bluuebunny/crossref_metadata_2025_split huggingface dataset:
High‐Energy Surf Zone Currents and Headland Rips at a Geologically Constrained Mesotidal Beach
Authors: Mouragues Arthur , Bonneton Philippe , Castelle Bruno , Marieu Vincent , Jak McCarroll R. , Rodriguez‐Padilla Isaac , Scott Tim , Sous Damien 
Published: October 2020

AbstractWe analyze Eulerian and Lagrangian measurements of wave‐induced circulation collected during a 3‐week field experiment at a high‐energy mesotidal barred beach with the presence of a 500‐m headland and a submerged reef. Small changes in wave and tide conditions were found to largely impact circulation patterns. Three main regimes were identified depending on offshore wave obliquity: (1) Under shore‐normal configuration, the flow was dominated by cross‐shore motions, except for moderate waves at low tide, with the presence of a quasi‐steady circulation cell on the reef. (2) Under shadowed configuration, an onshore‐directed current flowing away from the headland and a weak oscillating eddy were present outside and inside the shadow region, respectively. (3) Under deflection configuration, a deflection rip flowing against the headland and extending well beyond the surf zone was present, with activity maximized around low tide for moderate waves. Under 4‐m oblique waves, the deflection rip was active regardless of the tide with mean depth‐averaged velocities up to 0.7 m/s 800‐m offshore in 12‐m depth, with energetic low‐frequency fluctuations. Our results emphasize the ability of deflection rips to transport materials far offshore, suggesting that such rips can transport sediment beyond the depth of closure. This study indicates that a wide variety of wave‐driven circulation patterns can occur and sometimes coexist on beaches with prominent geological settings. Changes in the dominant driving mechanism can occur as a result of small changes in wave and tide conditions, resulting in more spatially and temporally variable circulation than along open sandy beaches.
A Survival Analysis of the Gulf Stream Warm Core Rings
Authors: Silva E. Nishchitha S. , Gangopadhyay Avijit , Fay Gavin , Welandawe Manushi K. V. , Gawarkiewicz Glen , Silver Adrienne M. , Monim Mahmud , Clark Jenifer 
Published: October 2020

AbstractSurvival of Gulf Stream (GS) warm core rings (WCRs) was investigated using a census consisting of a total of 961 rings formed during the period 1980–2017. Kaplan‐Meier survival probability and Cox hazard proportional models were used for the analysis. The survival analysis was performed for rings formed in four 5° zones between 75° W and 55° W. The radius, latitude, and distance from the shelf‐break of a WCR at formation all had a significant effect on the survival of WCRs. A pattern of higher survival was observed in WCRs formed in Zone 2 (70°–65° W) or Zone 3 (65°–60° W) and then demised in Zone 1 (75°–70° W). Survival probability of the WCRs increased to more than 70% for those formed within a latitude band from 39.5° to 41.5° N. Survival probability is reduced when the WCRs are formed near the New England Seamounts.
Genome-wide association study reveals new insights into the heritability and genetic correlates of developmental dyslexia
Authors: Gialluisi Alessandro , Andlauer Till F. M. , Mirza-Schreiber Nazanin , Moll Kristina , Becker Jessica , Hoffmann Per , Ludwig Kerstin U. , Czamara Darina , Pourcain Beate St , Honbolygó Ferenc , Tóth Dénes , Csépe Valéria , Huguet Guillaume , Chaix Yves , Iannuzzi Stephanie , Demonet Jean-Francois , Morris Andrew P. , Hulslander Jacqueline , Willcutt Erik G. , DeFries John C. , Olson Richard K. , Smith Shelley D. , Pennington Bruce F. , Vaessen Anniek , Maurer Urs , Lyytinen Heikki , Peyrard-Janvid Myriam , Leppänen Paavo H. T. , Brandeis Daniel , Bonte Milene , Stein John F. , Talcott Joel B. , Fauchereau Fabien , Wilcke Arndt , Kirsten Holger , Müller Bent , Francks Clyde , Bourgeron Thomas , Monaco Anthony P. , Ramus Franck , Landerl Karin , Kere Juha , Scerri Thomas S. , Paracchini Silvia , Fisher Simon E. , Schumacher Johannes , Nöthen Markus M. , Müller-Myhsok Bertram , Schulte-Körne Gerd 
Published: October 2020

AbstractDevelopmental dyslexia (DD) is a learning disorder affecting the ability to read, with a heritability of 40–60%. A notable part of this heritability remains unexplained, and large genetic studies are warranted to identify new susceptibility genes and clarify the genetic bases of dyslexia. We carried out a genome-wide association study (GWAS) on 2274 dyslexia cases and 6272 controls, testing associations at the single variant, gene, and pathway level, and estimating heritability using single-nucleotide polymorphism (SNP) data. We also calculated polygenic scores (PGSs) based on large-scale GWAS data for different neuropsychiatric disorders and cortical brain measures, educational attainment, and fluid intelligence, testing them for association with dyslexia status in our sample. We observed statistically significant (p  < 2.8 × 10−6) enrichment of associations at the gene level, forLOC388780(20p13; uncharacterized gene), and forVEPH1(3q25), a gene implicated in brain development. We estimated an SNP-based heritability of 20–25% for DD, and observed significant associations of dyslexia risk with PGSs for attention deficit hyperactivity disorder (atpT = 0.05 in the training GWAS: OR = 1.23[1.16; 1.30] per standard deviation increase;p  = 8 × 10−13), bipolar disorder (1.53[1.44; 1.63];p = 1 × 10−43), schizophrenia (1.36[1.28; 1.45];p = 4 × 10−22), psychiatric cross-disorder susceptibility (1.23[1.16; 1.30];p = 3 × 10−12), cortical thickness of the transverse temporal gyrus (0.90[0.86; 0.96];p = 5 × 10−4), educational attainment (0.86[0.82; 0.91];p = 2 × 10−7), and intelligence (0.72[0.68; 0.76];p = 9 × 10−29). This study suggests an important contribution of common genetic variants to dyslexia risk, and novel genomic overlaps with psychiatric conditions like bipolar disorder, schizophrenia, and cross-disorder susceptibility. Moreover, it revealed the presence of shared genetic foundations with a neural correlate previously implicated in dyslexia by neuroimaging evidence.
Genetic alterations of SUGP1 mimic mutant-SF3B1 splice pattern in lung adenocarcinoma and other cancers
Authors: Alsafadi Samar , Dayot Stephane , Tarin Malcy , Houy Alexandre , Bellanger Dorine , Cornella Michele , Wassef Michel , Waterfall Joshua J. , Lehnert Erik , Roman-Roman Sergio , Stern Marc-Henri , Popova Tatiana 
Published: October 2020

AbstractGenes involved in 3′-splice site recognition during mRNA splicing constitute an emerging class of oncogenes. SF3B1 is the most frequently mutated splicing factor in cancer, and SF3B1 mutants corrupt branchpoint recognition leading to usage of cryptic 3′-splice sites and subsequent aberrant junctions. For a comprehensive determination of alterations leading to this splicing pattern, we performed a pan-TCGA screening for SF3B1-specific aberrant acceptor usage. While the most of aberrant 3′-splice patterns were explained by SF3B1 mutations, we also detected nine SF3B1 wild-type tumors (including five lung adenocarcinomas). Genomic profile analysis of these tumors identified somatic mutations combined with loss-of-heterozygosity in the splicing factor SUGP1 in five of these cases. Modeling of SUGP1 loss and mutations in cell lines showed that both alterations induced mutant-SF3B1-like aberrant splicing. Our study provides definitive evidence that genetic alterations of SUGP1 genocopy SF3B1 mutations in lung adenocarcinoma and other cancers.
An enhanced genetic model of relapsed IGH-translocated multiple myeloma evolutionary dynamics
Authors: Hoang Phuc H. , Cornish Alex J. , Sherborne Amy L. , Chubb Daniel , Kimber Scott , Jackson Graham , Morgan Gareth J. , Cook Gordon , Kinnersley Ben , Kaiser Martin , Houlston Richard S. 
Published: October 2020

AbstractMost patients with multiple myeloma (MM) die from progressive disease after relapse. To advance our understanding of MM evolution mechanisms, we performed whole-genome sequencing of 80IGH-translocated tumour-normal newly diagnosed pairs and 24 matched relapsed tumours from the Myeloma XI trial. We identify multiple events as potentially important for survival and therapy-resistance at relapse including driver point mutations (e.g.,TET2), translocations (MAP3K14), lengthened telomeres, and increased genomic instability (e.g., 17p deletions). Despite heterogeneous mutational processes contributing to relapsed mutations across MM subtypes, increased AID/APOBEC activity is particularly associated with shorter progression time to relapse, and contributes to higher mutational burden at relapse. In addition, we identify three enhanced major clonal evolution patterns of MM relapse, independent of treatment strategies and molecular karyotypes, questioning the viability of “evolutionary herding” approach in treating drug-resistant MM. Our data show that MM relapse is associated with acquisition of new mutations and clonal selection, and suggest APOBEC enzymes among potential targets for therapy-resistant MM.
Whole genome sequence analysis of pulmonary function and COPD in 19,996 multi-ethnic participants
Authors: Zhao Xutong , Qiao Dandi , Yang Chaojie , Kasela Silva , Kim Wonji , Ma Yanlin , Shrine Nick , Batini Chiara , Sofer Tamar , Taliun Sarah A. Gagliano , Sakornsakolpat Phuwanat , Balte Pallavi P. , Prokopenko Dmitry , Yu Bing , Lange Leslie A. , Dupuis Josée , Cade Brian E. , Lee Jiwon , Gharib Sina A. , Daya Michelle , Laurie Cecelia A. , Ruczinski Ingo , Cupples L. Adrienne , Loehr Laura R. , Bartz Traci M. , Morrison Alanna C. , Psaty Bruce M. , Vasan Ramachandran S. , Wilson James G. , Taylor Kent D. , Durda Peter , Johnson W. Craig , Cornell Elaine , Guo Xiuqing , Liu Yongmei , Tracy Russell P. , Ardlie Kristin G. , Aguet François , VanDenBerg David J. , Papanicolaou George J. , Rotter Jerome I. , Barnes Kathleen C. , Jain Deepti , Nickerson Deborah A. , Muzny Donna M. , Metcalf Ginger A. , Doddapaneni Harshavardhan , Dugan-Perez Shannon , Gupta Namrata , Gabriel Stacey , Rich Stephen S. , O’Connor George T. , Redline Susan , Reed Robert M. , Laurie Cathy C. , Daviglus Martha L. , Preudhomme Liana K. , Burkart Kristin M. , Kaplan Robert C. , Wain Louise V. , Tobin Martin D. , London Stephanie J. , Lappalainen Tuuli , Oelsner Elizabeth C. , Abecasis Goncalo R. , Silverman Edwin K. , Barr R. Graham ,   NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium,   TOPMed Lung Working Group, Cho Michael H. , Manichaikul Ani 
Published: October 2020

AbstractChronic obstructive pulmonary disease (COPD), diagnosed by reduced lung function, is a leading cause of morbidity and mortality. We performed whole genome sequence (WGS) analysis of lung function and COPD in a multi-ethnic sample of 11,497 participants from population- and family-based studies, and 8499 individuals from COPD-enriched studies in the NHLBI Trans-Omics for Precision Medicine (TOPMed) Program. We identify at genome-wide significance 10 known GWAS loci and 22 distinct, previously unreported loci, including two common variant signals from stratified analysis of African Americans. Four novel common variants within the regions of PIAS1, RGN (two variants) and FTO show evidence of replication in the UK Biobank (European ancestry n ~ 320,000), while colocalization analyses leveraging multi-omic data from GTEx and TOPMed identify potential molecular mechanisms underlying four of the 22 novel loci. Our study demonstrates the value of performing WGS analyses and multi-omic follow-up in cohorts of diverse ancestry.
Immunodominant proteins P1 and P40/P90 from human pathogen Mycoplasma pneumoniae
Authors: Vizarraga David , Kawamoto Akihiro , Matsumoto U. , Illanes Ramiro , Pérez-Luque Rosa , Martín Jesús , Mazzolini Rocco , Bierge Paula , Pich Oscar Q. , Espasa Mateu , Sanfeliu Isabel , Esperalba Juliana , Fernández-Huerta Miguel , Scheffer Margot P. , Pinyol Jaume , Frangakis Achilleas S. , Lluch-Senar Maria , Mori Shigetarou , Shibayama Keigo , Kenri Tsuyoshi , Kato Takayuki , Namba Keiichi , Fita Ignacio , Miyata Makoto , Aparicio David 
Published: October 2020

AbstractMycoplasma pneumoniae is a bacterial human pathogen that causes primary atypical pneumonia. M. pneumoniae motility and infectivity are mediated by the immunodominant proteins P1 and P40/P90, which form a transmembrane adhesion complex. Here we report the structure of P1, determined by X-ray crystallography and cryo-electron microscopy, and the X-ray structure of P40/P90. Contrary to what had been suggested, the binding site for sialic acid was found in P40/P90 and not in P1. Genetic and clinical variability concentrates on the N-terminal domain surfaces of P1 and P40/P90. Polyclonal antibodies generated against the mostly conserved C-terminal domain of P1 inhibited adhesion of M. pneumoniae, and serology assays with sera from infected patients were positive when tested against this C-terminal domain. P40/P90 also showed strong reactivity against human infected sera. The architectural elements determined for P1 and P40/P90 open new possibilities in vaccine development against M. pneumoniae infections.
Analysis of translating mitoribosome reveals functional characteristics of translation in mitochondria of fungi
Authors: Itoh Yuzuru , Naschberger Andreas , Mortezaei Narges , Herrmann Johannes M. , Amunts Alexey 
Published: October 2020

AbstractMitoribosomes are specialized protein synthesis machineries in mitochondria. However, how mRNA binds to its dedicated channel, and tRNA moves as the mitoribosomal subunit rotate with respect to each other is not understood. We report models of the translating fungal mitoribosome with mRNA, tRNA and nascent polypeptide, as well as an assembly intermediate. Nicotinamide adenine dinucleotide (NAD) is found in the central protuberance of the large subunit, and the ATPase inhibitory factor 1 (IF1) in the small subunit. The models of the active mitoribosome explain how mRNA binds through a dedicated protein platform on the small subunit, tRNA is translocated with the help of the protein mL108, bridging it with L1 stalk on the large subunit, and nascent polypeptide paths through a newly shaped exit tunnel involving a series of structural rearrangements. An assembly intermediate is modeled with the maturation factor Atp25, providing insight into the biogenesis of the mitoribosomal large subunit and translation regulation.
Synapse type-specific proteomic dissection identifies IgSF8 as a hippocampal CA3 microcircuit organizer
Authors: Apóstolo Nuno , Smukowski Samuel N. , Vanderlinden Jeroen , Condomitti Giuseppe , Rybakin Vasily , ten Bos Jolijn , Trobiani Laura , Portegies Sybren , Vennekens Kristel M. , Gounko Natalia V. , Comoletti Davide , Wierda Keimpe D. , Savas Jeffrey N. , de Wit Joris 
Published: October 2020

AbstractExcitatory and inhibitory neurons are connected into microcircuits that generate circuit output. Central in the hippocampal CA3 microcircuit is the mossy fiber (MF) synapse, which provides powerful direct excitatory input and indirect feedforward inhibition to CA3 pyramidal neurons. Here, we dissect its cell-surface protein (CSP) composition to discover novel regulators of MF synaptic connectivity. Proteomic profiling of isolated MF synaptosomes uncovers a rich CSP composition, including many CSPs without synaptic function and several that are uncharacterized. Cell-surface interactome screening identifies IgSF8 as a neuronal receptor enriched in the MF pathway. Presynaptic Igsf8 deletion impairs MF synaptic architecture and robustly decreases the density of bouton filopodia that provide feedforward inhibition. Consequently, IgSF8 loss impairs excitation/inhibition balance and increases excitability of CA3 pyramidal neurons. Our results provide insight into the CSP landscape and interactome of a specific excitatory synapse and reveal IgSF8 as a critical regulator of CA3 microcircuit connectivity and function.
Evolution of DNA replication origin specification and gene silencing mechanisms
Authors: Hu Y. , Tareen A. , Sheu Y-J. , Ireland W. T. , Speck C. , Li H. , Joshua-Tor L. , Kinney J. B. , Stillman B. 
Published: October 2020

AbstractDNA replication in eukaryotic cells initiates from replication origins that bind the Origin Recognition Complex (ORC). Origin establishment requires well-defined DNA sequence motifs in Saccharomyces cerevisiae and some other budding yeasts, but most eukaryotes lack sequence-specific origins. A 3.9 Å structure of S. cerevisiae ORC-Cdc6-Cdt1-Mcm2-7 (OCCM) bound to origin DNA revealed that a loop within Orc2 inserts into a DNA minor groove and an α-helix within Orc4 inserts into a DNA major groove. Using a massively parallel origin selection assay coupled with a custom mutual-information-based modeling approach, and a separate analysis of whole-genome replication profiling, here we show that the Orc4 α-helix contributes to the DNA sequence-specificity of origins in S. cerevisiae and Orc4 α-helix mutations change genome-wide origin firing patterns. The DNA sequence specificity of replication origins, mediated by the Orc4 α-helix, has co-evolved with the gain of ORC-Sir4-mediated gene silencing and the loss of RNA interference.
Pan-neuroblastoma analysis reveals age- and signature-associated driver alterations
Authors: Brady Samuel W. , Liu Yanling , Ma Xiaotu , Gout Alexander M. , Hagiwara Kohei , Zhou Xin , Wang Jian , Macias Michael , Chen Xiaolong , Easton John , Mulder Heather L. , Rusch Michael , Wang Lu , Nakitandwe Joy , Lei Shaohua , Davis Eric M. , Naranjo Arlene , Cheng Cheng , Maris John M. , Downing James R. , Cheung Nai-Kong V. , Hogarty Michael D. , Dyer Michael A. , Zhang Jinghui 
Published: October 2020

AbstractNeuroblastoma is a pediatric malignancy with heterogeneous clinical outcomes. To better understand neuroblastoma pathogenesis, here we analyze whole-genome, whole-exome and/or transcriptome data from 702 neuroblastoma samples. Forty percent of samples harbor at least one recurrent driver gene alteration and most aberrations, including MYCN, ATRX, and TERT alterations, differ in frequency by age. MYCN alterations occur at median 2.3 years of age, TERT at 3.8 years, and ATRX at 5.6 years. COSMIC mutational signature 18, previously associated with reactive oxygen species, is the most common cause of driver point mutations in neuroblastoma, including most ALK and Ras-activating variants. Signature 18 appears early and is continuous throughout disease evolution. Signature 18 is enriched in neuroblastomas with MYCN amplification, 17q gain, and increased expression of mitochondrial ribosome and electron transport-associated genes. Recurrent FGFR1 variants in six patients, and ALK N-terminal structural alterations in five samples, identify additional patients potentially amenable to precision therapy.
Exploring and applying the substrate promiscuity of a C-glycosyltransferase in the chemo-enzymatic synthesis of bioactive C-glycosides
Authors: Xie Kebo , Zhang Xiaolin , Sui Songyang , Ye Fei , Dai Jungui 
Published: October 2020

AbstractBioactive natural C-glycosides are rare and chemical C-glycosylation faces challenges while enzymatic C-glycosylation catalyzed by C-glycosyltransferases provides an alternative way. However, only a small number of C-glycosyltransferases have been found, and most of the discovered C-glycosyltransferases prefer to glycosylate phenols with an acyl side chain. Here, a promiscuous C-glycosyltransferase, AbCGT, which is capable of C-glycosylating scaffolds lacking acyl groups, is identified from Aloe barbadensis. Based on the substrate promiscuity of AbCGT, 16 C-glycosides with inhibitory activity against sodium-dependent glucose transporters 2 are chemo-enzymatically synthesized. The C-glycoside 46a shows hypoglycemic activity in diabetic mice and is biosynthesized with a cumulative yield on the 3.95 g L‒1 scale. In addition, the key residues involved in the catalytic selectivity of AbCGT are explored. These findings suggest that AbCGT is a powerful tool in the synthesis of lead compounds for drug discovery and an example for engineering the catalytic selectivity of C-glycosyltransferases.
PN/PAs-WSe2 van der Waals heterostructures for solar cell and photodetector
Authors: Zheng Xinyi , Wei Yadong , Pang Kaijuan , Kaner Tolbert Ngeywo , Kong Dalin , Xu Xiaodong , Yang Jianqun , Li Xingji , Li Weiqi 
Published: October 2020

AbstractBy first-principles calculations, we investigate the geometric stability, electronic and optical properties of the type-II PN-WSe2 and type-I PAs-WSe2 van der Waals heterostructures(vdWH). They are p-type semiconductors with indirect band gaps of 1.09 eV and 1.08 eV based on PBE functional respectively. By applying the external gate field, the PAs-WSe2 heterostructure would transform to the type-II band alignment from the type-I. With the increasing of magnitude of the electric field, two heterostructures turn into the n-type semiconductors and eventually into metal. Especially, PN/PAs-WSe2 vdWH are both high refractive index materials at low frequencies and show negative refractive index at high frequencies. Because of the steady absorption in ultraviolet region, the PAs-WSe2 heterostructure is a highly sensitive UV detector material with wide spectrum. The type-II PN-WSe2 heterostructure possesses giant and broadband absorption in the near-infrared and visible regions, and its solar power conversion efficiency of 13.8% is higher than the reported GaTe–InSe (9.1%), MoS2/p-Si (5.23%) and organic solar cells (11.7%). It does project PN-WSe2 heterostructure a potential for application in excitons-based solar cells.
Urbanization and food consumption in India
Authors: Pandey Bhartendu , Reba Meredith , Joshi P. K. , Seto Karen C. 
Published: October 2020

AbstractThe shift towards urban living is changing food demand. Past studies on India show significant urban–rural differences in food consumption. However, a scientific understanding of the underlying relationships between urbanization and food consumption is limited. This study provides the first detailed analysis of how urbanization influences both quantity and diversity of food consumption in India by harnessing the strength of multiple datasets, including consumer expenditure surveys, satellite imagery, and census data. Our statistical analysis shows three main findings. First, in contrast to existing studies, we find that much of the variation in food consumption quantity is due to income and not urbanization. After controlling for income and state-level differences, our results show that average consumption is higher in urban than rural areas for fewer than 10% of all commodities. That is, there is nearly no difference in average consumption between urban and rural residents. Second, we find the influence of urbanization as a population share on food consumption diversity to be statistically insignificant (p-value > 0.1). Instead, the results show that infrastructure, market access, percentage working women in urban areas, and norms and institutions have a statistically significant influence. Third, all covariates of food consumption diversity we tested were found to be associated with urbanization. This suggests that urbanization influences on food consumption are both indirect and multidimensional. These results show that increases in the urban population size alone do not explain changes in food consumption in India. If we are to understand how food consumption may change in the future due to urbanization, the study points to the need for a more complex and multidimensional understanding of the urbanization process that goes beyond demographic shifts.