bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hydrogen sulfide toxicity inhibits primary root growth through the ROS-NO pathway
Authors: Zhang Ping , Luo Qiong , Wang Ruling , Xu Jin 
Published: April 2017

AbstractHigh concentrations of hydrogen sulfide (H2S) are toxic to plants and inhibit their growth. Previous research indicated that high concentrations of H2S modulate the root system architecture (RSA) by affecting auxin transport; however, the signaling pathway underlying this process remains unclear. Here, we investigated the effects of exogenous sodium hydrosulfide (NaHS), an H2S donor, on primary root (PR) growth in Arabidopsis using pharmacological, physiological, and genetic approaches. H2S toxicity repressed PR growth by triggering a signal transduction pathway involving reactive oxygen species (ROS) accumulation, MITOGEN-ACTIVATED PROTEIN KINASE 6 (MPK6) activation, and nitric oxide (NO) production. Respiratory burst oxidase homolog mutants and an NO synthase mutant were less sensitive to NaHS, suggesting that both ROS and NO mediate the inhibitory effects of H2S on PR growth. We found that exogenous H2S-activated ROS production was required for NO generation and that MPK6 mediated H2S-induced NO production. MPK6 was shown to function downstream of ROS and upstream of NO. Finally, we demonstrated that exogenous H2S repressed the distribution of auxin and reduced the meristematic cell division potential in root tips, and NO was involved in this process.
Augmentation of working memory training by transcranial direct current stimulation (tDCS)
Authors: Ruf Steffen Philipp , Fallgatter Andreas J. , Plewnia Christian 
Published: April 2017

AbstractTranscranial direct current stimulation (tDCS) to the dorsolateral prefrontal cortex (dlPFC) can modulate working memory (WM) performance. However, evidence regarding the enhancement of WM training, its sustainability and transferability is ambiguous. Since WM functioning appears to be lateralized in respect to stimulus characteristics, this study examined the difference between task-congruent (spatial-right, verbal-left), task-incongruent (spatial-left, verbal-right) and sham tDCS in regards to the efficacy of WM training. In a randomized, sham-controlled experiment, 71 healthy adults trained on a spatial or verbal adaptive n-back task. After a baseline session, anodal or sham tDCS (1 mA) to the right or left dlPFC was applied during the next three training sessions. Sustainability of training gains and near-transfer (verbal or spatial 3-back task) were tested in a fourth training and a follow-up session. Compared to sham stimulation, we found a steeper learning curve when WM training was combined with task-congruent tDCS. This advantage was also present compared to task-incongruent tDCS. Moreover, these effects lasted for up to nine months and transferred to the respective untrained task. These long-lasting, transferable, task-specific effects demonstrate a behaviorally relevant and sustainable facilitation of neuroplastic processes by tDCS that could be harnessed for the treatment of disorders associated with deficient WM.
Reply to ‘Comments on “Evidence of the hydrogen release mechanism in bulk MgH2”’
Authors: Nogita Kazuhiro , Tran Xuan Q. , Yamamoto Tomokazu , Tanaka Eishi , McDonald Stuart D. , Gourlay Christopher M. , Yasuda Kazuhiro , Matsumura Syo 
Published: April 2017

AbstractIn a comment on our Article “Evidence of the hydrogen release mechanism in bulk MgH2”, Surrey et al. assert that the MgH2 sample we studied was not MgH2 at any time but rather MgO; and that the transformation we observed was the formation of Kirkendall voids due to the outward diffusion of Mg. We address these issues in this reply.
BMP6 Regulates Proliferation and Apoptosis of Human Sertoli Cells Via Smad2/3 and Cyclin D1 Pathway and DACH1 and TFAP2A Activation
Authors: Wang Hong , Yuan Qingqing , Sun Min , Niu Minghui , Wen Liping , Fu Hongyong , Zhou Fan , Chen Zheng , Yao Chencheng , Hou Jingmei , Shen Ruinan , Lin Qisheng , Liu Wenjie , Jia Ruobing , Li Zheng , He Zuping 
Published: April 2017

AbstractSertoli cells are essential for regulating normal spermatogenesis. However, the mechanisms underlying human Sertoli cell development remain largely elusive. Here we examined the function and signaling pathways of BMP6 in regulating human Sertoli cells. RT-PCR, immunocytochemistry and Western blots revealed that BMP6 and its multiple receptors were expressed in human Sertoli cells. CCK-8 and EDU assays showed that BMP6 promoted the proliferation of Sertoli cells. Conversely, BMP6 siRNAs inhibited the division of these cells. Annexin V/PI assay indicated that BMP6 reduced the apoptosis in human Sertoli cells, whereas BMP6 knockdown assumed reverse effects. BMP6 enhanced the expression levels of ZO1, SCF, GDNF and AR in human Sertoli cells, and ELISA assay showed an increase of SCF by BMP6 and a reduction by BMP6 siRNAs. Notably, Smad2/3 phosphorylation and cyclin D1 were enhanced by BMP6 and decreased by BMP6 siRNAs in human Sertoli cells. The levels of DACH1 and TFAP2A were increased by BMP6 and reduced by BMP6 siRNAs, and the growth of human Sertoli cells was inhibited by these siRNAs. Collectively, these results suggest that BMP6 regulates the proliferation and apoptosis of human Sertoli cells via activating the Smad2/3/cyclin D1 and DACH1 and TFAP2A pathway.
Calcium oxalate crystals and oxalate induce an epithelial-to-mesenchymal transition in the proximal tubular epithelial cells: Contribution to oxalate kidney injury
Authors: Convento Marcia Bastos , Pessoa Edson Andrade , Cruz Edgar , da Glória Maria Aparecida , Schor Nestor , Borges Fernanda Teixeira 
Published: April 2017

AbstractTGF-β1 is the main mediator of epithelial-to-mesenchymal transition (EMT). Hyperoxaluria induces crystalluria, interstitial fibrosis, and progressive renal failure. This study analyzed whether hyperoxaluria is associated with TGF-β1 production and kidney fibrosis in mice and if oxalate or calcium oxalate (CaOx) could induce EMT in proximal tubule cells (HK2) and therefore contribute to the fibrotic process. Hyperoxaluria was induced by adding hydroxyproline and ethylene glycol to the mice’s drinking water for up to 60 days. Renal function and oxalate and urinary crystals were evaluated. Kidney collagen production and TGF-β1 expression were assessed. EMT was analyzed in vitro according to TGF-β1 production, phenotypic characterization, invasion, cell migration, gene and protein expression of epithelial and mesenchymal markers. Hyperoxaluric mice showed a decrease in renal function and an increase in CaOx crystals and Ox urinary excretion. The deposition of collagen in the renal interstitium was observed. HK2 cells stimulated with Ox and CaOx exhibited a decreased expression of epithelial as well as increased expression mesenchymal markers; these cells presented mesenchymal phenotypic changes, migration, invasiveness capability and TGF-β1 production, characterizing EMT. Treatment with BMP-7 or its overexpression in HK2 cells was effective at preventing it. This mechanism may contribute to the fibrosis observed in hyperoxaluria.
A staged screening of registered drugs highlights remyelinating drug candidates for clinical trials
Authors: Eleuteri C. , Olla S. , Veroni C. , Umeton R. , Mechelli R. , Romano S. , Buscarinu MC. , Ferrari F. , Calò G. , Ristori G. , Salvetti M. , Agresti C. 
Published: April 2017

AbstractThere is no treatment for the myelin loss in multiple sclerosis, ultimately resulting in the axonal degeneration that leads to the progressive phase of the disease. We established a multi-tiered platform for the sequential screening of drugs that could be repurposed as remyelinating agents. We screened a library of 2,000 compounds (mainly Food and Drug Administration (FDA)-approved compounds and natural products) for cellular metabolic activity on mouse oligodendrocyte precursors (OPC), identifying 42 molecules with significant stimulating effects. We then characterized the effects of these compounds on OPC proliferation and differentiation in mouse glial cultures, and on myelination and remyelination in organotypic cultures. Three molecules, edaravone, 5-methyl-7-methoxyisoflavone and lovastatin, gave positive results in all screening tiers. We validated the results by retesting independent stocks of the compounds, analyzing their purity, and performing dose-response curves. To identify the chemical features that may be modified to enhance the compounds’ activity, we tested chemical analogs and identified, for edaravone, the functional groups that may be essential for its activity. Among the selected remyelinating candidates, edaravone appears to be of strong interest, also considering that this drug has been approved as a neuroprotective agent for acute ischemic stroke and amyotrophic lateral sclerosis in Japan.
A 3q gene signature associated with triple negative breast cancer organ specific metastasis and response to neoadjuvant chemotherapy
Authors: Qian Jun , Chen Heidi , Ji Xiangming , Eisenberg Rosana , Chakravarthy A. Bapsi , Mayer Ingrid A. , Massion Pierre P. 
Published: April 2017

AbstractTriple negative breast cancers (TNBC) are aggressive tumors, with high rates of metastatic spread and targeted therapies are critically needed. We aimed to assess the prognostic and predictive value of a 3q 19-gene signature identified previously from lung cancer in a collection of 4,801 breast tumor gene expression data. The 3q gene signature had a strong association with features of aggressiveness such as high grade, hormone receptor negativity, presence of a basal-like or TNBC phenotype and reduced distant metastasis free survival. The 3q gene signature was strongly associated with lung metastasis only in TNBC (P < 0.0001, Hazard ratio (HR) 1.44, 95% confidence interval (CI), 1.31–1.60), significantly associated with brain but not bone metastasis regardless of TNBC status. The association of one 3q driver gene FXR1 with distant metastasis in TNBC (P = 0.01) was further validated by immunohistochemistry. In addition, the 3q gene signature was associated with better response to neoadjuvant chemotherapy in TNBC (P < 0.0001) but not in non-TNBC patients. Our study suggests that the 3q gene signature is a novel prognostic marker for lung and/or brain metastasis and a predictive marker for the response to neoadjuvant chemotherapy in TNBC, implying a potential role for 3q genes in the mechanism of organ-specific metastasis.
Identification of dominating factors affecting vadose zone vulnerability by a simulation method
Authors: Li Juan , Xi Beidou , Cai Wutian , Yang Yang , Jia Yongfeng , Li Xiang , Lv Yonggao , Lv Ningqing , Huan Huan , Yang Jinjin 
Published: April 2017

AbstractThe characteristics of vadose zone vulnerability dominating factors (VDFs) are closely related to the migration and transformation mechanisms of contaminants in the vadose zone, which directly affect the state of the contaminants percolating to the groundwater. This study analyzes the hydrogeological profile of the pore water regions in the vadose zone, and conceptualizes the vadose zone as single lithologic, double lithologic, or multi lithologic. To accurately determine how the location of the pollution source influences the groundwater, we classify the permeabilities (thicknesses) of different media into clay-layer and non-clay-layer permeabilities (thicknesses), and introduce the maximum pollution thickness. Meanwhile, the physicochemical reactions of the contaminants in the vadose zone are represented by the soil adsorption and soil degradability. The VDFs are determined from the factors and parameters in groundwater vulnerability assessment. The VDFs are identified and sequenced in simulations and a sensitivity analysis. When applied to three polluted sites in China, the method improved the weighting of factors in groundwater vulnerability assessment, and increased the reliability of predicting groundwater vulnerability to contaminants.
Introducing the ESAT-6 free IGRA, a companion diagnostic for TB vaccines based on ESAT-6
Authors: Ruhwald Morten , de Thurah Lena , Kuchaka Davis , Zaher Mostafa Rafaat , Salman Ahmed M. , Abdel-Ghaffar Abdel-Rahman , Shoukry Faten Aly , Michelsen Sascha Wilk , Soborg Bolette , Blauenfeldt Thomas , Mpagama Stellah , Hoff Søren T. , Agger Else Marie , Rosenkrands Ida , Aagard Claus , Kibiki Gibson , El-Sheikh Nabila , Andersen Peter 
Published: April 2017

AbstractThere is a need for an improved vaccine for tuberculosis. ESAT-6 is a cardinal vaccine antigen with unique properties and is included in several vaccine candidates in development. ESAT-6 is also the core antigen in the IFN-γ release assays (IGRA) used to diagnose latent infection, rendering IGRA tests unspecific after vaccination. This challenge has prompted the development of a companion diagnostic for ESAT-6 based vaccines, an ESAT-6 free IGRA. We screened a panel of seven potential new diagnostic antigens not recognized in BCG vaccinated individuals. Three highly recognized antigens EspC, EspF and Rv2348c were identified and combined with CFP10 in an ESAT-6 free antigen cocktail. The cocktail was prepared in a field-friendly format, lyophilized with heparin in ready-to-use vacutainer tubes. The diagnostic performance of the ESAT-6 free IGRA was determined in a cross-validation study. Compared IGRA, the ESAT-6 free IGRA induced a comparable magnitude of IFN-γ release, and the diagnostic performance was on par with Quantiferon (sensitivity 84% vs 79%; specificity 99% vs 97%). The comparable performance of the ESAT-6 free IGRA to IGRA suggests potential as companion diagnostic for ESAT-6 containing vaccines and as adjunct test for latent infection.
Multi-color electron microscopy by element-guided identification of cells, organelles and molecules
Authors: Scotuzzi Marijke , Kuipers Jeroen , Wensveen Dasha I. , de Boer Pascal , Hagen Kees W. , Hoogenboom Jacob P. , Giepmans Ben N. G. 
Published: April 2017

AbstractCellular complexity is unraveled at nanometer resolution using electron microscopy (EM), but interpretation of macromolecular functionality is hampered by the difficulty in interpreting grey-scale images and the unidentified molecular content. We perform large-scale EM on mammalian tissue complemented with energy-dispersive X-ray analysis (EDX) to allow EM-data analysis based on elemental composition. Endogenous elements, labels (gold and cadmium-based nanoparticles) as well as stains are analyzed at ultrastructural resolution. This provides a wide palette of colors to paint the traditional grey-scale EM images for composition-based interpretation. Our proof-of-principle application of EM-EDX reveals that endocrine and exocrine vesicles exist in single cells in Islets of Langerhans. This highlights how elemental mapping reveals unbiased biomedical relevant information. Broad application of EM-EDX will further allow experimental analysis on large-scale tissue using endogenous elements, multiple stains, and multiple markers and thus brings nanometer-scale ‘color-EM’ as a promising tool to unravel molecular (de)regulation in biomedicine.
Genome-wide identification and functional prediction of cold and/or drought-responsive lncRNAs in cassava
Authors: Li Shuxia , Yu Xiang , Lei Ning , Cheng Zhihao , Zhao Pingjuan , He Yuke , Wang Wenquan , Peng Ming 
Published: April 2017

AbstractCold and drought stresses seriously affect cassava (Manihot esculenta) plant growth and yield. Recently, long noncoding RNAs (lncRNAs) have emerged as key regulators of diverse cellular processes in mammals and plants. To date, no systematic screening of lncRNAs under abiotic stress and their regulatory roles in cassava has been reported. In this study, we present the first reference catalog of 682 high-confidence lncRNAs based on analysis of strand-specific RNA-seq data from cassava shoot apices and young leaves under cold, drought stress and control conditions. Among them, 16 lncRNAs were identified as putative target mimics of cassava known miRNAs. Additionally, by comparing with small RNA-seq data, we found 42 lncNATs and sense gene pairs can generate nat-siRNAs. We identified 318 lncRNAs responsive to cold and/or drought stress, which were typically co-expressed concordantly or discordantly with their neighboring genes. Trans-regulatory network analysis suggested that many lncRNAs were associated with hormone signal transduction, secondary metabolites biosynthesis, and sucrose metabolism pathway. The study provides an opportunity for future computational and experimental studies to uncover the functions of lncRNAs in cassava.
Plk1 Regulates the Repressor Function of FoxM1b by inhibiting its Interaction with the Retinoblastoma Protein
Authors: Mukhopadhyay Nishit K. , Chand Vaibhav , Pandey Akshay , Kopanja Dragana , Carr Janai R. , Chen Yi-Ju , Liao Xiubei , Raychaudhuri Pradip 
Published: April 2017

AbstractFoxM1b is a cell cycle-regulated transcription factor, whose over-expression is a marker for poor outcome in cancers. Its transcriptional activation function requires phosphorylation by Cdk1 or Cdk2 that primes FoxM1b for phosphorylation by Plk1, which triggers association with the co-activator CBP. FoxM1b also possesses transcriptional repression function. It represses the mammary differentiation gene GATA3 involving DNMT3b and Rb. We investigated what determines the two distinct functions of FoxM1b: activation and repression. We show that Rb binds to the C-terminal activation domain of FoxM1b. Analyses with phospho-defective and phospho-mimetic mutants of FoxM1b identified a critical role of the Plk1 phosphorylation sites in regulating the binding of FoxM1b to Rb and DNMT3b. That is opposite of what was seen for the interaction of FoxM1b with CBP. We show that, in addition to GATA3, FoxM1b also represses the mammary luminal differentiation marker FoxA1 by promoter-methylation, and that is regulated by the Plk1 phosphorylation sites in FoxM1b. Our results show that the Plk1 phosphorylation sites in FoxM1b serve as a regulator for its repressor function, and they provide insights into how FoxM1b inhibits differentiation genes and activates proliferation genes during cancer progression.
Sensory genes identification with head transcriptome of the migratory armyworm, Mythimna separata
Authors: Liu Zhenxing , Wang Xiaoyun , Lei Chaoliang , Zhu Fen 
Published: April 2017

AbstractSensory system plays important roles in a wide array of insect’s behavior and physiological events, including the host landing and locating, feeding, flying, sex responding, mating and oviposition which happen independently and in sequence. The armyworm Mythimna separata (Lepidoptera: Noctuidae) of migratory insect is destructive for alimentarn crop and economic crop throughout the world. Here we present the high throughput sequencing of the head transcriptome and identify members of the major sensory genes which are crucial for armyworm’s success worldwide, including 8 opsins, 22 chemosensory proteins, 50 odorant binding proteins, 60 odorant receptors, 8 gustatory receptors, 24 ionotropic receptors, and 2 sensory neuron membrane proteins. It is worth noting that a duplication of the LW opsin gene exists in this insect. Several genes were clustered with functionally validated genes, such as Co-receptors of OR and IR, PBPs, PRs, CO2 GRs, bitter GRs and sweet GRs, were also identified. The transcriptome gene library provided the basis for further studies that elucidate the fundamental molecular mechanism of biology and control in M. separata. Our research exhibits the first comprehensive catalogue of the sensory genes fundamental for success and distribution in M. separata, which are potential novel targets for pest control strategies.
Origin and spread of human mitochondrial DNA haplogroup U7
Authors: Sahakyan Hovhannes , Hooshiar Kashani Baharak , Tamang Rakesh , Kushniarevich Alena , Francis Amirtharaj , Costa Marta D , Pathak Ajai Kumar , Khachatryan Zaruhi , Sharma Indu , van Oven Mannis , Parik Jüri , Hovhannisyan Hrant , Metspalu Ene , Pennarun Erwan , Karmin Monika , Tamm Erika , Tambets Kristiina , Bahmanimehr Ardeshir , Reisberg Tuuli , Reidla Maere , Achilli Alessandro , Olivieri Anna , Gandini Francesca , Perego Ugo A. , Al-Zahery Nadia , Houshmand Massoud , Sanati Mohammad Hossein , Soares Pedro , Rai Ekta , Šarac Jelena , Šarić Tena , Sharma Varun , Pereira Luisa , Fernandes Veronica , Černý Viktor , Farjadian Shirin , Singh Deepankar Pratap , Azakli Hülya , Üstek Duran , Ekomasova Natalia , Kutuev Ildus , Litvinov Sergei , Bermisheva Marina , Khusnutdinova Elza K. , Rai Niraj , Singh Manvendra , Singh Vijay Kumar , Reddy Alla G. , Tolk Helle-Viivi , Cvjetan Svjetlana , Lauc Lovorka Barac , Rudan Pavao , Michalodimitrakis Emmanuel N. , Anagnou Nicholas P. , Pappa Kalliopi I. , Golubenko Maria V. , Orekhov Vladimir , Borinskaya Svetlana A , Kaldma Katrin , Schauer Monica A. , Simionescu Maya , Gusar Vladislava , Grechanina Elena , Govindaraj Periyasamy , Voevoda Mikhail , Damba Larissa , Sharma Swarkar , Singh Lalji , Semino Ornella , Behar Doron M. , Yepiskoposyan Levon , Richards Martin B. , Metspalu Mait , Kivisild Toomas , Thangaraj Kumarasamy , Endicott Phillip , Chaubey Gyaneshwer , Torroni Antonio , Villems Richard 
Published: April 2017

AbstractHuman mitochondrial DNA haplogroup U is among the initial maternal founders in Southwest Asia and Europe and one that best indicates matrilineal genetic continuity between late Pleistocene hunter-gatherer groups and present-day populations of Europe. While most haplogroup U subclades are older than 30 thousand years, the comparatively recent coalescence time of the extant variation of haplogroup U7 (~16–19 thousand years ago) suggests that its current distribution is the consequence of more recent dispersal events, despite its wide geographical range across Europe, the Near East and South Asia. Here we report 267 new U7 mitogenomes that – analysed alongside 100 published ones – enable us to discern at least two distinct temporal phases of dispersal, both of which most likely emanated from the Near East. The earlier one began prior to the Holocene (~11.5 thousand years ago) towards South Asia, while the later dispersal took place more recently towards Mediterranean Europe during the Neolithic (~8 thousand years ago). These findings imply that the carriers of haplogroup U7 spread to South Asia and Europe before the suggested Bronze Age expansion of Indo-European languages from the Pontic-Caspian Steppe region.
Transgenerational transmission of a stress-coping phenotype programmed by early-life stress in the Japanese quail
Authors: Zimmer Cédric , Larriva Maria , Boogert Neeltje J. , Spencer Karen A. 
Published: April 2017

AbstractAn interesting aspect of developmental programming is the existence of transgenerational effects that influence offspring characteristics and performance later in life. These transgenerational effects have been hypothesized to allow individuals to cope better with predictable environmental fluctuations and thus facilitate adaptation to changing environments. Here, we test for the first time how early-life stress drives developmental programming and transgenerational effects of maternal exposure to early-life stress on several phenotypic traits in their offspring in a functionally relevant context using a fully factorial design. We manipulated pre- and/or post-natal stress in both Japanese quail mothers and offspring and examined the consequences for several stress-related traits in the offspring generation. We show that pre-natal stress experienced by the mother did not simply affect offspring phenotype but resulted in the inheritance of the same stress-coping traits in the offspring across all phenotypic levels that we investigated, shaping neuroendocrine, physiological and behavioural traits. This may serve mothers to better prepare their offspring to cope with later environments where the same stressors are experienced.