bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recertification Exam Performance in General Surgery is Associated With Subsequent Loss of License Actions
Authors: Jones Andrew T. , Kopp Jason P. , Malangoni Mark A. 
Published: April 2019

Objectives:
To measure associations between first-time performance on the American Board of Surgery (ABS) recertification exam with subsequent state medical licensing board disciplinary actions.

Background:
Time-limited board certification has been criticized as unnecessary. Few studies have examined the relationship between recertification exam performance and outcomes.

Methods:
Retrospective analysis of loss-of-license action rates for general surgeons who were initially certified by the ABS from 1976 to 2005 and attempted to take a surgery recertification exam. Disciplinary actions from 1976 to 2016 were obtained from the Disciplinary Action Notification System through the American Board of Medical Specialties.

Results:
A total of 14,169 general surgeons attempted to pass the surgery recertification exam. The rate of loss-of-license actions was significantly higher for surgeons who failed their first exam attempt [incidence rate 3.41, 95% confidence interval (CI) 2.27–4.56] than those who passed on their first attempt (incidence rate .01, 95% CI 0.87–1.14). A Cox proportional-hazards regression model found that the adjusted hazard rate for loss-of-license actions for surgeons who failed their first recertification exam were significantly higher than those who passed their first attempt after adjusting for multiple surgeon characteristics (adjusted hazard rate 2.98, 95% CI 1.85–4.81).

Conclusions:
Failing the first recertification exam attempt was associated with a greater rate of subsequent loss-of-license actions. These results suggest that demonstrating sufficient surgical knowledge is a significant predictor of future loss-of-license actions.
Proteoliposomes as energy transferring nanomaterials: enhancing the spectral range of light-harvesting proteins using lipid-linked chromophores
Authors: Hancock Ashley M. , Meredith Sophie A. , Connell Simon D. A. , Jeuken Lars J. C. , Adams Peter G. 
Published: April 2019

AbstractBiology provides a suite of optically-active nanomaterials in the form of “light harvesting” protein-chlorophyll complexes, however, these have drawbacks including their limited spectral range. We report the generation of model lipid membranes (proteoliposomes) incorporating the photosynthetic protein Light-Harvesting Complex II (LHCII) and lipid-tethered Texas Red (TR) chromophores that act as a “bio-hybrid” energy transferring nanomaterial. The effective spectral range of the protein is enhanced due to highly efficient energy transfer from the TR chromophores (up to 94%), producing a marked increase in LHCII fluorescence (up to 3x). Our self-assembly procedure offers excellent modularity allowing the incorporation of a range of concentrations of energy donors (TR) and acceptors (LHCII), allowing the energy transfer efficiency (ETE) and LHCII fluorescence to be tuned as desired. Fluorescence Lifetime Imaging Microscopy (FLIM) provides single-proteoliposome-level quantification of ETE, revealing distributions within the population and proving that functionality is maintained on a surface. Our membrane-based system acts as a controllable light harvesting nanomaterial with potential applications as thin films in photo-active devices.Table of Contents Figure
Geothermal stickleback populations prefer cool water despite multigenerational exposure to a warm environment
Authors: Pilakouta Natalie , Killen Shaun S. , Kristjánsson Bjarni K. , Skúlason Skúli , Lindström Jan , Metcalfe Neil B. , Parsons Kevin J. 
Published: April 2019

ABSTRACTGiven the threat of climate change to biodiversity, a growing number of studies are investigating the potential for organisms to adapt to rising temperatures. Earlier work has predicted that physiological adaptation to climate change will be accompanied by a shift in temperature preferences, but empirical evidence for this is lacking. Here, we test whether exposure to different thermal environments has led to changes in preferred temperatures in the wild. Our study takes advantage of a ‘natural experiment’ in Iceland, where freshwater populations of threespine sticklebacks (Gasterosteus aculeatus) are found in waters warmed by geothermal activity year-round (warm habitats), adjacent to populations in ambient-temperature lakes (cold habitats). We used a shuttle-box approach to measure temperature preferences of wild-caught sticklebacks from three warm-cold population pairs. Our prediction was that fish from warm habitats would prefer higher water temperatures than those from cold habitats. We found no support for this, as fish from both warm and cold habitats had an average preferred temperature of 13°C. Thus, our results challenge the assumption that there will be a shift in ectotherm temperature preferences in response to climate change. In addition, since warm-habitat fish can persist at relatively high temperatures despite a lower temperature preference, this suggests that preferred temperature alone may be a poor indicator of a population’s adaptive potential to a novel thermal environment.
A bifunctional ATPase drives tad pilus extension and retraction
Authors: Ellison Courtney K. , Kan Jingbo , Chlebek Jennifer L. , Hummels Katherine R. , Panis Gaёl , Viollier Patrick H. , Biais Nicolas , Dalia Ankur B. , Brun Yves V. 
Published: April 2019

AbstractMolecular motors convert chemical energy directly into mechanical work1and are found in all domains of life2. These motors are critical to intracellular transport3, motility4,5, macromolecular protein assembly3,6, and many essential processes7. A wide-spread class of related bacterial motors drive the dynamic activity of extracellular fibers, such as type IV pili (T4P), that are extended and retracted using so-called secretion motor ATPases. Among these, the tightadherence (tad) pili are critical for surface sensing, surface attachment, and biofilm formation8–10. How tad pili undergo dynamic cycles of extension and retraction8despite lacking a dedicated retraction motor ATPase has remained a mystery. Here we find that a bifunctional pilus motor ATPase, CpaF, drives both activities through ATP hydrolysis. Specifically, we show that mutations within the ATP hydrolysis active site ofCaulobacter crescentusCpaF result in a correlated reduction in the rates of extension and retraction. Moreover, a decrease in the rate of ATP hydrolysis directly scales with a decrease in the force of retraction and reduced dynamics in these CpaF mutants. This mechanism of motor protein bifunctionality extends to another genus of tad-bearing bacteria. In contrast, the T4aP subclass of pili possess dedicated extension and retraction motor ATPase paralogs. We show that these processes are uncoupled using a slow ATP hydrolysis mutation in the extension ATPase of competence T4aP ofVibrio choleraethat decreases the rate of extension but has no effect on the rate of retraction. Thus, a single motor ATPase is able to drive the bidirectional processes of pilus fiber extension and retraction.
Evolution of Yin and Yang isoforms of a chromatin remodeling subunit results in the creation of two genes
Authors: Xu Wen , Long Lijiang , Zhao Yuehui , Stevens Lewis , Ellis Ronald E. , McGrath Patrick T. 
Published: April 2019

AbstractGenes can encode multiple isoforms, broadening their functions and providing a molecular substrate to evolve phenotypic diversity. Evolution of isoform function is a potential route to adapt to new environments. Here we show thatde novo, beneficial alleles in thenurf-1gene fixed in two laboratory strains ofC. elegansafter isolation from the wild in 1951, before methods of cryopreservation were developed.nurf-1encodes an ortholog of BPTF, a large (>300kD) multidomain subunit of the NURF chromatin remodeling complex. Using CRISPR-Cas9 genome editing and transgenic rescue, we demonstrate that inC. elegans,nurf-1has split into two, largely non-overlapping isoforms (NURF-1.B and NURF-1.D, which we call Yin and Yang) that share only two of 26 exons. Both isoforms are essential for normal gametogenesis but have opposite effects on male/female gamete differentiation. Reproduction in hermaphrodites, which involves production of both sperm and oocytes, requires a balance of these opposing Yin and Yang isoforms. Transgenic rescue and genetic position of the fixed mutations suggest that different isoforms are modified in each laboratory strain. In a related clade ofCaenorhabditisnematodes, the shared exons have duplicated, resulting in the split of the Yin and Yang isoforms into separate genes, each containing approximately 200 amino acids of duplicated sequence that has undergone accelerated protein evolution following the duplication. Associated with this duplication event is the loss of two additionalnurf-1transcripts, including the long-form transcript and a newly identified, highly expressed transcript encoded by the duplicated exons. We propose these lost transcripts are non-functional biproducts necessary to transcribe the Yin and Yang transcripts in the same cells. Our work suggests that evolution ofnurf-1isoforms in nematodes creates adaptive conflict that can be resolved by the creation of new, independent genes.
DeepInterface: Protein-protein interface validation using 3D Convolutional Neural Networks
Authors: Balci A.T. , Gumeli C. , Hakouz A. , Yuret D. , Keskin O. , Gursoy Attila 
Published: April 2019

AbstractMotivationProtein–protein interactions are crucial in almost all biological processes. Proteins interact through their interfaces. It is important to determine how proteins interact through interfaces to understand protein binding mechanisms and to predict new protein-protein interactions.ResultsWe present DeepInterface, a deep learning based method which predicts, for a given protein complex, if the interface between the proteins of a complex is a true interface or not. The model is a 3-dimensional convolutional neural networks model and the positive datasets are obtained from all complexes in the Protein Data Bank, the negative datasets are the incorrect solutions of the docking decoys. The model analyzes a given interface structure and outputs the probability of the given structure being an interface. The accuracy of the model for several interface data sets, including PIFACE, PPI4DOCK, DOCKGROUND is approximately 88% in the validation dataset and 75% in the test dataset. The method can be used to improve the accuracy of template based PPI predictions.
Single cell RNA-seq reveals cellular diversity and developmental characteristics of human infant retina
Authors: Zhong Jixing , Chen Dongsheng , Hu Fangyuan , Chen Fang , Xu Zaoxu , Fang Jian , Xu Jianjiang , Wang Shiyou , Liang Langchao , Chai Chaochao , Ding Xiangning , Zhu Jiacheng , Ding Peiwen , Xia Jun , Jiang Sanjie , Li Wei , Gao Ya , Zhang Jianguo , Li Jiankang , Xu Ping , Gao Fengjuan , Wang Dandan , Zhang Daowei , Huang Jie , Qu Shoufang , Zhang Shenghai , Wu Jihong , Sun Xinghuai 
Published: April 2019

AbstractRetina, located in the innermost layer of the eye of human, holds the decisive role in visual perception. Dissecting the heterogeneity of retina is essential for understanding the mechanism of vision formation and even the development of central nervous system (CNS). Here, we performed single cell RNA-seq, analyzed 57,832 cells from human infant donors, resulting in 20 distinct clusters representing major cell types in retina: rod photoreceptors, cone photoreceptors, bipolar cells, horizontal cells, amacrine cells, Muller glia cells and microglia. We next constructed extensive networks of intercellular communication and identified ligand-receptor interactions playing crucial roles in regulating neural cell development and immune homeostasis in retina. Though re-clustering, we identified known subtypes in cone PRs and additional unreported subpopulations and corresponding markers in rod PRs as well as bipolar cells. Additionally, we linked inherited retinal disease to certain cell subtypes or subpopulations through enrichment analysis. Intriguingly, we found that status and functions of photoreceptors changed drastically between early and late retina. Overall, our study offers the first retinal cell atlas in human infants, dissecting the heterogeneity of retina and identifying the key molecules in the developmental process, which provides an important resource that will pave the way for retina development mechanism research and regenerative medicine concerning retinal biology.
Bactofilins form non-polar filaments that bind to membranes directly
Authors: Deng Xian , Gonzalez Llamazares Andres , Wagstaff James , Hale Victoria L. , Cannone Giuseppe , McLaughlin Stephen H. , Kureisaite-Ciziene Danguole , Löwe Jan 
Published: April 2019

AbstractBactofilins are small beta-helical proteins that form cytoskeletal filaments in a range of bacteria. Bactofilins have diverse functions: filaments inCaulobacter crescentusare involved in cell stalk formation whereasMyxococcus xanthusfilaments aid chromosome segregation and motility. The precise molecular architecture of bactofilin filaments has remained unclear. Here we revealed by sequence analyses and electron microscopy that in addition to wide distribution across bacteria and archaea, bactofilins are also present in a few eukaryotic cells such as oomycetes. The sole bactofilin fromThermus thermophiluswas demonstrated to form constitutive filaments and cryo-EM analysis revealed that protofilaments formed through end-to-end association of the beta-helical domains. Using a nanobody againstThermusbactofilin we determined the near-atomic filament structure, showing that the filaments are non-polar, with subunits arranged head-to-head and tail-to-tail. A polymerisation-impaired mutant F105R, that disrupts one of the two protofilament interfaces, enabled crystallisation. The crystal structure also revealed non-polar protofilaments, and the dominance of the beta-stacking interface that formed despite the inhibiting mutation. To confirm the generality of the lack of polarity, we performed co-evolutionary analysis of a large set of sequences. Finally, usingThermusbactofilin, we determined that the N-terminal disordered tail of the protein is responsible for direct binding to lipid membranes both on liposomes and by electron cryotomography inE. colicells. The tail is conserved, suggesting that membrane binding is likely a general feature of these very common but only recently discovered filaments of the prokaryotic cytoskeleton.
Mutant p53 Drives Clonal Hematopoiesis through Modulating Epigenetic Pathway
Authors: Chen Sisi , Wang Qiang , Yu Hao , Capitano Maegan L. , Vemula Sasidhar , Nabinger Sarah C. , Gao Rui , Yao Chonghua , Kobayashi Michihiro , Geng Zhuangzhuang , Fahey Aidan , Henley Danielle , Liu Stephen Z. , Wolf Eric R. , Ramdas Baskar , Cai Zhigang , Gao Hongyu , Luo Na , Sun Yang , Wong Terrence N. , Link Daniel C. , Liu Yunlong , Boswell H. Scott , Mayo Lindsey D. , Huang Gang , Kapur Reuben , Yoder Mervin C. , Broxmeyer Hal E. , Gao Zhonghua , Liu Yan 
Published: April 2019

AbstractClonal hematopoiesis of indeterminate potential (CHIP) increases with age and is associated with increased risks of hematological malignancies. WhileTP53mutations have been identified in CHIP, the molecular mechanisms by which mutant p53 promotes hematopoietic stem and progenitor cell (HSPC) expansion are largely unknown. We discovered that mutant p53 confers a competitive advantage to HSPCs following transplantation and promotes HSPC expansion after radiation-induced stress. Mechanistically, mutant p53 interacts with EZH2 and enhances its association with the chromatin, thereby increasing the levels of H3K27me3 in genes regulating HSPC self-renewal and differentiation. Further, genetic and pharmacological inhibition of EZH2 decrease the repopulating potential of p53 mutant HSPCs. Thus, we have uncovered an epigenetic mechanism by which mutant p53 drives clonal hematopoiesis. Our work will likely establish epigenetic regulator EZH2 as a novel therapeutic target for preventing CHIP progression and treating hematological malignancies withTP53mutations.
Metabolic control of YAP via the acto-myosin system during liver regeneration
Authors: Meyer Kirstin , Morales-Navarrete Hernan , Seifert Sarah , Wilsch-Braeuninger Michaela , Dahmen Uta , Tanaka Elly M. , Brusch Lutz , Kalaidzidis Yannis , Zerial Marino 
Published: April 2019

AbstractThe mechanisms of organ size control remain poorly understood. A key question is how cells collectively sense the overall status of a tissue. We addressed this problem focusing on mouse liver regeneration, which is controlled by Hippo signalling. Using digital tissue reconstruction and quantitative image analysis, we found that the apical surface of hepatocytes forming the bile canalicular network expands concomitant with an increase of F-actin and phospho-Myosin, to compensate an overload of bile acids. Interestingly, these changes are sensed by the Hippo transcriptional co-activator YAP, which localizes to the apical F-actin-rich region and translocates to the nucleus in dependence of the acto-myosin system. This mechanism tolerates moderate bile acid fluctuations under tissue homeostasis, but activates YAP in response to sustained bile acid overload. Using an integrated biophysical-biochemical model of bile pressure and Hippo signalling, we explained this behaviour by the existence of a mechano-sensory mechanism that activates YAP in a switch-like manner. We propose that the apical surface of hepatocytes acts as a self-regulatory mechano-sensory system that responds to critical levels of bile acids as readout of tissue status.
A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank
Authors: Shen Xueyi , Howard David M , Adams Mark J ,   23andMe Research Team, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Deary Ian J , Whalley Heather C , McIntosh Andrew M 
Published: April 2019

AbstractDepression is the leading cause of worldwide disability but there remains considerable uncertainty regarding its neural and behavioural associations. Depression is known to be heritable with a polygenic architecture, and results from genome-wide associations studies are providing summary statistics with increasing polygenic signal that can be used to estimate genetic risk scores for prediction in independent samples. This provides a timely opportunity to identify traits that are associated with polygenic risk of depression in the large and consistently phenotyped UK Biobank sample. Using the Psychiatric Genomics Consortium (PGC), 23andMe and non-imaging UK Biobank datasets as reference samples, we estimated polygenic risk scores for depression (depression-PRS) in a discovery sample of 10,674 people and a replication sample of 11,214 people from the UK Biobank Imaging Study, testing for associations with 210 behavioural and 278 neuroimaging phenotypes. In the discovery sample, 93 traits were significantly associated with depression-PRS after multiple testing correction. Among these, 92 traits were in the same direction, and 69 were significant in the replication analysis. For imaging traits that replicated across samples, higher depression-PRS was associated with lower global white matter microstructure, association-fibre and thalamic-radiation microstructural integrity (absolute β: 0.023 to 0.040, PFDR: 0.045 to 3.92×10-4). Mendelian Randomisation analysis showed a causal effect of liability to depression on these structural brain measures (β: 0.125 to 0.707, pFDR<0.048). Replicated behavioural traits that positively associated with depression-PRS included sleep problems, smoking status, measures of pain and stressful life experiences, and those negatively associated with depression-PRS included subjective ratings of physical health (absolute β: 0.014 to 0.180, PFDR: 0.046 to 8.54×10-15). Effect of depression PRS on mental health in the presence of reported childhood trauma, stressful life events and those living in more socially deprived areas showed increased variance explained by 1.42 – 4.08 times (pFDR for their interaction with depression-PRS: 0.049 to 0.003). Overall, the present study revealed replicable associations between depression-PRS and white matter microstructure that appeared to be a causal consequence of liability to depression. Analyses provided further evidence that greater effects of polygenic risk of depression are found in individuals exposed to risk-conferring environments.
ADrosophilalarval premotor/motor neuron connectome generating two behaviors via distinct spatio-temporal muscle activity
Authors: Zarin Aref Arzan , Mark Brandon , Cardona Albert , Litwin-Kumar Ashok , Doe Chris Q. 
Published: April 2019

AbstractAnimals generate diverse motor behaviors, yet how the same motor neurons generate distinct behaviors remains an open question.Drosophilalarvae have multiple behaviors – e.g. forward crawling, backward crawling, self-righting and escape – and all of the body wall motor neurons (MNs) driving these behaviors have been identified. Despite impressive progress in mapping larval motor circuits, the role of most motor neurons in locomotion remains untested, the majority of premotor neurons (PMNs) remain to be identified, and a full understanding of proprioceptor-PMN-MN connectivity is missing. Here we report a comprehensive larval proprioceptor-PMN-MN connectome; describe individual muscle/MN phase activity during both forward and backward locomotor behaviors; identify PMN-MN connectivity motifs that could generate muscle activity phase relationships, plus selected experimental validation; identify proprioceptor-PMN connectivity that provides an anatomical explanation for the role of proprioception in promoting locomotor velocity; and identify a new candidate escape motor circuit. Finally, we generate a recurrent network model that produces the observed sequence of motor activity, showing that the identified pool of premotor neurons is sufficient to generate two distinct larval behaviors. We conclude that different locomotor behaviors can be generated by a specific group of premotor neurons generating behavior-specific motor rhythms.
Genetic divergence outpaces phenotypic divergence among threespine stickleback populations in old freshwater habitats
Authors: Currey Mark C. , Bassham Susan L. , Cresko William A. 
Published: April 2019

ABSTRACTSpecies such as threespine stickleback fish that are distributed across landscapes with divergent selective environments and that have diversified on different time scales can be valuable for understanding evolutionary processes. Here we synthesize high resolution genotypic and phenotypic data to explore a largely unstudied distribution of threespine stickleback populations living in marine and freshwater habitats along coastal and inland regions of northwestern Oregon. Because many inland aquatic habitats of Oregon were not glaciated during the last ice age, we hypothesized that some extant Oregon lake and river stickleback are descended from freshwater populations that were established long before the well-studied, postglacial freshwater populations of Alaska. Here we characterize the major phenotypic and genetic axes of differentiation in Oregon stickleback, and compare these patterns to their Alaska counterparts currently inhabiting regions that were covered by ice during the last glacial maximum. Phenotypic variation in Oregon stickleback is predictably partitioned between oceanic and freshwater habitats. However, we also found that genetic divergence in Oregon ecotypes is much greater than divergence among studied stickleback populations in Alaska. Additionally, we report a surprising phenotypic and genetic affinity between oceanic stickleback with freshwater populations that live far inland in two Oregon river basins.