bt. A SigK consensus sequence is present upstream of genes encoding hair-like nap proteins (bclA and bclB), basal layer proteins (bxpA, bxpB, cotB and exsY ) and inosine hydrolase (iunH). Mutation of sigK decreased the transcriptional activities of all these genes, indicating that the transcription of these genes is controlled by SigK. Furthermore, mutation of gerE decreased the transcriptional activities of bclB, bxpB, cotB and iunH but increased the expression of bxpA and GerE binds to the promoters of bclB, bxpB, cotB, bxpA and iunH. These results suggest that GerE directly regulates the transcription of these genes, increasing the expression of bclB, bxpB, cotB and iunH and decreasing that of bxpA. These findings provide insight into the exosporium assembly process at the transcriptional level.
Virus-specific antibodies allow viral replication in the marginal zone, thereby promoting CD8+ T-cell priming and viral control
Authors: Duhan Vikas , Khairnar Vishal , Friedrich Sarah-Kim , Zhou Fan , Gassa Asmae , Honke Nadine , Shaabani Namir , Gailus Nicole , Botezatu Lacramioara , Khandanpour Cyrus , Dittmer Ulf , Häussinger Dieter , Recher Mike , Hardt Cornelia , Lang Philipp A. , Lang Karl S. 
Published: January 2016

AbstractClinically used human vaccination aims to induce specific antibodies that can guarantee long-term protection against a pathogen. The reasons that other immune components often fail to induce protective immunity are still debated. Recently we found that enforced viral replication in secondary lymphoid organs is essential for immune activation. In this study we used the lymphocytic choriomeningitis virus (LCMV) to determine whether enforced virus replication occurs in the presence of virus-specific antibodies or virus-specific CD8+ T cells. We found that after systemic recall infection with LCMV-WE the presence of virus-specific antibodies allowed intracellular replication of virus in the marginal zone of spleen. In contrast, specific antibodies limited viral replication in liver, lung and kidney. Upon recall infection with the persistent virus strain LCMV-Docile, viral replication in spleen was essential for the priming of CD8+ T cells and for viral control. In contrast to specific antibodies, memory CD8+ T cells inhibited viral replication in marginal zone but failed to protect mice from persistent viral infection. We conclude that virus-specific antibodies limit viral infection in peripheral organs but still allow replication of LCMV in the marginal zone, a mechanism that allows immune boosting during recall infection and thereby guarantees control of persistent virus.
Ligand-based virtual screening and inductive learning for identification of SIRT1 inhibitors in natural products
Authors: Sun Yunan , Zhou Hui , Zhu Hongmei , Leung Siu-wai 
Published: January 2016

AbstractSirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent deacetylase and its dysregulation can lead to ageing, diabetes and cancer. From 346 experimentally confirmed SIRT1 inhibitors, an inhibitor structure pattern was generated by inductive logic programming (ILP) with DMax Chemistry Assistant software. The pattern contained amide, amine and hetero-aromatic five-membered rings, each of which had a hetero-atom and an unsubstituted atom at a distance of 2. According to this pattern, a ligand-based virtual screening of 1 444 880 active compounds from Chinese herbs identified 12 compounds as inhibitors of SIRT1. Three compounds (ZINC08790006, ZINC08792229 and ZINC08792355) had high affinity (−7.3, −7.8 and −8.6 kcal/mol, respectively) for SIRT1 as estimated by molecular docking software AutoDock Vina. This study demonstrated a use of ILP and background knowledge in machine learning to facilitate virtual screening.
Population Connectivity Measures of Fishery-Targeted Coral Reef Species to Inform Marine Reserve Network Design in Fiji
Authors: Eastwood Erin K. , López Elora H. , Drew Joshua A. 
Published: January 2016

AbstractCoral reef fish serve as food sources to coastal communities worldwide, yet are vulnerable to mounting anthropogenic pressures like overfishing and climate change. Marine reserve networks have become important tools for mitigating these pressures and one of the most critical factors in determining their spatial design is the degree of connectivity among different populations of species prioritized for protection. To help inform the spatial design of an expanded reserve network in Fiji, we used rapidly evolving mitochondrial genes to investigate connectivity patterns of three coral reef species targeted by fisheries in Fiji: Epinephelus merra (Serranidae), Halichoeres trimaculatus (Labridae) and Holothuria atra (Holothuriidae). The two fish species, E. merra and Ha. trimaculatus, exhibited low genetic structuring and high amounts of gene flow, whereas the sea cucumber Ho. atra displayed high genetic partitioning and predominantly westward gene flow. The idiosyncratic patterns observed among these species indicate that patterns of connectivity in Fiji are likely determined by a combination of oceanographic and ecological characteristics. Our data indicate that in the cases of species with high connectivity, other factors such as representation or political availability may dictate where reserves are placed. In low connectivity species, ensuring upstream and downstream connections is critical.
Dmy initiates masculinity by altering Gsdf/Sox9a2/Rspo1 expression in medaka (Oryzias latipes)
Authors: Chakraborty Tapas , Zhou Lin Yan , Chaudhari Aparna , Iguchi Taisen , Nagahama Y. 
Published: January 2016

AbstractDespite identification of several sex-determining genes in non-mammalian vertebrates, their detailed molecular cascades of sex determination/differentiation are not known. Here, we used a novel RNAi to characterise the molecular mechanism of Dmy (the sex-determining gene of medaka)-mediated masculinity in XY fish. Dmy knockdown (Dmy-KD) suppressed male pathway (Gsdf, Sox9a2, etc.) and favoured female cascade (Rspo1, etc.) in embryonic XY gonads, resulting in a fertile male-to-female sex-reversal. Gsdf, Sox9a2 and Rspo1 directly interacted with Dmy and co-injection of Gsdf and Sox9a2 re-established masculinity in XY-Dmy-KD transgenics, insinuating that Dmy initiates masculinity by stimulating and suppressing Gsdf/Sox9a2 and Rspo1 expression, respectively. Gonadal expression of Wt1a starts prior to Dmy and didn’t change upon Dmy-KD. Furthermore, Wt1a stimulated the promoter activity of Dmy, suggesting Wt1a as a regulator of Dmy. These findings provide new insights into the role of vertebrate sex-determining genes associated with the molecular interplay between the male and female pathways.
Panel-based NGS Reveals Novel Pathogenic Mutations in Autosomal Recessive Retinitis Pigmentosa
Authors: Perez-Carro Raquel , Corton Marta , Sánchez-Navarro Iker , Zurita Olga , Sanchez-Bolivar Noelia , Sánchez-Alcudia Rocío , Lelieveld Stefan H. , Aller Elena , Lopez-Martinez Miguel Angel , López-Molina Mª Isabel , Fernandez-San Jose Patricia , Blanco-Kelly Fiona , Riveiro-Alvarez Rosa , Gilissen Christian , Millan Jose M , Avila-Fernandez Almudena , Ayuso Carmen 
Published: January 2016

AbstractRetinitis pigmentosa (RP) is a group of inherited progressive retinal dystrophies (RD) characterized by photoreceptor degeneration. RP is highly heterogeneous both clinically and genetically, which complicates the identification of causative genes and mutations. Targeted next-generation sequencing (NGS) has been demonstrated to be an effective strategy for the detection of mutations in RP. In our study, an in-house gene panel comprising 75 known RP genes was used to analyze a cohort of 47 unrelated Spanish families pre-classified as autosomal recessive or isolated RP. Disease-causing mutations were found in 27 out of 47 cases achieving a mutation detection rate of 57.4%. In total, 33 pathogenic mutations were identified, 20 of which were novel mutations (60.6%). Furthermore, not only single nucleotide variations but also copy-number variations, including three large deletions in theUSH2AandEYSgenes, were identified. Finally seven out of 27 families, displaying mutations in theABCA4, RP1, RP2andUSH2Agenes, could be genetically or clinically reclassified. These results demonstrate the potential of our panel-based NGS strategy in RP diagnosis.
Atmospheric controls on the precipitation isotopes over the Andaman Islands, Bay of Bengal
Authors: Chakraborty S. , Sinha N. , Chattopadhyay R. , Sengupta S. , Mohan P. M. , Datye A. 
Published: January 2016

AbstractIsotopic analysis of precipitation over the Andaman Island, Bay of Bengal was carried out for the year 2012 and 2013 in order to study the atmospheric controls on rainwater isotopic variations. The oxygen and hydrogen isotopic compositions are typical of the tropical marine sites but show significant variations depending on the ocean-atmosphere conditions; maximum depletion was observed during the tropical cyclones. The isotopic composition of rainwater seems to be controlled by the dynamical nature of the moisture rather than the individual rain events. Precipitation isotopes undergo systematic depletions in response to the organized convection occurring over a large area and are modulated by the integrated effect of convective activities. Precipitation isotopes appear to be linked with the monsoon intraseasonal variability in addition to synoptic scale fluctuations. During the early to mid monsoon the amount effect arose primarily due to rain re-evaporation but in the later phase it was driven by moisture convergence rather than evaporation. Amount effect had distinct characteristics in these two years, which appeared to be modulated by the intraseasonal variability of monsoon. It is shown that the variable nature of amount effect limits our ability to reconstruct the past-monsoon rainfall variability on annual to sub-annual time scale.
Resistive Switching Memory Phenomena in PEDOT PSS: Coexistence of Switchable Diode Effect and Write Once Read Many Memory
Authors: Nguyen Viet Cuong , Lee Pooi See 
Published: January 2016

AbstractWe study resistive switching memory phenomena in conducting polymer PEDOT PSS. In the same film, there are two types of memory behavior coexisting; namely, the switchable diode effect and write once read many memory. This is the first report on switchable diode phenomenon based on conducting organic materials. The effect was explained as charge trapping of PEDOT PSS film and movement of proton. The same PEDOT PSS device also exhibits write once read many memory (WORM) phenomenon which arises due to redox reaction that reduces PEDOT PSS and renders it non-conducting. The revelation of these two types of memory phenomena in PEDOT PSS highlights the remarkable versatility of this conducting conjugated polymer.
Breaking sarcomeres by in vitro exercise
Authors: Orfanos Zacharias , Gödderz Markus P. O. , Soroka Ekaterina , Gödderz Tobias , Rumyantseva Anastasia , van der Ven Peter F. M. , Hawke Thomas J. , Fürst Dieter O. 
Published: January 2016

AbstractEccentric exercise leads to focal disruptions in the myofibrils, referred to as “lesions”. These structures are thought to contribute to the post-exercise muscle weakness and to represent areas of mechanical damage and/or remodelling. Lesions have been investigated in human biopsies and animal samples after exercise. However, this approach does not examine the mechanisms behind lesion formation, or their behaviour during contraction. To circumvent this, we used electrical pulse stimulation (EPS) to simulate exercise in C2C12 myotubes, combined with live microscopy. EPS application led to the formation of sarcomeric lesions in the myotubes, resembling those seen in exercised mice, increasing in number with the time of application or stimulation intensity. Furthermore, transfection with an EGFP-tagged version of the lesion and Z-disc marker filamin-C allowed us to observe the formation of lesions using live cell imaging. Finally, using the same technique we studied the behaviour of these structures during contraction and observed them to be passively stretching. This passive behaviour supports the hypothesis that lesions contribute to the post-exercise muscle weakness, protecting against further damage. We conclude that EPS can be reliably used as a model for the induction and study of sarcomeric lesions in myotubesin vitro.
Exponential decay of spatial correlation in driven diffusive system: A universal feature of macroscopic homogeneous state
Authors: Hao Qing-Yi , Jiang Rui , Hu Mao-Bin , Jia Bin , Wang Wen-Xu 
Published: January 2016

AbstractDriven diffusive systems have been a paradigm for modelling many physical, chemical and biological transport processes. In the systems, spatial correlation plays an important role in the emergence of a variety of nonequilibrium phenomena and exhibits rich features such as pronounced oscillations. However, the lack of analytical results of spatial correlation precludes us from fully understanding the effect of spatial correlation on the dynamics of the system. Here we offer precise analytical predictions of the spatial correlation in a typical driven diffusive system, namely facilitated asymmetric exclusion process. We find theoretically that the correlation between two sites decays exponentially as their distance increases, which is in good agreement with numerical simulations. Furthermore, we find the exponential decay is a universal property of macroscopic homogeneous state in a broad class of 1D driven diffusive systems. Our findings deepen the understanding of many nonequilibrium phenomena resulting from spatial correlation in driven diffusive systems.
Accelerated soil carbon turnover under tree plantations limits soil carbon storage
Authors: Chen Guangshui , Yang Yusheng , Yang Zhijie , Xie Jinsheng , Guo Jianfen , Gao Ren , Yin Yunfeng , Robinson David 
Published: January 2016

AbstractThe replacement of native forests by tree plantations is increasingly common globally, especially in tropical and subtropical areas. Improving our understanding of the long-term effects of this replacement on soil organic carbon (SOC) remains paramount for effectively managing ecosystems to mitigate anthropogenic carbon emissions. Meta-analyses imply that native forest replacement usually reduces SOC stocks and may switch the forest from a net sink to a net source of atmospheric carbon. Using a long-term chronosequence during which areas of subtropical native forest were replaced by Chinese fir, we show by direct measurement that plantations have significantly accelerated SOC turnover compared with native forest, an effect that has persisted for almost a century. The immediate stimulation of SOC decomposition was caused by warmer soil before the closure of the plantation’s canopy. Long-term reductions in SOC mean residence times were coupled to litter inputs. Faster SOC decomposition was associated with lower soil microbial carbon use efficiency, which was due to smaller litter inputs and reduced nutrient availabilities. Our results indicate a previously unelucidated control on long-term SOC dynamics in native forests and demonstrate a potential constraint on climate mitigation when such forests are replaced by plantations.
Mycobacterium Lysine ε-aminotransferase is a novel alarmone metabolism related persister gene via dysregulating the intracellular amino acid level
Authors: Duan Xiangke , Li Yunsong , Du Qinglin , Huang Qinqin , Guo Siyao , Xu Mengmeng , Lin Yanping , Liu Zhidong , Xie Jianping 
Published: January 2016

AbstractBacterial persisters, usually slow-growing, non-replicating cells highly tolerant to antibiotics, play a crucial role contributing to the recalcitrance of chronic infections and treatment failure. Understanding the molecular mechanism of persister cells formation and maintenance would obviously inspire the discovery of new antibiotics. The significant upregulation of Mycobacterium tuberculosis Rv3290c, a highly conserved mycobacterial lysine ε-aminotransferase (LAT) during hypoxia persistent model, suggested a role of LAT in persistence. To test this, a lat deleted Mycobacterium smegmatis was constructed. The expression of transcriptional regulator leucine-responsive regulatory protein (LrpA) and the amino acids abundance in M. smegmatis lat deletion mutants were lowered. Thus, the persistence capacity of the deletion mutant was impaired upon norfloxacin exposure under nutrient starvation. In summary, our study firstly reported the involvement of mycobacterium LAT in persister formation and possibly through altering the intracellular amino acid metabolism balance.
Transition from freshwater to seawater reshapes the skin-associated microbiota of Atlantic salmon
Authors: Lokesh Jep , Kiron Viswanath 
Published: January 2016

AbstractKnowledge concerning shifts in microbiota is important in order to elucidate the perturbations in the mucosal barrier during the transitional life stages of the host. In the present study, a 16S rRNA gene sequencing technique was employed to examine the compositional changes and presumptive functions of the skin-associated bacterial communities of Atlantic salmon reared under controlled laboratory conditions and transferred from freshwater to seawater. Proteobacteria was the dominant phylum in salmon from both freshwater (45%) and seawater (above 89%). Bacteroidetes, Actinobacteria, Firmicutes, Cyanobacteria and Verrucomicrobia were the most abundant phyla in salmon from freshwater. The transition to seawater influenced the OTU richness and evenness. The high abundance (~62%) of the genus Oleispira made Proteobacteria the most significantly abundant phylum in salmon from seawater. The predictive functional profile suggested that the communities had the ability to extract energy from amino acids in order to maintain their metabolism and scavenge and biosynthesise compounds to make structural changes and carry out signalling for their survival. These findings need to be further explored in relation to metabolic processes, the fish genotype and the environment.
Different hydrogen isotope fractionations during lipid formation in higher plants: Implications for paleohydrology reconstruction at a global scale
Authors: Liu Jinzhao , Liu Weiguo , An Zhisheng , Yang Hong 
Published: January 2016

AbstractLeaf wax δDn-alkane values have shown to differ significantly among plant life forms (e.g., among grasses, shrubs and trees) in higher plants. However, the underlying causes for the differences in leaf wax δDn-alkane values among different plant life forms remain poorly understood. In this study, we observed that leaf wax δDn-alkane values between major high plant lineages (eudicots versus monocots) differed significantly under the same environmental conditions. Such a difference primarily inherited from different hydrogen biosynthetic fractionations (εwax-lw). Based upon a reanalysis of the available leaf wax δDn-alkane dataset from modern plants in the Northern Hemisphere, we discovered that the apparent hydrogen fractionation factor (εwax-p) between leaf wax δDn-alkane values of major angiosperm lineages and precipitation δD values exhibited distinguishable distribution patterns at a global scale, with an average of −140‰ for monocotyledonous species, −107‰ for dicotyledonous species. Additionally, variations of leaf wax δDn-alkane values and the εwax-p values in gymnosperms are similar to those of dicotyledonous species. Therefore, the data let us believe that biological factors inherited from plant taxonomies have a significant effect on controlling leaf wax δDn-alkane values in higher plants.