bluuebunny/crossref_metadata_2025_split huggingface dataset:
Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event
Authors: Paraskevis D. , Kostaki E.G. , Magiorkinis G. , Panayiotakopoulos G. , Tsiodras S. 
Published: January 2020

AbstractBackgroundA novel coronavirus (2019-nCoV) associated with human to human transmission and severe human infection has been recently reported from the city of Wuhan in China. Our objectives were to characterize the genetic relationships of the 2019-nCoV and to search for putative recombination within the subgenus of sarbecovirus.MethodsPutative recombination was investigated by RDP4 and Simplot v3.5.1 and discordant phylogenetic clustering in individual genomic fragments was confirmed by phylogenetic analysis using maximum likelihood and Bayesian methods.ResultsOur analysis suggests that the 2019-nCoV although closely related to BatCoV RaTG13 sequence throughout the genome (sequence similarity 96.3%), shows discordant clustering with the Bat-SARS-like coronavirus sequences. Specifically, in the 5’-part spanning the first 11,498 nucleotides and the last 3’-part spanning 24,341-30,696 positions, 2019-nCoV and RaTG13 formed a single cluster with Bat-SARS-like coronavirus sequences, whereas in the middle region spanning the 3’-end of ORF1a, the ORF1b and almost half of the spike regions, 2019-nCoV and RaTG13 grouped in a separate distant lineage within the sarbecovirus branch.ConclusionsThe levels of genetic similarity between the 2019-nCoV and RaTG13 suggest that the latter does not provide the exact variant that caused the outbreak in humans, but the hypothesis that 2019-nCoV has originated from bats is very likely. We show evidence that the novel coronavirus (2019-nCov) is not-mosaic consisting in almost half of its genome of a distinct lineage within the betacoronavirus. These genomic features and their potential association with virus characteristics and virulence in humans need further attention.
DNA methylation derived immune cell profiles, CpG markers of inflammation, and pancreatic cancer risk
Authors: Michaud Dominique S. , Ruan Mengyuan , Koestler Devin C. , Alonso Lola , Molina-Montes Esther , Pei Dong , Marsit Carmen J. , De Vivo Immaculata , Malats Núria , Kelsey Karl T. 
Published: January 2020

AbstractPancreatic cancer is projected to become the second most common cause of cancer death over the next 5 years. Since inflammation is thought to be a common trajectory for disease initiation, we sought to prospectively characterize immune profiles using DNA methylation markers to examine whether they play a key role in pancreatic cancer risk. In a nested case-control study pooling three U.S. prospective cohort studies, DNA methylation was measured in prediagnostic leukocytes of incident pancreatic cancer cases and matched controls using the Illumina MethylationEPIC array. Differentially methylated regions were used to predict immune cell types and CpGs previously associated with blood inflammatory markers were selected for the analysis. DNA methylation data from a retrospective case-control study conducted in Spain (PanGenEU) was used for independent replication of results. Immune cell proportions and ratio of cell proportions were not associated with pancreatic cancer risk in the nested case-control study. Methylation extent of CpGs residing in or near gene MNDA was significantly associated with pancreatic cancer risk in the nested case-control study and replicated in PanGenEU. In the nested case-control study, the associations were present 10 or more years prior to cancer diagnosis. Methylation of a promoter CpG of gene PIM-1 was associated with pancreatic cancer survival in both studies. We identified several CpGs that may play a role in pancreatic carcinogenesis using a targeted approach for the selection of inflammation-based CpGs in two large, independent studies conducted in different countries with distinct study designs.
Evolution of vertebrate gill covers via shifts in an ancient Pou3f3 enhancer
Authors: Barske Lindsey , Fabian Peter , Hirschberger Christine , Jandzik David , Square Tyler , Xu Pengfei , Nelson Nellie , Yu Haoze Vincent , Medeiros Daniel M. , Gillis J. Andrew , Crump J. Gage 
Published: January 2020

SummaryWhereas the gill chambers of extant jawless vertebrates (lampreys and hagfish) open directly into the environment, jawed vertebrates evolved skeletal appendages that promote the unidirectional flow of oxygenated water over the gills. A major anatomical difference between the two jawed vertebrate lineages is the presence of a single large gill cover in bony fishes versus separate covers for each gill chamber in cartilaginous fishes. Here we find that these divergent gill cover patterns correlate with the pharyngeal arch expression of Pou3f3 orthologs. We identify a Pou3f3 arch enhancer that is deeply conserved from cartilaginous fish through humans but undetectable in lampreys, with minor sequence differences in the bony versus cartilaginous fish enhancers driving the corresponding single versus multiple gill arch expression patterns. In zebrafish, loss of Pou3f3 gene function disrupts gill cover formation, and forced expression of Pou3f3b in the gill arches generates ectopic skeletal elements resembling the multiple gill cover pattern of cartilaginous fishes. Emergence of this Pou3f3 enhancer >430 mya and subsequent modifications may thus have contributed to the acquisition and diversification of gill covers and respiratory strategies during gnathostome evolution.
AVibrio choleraeCore Genome Multilocus Sequence Typing Scheme to Facilitate the Epidemiological Study of Cholera
Authors: Liang Kevin Y. H. , Orata Fabini D. , Islam Mohammad Tarequl , Nasreen Tania , Alam Munirul , Tarr Cheryl L. , Boucher Yann F. 
Published: January 2020

ABSTRACTCore genome multilocus sequence typing (cgMLST) has gained popularity in recent years in epidemiological research and subspecies level classification. cgMLST retains the intuitive nature of traditional MLST but offers much greater resolution by utilizing significantly larger portions of the genome. Here, we introduce a cgMLST scheme forVibrio cholerae, a bacterium abundant in marine and freshwater environments and the etiologic agent of cholera. A set of 2,443 core genes ubiquitous inV. choleraewere used to analyze a comprehensive dataset of 1,262 clinical and environmental strains collected from 52 countries, including 65 newly sequenced genomes in this study. We established a sublineage threshold based on 133 allelic differences that creates clusters nearly identical to traditional MLST types, providing backwards compatibility to new cgMLST classifications. We also defined an outbreak threshold based on seven allelic differences that is capable of identifying strains from the same outbreak and closely related isolates which could give clues on outbreak origin. Using cgMLST, we confirmed the South Asian origin of modern epidemics and identified clustering affinity among sublineages of environmental isolates from the same geographic origin. Advantages of this method are highlighted by direct comparison with existing classification methods, such as MLST and single nucleotide polymorphism-based methods. cgMLST outperforms all existing methods in terms of resolution, standardization, and ease-of-use. We anticipate this scheme will serve as a basis for a universally applicable and standardized classification system forV. choleraeresearch and epidemiological surveillance in the future. This cgMLST scheme is publicly available on PubMLST (https://pubmlst.org/vcholerae/).IMPORTANCEToxigenicVibrio choleraeof the O1 and O139 serogroups are the causative agent of cholera, an acute diarrheal disease that plagued the world for centuries, if not millennia. Here, we introduce a core genome multilocus sequence typing (cgMLST) scheme forV. cholerae. Using cgMLST, we established an outbreak threshold that can efficiently identify outbreak related strains and potential sources of introduction. We also defined a sublineage threshold that is similar to traditional MLST sequence type which will provide context to this new typing method by relating it to previous MLST results. cgMLST outperforms all existing methods in terms of resolution, standardization, and ease-of-use, making this scheme the most suitable method forV. choleraetyping and surveillance worldwide.
Loss of function of the mitochondrial peptidase PITRM1 induces proteotoxic stress and Alzheimer’s disease-like pathology in human cerebral organoids
Authors: Ivanyuk Dina , Pérez María José , Panagiotakopoulou Vasiliki , Di Napoli Gabriele , Brunetti Dario , Al-Shaana Rawaa , Kaeser Stephan A. , Jucker Mathias , Zeviani Massimo , Viscomi Carlo , Deleidi Michela 
Published: January 2020

AbstractMutations in pitrilysin metallopeptidase 1 (PITRM1), a mitochondrial protease involved in mitochondrial precursor processing and degradation, result in a slow-progressive syndrome, characterized by cerebellar ataxia, psychotic episodes and obsessive behavior as well as cognitive decline. To investigate the pathogenetic mechanisms of mitochondrial presequence processing, we employed cortical neurons and cerebral organoids generated from PITRM1 knockout human induced pluripotent stem cells (iPSCs). PITRM1 deficiency strongly induced mitochondrial unfolded protein response (UPRmt) and enhanced mitochondrial clearance in iPSC-derived neurons. Furthermore, we observed increased levels of amyloid precursor protein and amyloid β in PITRM1 knockout neurons. However, neither cell death nor protein aggregates were observed in 2D iPSC-derived cortical neuronal cultures. On the contrary, cerebral organoids generated from PITRM1 knockout iPSCs spontaneously developed over time pathological features of Alzheimer’s disease (AD), including accumulation of protein aggregates, tau pathology, and neuronal cell death. Importantly, we provide evidence for a protective role of UPRmtand mitochondrial clearance against impaired mitochondrial presequence processing and proteotoxic stress. In summary, we propose a novel concept of PITRM1-linked neurological syndrome whereby defects of mitochondrial presequence processing induce an early activation of UPRmtthat, in turn, modulates cytosolic quality control pathways. Thus our work supports a mechanistic link between mitochondrial function and common neurodegenerative proteinopathies.
Rapid event-related, BOLD, NHP: choose two out of three
Authors: Pelekanos Vassilis , Mok Robert M. , Joly Olivier , Ainsworth Matthew , Kyriazis Diana , Kelly Maria G. , Bell Andrew H. , Kriegeskorte Nikolaus 
Published: January 2020

AbstractHuman functional magnetic resonance imaging (fMRI) typically employs the blood-oxygen-level-dependent (BOLD) contrast mechanism. In non-human primates (NHP), contrast enhancement is possible using monocrystalline iron-oxide nanoparticles (MION) contrast agent, which has a more temporally extended response function. However, using BOLD fMRI in NHP is desirable for interspecies comparison, and the faster response of the BOLD signal promises to be beneficial to rapid event-related (rER) designs. Here, we used rER BOLD fMRI in macaque monkeys while viewing real-world images, and found visual responses and category-selectivity consistent with previous studies. However, activity estimates were very noisy, suggesting that the lower contrast-to-noise ratio of BOLD, suboptimal behavioural performance, and motion artefacts, in combination, render rER BOLD fMRI challenging in NHP. Previous studies have shown that rER monkey fMRI is possible with MION, despite its prolonged response function. To understand this, we conducted simulations of the BOLD and MION response during rER designs, and found that no matter how fast the design, the greater amplitude of the MION response outweighs the contrast loss caused by greater temporal smoothing. We conclude that although any two of the three elements (rER, BOLD, NHP) have been shown to work well, the combination of all three is particularly challenging.
An instructive role for IL7RA in the development of human B-cell precursor leukemia
Authors: Geron Ifat , Savino Angela Maria , Tal Noa , Brown John , Turati Virginia , James Chela , Sarno Jolanda , Lee Yu Nee , Gil Avigail Rein , Fishman Hila , Birger Yehudit , Muler Inna , Hameiri-Grossman Michal , Davis Kara Lynn , Marcu-Malina Victoria , Parnas Oren , Fischer Ute , Müschen Markus , Borkhardt Arndt , Kirsch Ilan Richard , Nagler Arnon , Enver Tariq , Izraeli Shai 
Published: January 2020

AbstractB-cell precursor acute lymphoblastic leukemia (BCP-ALL) is preceded by a clinically silent pre-leukemia. Experimental models that authentically re-capitulate disease initiation and progression in human cells are lacking. We previously described activating mutations in interleukin 7 receptor alpha (IL7RA) that are associated with the poor-prognosis Philadelphia-like (Ph-like) subtype of BCP-ALL. Whether IL7RA signaling has a role in initiation of human BCP-ALL is unknown.IL7RA is essential for mouse B-cell development; however, patients with truncatingIL7RAgermline mutations develop normal mature B-cell populations. Herein, we explore the consequences of aberrant IL7RA signaling activation in human hematopoietic progenitors on malignant B-cell development.Transplantation of human cord-blood hematopoietic progenitors transduced with activated mutant IL7RA into NOD/LtSz-scid IL2Rγnullmice resulted in B-cell differentiation arrest with aberrant expression of CD34+and persistence of pro-B cells that survive despite failing to achieve productive rearrangement of immunoglobulin V(D)J gene segments. Activation of IL7RA signaling enhanced self-renewal and facilitated the development of a BCP-ALL in secondary transplanted mice. The development of leukemia was associated with spontaneous acquired deletions in CDKN2A/B and IKZF1 similar to what is observed in Ph-like BCP-ALL in humans. Single cell gene expression analysis suggested that pre-leukemic cells resided within a subpopulation of early B-cell precursors with CD34+CD10highCD19lowimmunophenotype.The development of a bona fide BCP-ALL from IL7RA transduced cells supports the hypothesis that aberrant activation of the IL7RA pathway in human B-cell lineage progenitors has an instructive role by creating a pre-leukemic state which is vulnerable to transformation. These are the first demonstrations of a role for IL7RA in human B-cell differentiation and of a de-novo Ph-like BCP-ALL development from normal human hematopoietic progenitorsin vivo.
The complete chloroplast genome sequence of American elm (Ulmus americana) and comparative genomics of related species
Authors: Ebrahimi Aziz , Antonides Jennifer D. , Pinchot Cornelia C. , Slavicek James M. , Flower Charles E. , Woeste Keith E. 
Published: January 2020

ABSTRACTAmerican elm,Ulmus americanaL., was cultivated widely in USA and Canada as a landscape tree, but the genome of this important species is poorly characterized. For the first time, we describe the sequencing and assembly of the chloroplast genomes of two American elm genotypes (RV16 and Am57845). The complete chloroplast genome ofU. americanaranged from 158,935-158,993 bp. The genome contains 127 genes, including 85 protein-coding genes, 34 tRNA genes and 8 rRNA genes. Between the two American elm chloroplasts we sequenced, we identified 240 sequence variants (SNPs and indels). To evaluate the phylogeny of American elm, we compared the chloroplast genomes of two American elms along with seven Asian elm species and twelve other chloroplast genomes available through the NCBI database. As expected,Ulmuswas closely related toMorusandCannabis, as all three genera are assigned to the Urticales. Comparison of American elm with Asian elms revealed thattrnH was absent from the chloroplast of American elm but not most Asian elms; conversely,petB,petD,psbL,trnK, andrps16 are present in the American elm but absent from all Asian elms. The complete chloroplast genome ofU. americanawill provide useful genetic resources for characterizing the genetic diversity ofU. americanaand potentially help to conserve natural populations of American elm.
Precise mapping of new group I introns in tRNA genes
Authors: Williams Kelly P. 
Published: January 2020

ABSTRACTBacterial tRNA have been found interrupted at various positions in the anticodon loop by group I introns, in four types. The primary bioinformatic tool for group I intron discovery is a covariance model that can identify conserved features in the catalytic core and can sometimes identify the typical uridine residue at the -1 position, preceding the 5-prime splice site, but cannot identify the typical guanidine residue at the omega position, preceding the 3-prime splice site, to achieve precise mapping. One approach to complete the automation of group I intron mapping is to focus instead on the exons, which is enabled by the regularity of tRNAs. We develop a software module, within a larger package (tFind) aimed at mapping bacterial tRNA and tmRNA genes precisely, that expands this list of four known classes of intron-interrupted tRNAs to 21 cases. A new covariance model for these introns is presented. The wobble base pair formed by the -1 uridine is considered a determinant of the 5-prime splice site, yet one reasonably large new type bears a cytidine nucleotide at that position.
Cooperativity of membrane-protein and protein-protein interactions control membrane remodeling by epsin 1 and regulate clathrin-mediated endocytosis
Authors: Kroppen Benjamin , Teske Nelli , Yambire King F. , Denkert Niels , Murkhejee Indrani , Tarasenko Daryna , Jaipuria Garima , Zweckstetter Markus , Milosevic Ira , Steinem Claudia , Meinecke Michael 
Published: January 2020

AbstractMembrane remodeling is a critical process for many membrane trafficking events, including clathrin-mediated endocytosis. Several molecular mechanisms for protein induced membrane curvature have been described in some detail. Contrary, the effect that the physico-chemical properties of the membrane has on these processes is far less well understood. Here, we show that the membrane binding and curvature-inducing ENTH domain of epsin1 is regulated by phosphatidylserine (PS). ENTH binds to membranes in a PI(4,5)P2-dependent manner but only induces curvature in the presence of PS. On PS-containing membranes, the ENTH domain forms rigid homo-oligomers and assembles into clusters. Membrane binding and membrane remodeling can be separated by structure-to-function mutants. Such oligomerization mutants bind to membranes but do not show membrane remodeling activity. In vivo they are not able to rescue defects in epidermal growth factor receptor (EGFR) endocytosis in epsin knock-down cells. Together, these data show that the membrane lipid composition is important for the regulation of protein-dependent membrane deformation during clathrin-mediated endocytosis.
Disparities in information on Long-Acting Reversible Contraceptives available to college students on student health center websites in USA
Authors: Kulkarni Anagha , Belsare Tejasvi , Shah Risha , Yu Yu Diana , Holschuh Carrie , Kakar Venoo , Modrek Sepideh , Smirnova Anastasia 
Published: January 2020

AbstractLong Acting Reversible Contraceptive (LARC) methods are among the most effective birth control approaches for adolescent and young adults yet information on these methods is not widespread. We examine LARC information provided by Student Health Centers (SHC) websites from Universities across the USA to document disparities in access to information on these important contraception methods for college students. We find that compared to EC, Condoms, (plus Pap smear as control), LARC is mentioned less frequently than the others and 73% of schools have no LARC content on their SHC websites. There is no standardization in how the sexual and reproductive health information is organized on SHC websites, which might hinder access. When LARC information does exist, readability and accessibility vary. Universities having high rates of the student body who are African American or female are less likely to provide LARC information on their SHC website and universities situated in more rural settings are less likely to post LARC information on their websites.
Identifying Priority Landscapes for Conservation of Snow Leopards in Pakistan
Authors: Hameed Shoaib , ud Din Jaffar , Ali Hussain , Kabir Muhammad , Younas Muhammad , Hao Wang , Bischof Richard , Nawaz Muhammad Ali 
Published: January 2020

AbstractPakistan’s total estimated snow leopard habitat is about 80,000 km2of which about half is considered prime. However, this preliminary demarcation was not always in close agreement with the actual distribution—the discrepancy may be huge at the local and regional level. Recent technological developments like camera trapping and molecular genetics allow for collecting reliable presence records that could be used to construct realistic species distribution based on empirical data and advanced mathematical approaches like MaxEnt. Current study followed this approach to construct accurate distribution of the species in Pakistan. Moreover, movement corridors, among different landscapes, were also identified through the circuit theory. The habitat suitability map, generated from 384 presence points and 28 environmental variables, scored the snow leopard’s assumed range in Pakistan, from 0 to 0.97. A large shear of previously known range represented low-quality habitat, including areas in lower Chitral, Swat, Astore and Kashmir. Conversely, Khunjerab, Misgar, Chapursan, Qurumber, Broghil, and Central Karakoram represented high-quality habitats. Variables with higher contribution in the MaxEnt model were precipitation of driest month (34%), annual mean temperature (19.5%), mean diurnal range of temperature (9.8%), annual precipitation (9.4%) and river density (9.2). The validation texts suggest a good model fit, and strong prediction power.The connectivity analysis revealed that the population in the Hindukush landscape appears to be more connected with the population in Afghanistan as compared to other populations in Pakistan. Similarly, the Pamir-Karakoram population is better connected with China and Tajikistan, while the Himalayan population was with the population in India.Current study allows for proposing three model landscapes to be considered under GSLEP agenda as regional priority areas, to safeguard safeguard future of the species in the long run. These landsacpes fall in mountain ranges of the Himalaya, Hindu Kush and Karakoram-Pamir, respectively. We also identified gaps in existing protected areas network, and suggest new protected areas in Chitral and Gilgit-Baltistan to protect critical habitats of snow leopard in Pakistan.