bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clearance of Indocyanine Green in Severe Pediatric Burns
Authors: Diaz Eva C. , Herndon David Newcomb , Cleves Mario Alberto , Mlcak Ronald P. , Aarsland Asle , Børsheim Elisabet 
Published: December 2018

BACKGROUND
Clearance of indocyanine green dye (ICGc) reflects sinusoidal perfusion and hepatocyte cell membrane function. Thus, ICGc is a reflection of the functional reserve of intact hepatocytes. The purpose of this study was to identify predictors of ICGc in severely burned children during the acute hospitalization and at the time of discharge from the intensive care unit (ICU). A secondary aim was to determine the relationship between liver size and patient ICGc.

METHODS
Twenty-six children (0.8–17 years old) with 35% or greater total body surface area burned (%TBSA-B) were included. Assessment of ICGc (in milliliters per minute per meter squared) was done during the acute hospitalization (median: 6 days after admission, median: 14 days postburn) and at the time of discharge from the ICU (median: 19 days after admission, median: 27 days postburn). Age, TBSA-B, % third-degree burns, inhalation injury, preexisting chronic malnutrition, hematocrit, liver dysfunction, and time from burn injury were incorporated in multiple linear regressions as predictive variables of ICGc. Only variables with p < 0.05 were retained in the final models.

RESULTS
Time from injury and age were the strongest predictors of ICGc during the acute admission but not at the time of discharge from the ICU. Time from injury was negatively associated with ICGc, whereas age was positively associated. At the time of discharge from the ICU, ICGc was increased in proportion to the %TBSA-B, whereas inhalation injury and preexisting chronic malnutrition were associated with lower ICGc. There was no correlation between change-to-predicted liver length and ICGc.

CONCLUSIONS
The intrinsic ability of the liver to extract ICG from plasma was lower in younger burned patients during the acute admission and in those with preexisting chronic malnutrition and inhalation injury at the time of discharge from the ICU.

LEVEL OF EVIDENCE
Prognostic/Epidemiologic, level III.
Risk taking and impulsive behaviour: fundamental discoveries, theoretical perspectives and clinical implications
Authors: Isles Anthony R. , Winstanley Catharine A. , Humby Trevor 
Published: December 2018

Our willingness to take risks, our ability to wait or the speed with which to make decisions are central features of our personality. However, it is now recognized that impulsive and risk-taking behaviours are not a unitary construct, and different aspects can be both psychologically and neurally dissociated. The range of neurochemicals and brain systems that govern these behaviours is extensive, and this may be a contributing factor to the phenotypic range seen in the human population. However, this variety can also be pathological as extremes in risk-taking and impulsive behaviours are characteristics of many neuropsychiatric and indeed neurodegenerative disorders. This spans obsessive–compulsive disorder, where behaviour becomes ridged and non-spontaneous, to the nonsensical risk-taking seen in gambling and drug taking.
This article is part of the theme issue ‘Risk taking and impulsive behaviour: fundamental discoveries, theoretical perspectives and clinical implications'.
Impulsivities and addictions: a multidimensional integrative framework informing assessment and interventions for substance use disorders
Authors: Vassileva Jasmin , Conrod Patricia J. 
Published: December 2018

Impulse control is becoming a critical survival skill for the twenty-first century. Impulsivity is implicated in virtually all externalizing behaviours and disorders, and figures prominently in the aetiology and long-term sequelae of substance use disorders (SUDs). Despite its robust clinical and predictive validity, the study of impulsivity is complicated by its multidimensional nature, characterized by a variety of trait-like personality dimensions, as well as by more state-dependent neurocognitive dimensions, with variable convergence across measures. This review provides a hierarchical framework for linking self-report and neurocognitive measures to latent constructs of impulsivity and, in turn, to different psychopathology vulnerabilities, including substance-specific addictions and comorbidities. Impulsivity dimensions are presented as novel behavioural targets for prevention and intervention. Novel treatment approaches addressing domains of impulsivity are reviewed and recommendations for future directions in research and clinical interventions for SUDs are offered.This article is part of the theme issue ‘Risk taking and impulsive behaviour: fundamental discoveries, theoretical perspectives and clinical implications’.
Multiple mutations acquired into canine RecQ-like helicases encoded by the aneuploid genome of transmissible sarcoma
Authors: Kapulkin Wadim J. 
Published: December 2018

ABSTRACTSticker sarcoma – a highly aneuploid, contagious neoplasm circulating in a domestic dog population - is broadly referred as a canine transmissible venereal tumour (CTVT). The karyotype of transmissible Sticker sarcoma appears as a collage of numerical and structural aberrations; the CTVT genome represents the generalized but stable neoplastic aneuploidy of monoclonal origins. Presented is an analysis of genetic events and variants underlying the aneuploid genomic structure of Sticker sarcoma described previously by Murchison et al. (2014) and Decker et al. (2015). Here we explored the above CTVT genomic compendia and mined the existing data - specifically looking for cases of convergence of multiple non-synonymous variants onto a single gene - the mutational patterns indicative for Knudsonian ‘two-hit’ kinetics. A Table I is given, providing theoretical estimates of retaining the intact wild-type copy, expected as a function of a cumulative mutational convergence observed in unphased sequence consensus. We demonstrate that the two canine RecQ-like helicases: Bloom syndrome helicase and RECQL4, encoded by the aneuploid transmissible tumour, have accumulated a multitude of different mutations. Among the sets of most intensely mutated transmissible sarcoma genes, we also identified a canine FANCD2 – yet another previously unnoticed multiple-hit candidate factor. We discuss a possible role of mutated RecQ-like helicases and other cooperating factors, perceivably involved in the maintenance of the neoplastic aneuploidy. We suggest the proposed cooperative actions of CTVT RecQ-like DNA helicases could be relevant interpreting whether variants contributing to RecQ-dependent karyotypic traits, respond to selective pressures that preserve the aneuploid genomic structure of transmissible Sticker sarcoma.
Transcriptome landscape of a thermal-tolerant coral endosymbiont reveals molecular signatures of symbiosis and dysbiosis
Authors: Bellantuono Anthony J. , Dougan Katherine E. , Granados-Cifuentes Camila , Rodriguez-Lanetty Mauricio 
Published: December 2018

AbstractWarming oceans disrupt the critical endosymbiosis between corals and their photosynthetic dinoflagellate endosymbionts of the family Symbiodiniaceae.Durusdinium trenchiiis a heat-tolerant species of Symbiodiniaceae and enhances survival of its coral host, but the basis for tolerance is largely unknown. To identify the underpinnings of heat tolerance and symbiosis, we compared thein hospiteand free-living transcriptomes ofD. trenchiiunder stable temperature conditions and acute hyperthermal stress. We discovered that under stable conditions,in hospitecells exhibit lower transcriptional activity than free-living counterparts, suggesting the shutdown of genes uniquely required for a free-living lifestyle. However, under hyperthermal stress the transcriptional response was largerin hospite, indicating an exacerbated stress environment within the host cell. Significantly, we unraveled the molecular signatures of symbiont heat tolerance within the host, which is a critical step to enable the development of engineered endosymbionts as a tool for restoration of coral reefs.
Duffy Antigen Expression in Erythroid Bone Marrow Precursor Cells of Genotypically Duffy Negative Individuals
Authors: Dechavanne Célia , Dechavanne Sebastien , Metral Sylvain , Roeper Brooke , Krishnan Sushma , Fong Rich , Bennett Seth , Carias Lenore , Chen Edwin , Salinas Nichole D. , Ghosh Anil , Tolia Niraj H. , Woost Philip G. , Jacobberger James W. , Colin Yves , Gamain Benoit , King Christopher L. , Zimmerman Peter A. 
Published: December 2018

AbstractThe gene encoding the Duffy blood group protein (Fy, CD234; additional designations Duffy Antigen Receptor of Chemokines [DARC] and Atypical Chemokine Receptor 1 [ACKR1]) is characterized by a SNP in a GATA-1 transcription factor binding site associated with the erythrocyte silent (ES) phenotype.FYEShomozygous people are viewed to be highly resistant to blood stage infection withPlasmodium vivax. Increasingly, however, studies are reportingP. vivaxinfections in Fy-negative individuals across malarious African countries whereFYESapproaches genetic fixation. This suggests thatP. vivaxhas evolved a Fy-independent RBC invasion pathway, or that the GATA-1 SNP does not abolish Fy expression. Here, we tested the second hypothesis through binding studies to erythroid lineage cells using recombinantP. vivaxDuffy binding protein, the parasite’s invasion ligand and Fy6-specific antibodies. We first observed variable Fy expression on circulating RBCs, irrespective ofFYgenotype;FYESRBCs were periodically Fy-positive. Furthermore, during thein vitroerythroid differentiation of CD34+ cells and onex vivobone marrow samples, we observed Fy expression on erythroid precursor cells fromFYESpeople. Finally, the Fy6-specific nanobody, CA111 was used to capture Fy from the surface ofFYESRBCs. Our findings reveal that the GATA-1 SNP does not fully abolish Fy expression and provide insight on potential susceptibility of Fy-negative people to vivax malaria.SignificanceDuffy blood group negativity results from a single nucleotide polymorphism (SNP) in the gene promoter, and reaches genetic fixation in many African ethnicities. Because the Duffy protein (Fy) is an important contact point duringPlasmodium vivaxhuman red blood cell invasion, Fy-negativity is considered to confer resistance toP. vivaxmalaria. With recent studies in African countries reportingP. vivaxinfection in Fy-negative people, we studied Fy expression across erythroid development. Here we report that theFYpromoter SNP does not abolish Fy protein expression in erythroid progenitors developing in the bone marrow. These results further emphasizes the importance of reticulocytes as targets forP. vivaxblood stage infection and propose a mechanism forP. vivaxinfections in Fy-negative people.
Mapping and characterization of structural variation in 17,795 deeply sequenced human genomes
Authors: Abel Haley J. , Larson David E. , Chiang Colby , Das Indraniel , Kanchi Krishna L. , Layer Ryan M. , Neale Benjamin M. , Salerno William J. , Reeves Catherine , Buyske Steven ,   NHGRI Centers for Common Disease Genomics, Matise Tara C. , Muzny Donna M. , Zody Michael C. , Lander Eric S. , Dutcher Susan K. , Stitziel Nathan O. , Hall Ira M. 
Published: December 2018

ABSTRACTA key goal of whole genome sequencing (WGS) for human genetics studies is to interrogate all forms of variation, including single nucleotide variants (SNV), small insertion/deletion (indel) variants and structural variants (SV). However, tools and resources for the study of SV have lagged behind those for smaller variants. Here, we used a cloud-based pipeline to map and characterize SV in 17,795 deeply sequenced human genomes from common disease trait mapping studies. We publicly release site-frequency information to create the largest WGS-based SV resource to date. On average, individuals carry 2.9 rare SVs that alter coding regions, which affect the dosage or structure of 4.2 genes and account for 4.0-11.2% of rare high-impact coding alleles. Based on a computational model, we estimate that SVs account for 17.2% of rare alleles genome-wide whose predicted deleterious effects are equivalent to loss-of-function (LoF) coding alleles; ~90% of such SVs are non-coding deletions (mean 19.1 per genome). We report 158,991 ultra-rare SVs and show that ~2% of individuals carry ultra-rare megabase-scale SVs, nearly half of which are balanced and/or complex rearrangements. Finally, we exploit this resource to infer the dosage sensitivity of genes and non-coding elements, revealing strong trends related to regulatory element class, conservation and cell-type specificity. This work will help guide SV analysis and interpretation in the era of WGS.
Cyclic Nucleotide-Gated Ion Channel 2 modulates auxin homeostasis and signaling
Authors: Chakraborty Sonhita , Toyota Masatsugu , Moeder Wolfgang , Chin Kimberley , Fortuna Alex , Champigny Marc , Vanneste Steffen , Gilroy Simon , Beeckman Tom , Nambara Eiji , Yoshioka Keiko 
Published: December 2018

ABSTRACTCyclic Nucleotide Gated Ion Channels (CNGCs) have been firmly established as Ca2+-conducting ion channels that regulate a wide variety of physiological responses in plants. CNGC2 has been implicated in plant immunity and Ca2+signaling due to the autoimmune phenotypes exhibited by null mutants ofCNGC2. However,cngc2mutants display additional phenotypes that are unique among autoimmune mutants, suggesting that CNGC2 has functions beyond defense and generates distinct Ca2+signals in response to different triggers. In this study we found thatcngc2mutants showed reduced gravitropism, consistent with a defect in auxin signaling. This was mirrored in the diminished auxin response detected by the auxin reporters DR5::GUS and DII-VENUS and in a strongly impaired auxin-induced Ca2+response. Moreover, thecngc2mutant exhibits higher levels of the endogenous auxin indole-3-acetic acid (IAA), indicating that excess auxin incngc2causes its pleiotropic phenotypes. These auxin signaling defects and the autoimmunity syndrome ofcngc2could be suppressed by loss-of-function mutations in the auxin biosynthesis geneYUCCA6(YUC6), as determined by identification of thecngc2suppressor mutantrepressor of cngc2(rdd1) as an allele ofYUC6. A loss-of-function mutation in the upstream auxin biosynthesis geneTRYPTOPHAN AMINOTRANSFERASE OF ARABIDOPSIS(TAA1, WEAK ETHYLENE INSENSITIVE8) also suppressed thecngc2phenotypes, further supporting the tight relationship between CNGC2 and the TAA–YUC-dependent auxin biosynthesis pathway. Taking these results together, we propose that the Ca2+signal generated by CNGC2 is a part of the negative feedback regulation of auxin homeostasis in which CNGC2 balances cellular auxin perception by influencing auxin biosynthesis.
Stochastic transcriptional pulses orchestrate flagellum biosynthesis in E. coli
Authors: Kim J. Mark , Garcia-Alcala Mayra , Balleza Enrique , Cluzel Philippe 
Published: December 2018

AbstractThe classic picture of flagellum biosynthesis in E. coli, inferred from population measurements, describes a tightly controlled, deterministic transcriptional program. In individual E. coli cells, we discover that flagellar promoters are in fact stochastically activated in pulses. Such pulses comprise coordinated ‘on’ and ‘off’ states of promoter activity, each of which can span multiple generations. We demonstrate that this pulsing program obeys the regulatory logic of flagellar assembly, which dictates whether some promoters skip pulses. Remarkably, pulses in this transcriptional network appear to be actually governed by a post-translational circuit. Our results suggest that even topologically simple transcriptional networks can generate unexpectedly rich temporal dynamics and phenotypic heterogeneities.
Structural basis of recognition and destabilization of histone H2B ubiquitinated nucleosome by DOT1L histone H3 Lys79 methyltransferase
Authors: Jang Seongmin , Kang Chanshin , Yang Han-Sol , Jung Taeyang , Hebert Hans , Chung Ka Young , Kim Seung Joong , Hohng Sungchul , Song Ji-Joon 
Published: December 2018

AbstractDOT1L is a histone H3 Lys79 methyltransferase whose activity is stimulated by histone H2B Lys120 ubiquitination, suggesting cross-talk between histone H3 methylation and H2B-ubiquitination. Here, we present cryo-EM structures of DOT1L complex with unmodified and H2B-ubiquitinated nucleosomes, showing that DOT1L recognizes H2B-ubiquitin and the H2A/H2B acidic patch through a C-terminal hydrophobic helix and an arginine anchor in DOT1L respectively. Furthermore, the structures combined with single-molecule FRET experiment show that H2B-ubiquitination enhances a non-catalytic function of DOT1L destabilizing nucleosome. These results establish the molecular basis of the cross-talk between H2B ubiquitination and H3 Lys79 methylation as well as nucleosome destabilization by DOT1L.
Automated nuclear cartography reveals conserved sperm chromosome territory localization across 2 million years of mouse evolution
Authors: Skinner Benjamin Matthew , Bacon Joanne , Rathje Claudia Cattoni , Larson Erica Lee , Kopania Emily Emiko Konishi , Good Jeffrey Martin , Affara Nabeel Ahmed , Ellis Peter James Ivor 
Published: December 2018

AbstractMeasurements of nuclear organization in asymmetric nuclei in 2D images have traditionally been manual. This is exemplified by attempts to measure chromosome position in sperm samples, typically by dividing the nucleus into zones, and manually scoring which zone a FISH signal lies in. This is time consuming, limiting the number of nuclei that can be analyzed, and prone to subjectivity. We have developed a new approach for automated mapping of FISH signals in asymmetric nuclei, integrated into an existing image analysis tool for nuclear morphology. Automatic landmark detection defines equivalent structural regions in each nucleus, then dynamic warping of the FISH images to a common shape allows us to generate a composite of the signal within the entire cell population. Using this approach, we mapped the positions of the sex chromosomes and two autosomes in three mouse lineages (Musmusculus domesticus, Mus musculus musculusandMus spretus). We found that in all three, chromosomes 11 and 19 tend to interact with each other, but are shielded from interactions with the sex chromosomes. This organization is conserved across 2 million years of mouse evolution.
Leveraging protein dynamics to identify cancer mutational hotspots in 3D-structures
Authors: Kumar Sushant , Clarke Declan , Gerstein Mark B. 
Published: December 2018

AbstractLarge-scale exome sequencing of tumors has enabled the identification of cancer drivers using recurrence and clustering-based approaches. Some of these methods also employ three-dimensional protein structures to identify mutational hotspots in cancer-associated genes. In determining such mutational clusters in structures, existing approaches overlook protein dynamics, despite the essential role of dynamics in protein functionality. In this work, we present a framework to identify driver genes using a dynamics-based search of mutational hotspot communities. After partitioning 3D structures into distinct communities of residues using anisotropic network models, we map variants onto the partitioned structures. We then search for signals of positive selection among these residue communities to identify putative drivers. We applied our method using the TCGA pan-cancer atlas missense mutation catalog. Overall, our analyses predict one or more mutational hotspots within the resolved structures of 434 genes. Ontological and pathway enrichment analyses implicate genes with predicted hotspots to be enriched in biological processes associated with tumor progression. Additionally, a comparison between our approach and existing hotspot detection methods that use structural data suggests that the inclusion of dynamics significantly increases the sensitivity of driver detection.
Molecular Crowding Tunes Material States of Ribonucleoprotein Condensates
Authors: Kaur Taranpreet , Alshareedah Ibraheem , Wang Wei , Ngo Jason , Moosa Mahdi Muhammad , Banerjee Priya R. 
Published: December 2018

AbstractRibonucleoprotein (RNP) granules are membraneless liquid condensates that dynamically form, dissolve, and mature into a gel-like state in response to changing cellular environment. RNP condensation is largely governed by the promiscuous attractive inter-chain interactions, mediated by low-complexity domains (LCDs). Using an archetypal disordered RNP, Fused in Sarcoma (FUS), here we study how molecular crowding impacts the RNP liquid condensation. We observe that the liquid-liquid coexistence boundary of FUS is lowered by polymer crowders, consistent with the excluded volume model. With increasing bulk crowder concentration, RNP partition increases and the diffusion rate decreases in the condensed phase. Furthermore, we show that RNP condensates undergo substantial hardening wherein protein-dense droplets transition from viscous fluid to a viscoelastic gel-like state in a crowder concentration-dependent manner. Utilizing two distinct LCDs that broadly represent the most commonly occurring sequence motifs driving RNP phase transition, we reveal that the impact of crowding is largely independent of LCD charge/sequence patterns. These results are consistent with a thermodynamic model of crowder-mediated depletion interaction where inter-RNP attraction is enhanced by molecular crowding. The depletion force is likely to play key roles in tuning the physical properties of RNP condensates within a crowded intracellular space.
The convoluted evolutionary history of the capped-golden langur lineage (Cercopithecidae: Colobinae) – concatenation versus coalescent analyses
Authors: Arekar Kunal , Parigi Abhijna , Karanth K. Praveen 
Published: December 2018

AbstractEvolutionary studies have traditionally relied on concatenation based methods to reconstruct relationships from multiple markers. However, due to limitations of concatenation analyses, recent studies have proposed coalescent based methods to address evolutionary questions. Results from these methods tend to diverge from each other under situations where there is incomplete lineage sorting or hybridization. Here we used concatenation as well as multispecies coalescent (MSC) methods to understand the evolutionary origin of capped and golden langur (CG) lineage. Previous molecular studies have retrieved conflicting phylogenies, with mitochondrial tree grouping CG lineage with a largely Indian genus Semnopithecus, while nuclear markers support their affinities with a Southeast Asian genus, Trachypithecus. However, as pointed by others, the use of nuclear copies of mitochondrial DNA in the above studies might have generated the discordance. Because of this discordance, the phylogenetic position of CG lineage has been much debated in recent times. In this study, we have used nine nuclear and eight mitochondrial markers. Concatenated nuclear as well as the mitochondrial dataset recovered congruent relationships where CG lineage was sister to Trachypithecus. However nuclear species tree estimated using different MSC methods were incongruent with the above result, suggesting presence of incomplete lineage sorting (ILS)/hybridisation. Furthermore, CG lineage is morphologically intermediate between Semnopithecus and Trachypithecus. Based on this evidence, we argue that CG lineage evolved through hybridisation between Semnopithecus and Trachypithecus. Finally, we reason that both concatenation as well as coalescent methods should be used in conjunction for better understanding of various evolutionary hypotheses.