bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expanding the Genetic Architecture of Nicotine Dependence and its Shared Genetics with Multiple Traits: Findings from the Nicotine Dependence GenOmics (iNDiGO) Consortium
Authors: Quach Bryan C. , Bray Michael J. , Gaddis Nathan C. , Liu Mengzhen , Palviainen Teemu , Minica Camelia C. , Zellers Stephanie , Sherva Richard , Aliev Fazil , Nothnagel Michael , Young Kendra A. , Marks Jesse A. , Young Hannah , Carnes Megan U. , Guo Yuelong , Waldrop Alex , Sey Nancy Y.A. , Landi Maria T. , McNeil Daniel W. , Drichel Dmitriy , Farrer Lindsay A. , Markunas Christina A. , Vink Jacqueline M. , Hottenga Jouke-Jan , Iacono William G. , Kranzler Henry R. , Saccone Nancy L. , Neale Michael C. , Madden Pamela , Rietschel Marcella , Marazita Mary L. , McGue Matthew , Won Hyejung ,   Georg Winterer and the German Nicotine Cohort Study, Grucza Richard , Dick Danielle M. , Gelernter Joel , Caporaso Neil E. , Baker Timothy B. , Boomsma Dorret I. , Kaprio Jaakko , Hokanson John E. , Vrieze Scott , Bierut Laura J. , Johnson Eric O. , Hancock Dana B. 
Published: January 2020

AbstractCigarette smoking is the leading cause of preventable morbidity and mortality. Knowledge is evolving on genetics underlying initiation, regular smoking, nicotine dependence (ND), and cessation. We performed a genome-wide association study using the Fagerström Test for ND (FTND) in 58,000 smokers of European or African ancestry. Five genome-wide significant loci, including two novel lociMAGI2/GNAI1(rs2714700) andTENM2(rs1862416) were identified, and loci reported for other smoking traits were extended to ND. Using the heaviness of smoking index (HSI) in the UK Biobank (N=33,791), rs2714700 was consistently associated, but rs1862416 was not associated, likely reflecting ND features not captured by the HSI. Both variants werecis-eQTLs (rs2714700 forMAGI2-AS3in hippocampus, rs1862416 forTENM2in lung), and expression of genes spanning ND-associated variants was enriched in cerebellum. SNP-based heritability of ND was 8.6%, and ND was genetically correlated with 17 other smoking traits (rg=0.40–0.95) and co-morbidities. Our results emphasize the FTND as a composite phenotype that expands genetic knowledge of smoking, including loci specific to ND.
Disentangling the effects of sampling scale and size on the shape of species abundance distributions
Authors: de Lima Renato A. Ferreira , Condé Paula Alves , Banks-Leite Cristina , Campos Renata C. , Hernández Malva I. Medina , Rodrigues Ricardo R. , Prado Paulo I. 
Published: January 2020

AbstractMany authors have tried to explain the shape of the species abundance distribution (SAD). Some of them have suggested that sampling scale is an important factor shaping SADs. These suggestions, however, did not consider the indirect and well-known effect of sample size, which increases as samples are combined to generate SADs at larger scales. Here, we separate the effects of sample size and sampling scale on the shape of the SAD for three groups of organisms (trees, beetles and birds) sampled in the Brazilian Atlantic Forest. We compared the observed SADs at different sampling scales with simulated SADs having the same richness, relative abundances but comparable sample sizes, to show that the main effect shaping SADs is sample size and not sampling scale. The effect of scale was minor and deviations between observed and simulated SADs were present only for beetles. For trees, the match between observed and simulated SADs was improved at all scales when we accounted for conspecific aggregation, which was even more important than the sampling scale effect. We build on these results to propose a conceptual framework where observed SADs are shaped by three main factors, in decreasing order of importance: sample size, conspecific aggregation and beta diversity. Therefore, studies comparing SADs across sites or scales should use sampling and/or statistical approaches capable of disentangling these three effects on the shape of SADs.
Impact of b-value on estimates of apparent fibre density
Authors: Genc Sila , Tax Chantal M.W. , Raven Erika P. , Chamberland Maxime , Parker Greg D. , Jones Derek K. 
Published: January 2020

AbstractRecent advances in diffusion magnetic resonance imaging (dMRI) analysis techniques have improved our understanding of fibre-specific variations in white matter microstructure. Increasingly, studies are adopting multi-shell dMRI acquisitions to improve the robustness of dMRI-based inferences. However, the impact of b-value choice on the estimation of dMRI measures such as apparent fibre density (AFD) derived from spherical deconvolution is not known. Here, we investigate the impact of b-value sampling scheme on estimates of AFD. First, we performed simulations to assess the correspondence between AFD and simulated intra-axonal signal fraction across multiple b-value sampling schemes. We then studied the impact of sampling scheme on the relationship between AFD and age in a developmental population (n=78) aged 8-18 (mean=12.4, SD=2.9 years) using hierarchical clustering and whole brain fixel-based analyses. Multi-shell dMRI data were collected at 3.0T using ultra-strong gradients (300 mT/m), using 6 diffusion-weighted shells ranging from 0 – 6000 s/mm2. Simulations revealed that the correspondence between estimated AFD and simulated intra-axonal signal fraction was improved with high b-value shells due to increased suppression of the extra-axonal signal. These results were supported byin vivodata, as sensitivity to developmental age-relationships was improved with increasing b-value (b=6000 s/mm2, median R2= .34; b=4000 s/mm2, median R2= .29; b=2400 s/mm2, median R2= .21; b=1200 s/mm2, median R2= .17) in a tract-specific fashion. Overall, estimates of AFD and age-related microstructural development were better characterised at high diffusion-weightings due to improved correspondence with intra-axonal properties.
Can we predict real-time fMRI neurofeedback learning success from pre-training brain activity?
Authors: Haugg Amelie , Sladky Ronald , Skouras Stavros , McDonald Amalia , Craddock Cameron , Kirschner Matthias , Herdener Marcus , Koush Yury , Papoutsi Marina , Keynan Jackob N. , Hendler Talma , Kadosh Kathrin Cohen , Zich Catharina , MacInnes Jeff , Adcock Alison , Dickerson Kathryn , Chen Nan-Kuei , Young Kymberly , Bodurka Jerzy , Yao Shuxia , Becker Benjamin , Auer Tibor , Schweizer Renate , Pamplona Gustavo , Emmert Kirsten , Haller Sven , Van De Ville Dimitri , Blefari Maria-Laura , Kim Dong-Youl , Lee Jong-Hwan , Marins Theo , Fukuda Megumi , Sorger Bettina , Kamp Tabea , Liew Sook-Lei , Veit Ralf , Spetter Maartje , Weiskopf Nikolaus , Scharnowski Frank 
Published: January 2020

AbstractNeurofeedback training has been shown to influence behavior in healthy participants as well as to alleviate clinical symptoms in neurological, psychosomatic, and psychiatric patient populations. However, many real-time fMRI neurofeedback studies report large interindividual differences in learning success. The factors that cause this vast variability between participants remain unknown and their identification could enhance treatment success. Thus, here we employed a meta-analytic approach including data from 24 different neurofeedback studies with a total of 401 participants, including 140 patients, to determine whether levels of activity in target brain regions during pre-training functional localizer or no-feedback runs (i.e., self-regulation in the absence of neurofeedback) could predict neurofeedback learning success. We observed a slightly positive correlation between pre-training activity levels during a functional localizer run and neurofeedback learning success, but we were not able to identify common brain-based success predictors across our diverse cohort of studies. Therefore, advances need to be made in finding robust models and measures of general neurofeedback learning, and in increasing the current study database to allow for investigating further factors that might influence neurofeedback learning.
Polycomb regulation is coupled to cell cycle transition in pluripotent stem cells
Authors: Asenjo Helena G. , Gallardo Amador , López-Onieva Lourdes , Tejada Irene , Martorell-Marugán Jordi , Carmona-Sáez Pedro , Landeira David 
Published: January 2020

SummaryWhen self-renewing pluripotent cells receive a differentiation signal, ongoing cell duplication needs to be coordinated with entry into a differentiation program. Accordingly, transcriptional activation of lineage specifiers genes and cell differentiation is confined to the G1-phase of the cell cycle by unknown mechanisms. We found that Polycomb repressive complex 2 (PRC2) subunits are differentially recruited to lineage specifier gene promoters across cell cycle in mouse embryonic stem cells (mESCs). Jarid2 and the catalytic subunit Ezh2 are dramatically accumulated at target promoters during S and G2, while the transcriptionally activating subunits EPOP and EloB are enriched during G1. Importantly, fluctuations in the recruitment of PRC2 subunits promote changes in RNA synthesis and RNA polymerase II binding that are compromised in Jarid2 -/- mESCs. Overall, we show that differential recruitment of PRC2 subunits across cell cycle enables the establishment of a chromatin state that facilitates the induction of cell differentiation in G1.
Post-transcriptional modulation of the SigF regulon inMycobacterium smegmatisby the PhoH2 toxin-antitoxin
Authors: Andrews Emma S.V. , Rzoska-Smith Elizabeth , Arcus Vickery L. 
Published: January 2020

AbstractPhoH2 proteins are highly conserved across bacteria and archaea yet their biological function is poorly characterised. We examined the growth profiles ofMycobacterium smegmatisstrainsmc2155andmc2155 ΔphoH2and observed the same growth profile and growth rate in a variety of conditions. In light of the comparable growth rates, we used RNAseq to provide a snapshot of the differences between the transcriptomes ofM. smegmatis mc2155andM. smegmatis mc2155 ΔphoH2during normal growth. At 48 hours, elevated expression of thesigFregulon and its predicted regulatory cascade was observed inΔphoH2relative to wild type. In biochemical assays, PhoH2 showed specific activity towardsigFmRNA insinuating a role of PhoH2 in modulating the pool ofsigFmRNA in the cell during normal growth, adding further complexity to the repertoire of reported mechanisms of post-translational regulation. Multiple copies of the preferred target site of PhoH2 were identified in loops of thesigFmRNA structure, leading us to propose a mechanism for the activity of PhoH2 that is initiated after assembly on specific single-stranded loops of RNA. We hypothesise that PhoH2 is a toxin-antitoxin that contributes to the regulation of SigF at a post-transcriptional level through targeted activity onsigFmRNA. This work presents the first evidence for post-transcriptional regulation of SigF along with the biological function of PhoH2 fromM. smegmatis. This also has implications for the highly conserved PhoH2 toxin-antitoxin module across the mycobacteria including the important human pathogenM. tuberculosis.
The distribution of functional N-cycle related genes and nitrogen in soil profiles fertilized with mineral and organic N fertilizer
Authors: Zilio Massimo , Motta Silvia , Tambone Fulvia , Scaglia Barbara , Boccasile Gabriele , Squartini Andrea , Adani Fabrizio 
Published: January 2020

AbstractNitrogen (N) fertilizers applied to agricultural soils result in the release of nitrogen, mainly nitrate (NO3-) in addition to nitrous oxide (N2O) and ammonia (NH3), into the environment. Nitrogen transformation in soil is a complex process and the soil microbial population can regulate the potential for N mineralization, nitrification and denitrification. Here we show that agricultural soils under standard agricultural N-management are consistently characterized by a high presence of gene copies for some of the key biological activities related to the N-cycle. This led to a strong NO3-reduction (75%) passing from the soil surface (15.38 ± 11.36 g N-NO3kg-1on average) to 1 m deep layer (3.92 ± 4.42 g N-NO3kg-1on average), and ensured low nitrate presence in the deepest layer. Under these circumstances the other soil properties play a minor role in reducing soil nitrate presence in soil. However, with excessive N fertilization, the abundance of bacterial gene copies is not sufficient to explain N leaching in soil and other factors, i.e. soil texture and rainfall, become more important in controlling these aspects.
Temporal dynamics of GABA and Glx in the visual cortex
Authors: Rideaux Reuben 
Published: January 2020

ABSTRACTMagnetic resonance spectroscopy (MRS) can be used in vivo to quantify neurometabolite concentration and provide evidence for the involvement of different neurotransmitter systems, e.g., inhibitory and excitatory, in sensory and cognitive processes. The relatively low signal-to-noise of MRS measurements has shaped the types of questions that it has been used to address. In particular, temporal resolution is often sacrificed in MRS studies to achieve sufficient signal to produce a reliable estimate of neurometabolite concentration. Here we apply novel analyses with large datasets from human participants (both sexes) to reveal the dynamics of GABA+ and Glx in visual cortex while participants are at rest (with eyes closed) and compare this with changes in posterior cingulate cortex. We find that the dynamic concentration of GABA+ and Glx in visual cortex drifts in opposite directions, that is, GABA+ decreases while Glx increases over time. Further, we find that in visual, but not posterior cingulate cortex, the concentration of GABA+ predicts that of Glx 120 s later, such that a change in GABA+ is correlated with a subsequent opposite change in Glx. Together, these results expose novel temporal trends and interdependencies of primary neurotransmitters in visual cortex. More broadly, we demonstrate the feasibility of using MRS to investigate in vivo dynamic changes of neurometabolites.SIGNIFICANCE STATEMENTUsing large datasets of magnetic resonance spectroscopy acquisitions from human participants, we develop novel analyses to investigate the temporal dynamics of neurometabolite concentration in visual cortex. We find that while participants are at rest, the concentration of GABA+ and Glx drifts in opposite directions, that is, GABA+ decreases while Glx increases over time. Further, we find that the concentration of GABA+ predicts that of Glx 120 s later, such that a change in GABA+ is correlated with a subsequent opposite change in Glx. We show these phenomena are regionally localized to visual cortex.
A minimum reporting standard for multiple sequence alignments
Authors: Wong Thomas KF , Kalyaanamoorthy Subha , Meusemann Karen , Yeates David K , Misof Bernhard , Jermiin Lars S 
Published: January 2020

ABSTRACTMultiple sequence alignments (MSAs) play a pivotal role in studies of molecular sequence data, but nobody has developed a minimum reporting standard (MRS) to quantify the completeness of MSAs in terms of completely-specified nucleotides or amino acids. We present an MRS that relies on four simple completeness metrics. The metrics are implemented in AliStat, a program developed to support the MRS. A survey of published MSAs illustrates the benefits and unprecedented transparency offered by the MRS.
Role of astrogial Connexin 43 in pneumococcal meningitis and pneumolysin cytotoxicity
Authors: Bello Chakir , Smail Yasmine , Sainte-Rose Vincent , Podglajen Isabelle , Gilbert Alice , Moreira Vanessa Oliveira , Chrétien Fabrice , Salmon Martine Cohen , Van Nhieu Guy Tran 
Published: January 2020

Introductory paragraphStreptococcus pneumoniaeor pneumococcus (PN) is a major causative agent of bacterial meningitis with high mortality in young infants and elderly people. The mechanism underlying PN crossing of the blood brain barrier (BBB) remains poorly understood. Here, we show that the gap junctional component connexin 43 expressed in astrocytes (aCx43) plays a major role in PN meningitis. Following intravenous PN challenge, mice deficient for aCx43 developed milder symptoms and showed severely reduced bacterial counts in the brain. We show a role for aCx43 in the PN-induced fragmentation of astrocytic GFAP filaments associated with bacterial translocation across endothelial vessels and replication in the brain cortex. aCx43 triggers the PN- and Ply-dependent GFAP fragmentation and nuclear shrinkage inin vitrocultured astrocytes. We showed that purified pneumolysin (Ply) co-opted Cx43 to promote the permeabilization and cytosolic calcium (Ca2+) increase of host cells, a process sensitive to extracellular ATP depletion. These results point to aCx43 as a major player during bacterial meningitis and extend cytolytic mechanisms implicating other host cell plasma membrane channels proposed for small pore-forming toxins, to Ply, a cholesterol-dependent cytolysin, at concentrations relevant to bacterial infection.
Characterization of Prenylated C-terminal Peptides Using a Novel Capture Technique Coupled with LCMS
Authors: Wilkins James A. , Kaasik Krista , Chalkley Robert J. , Burlingame Al L. 
Published: January 2020

ABSTRACTPost-translational modifications play a critical and diverse role in regulating cellular activities. Despite their fundamentally important role in cellular function, there has been no report to date of an effective generalized approach to the targeting, extraction and characterization of the critical c-terminal regions of natively prenylated proteins. Various chemical modification and metabolic labelling strategies in cell culture have been reported. However, their applicability is limited to cell culture systems and does not allow for analysis of tissue samples. The chemical characteristics (hydrophobicity, low abundance, highly basic charge) of many of the c-terminal regions of prenylated proteins have impaired the use of standard proteomic workflows. In this context, we sought a direct approach to the problem in order to examine these proteins in tissue without the use of labelling. Here we demonstrate that prenylated proteins can be captured on chromatographic resins functionalized with mixed disulfide functions. Protease treatment of resin-bound proteins using chymotryptic digestion revealed peptides from many known prenylated proteins. Exposure of the protease-treated resin to reducing agents and hydro organic mixtures released c-terminal peptides with intact prenyl groups along with other enzymatic modifications expected in this protein family. Database and search parameters were selected to allow for c-terminal modifications unique to these molecules such as CAAX box processing and c-terminal methylation. In summary, we present a direct approach to enrich and obtain information at a molecular level of detail about prenylation of proteins from tissue and cell extracts using high performance LCMS without the need for metabolic labeling and derivatization.Abstract Figure
Dynamics of sphingolipids and the serine-palmitoyltransferase complex in oligodendrocytes during myelination
Authors: Davis Deanna L. , Mahawar Usha , Pope Victoria S. , Allegood Jeremy , Sato-Bigbee Carmen , Wattenberg Binks W. 
Published: January 2020

AbstractMyelin is a unique, lipid-rich membrane structure that accelerates neurotransmission and supports neuronal function. Sphingolipids are critical components of myelin. Here we examined sphingolipid synthesis during the peak period of myelination in the postnatal rat brain. Importantly, we made measurements in isolated oligodendrocytes, the myelin-producing cells in the central nervous system. We analyzed sphingolipid distribution and levels of critical enzymes and regulators in the sphingolipid biosynthetic pathway, with a focus on the serine palmitoyltransferase (SPT) complex, the rate-limiting step in this pathway. During myelination levels of the major SPT subunits increased and oligodendrocyte maturation was accompanied by extensive alterations in the composition of the SPT complex. These included changes in the relative levels of alternate catalytic subunits, SPTLC2 and −3, the relative levels of isoforms of the small subunits ssSPTa and –b, and in the isoform distribution of the SPT regulators, the ORMDLs. As myelination progressed there were distinct changes in both the nature of the sphingoid backbone and the N-acyl chains incorporated into sphingolipids. The distribution of these changes among sphingolipid family members indicates that there is selective channeling of the ceramide backbone towards specific downstream metabolic pathways during myelination.
Single-cell transcriptome maps of myeloid blood cell lineages inDrosophila
Authors: Cho Bumsik , Yoon Sang-Ho , Lee Daewon , Koranteng Ferdinand , Tattikota Sudhir Gopal , Cha Nuri , Shin Mingyu , Do Hobin , Hu Yanhui , Oh Sue Young , Moon Seok Jun , Perrimon Norbert , Nam Jin-Wu , Shim Jiwon 
Published: January 2020

SUMMARYDrosophilalymph gland, the larval hematopoietic organ comprised of prohemocytes and hemocytes, has been a valuable model for understanding mechanisms underlying hematopoiesis and immunity. Three types of mature hemocytes have been characterized in the lymph gland: plasmatocytes, lamellocytes, and crystal cells, which are analogous to vertebrate myeloid cells. Here, we used single-cell RNA sequencing to comprehensively analyze heterogeneity of developing hemocytes in the lymph gland, and discovered novel hemocyte types, stem-like prohemocytes, and intermediate prohemocytes. Additionally, we identified the emergence of the lamellocyte lineage following active cellular immunity caused by wasp infestation. We unraveled similarities and differences between embryonically derived- and larval lymph gland hemocytes. Finally, the comparison ofDrosophilalymph gland hemocytes and human immune cells highlights similarities between prohemocytes and hematopoietic stem cell, and between mature hemocytes and myeloid cells across species. Altogether, our study provides detailed insights on the development and evolution of hematopoiesis at single-cell resolution.