bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bacterial contributions to delignification and lignocellulose degradation in forest soils with metagenomic and quantitative stable isotope probing
Authors: Wilhelm Roland C , Singh Rahul , Eltis Lindsay D , Mohn William W 
Published: September 2018

AbstractDelignification, or lignin-modification, facilitates the decomposition of lignocellulose in woody plant biomass. The extant diversity of lignin-degrading bacteria and fungi is underestimated by culture-dependent methods, limiting our understanding of the functional and ecological traits of decomposers populations. Here, we describe the use of stable isotope probing (SIP) coupled with amplicon and shotgun metagenomics to identify and characterize the functional attributes of lignin, cellulose and hemicellulose-degrading fungi and bacteria in coniferous forest soils from across North America. We tested the extent to which catabolic genes partitioned among different decomposer taxa; the relative roles of bacteria and fungi, and whether taxa or catabolic genes correlated with variation in lignocellulolytic activity, measured as the total assimilation of 13C-label into DNA and phospholipid fatty acids. We found high overall bacterial degradation of our model lignin substrate, particularly by gram-negative bacteria (Comamonadaceae and Caulobacteraceae), while fungi were more prominent in cellulose-degradation. Very few taxa incorporated 13C-label from more than one lignocellulosic polymer, suggesting specialization among decomposers. Collectively, members of Caulobacteraceae could degrade all three lignocellulosic polymers, providing new evidence for their importance in lignocellulose degradation. Variation in lignin-degrading activity was better explained by microbial community properties, such as catabolic gene content and community structure, than cellulose-degrading activity. SIP significantly improved shotgun metagenome assembly resulting in the recovery of several high-quality draft metagenome-assembled genomes and over 7500 contigs containing unique clusters of carbohydrate-active genes. These results improve understanding of which organisms, conditions and corresponding functional genes contribute to lignocellulose decomposition.
Neuroprotective efficacy of P7C3 compounds in primate hippocampus
Authors: Bauman Melissa D. , Schumann Cynthia M. , Carlson Erin L. , Taylor Sandra L. , Vázquez-Rosa Edwin , Cintrón-Pérez Coral J. , Shin Min-Kyoo , Williams Noelle S. , Pieper Andrew A. 
Published: September 2018

AbstractThere is a critical need for translating basic science discoveries into new therapeutics for patients suffering from difficult to treat neuropsychiatric and neurodegenerative conditions. Previously, a target-agnostic in vivo screen in mice identified P7C3 aminopropyl carbazole as capable of enhancing the net magnitude of postnatal neurogenesis by protecting young neurons from death. Subsequently, neuroprotective efficacy of P7C3 compounds in a broad spectrum of preclinical rodent models has also been observed. An important next step in translating this work to patients is to determine whether P7C3 compounds exhibit similar efficacy in primates. Adult male rhesus monkeys received daily oral P7C3-A20 or vehicle for 38 weeks. During weeks 2–11, monkeys received weekly injection of 5′-bromo-2-deoxyuridine (BrdU) to label newborn cells, the majority of which would normally die over the following 27 weeks. BrdU+ cells were quantified using unbiased stereology. Separately in mice, the proneurogenic efficacy of P7C3-A20 was compared to that of NSI-189, a proneurogenic drug currently in clinical trials for patients with major depression. Orally-administered P7C3-A20 provided sustained plasma exposure, was well-tolerated, and elevated the survival of hippocampal BrdU+ cells in nonhuman primates without adverse central or peripheral tissue effects. In mice, NSI-189 was shown to be pro-proliferative, and P7C3-A20 elevated the net magnitude of hippocampal neurogenesis to a greater degree than NSI-189 through its distinct mechanism of promoting neuronal survival. This pilot study provides evidence that P7C3-A20 safely protects neurons in nonhuman primates, suggesting that the neuroprotective efficacy of P7C3 compounds is likely to translate to humans as well.
The antipsychotic agent trifluoperazine hydrochloride suppresses triple-negative breast cancer tumor growth and brain metastasis by inducing G0/G1 arrest and apoptosis
Authors: Feng Zhanzhan , Xia Yong , Gao Tiantao , Xu Fuyan , Lei Qian , Peng Cuiting , Yang Yufei , Xue Qiang , Hu Xi , Wang Qianqian , Wang Ranran , Ran Zhiqiang , Zeng Zhilin , Yang Nan , Xie Zixin , Yu Luoting 
Published: September 2018

AbstractWomen with aggressive triple-negative breast cancer (TNBC) are at high risk of brain metastasis, which has no effective therapeutic option partially due to the poor penetration of drugs across the blood−brain barrier. Trifluoperazine (TFP) is an approved antipsychotic drug with good bioavailability in brain and had shown anticancer effect in several types of cancer. It drives us to investigate its activities to suppress TNBC, especially the brain metastasis. In this study, we chose three TNBC cell lines MDA-MB-468, MDA-MB-231, and 4T1 to assess its anticancer activities along with the possible mechanisms. In vitro, it induced G0/G1 cell cycle arrest via decreasing the expression of both cyclinD1/CDK4 and cyclinE/CDK2, and stimulated mitochondria-mediated apoptosis. In vivo, TFP suppressed the growth of subcutaneous xenograft tumor and brain metastasis without causing detectable side effects. Importantly, it prolonged the survival of mice bearing brain metastasis. Immunohistochemical analysis of Ki67 and cleaved caspase-3 indicated TFP could suppress the growth and induce apoptosis of cancer cells in vivo. Taken together, TFP might be a potential available drug for treating TNBC with brain metastasis, which urgently needs novel treatment options.
Dye-incorporated coordination polymers for direct photocatalytic trifluoromethylation of aromatics at metabolically susceptible positions
Authors: Zhang Tiexin , Guo Xiangyang , Shi Yusheng , He Cheng , Duan Chunying 
Published: September 2018

AbstractDirect trifluoromethylation of unactivated aromatic rings at metabolically susceptible positions is highly desirable in pharmaceutical applications. By incorporating thiophenes into the backbone of triphenylamine to enlarge its π-system, a new approach for constructing coordination polymers is reported for direct trifluoromethylation without prefunctionalization of the aryl precursors. The improved light-harvesting ability and well-modulated excited state redox potential of the designed polymers endow the generated CF3 radicals with suitable reactivity and enhance radical adduct oxidation in pores. The well-configurated interactions between the organic ligands distort the coordination geometry to create active interaction sites within the coordination polymer; thus, the substrates could be docked near the photoredox-active centres. The synergistic electronic and spatial effects in the confined pores balance the contradictory demands of electronic effects and reaction dynamics, achieving regio- and diastereoselective discrimination among reaction sites with unremarkable electronic/steric differences.
LOTUS domain protein MARF1 binds CCR4-NOT deadenylase complex to post-transcriptionally regulate gene expression in oocytes
Authors: Zhu Li , Kandasamy Suresh K. , Liao Susan E. , Fukunaga Ryuya 
Published: September 2018

AbstractPost-transcriptional regulation of gene expression plays an essential role during oocyte maturation. Here we report that Drosophila MARF1 (Meiosis Regulator And mRNA Stability Factor 1), which consists of one RNA-recognition motif and six tandem LOTUS domains with unknown molecular function, is essential for oocyte maturation. When tethered to a reporter mRNA, MARF1 post-transcriptionally silences reporter expression by shortening reporter mRNA poly-A tail length and thereby reducing reporter protein level. This activity is mediated by the MARF1 LOTUS domain, which binds the CCR4-NOT deadenylase complex. MARF1 binds cyclin A mRNA and shortens its poly-A tail to reduce Cyclin A protein level during oocyte maturation. This study identifies MARF1 as a regulator in oocyte maturation and defines the conserved LOTUS domain as a post-transcriptional effector domain that recruits CCR4-NOT deadenylase complex to shorten target mRNA poly-A tails and suppress their translation.
Correcting glucose-6-phosphate dehydrogenase deficiency with a small-molecule activator
Authors: Hwang Sunhee , Mruk Karen , Rahighi Simin , Raub Andrew G. , Chen Che-Hong , Dorn Lisa E. , Horikoshi Naoki , Wakatsuki Soichi , Chen James K. , Mochly-Rosen Daria 
Published: September 2018

AbstractGlucose-6-phosphate dehydrogenase (G6PD) deficiency, one of the most common human genetic enzymopathies, is caused by over 160 different point mutations and contributes to the severity of many acute and chronic diseases associated with oxidative stress, including hemolytic anemia and bilirubin-induced neurological damage particularly in newborns. As no medications are available to treat G6PD deficiency, here we seek to identify a small molecule that corrects it. Crystallographic study and mutagenesis analysis identify the structural and functional defect of one common mutant (Canton, R459L). Using high-throughput screening, we subsequently identify AG1, a small molecule that increases the activity of the wild-type, the Canton mutant and several other common G6PD mutants. AG1 reduces oxidative stress in cells and zebrafish. Furthermore, AG1 decreases chloroquine- or diamide-induced oxidative stress in human erythrocytes. Our study suggests that a pharmacological agent, of which AG1 may be a lead, will likely alleviate the challenges associated with G6PD deficiency.
Vibrational control of selective bond cleavage in dissociative chemisorption of methanol on Cu(111)
Authors: Chen Jialu , Zhou Xueyao , Zhang Yaolong , Jiang Bin 
Published: September 2018

AbstractControlling product branching ratios in a chemical reaction represents a desired but difficult achievement in chemistry. In this work, we demonstrate the first example of altering the branching ratios in a multichannel reaction, i.e., methanol dissociative chemisorption on Cu(111), via selectively exciting specific vibrational modes. To this end, we develop a globally accurate full-dimensional potential energy surface for the CH3OH/Cu(111) system and perform extensive vibrational state-selected molecular dynamics simulations. Our results show that O–H/C–H/C–O stretching vibrational excitations substantially enhance the respective bond scission processes, representing extraordinary bond selectivity. At a given total energy, the branching ratio of C–O/C–H dissociation can increase by as large as 100 times by exciting the C–O stretching mode which possesses an unprecedentedly strong vibrational efficacy on reactivity. This vibrational control can be realized by the well-designed experiment using a linearly polarized laser.
Computational design of chemogenetic and optogenetic split proteins
Authors: Dagliyan Onur , Krokhotin Andrey , Ozkan-Dagliyan Irem , Deiters Alexander , Der Channing J. , Hahn Klaus M. , Dokholyan Nikolay V. 
Published: September 2018

AbstractControlling protein activity with chemogenetics and optogenetics has proven to be powerful for testing hypotheses regarding protein function in rapid biological processes. Controlling proteins by splitting them and then rescuing their activity through inducible reassembly offers great potential to control diverse protein activities. Building split proteins has been difficult due to spontaneous assembly, difficulty in identifying appropriate split sites, and inefficient induction of effective reassembly. Here we present an automated approach to design effective split proteins regulated by a ligand or by light (SPELL). We develop a scoring function together with an engineered domain to enable reassembly of protein halves with high efficiency and with reduced spontaneous assembly. We demonstrate SPELL by applying it to proteins of various shapes and sizes in living cells. The SPELL server (spell.dokhlab.org) offers an automated prediction of split sites.
Chemogenetic generation of hydrogen peroxide in the heart induces severe cardiac dysfunction
Authors: Steinhorn Benjamin , Sorrentino Andrea , Badole Sachin , Bogdanova Yulia , Belousov Vsevolod , Michel Thomas 
Published: September 2018

AbstractOxidative stress plays an important role in the pathogenesis of many disease states. In the heart, reactive oxygen species are linked with cardiac ischemia/reperfusion injury, hypertrophy, and heart failure. While this correlation between ROS and cardiac pathology has been observed in multiple models of heart failure, the independent role of hydrogen peroxide (H2O2) in vitro and in vivo is unclear, owing to a lack of tools for precise manipulation of intracellular redox state. Here we apply a chemogenetic system based on a yeast D-amino acid oxidase to show that chronic generation of H2O2 in the heart induces a dilated cardiomyopathy with significant systolic dysfunction. We anticipate that chemogenetic approaches will enable future studies of in vivo H2O2 signaling not only in the heart, but also in the many other organ systems where the relationship between redox events and physiology remains unclear.
Tensorial neutron tomography of three-dimensional magnetic vector fields in bulk materials
Authors: Hilger A. , Manke I. , Kardjilov N. , Osenberg M. , Markötter H. , Banhart J. 
Published: September 2018

AbstractKnowing the distribution of a magnetic field in bulk materials is important for understanding basic phenomena and developing functional magnetic materials. Microscopic imaging techniques employing X-rays, light, electrons, or scanning probe methods have been used to quantify magnetic fields within planar thin magnetic films in 2D or magnetic vector fields within comparable thin volumes in 3D. Some years ago, neutron imaging has been demonstrated to be a unique tool to detect magnetic fields and magnetic domain structures within bulk materials. Here, we show how arbitrary magnetic vector fields within bulk materials can be visualized and quantified in 3D using a set of nine spin-polarized neutron imaging measurements and a novel tensorial multiplicative algebraic reconstruction technique (TMART). We first verify the method by measuring the known magnetic field of an electric coil and then investigate the unknown trapped magnetic flux within the type-I superconductor lead.
Spatio-temporal dynamics and aetiology of proliferative leg skin lesions in wild British finches
Authors: Lawson Becki , Robinson Robert A. , Fernandez Julia Rodriguez-Ramos , John Shinto K. , Benitez Laura , Tolf Conny , Risely Kate , Toms Mike P. , Cunningham Andrew A. , Williams Richard A. J. 
Published: September 2018

AbstractProliferative leg skin lesions have been described in wild finches in Europe although there have been no large-scale studies of their aetiology or epizootiology to date. Firstly, disease surveillance, utilising public reporting of observations of live wild finches was conducted in Great Britain (GB) and showed proliferative leg skin lesions in chaffinches (Fringilla coelebs) to be widespread. Seasonal variation was observed, with a peak during the winter months. Secondly, pathological investigations were performed on a sample of 39 chaffinches, four bullfinches (Pyrrhula pyrrhula), one greenfinch (Chloris chloris) and one goldfinch (Carduelis carduelis) with proliferative leg skin lesions and detected Cnemidocoptes sp. mites in 91% (41/45) of affected finches and from all species examined. Fringilla coelebs papillomavirus (FcPV1) PCR was positive in 74% (23/31) of birds tested: a 394 base pair sequence was derived from 20 of these birds, from all examined species, with 100% identity to reference genomes. Both mites and FcPV1 DNA were detected in 71% (20/28) of birds tested for both pathogens. Histopathological examination of lesions did not discriminate the relative importance of mite or FcPV1 infection as their cause. Development of techniques to localise FcPV1 within lesions is required to elucidate the pathological significance of FcPV1 DNA detection.
Simvastatin Protects Cardiomyocytes Against Endotoxin-induced Apoptosis and Up-regulates Survivin/NF-κB/p65 Expression
Authors: Nežić Lana , Škrbić Ranko , Amidžić Ljiljana , Gajanin Radoslav , Kuča Kamil , Jaćević Vesna 
Published: September 2018

AbstractThis study is aimed to investigate whether simvastatin induces cardiomyocytes survival signaling in endotoxin (lipopolysaccharide, LSP)-induced myocardial injury, and if so, further to determine a role of survivin in simvastatin-anti-apoptotic effect. Wistar rats were pretreated with simvastatin (10–40 mg/kg po) before a single non-lethal dose of LPS. In myocardial tissue, LPS induced structural disorganization of myofibrils with significant inflammatory infiltrate (cardiac damage score, CDS = 3.87 ± 0.51, p < 0.05), whereas simvastatin dose-dependently abolished structural changes induced by LPS (p < 0.01). Simvastatin in 20 mg/kg and 40 mg/kg pretreatment, dose dependently, attenuated myocardial apoptosis determined as apoptotic index (28.8 ± 4.5% and 18.9 ± 3.5, p < 0.05), decreased cleaved caspase-3 expression (32.1 ± 5.8%, p < 0.01), along with significant Bcl-xL expression in the simvastatin groups (p < 0.01). Interestingly, in the simvastatin groups were determined significantly increased expression of survivin (p < 0.01), but in negative correlation with cleaved caspase-3 and apoptotic indices (p < 0.01). Simvastatin has a cardioprotective effects against LPS induced apoptosis. The effect may be mediated by up-regulation of survivin via activation of NF-κB, which leads to reduced activation of caspase-3 and consequent apoptosis of cardiomyocytes in experimental sepsis.
Discovery of Novel Soluble Epoxide Hydrolase Inhibitors as Potent Vasodilators
Authors: Tripathi Neetika , Paliwal Sarvesh , Sharma Swapnil , Verma Kanika , Gururani Ritika , Tiwari Akanksha , Verma Amrita , Chauhan Monika , Singh Aarti , Kumar Dipak , Pant Aditya 
Published: September 2018

AbstractIn view of the role of sEH (soluble epoxide hydrolase) in hypertension, we have developed a rigorously validated pharmacophore model containing one HBA (Hydrogen Bond Acceptor), two HY (Hydrophobic) and one RA (Ring Aromatic) features. The model was used as a query to search the NCI (National Cancer Institute) and Maybridge database leading to retrieval of many compounds which were sorted on the basis of predicted activity, fit value and Lipinski’s violation. The selected compounds were docked into the active site of enzyme soluble epoxide hydrolase. Potential interactions were observed between the features of the identified hits and the amino acids present in the docking site. The three selected compounds were subjected to in vitro evaluation using enzyme- based assay and the isolated rat aortic model followed by cytotoxicity studies. The results demonstrate that the identified compounds are potent, safe and novel soluble epoxide hydrolase inhibitors.
Control of proline utilization by the Lrp-like regulator PutR in Caulobacter crescentus
Authors: Mouammine Annabelle , Eich Katharina , Frandi Antonio , Collier Justine 
Published: September 2018

AbstractCellular metabolism recently emerged as a central player modulating the bacterial cell cycle. The Alphaproteobacterium Caulobacter crescentus appears as one of the best models to study these connections, but its metabolism is still poorly characterized. Considering that it lives in oligotrophic environments, its capacity to use amino-acids is often critical for its growth. Here, we characterized the C. crescentus PutA bi-functional enzyme and showed that it is required for the utilization of proline as a carbon source. We also found that putA transcription and proline utilization by PutA are strictly dependent on the Lrp-like PutR activator. The activation of putA by PutR needs proline, which most likely acts as an effector molecule for PutR. Surprisingly, we also observed that an over-production of PutR leads to cell elongation in liquid medium containing proline, while it inhibits colony formation even in the absence of proline on solid medium. These cell division and growth defects were equally pronounced in a ΔputA mutant background, indicating that PutR can play other roles beyond the control of proline catabolism. Altogether, these findings suggest that PutR might connect central metabolism with cell cycle processes.
Reconstructing the evolutionary history of pandemic foot-and-mouth disease viruses: the impact of recombination within the emerging O/ME-SA/Ind-2001 lineage
Authors: Bachanek-Bankowska Katarzyna , Di Nardo Antonello , Wadsworth Jemma , Mioulet Valerie , Pezzoni Giulia , Grazioli Santina , Brocchi Emiliana , Kafle Sharmila Chapagain , Hettiarachchi Ranjani , Kumarawadu Pradeep Lakpriya , Eldaghayes Ibrahim M. , Dayhum Abdunaser S. , Meenowa Deodass , Sghaier Soufien , Madani Hafsa , Abouchoaib Nabil , Hoang Bui Huy , Vu Pham Phong , Dukpa Kinzang , Gurung Ratna Bahadur , Tenzin Sangay , Wernery Ulrich , Panthumart Alongkorn , Seeyo Kingkarn Boonsuya , Linchongsubongkoch Wilai , Relmy Anthony , Bakkali-Kassimi Labib , Scherbakov Alexei , King Donald P. , Knowles Nick J. 
Published: September 2018

AbstractFoot-and-mouth disease (FMD) is a highly contagious disease of livestock affecting animal production and trade throughout Asia and Africa. Understanding FMD virus (FMDV) global movements and evolution can help to reconstruct the disease spread between endemic regions and predict the risks of incursion into FMD-free countries. Global expansion of a single FMDV lineage is rare but can result in severe economic consequences. Using extensive sequence data we have reconstructed the global space-time transmission history of the O/ME-SA/Ind-2001 lineage (which normally circulates in the Indian sub-continent) providing evidence of at least 15 independent escapes during 2013–2017 that have led to outbreaks in North Africa, the Middle East, Southeast Asia, the Far East and the FMD-free islands of Mauritius. We demonstrated that sequence heterogeneity of this emerging FMDV lineage is accommodated within two co-evolving divergent sublineages and that recombination by exchange of capsid-coding sequences can impact upon the reconstructed evolutionary histories. Thus, we recommend that only sequences encoding the outer capsid proteins should be used for broad-scale phylogeographical reconstruction. These data emphasise the importance of the Indian subcontinent as a source of FMDV that can spread across large distances and illustrates the impact of FMDV genome recombination on FMDV molecular epidemiology.