bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crystal structure of Zika virus NS5 RNA-dependent RNA polymerase
Authors: Godoy Andre S. , Lima Gustavo M. A. , Oliveira Ketllyn I. Z. , Torres Naiara U. , Maluf Fernando V. , Guido Rafael V. C. , Oliva Glaucius 
Published: March 2017

AbstractThe current Zika virus (ZIKV) outbreak became a global health threat of complex epidemiology and devastating neurological impacts, therefore requiring urgent efforts towards the development of novel efficacious and safe antiviral drugs. Due to its central role in RNA viral replication, the non-structural protein 5 (NS5) RNA-dependent RNA-polymerase (RdRp) is a prime target for drug discovery. Here we describe the crystal structure of the recombinant ZIKV NS5 RdRp domain at 1.9 Å resolution as a platform for structure-based drug design strategy. The overall structure is similar to other flaviviral homologues. However, the priming loop target site, which is suitable for non-nucleoside polymerase inhibitor design, shows significant differences in comparison with the dengue virus structures, including a tighter pocket and a modified local charge distribution.
The soybean GmSNAP18 gene underlies two types of resistance to soybean cyst nematode
Authors: Liu Shiming , Kandoth Pramod K. , Lakhssassi Naoufal , Kang Jingwen , Colantonio Vincent , Heinz Robert , Yeckel Greg , Zhou Zhou , Bekal Sadia , Dapprich Johannes , Rotter Bjorn , Cianzio Silvia , Mitchum Melissa G. , Meksem Khalid 
Published: March 2017

AbstractTwo types of resistant soybean (Glycine max(L.) Merr.) sources are widely used against soybean cyst nematode (SCN,Heterodera glycinesIchinohe). These include Peking-type soybean, whose resistance requires both therhg1-aandRhg4alleles, and PI 88788-type soybean, whose resistance requires only therhg1-ballele. Multiple copy number of PI 88788-typeGmSNAP18,GmAAT, andGmWI12in one genomic segment simultaneously contribute torhg1-bresistance. Using an integrated set of genetic and genomic approaches, we demonstrate that therhg1-aPeking-typeGmSNAP18is sufficient for resistance to SCN in combination withRhg4. The two SNAPs (soluble NSF attachment proteins) differ by only five amino acids. Our findings suggest that Peking-typeGmSNAP18is performing a different role in SCN resistance than PI 88788-typeGmSNAP18. As such, this is an example of a pathogen resistance gene that has evolved to underlie two types of resistance, yet ensure the same function within a single plant species.
Direct amidation of esters with nitroarenes
Authors: Cheung Chi Wai , Ploeger Marten Leendert , Hu Xile 
Published: March 2017

AbstractEsters are one of the most common functional groups in natural and synthetic products, and the one-step conversion of the ester group into other functional groups is an attractive strategy in organic synthesis. Direct amidation of esters is particularly appealing due to the omnipresence of the amide moiety in biomolecules, fine chemicals, and drug candidates. However, efficient methods for direct amidation of unactivated esters are still lacking. Here we report nickel-catalysed reductive coupling of unactivated esters with nitroarenes to furnish in one step a wide range of amides bearing functional groups relevant to the development of drugs and agrochemicals. The method has been used to expedite the syntheses of bio-active molecules and natural products, as well as their post-synthetic modifications. Preliminary mechanistic study indicates a reaction pathway distinct from conventional amidation methods using anilines as nitrogen sources. The work provides a novel and efficient method for amide synthesis.
A coupled human-Earth model perspective on long-term trends in the global marine fishery
Authors: Galbraith E. D. , Carozza D. A. , Bianchi D. 
Published: March 2017

AbstractThe global wild marine fish harvest increased fourfold between 1950 and a peak value near the end of the 20th century, reflecting interactions between anthropogenic and ecological forces. Here, we examine these interactions in a bio-energetically constrained, spatially and temporally resolved model of global fisheries. We conduct historical hindcasts with the model, which suggest that technological progress can explain most of the 20th century increase of fish harvest. In contrast, projections extending this rate of technological progress into the future under open access suggest a long-term decrease in harvest due to over-fishing. Climate change is predicted to gradually decrease the global fish production capacity, though our model suggests that this is of secondary importance to social and economic factors. Our study represents a novel way to integrate human-ecological interactions within a single model framework for long-term simulations.
Domain-dependent effects of insulin and IGF-1 receptors on signalling and gene expression
Authors: Cai Weikang , Sakaguchi Masaji , Kleinridders Andre , Gonzalez-Del Pino Gonzalo , Dreyfuss Jonathan M. , O’Neill Brian T. , Ramirez Alfred K. , Pan Hui , Winnay Jonathon N. , Boucher Jeremie , Eck Michael J. , Kahn C. Ronald 
Published: March 2017

AbstractDespite a high degree of homology, insulin receptor (IR) and IGF-1 receptor (IGF1R) mediate distinct cellular and physiological functions. Here, we demonstrate how domain differences between IR and IGF1R contribute to the distinct functions of these receptors using chimeric and site-mutated receptors. Receptors with the intracellular domain of IGF1R show increased activation of Shc and Gab-1 and more potent regulation of genes involved in proliferation, corresponding to their higher mitogenic activity. Conversely, receptors with the intracellular domain of IR display higher IRS-1 phosphorylation, stronger regulation of genes in metabolic pathways and more dramatic glycolytic responses to hormonal stimulation. Strikingly, replacement of leucine973 in the juxtamembrane region of IR to phenylalanine, which is present in IGF1R, mimics many of these signalling and gene expression responses. Overall, we show that the distinct activities of the closely related IR and IGF1R are mediated by their intracellular juxtamembrane region and substrate binding to this region.
Rotiferan Hox genes give new insights into the evolution of metazoan bodyplans
Authors: Fröbius Andreas C. , Funch Peter 
Published: March 2017

AbstractThe phylum Rotifera consists of minuscule, nonsegmented animals with a unique body plan and an unresolved phylogenetic position. The presence of pharyngeal articulated jaws supports an inclusion in Gnathifera nested in the Spiralia. Comparison of Hox genes, involved in animal body plan patterning, can be used to infer phylogenetic relationships. Here, we report the expression of five Hox genes during embryogenesis of the rotifer Brachionus manjavacas and show how these genes define different functional components of the nervous system and not the usual bilaterian staggered expression along the anteroposterior axis. Sequence analysis revealed that the lox5-parapeptide, a key signature in lophotrochozoan and platyhelminthean Hox6/lox5 genes, is absent and replaced by different signatures in Rotifera and Chaetognatha, and that the MedPost gene, until now unique to Chaetognatha, is also present in rotifers. Collectively, our results support an inclusion of chaetognaths in gnathiferans and Gnathifera as sister group to the remaining spiralians.
Vitamin D ointment for prevention of radiation dermatitis in breast cancer patients
Authors: Nasser Nicola J. , Fenig Shlomit , Ravid Amiram , Nouriel Ariella , Ozery Naama , Gardyn Sara , Koren Ruth , Fenig Eyal 
Published: March 2017

AbstractRadiation dermatitis occurs frequently during adjuvant radiation therapy for breast cancer. Prevention of radiation dermatitis by applying various creams and ointments has a limited success, and Aqua cream which has urea as one of its active ingredients is used in many institutions as a preventive treatment. The primary goal of this study is to assess the effect of vitamin D (calcipotriol) ointment in prevention of radiodermatitis in breast cancer patients compared to Aqua cream. Twenty-three women with localized breast cancer who underwent breast-conserving surgery and opted to receive adjuvant radiotherapy to breast only were enrolled in this study. A cream containing an active vitamin D analog, calcipotriol (Daivonex), was randomly applied either to the medial or to the lateral half of the irradiated breast, while Aqua cream was applied to the complimentary half of the same breast along the whole treatment days, each day, after the delivery of radiation. Skin reaction was recorded and compared between the two halves of the breast. Vitamin D was well tolerated by patients with no local or systemic allergic reactions. Radiation dermatitis was not significantly different between both treatment arms. Topical vitamin D ointment is not superior to Aqua cream for prevention of radiation-induced dermatitis in women treated with adjuvant radiation for breast cancer.
Early-onset parkinsonism in a pedigree with phosphoglycerate kinase deficiency and a heterozygous carrier: do PGK-1 mutations contribute to vulnerability to parkinsonism?
Authors: Sakaue Satoshi , Kasai Takashi , Mizuta Ikuko , Suematsu Masaya , Osone Shinya , Azuma Yumiko , Imamura Toshihiko , Tokuda Takahiko , Kanno Hitoshi , El-Agnaf Omar M. A. , Morimoto Masafumi , Nakagawa Masanori , Hosoi Hajime , Mizuno Toshiki 
Published: March 2017

AbstractPhosphoglycerate kinase 1 (PGK-1) is a glycolytic enzyme encoded by PGK-1, which maps to the X chromosome. PGK-1 deficiency causes X-linked recessive hereditary chronic hemolytic anemia, myopathy, and neurological disorders due to insufficient ATP regeneration. Early-onset parkinsonism has occasionally been reported as a neurological complication of this condition. However, heterozygous carriers of PGK-1 deficiency were thought to be neurologically asymptomatic. Here, we report a boy with PGK-1 deficiency and his mother, a carrier of a heterozygous mutation in PGK-1, both of whom presented with early-onset parkinsonism. The boy developed parkinsonism at 9 years of age. His parkinsonism partially responded to levodopa treatment. 123l-metaiodobenzylguanidine (MIBG) uptake was normal. His mother, who exhibited normal PGK-1 activity in erythrocytes, developed parkinsonism at 36 years of age. Her symptoms were undistinguishable from those of Parkinson’s disease (PD), despite her normal uptake of MIBG. Neither a point mutation in nor multiplication of SNCA was found. Additionally, hotspots of LRRK2 and GBA were not mutated. To our knowledge, this report provides the first description of parkinsonism in a carrier of PGK-1 deficiency. Interestingly, PGK-1 is located within the confirmed susceptibility locus for PD known as PARK12. These observations suggest that PGK-1 mutations confer susceptibility to PD.
Enablers and determinants of the provision of written action plans to patients with asthma: a stratified survey of Canadian physicians
Authors: Djandji Fabienne , Lamontagne Alexandrine J. , Blais Lucie , Bacon Simon L. , Ernst Pierre , Grad Roland , Lavoie Kim L. , McKinney Martha L. , Desplats Eve , Ducharme Francine M. 
Published: March 2017

AbstractDespite national recommendations, most patients with asthma are not given a written action plan . The objectives were to ascertain physicians’ endorsement of potential enablers to providing a written action plan, and the determinants and proportion, of physician-reported use of a written action plan. We surveyed 838 family physicians, paediatricians, and emergency physicians in Quebec. The mailed questionnaire comprised 102 questions on asthma management, 11 of which pertained to written action plan and promising enablers. Physicians also selected a case vignette that best corresponded to their practice and reported their management. The survey was completed by 421 (56%) physicians (250 family physicians, 115 paediatricians and 56 emergency physicians); 43 (5.2%) reported providing a written action plan to ≥70% of their asthmatic patients and 126 (30%) would have used a written action plan in the selected vignette. Most (>60%) physicians highly endorsed the following enablers: patients requesting a written action plan, adding a blank written action plan to the chart, receiving a copy of the written action plan completed by a consultant, receiving a monetary compensation for its completion, and having another healthcare professional explain the completed written action plan to patients. Four determinants were significantly associated with providing a written action plan: being a paediatrician (RR:2.1), treating a child (RR:2.0), aiming for long-term asthma control (RR:2.5), and being aware of national recommendations to provide a written action plan to asthmatic patients (RR:2.9). A small minority of Quebec physicians reported providing a written action plan to most of their patients, revealing a huge care gap. Several enablers to improve uptake, highly endorsed by physicians, should be prioritised in future implementation efforts.
Helping children with reading difficulties: some things we have learned so far
Authors: McArthur Genevieve , Castles Anne 
Published: March 2017

AbstractA substantial proportion of children struggle to learn to read. This not only impairs their academic achievement, but increases their risk of social, emotional, and mental health problems. In order to help these children, reading scientists have worked hard for over a century to better understand the nature of reading difficulties and the people who have them. The aim of this perspective is to outline some of the things that we have learned so far, and to provide a framework for considering the causes of reading difficulties and the most effective ways to treat them.
SNPs in bone-related miRNAs are associated with the osteoporotic phenotype
Authors: De-Ugarte Laura , Caro-Molina Enrique , Rodríguez-Sanz Maria , García-Pérez Miguel Angel , Olmos José M. , Sosa-Henríquez Manuel , Pérez-Cano Ramón , Gómez-Alonso Carlos , Del Rio Luis , Mateo-Agudo Jesús , Blázquez-Cabrera José Antonio , González-Macías Jesús , Pino-Montes Javier del , Muñoz-Torres Manuel , Diaz-Curiel Manuel , Malouf Jorge , Cano Antonio , Pérez-Castrillon José Luis , Nogues Xavier , Garcia-Giralt Natalia , Diez-Perez Adolfo 
Published: March 2017

AbstractBiogenesis and function of microRNAs can be influenced by genetic variants in the pri-miRNA sequences leading to phenotypic variability. This study aims to identify single nucleotide polymorphisms (SNPs) affecting the expression levels of bone-related mature microRNAs and thus, triggering an osteoporotic phenotype. An association analysis of SNPs located in pri-miRNA sequences with bone mineral density (BMD) was performed in the OSTEOMED2 cohort (n = 2183). Functional studies were performed for assessing the role of BMD-associated miRNAs in bone cells. Two SNPs, rs6430498 in the miR-3679 and rs12512664 in the miR-4274, were significantly associated with femoral neck BMD. Further, we measured these BMD-associated microRNAs in trabecular bone from osteoporotic hip fractures comparing to non-osteoporotic bone by qPCR. Both microRNAs were found overexpressed in fractured bone. Increased matrix mineralization was observed after miR-3679-3p inhibition in human osteoblastic cells. Finally, genotypes of rs6430498 and rs12512664 were correlated with expression levels of miR-3679 and miR-4274, respectively, in osteoblasts. In both cases, the allele that generated higher microRNA expression levels was associated with lower BMD values. In conclusion, two osteoblast-expressed microRNAs, miR-3679 and miR-4274, were associated with BMD; their overexpression could contribute to the osteoporotic phenotype. These findings open new areas for the study of bone disorders.
A Convenient Cas9-based Conditional Knockout Strategy for Simultaneously Targeting Multiple Genes in Mouse
Authors: Chen Jiang , Du Yinan , He Xueyan , Huang Xingxu , Shi Yun S. 
Published: March 2017

AbstractThe most powerful way to probe protein function is to characterize the consequence of its deletion. Compared to conventional gene knockout (KO), conditional knockout (cKO) provides an advanced gene targeting strategy with which gene deletion can be performed in a spatially and temporally restricted manner. However, for most species that are amphiploid, the widely used Cre-flox conditional KO (cKO) system would need targeting loci in both alleles to be loxP flanked, which in practice, requires time and labor consuming breeding. This is considerably significant when one is dealing with multiple genes. CRISPR/Cas9 genome modulation system is advantaged in its capability in targeting multiple sites simultaneously. Here we propose a strategy that could achieve conditional KO of multiple genes in mouse with Cre recombinase dependent Cas9 expression. By transgenic construction of loxP-stop-loxP (LSL) controlled Cas9 (LSL-Cas9) together with sgRNAs targeting EGFP, we showed that the fluorescence molecule could be eliminated in a Cre-dependent manner. We further verified the efficacy of this novel strategy to target multiple sites by deleting c-Maf and MafB simultaneously in macrophages specifically. Compared to the traditional Cre-flox cKO strategy, this sgRNAs-LSL-Cas9 cKO system is simpler and faster, and would make conditional manipulation of multiple genes feasible.
A dataset of stereoscopic images and ground-truth disparity mimicking human fixations in peripersonal space
Authors: Canessa Andrea , Gibaldi Agostino , Chessa Manuela , Fato Marco , Solari Fabio , Sabatini Silvio P. 
Published: March 2017

AbstractBinocular stereopsis is the ability of a visual system, belonging to a live being or a machine, to interpret the different visual information deriving from two eyes/cameras for depth perception. From this perspective, the ground-truth information about three-dimensional visual space, which is hardly available, is an ideal tool both for evaluating human performance and for benchmarking machine vision algorithms. In the present work, we implemented a rendering methodology in which the camera pose mimics realistic eye pose for a fixating observer, thus including convergent eye geometry and cyclotorsion. The virtual environment we developed relies on highly accurate 3D virtual models, and its full controllability allows us to obtain the stereoscopic pairs together with the ground-truth depth and camera pose information. We thus created a stereoscopic dataset: GENUA PESTO—GENoa hUman Active fixation database: PEripersonal space STereoscopic images and grOund truth disparity. The dataset aims to provide a unified framework useful for a number of problems relevant to human and computer vision, from scene exploration and eye movement studies to 3D scene reconstruction.
The KIF1A homolog Unc-104 is important for spontaneous release, postsynaptic density maturation and perisynaptic scaffold organization
Authors: Zhang Yao V. , Hannan Shabab B. , Kern Jeannine V. , Stanchev Doychin T. , Koç Baran , Jahn Thomas R. , Rasse Tobias M. 
Published: March 2017

AbstractThe kinesin-3 family member KIF1A has been shown to be important for experience dependent neuroplasticity. In Drosophila, amorphic mutations in the KIF1A homolog unc-104 disrupt the formation of mature boutons. Disease associated KIF1A mutations have been associated with motor and sensory dysfunctions as well as non-syndromic intellectual disability in humans. A hypomorphic mutation in the forkhead-associated domain of Unc-104, unc-104bris, impairs active zone maturation resulting in an increased fraction of post-synaptic glutamate receptor fields that lack the active zone scaffolding protein Bruchpilot. Here, we show that the unc-104brismutation causes defects in synaptic transmission as manifested by reduced amplitude of both evoked and miniature excitatory junctional potentials. Structural defects observed in the postsynaptic compartment of mutant NMJs include reduced glutamate receptor field size, and altered glutamate receptor composition. In addition, we observed marked loss of postsynaptic scaffolding proteins and reduced complexity of the sub-synaptic reticulum, which could be rescued by pre- but not postsynaptic expression of unc-104. Our results highlight the importance of kinesin-3 based axonal transport in synaptic transmission and provide novel insights into the role of Unc-104 in synapse maturation.
Mevalonate Cascade Inhibition by Simvastatin Induces the Intrinsic Apoptosis Pathway via Depletion of Isoprenoids in Tumor Cells
Authors: Alizadeh Javad , Zeki Amir A. , Mirzaei Nima , Tewary Sandipan , Rezaei Moghadam Adel , Glogowska Aleksandra , Nagakannan Pandian , Eftekharpour Eftekhar , Wiechec Emilia , Gordon Joseph W. , Xu Fred. Y. , Field Jared T. , Yoneda Ken Y. , Kenyon Nicholas J. , Hashemi Mohammad , Hatch Grant M. , Hombach-Klonisch Sabine , Klonisch Thomas , Ghavami Saeid 
Published: March 2017

AbstractThe mevalonate (MEV) cascade is responsible for cholesterol biosynthesis and the formation of the intermediate metabolites geranylgeranylpyrophosphate (GGPP) and farnesylpyrophosphate (FPP) used in the prenylation of proteins. Here we show that the MEV cascade inhibitor simvastatin induced significant cell death in a wide range of human tumor cell lines, including glioblastoma, astrocytoma, neuroblastoma, lung adenocarcinoma, and breast cancer. Simvastatin induced apoptotic cell death via the intrinsic apoptotic pathway. In all cancer cell types tested, simvastatin-induced cell death was not rescued by cholesterol, but was dependent on GGPP- and FPP-depletion. We confirmed that simvastatin caused the translocation of the small Rho GTPases RhoA, Cdc42, and Rac1/2/3 from cell membranes to the cytosol in U251 (glioblastoma), A549 (lung adenocarcinoma) and MDA-MB-231(breast cancer). Simvastatin-induced Rho-GTP loading significantly increased in U251 cells which were reversed with MEV, FPP, GGPP. In contrast, simvastatin did not change Rho-GTP loading in A549 and MDA-MB-231. Inhibition of geranylgeranyltransferase I by GGTi-298, but not farnesyltransferase by FTi-277, induced significant cell death in U251, A549, and MDA-MB-231. These results indicate that MEV cascade inhibition by simvastatin induced the intrinsic apoptosis pathway via inhibition of Rho family prenylation and depletion of GGPP, in a variety of different human cancer cell lines.
The giant deep-sea octopus Haliphron atlanticus forages on gelatinous fauna
Authors: Hoving H.J.T. , Haddock S.H.D. 
Published: March 2017

AbstractFeeding strategies and predator-prey interactions of many deep-sea pelagic organisms are still unknown. This is also true for pelagic cephalopods, some of which are very abundant in oceanic ecosystems and which are known for their elaborate behaviors and central role in many foodwebs. We report on the first observations of the giant deep-sea octopus Haliphron atlanticus with prey. Using remotely operated vehicles, we saw these giant octopods holding medusae in their arms. One of the medusae could be identified as Phacellophora camtschatica (the egg-yolk jelly). Stomach content analysis confirmed predation on cnidarians and gelatinous organisms. The relationship between medusae and H. atlanticus is discussed, also in comparison with other species of the Argonautoidea, all of which have close relationships with gelatinous zooplankton.