bluuebunny/crossref_metadata_2025_split huggingface dataset:
More Than 25 Years of Pancreas Graft Survival After Simultaneous Pancreas and Kidney Transplantation: Experience From the World's Largest Series of Long-term Survivors
Authors: Parajuli Sandesh , Bath Natalie M. , Aziz Fahad , Garg Neetika , Muth Brenda , Djamali Arjang , Redfield Robert R. , Kaufman Dixon , Odorico Jon , Mandelbrot Didier , Sollinger Hans 
Published: September 2019

Background.
The first simultaneous pancreas and kidney (SPK) transplant was performed in 1966. Early procedures were associated with significant morbidity and mortality and were performed in very low numbers in select patients.

Methods.
This study includes all recipients of an SPK at the University of Wisconsin-Madison between 1986 and 1993, who were actively followed and had a functional pancreas allograft for >25 years as of October 31, 2018.

Results.
A total of 291 SPK were performed during the study period; of these, 39 patients still had a functional graft at last follow up and 9 (18.8%) pancreas grafts were lost due to patient death or graft failure after >25 years. At last follow up, all 39 patients with functional pancreas graft had at least one comorbidity, such as hypertension, hyperlipidemia, or coronary artery disease. Twenty-seven required enteric conversion; 11 patients experienced renal allograft failure (10 underwent a repeat kidney transplant); and 6 required amputation of part of the lower extremity. In the Cox regression analysis, bladder drained pancreas was associated with lower probability of prolonged pancreas graft survival (hazard ratio: 0.52; confidence interval: 0.32-0.85; P = 0.01).

Conclusions.
With careful and detailed follow-up and attention to complications, some recipients of pancreas grafts have outstanding outcomes. As the number of pancreas recipients with prolonged graft survival may be rising, healthcare providers should be aware of the management of complications associated with this unique group of patients.
A structured approach to evaluating life course hypotheses: Moving beyond analyses of exposed versus unexposed in the omics context
Authors: Zhu Yiwen , Simpkin Andrew J. , Suderman Matthew J. , Lussier Alexandre A. , Walton Esther , Dunn Erin C. , Smith Andrew D.A.C. 
Published: September 2019

AbstractBackgroundLife course epidemiology provides a framework for studying the effects of time-varying exposures on health outcomes. The structured life course modeling approach (SLCMA) is a theory-driven analytic method that empirically compares multiple prespecified life course hypotheses characterizing time-dependent exposure-outcome relationships to determine which theory best fits the observed data. However, the statistical properties of inference methods used with the SLCMA have not been investigated with high-dimensional omics outcomes.MethodsWe performed simulations and empirical analyses to evaluate the performance of the SLCMA when applied to genome-wide DNA methylation (DNAm). In the simulations, we compared five statistical inference tests used by SLCMA (n=700). For each, we assessed the familywise error rate (FWER), statistical power, and confidence interval coverage to determine whether inference based on these tests was valid in the presence of substantial multiple testing and small effect sizes, two hallmark challenges of inference from omics data. In the empirical analyses, we applied the SLCMA to evaluate the time-dependent relationship of childhood abuse with genome-wide DNAm (n=703).ResultsIn the simulations, selective inference and max-|t|-test performed best: both controlled FWER and yielded moderate statistical power. Empirical analyses using SLCMA revealed time-dependent effects of childhood abuse on DNA methylation.ConclusionsOur findings show that SLCMA, applied and interpreted appropriately, can be used in the omics setting to examine time-dependent effects underlying exposure-outcome elationships over the life course. We provide recommendations for applying the SLCMA in high-throughput settings, which we hope will encourage researchers to move beyond analyses of exposed versus unexposed.Key messagesThe structured life course modeling approach (SLCMA) is an effective approach to directly compare life course theories and can be scaled-up in the omics context to examine nuanced relationships between environmental exposures over the life course and biological processes.Of the five statistical inference tests assessed in simulations, we recommend the selective inference method and max-|t|-test for post-selection inference in omics applications of the SLCMA.In an empirical example, we revealed time-dependent effects of childhood abuse on DNA methylation using the SLCMA, with improvement in statistical power when accounting for covariates by applying the Frisch-Waugh-Lovell (FWL) theorem.Researchers should assess p-values in parallel with effects sizes and confidence intervals, as triangulating multiple forms of statistical evidence can strengthen inferences and point to new directions for replication.
Phasic dopamine enhances the distinct decoding and perceived salience of stimuli
Authors: Oettl Lars-Lennart , Scheller Max , Wieland Sebastian , Haag Franziska , Wolf David , Loeb Cathrin , Ravi Namasivayam , Durstewitz Daniel , Shusterman Roman , Russo Eleonora , Kelsch Wolfgang 
Published: September 2019

AbstractSubjects learn to assign value to stimuli that predict outcomes. Novelty, rewards or punishment evoke reinforcing phasic dopamine release from midbrain neurons to ventral striatum that mediates expected value and salience of stimuli in humans and animals. It is however not clear whether phasic dopamine release is sufficient to form distinct engrams that encode salient stimuli within these circuits. We addressed this question in awake mice. Evoked phasic dopamine induced plasticity selectively to the population encoding of coincidently presented stimuli and increased their distinctness from other stimuli. Phasic dopamine thereby enhanced the decoding of previously paired stimuli and increased their perceived salience. This dopamine-induced plasticity mimicked population coding dynamics of conditioned stimuli during reinforcement learning. These findings provide a network coding mechanism of how dopaminergic learning signals promote value assignment to stimulus representations.
Coupling Terrestrial Laser Scanning with 3D Fuel Biomass Sampling for Advancing Wildland Fuels Characterization
Authors: Rowell Eric , Loudermilk E. Louise , Hawley Christie , Pokswinski Scott , Seielstad Carl , Queen Lloyd , O’Brien Joseph J. , Hudak Andrew T. , Goodrick Scott , Hiers J. Kevin 
Published: September 2019

AbstractThe spatial pattern of surface fuelbeds in fire-dependent ecosystems are rarely captured using long-standing fuel sampling methods. New techniques, both field sampling and remote sensing, that capture vegetation fuel type, biomass, and volume at super fine-scales (cm to dm) in three-dimensions (3D) are critical to advancing forest fuel and wildland fire science. This is particularly true for computational fluid dynamics fire behavior models that operate in 3D and have implications for wildland fire operations and fire effects research. This study describes the coupling of new 3D field sampling data with terrestrial laser scanning (TLS) data to infer fine-scale fuel mass in 3D. We found that there are strong relationships between fine-scale mass and TLS occupied volume, porosity, and surface area, which were used to develop fine-scale prediction equations using TLS across vegetative fuel types, namely grasses and shrubs. The application of this novel 3D sampling technique to high resolution TLS data in this study represents a major advancement in understanding fire-vegetation feedbacks in highly managed fire-dependent ecosystems.
Angle-tuned Coil: A Focal Spot-size Adjustable Transcranial Magnetic Stimulator
Authors: Meng Qinglei , Bagherzadeh Hedyeh , Loiacono Julian , Du Xiaoming , Hong Elliot , Yang Yihong , Lu Hanbing , Choa Fow-Sen 
Published: September 2019

AbstractBackgroundConventional transcranial magnetic stimulation (TMS) coils are limited by the depth-focality tradeoff rule and the emission field intensity from coils with either small or large apertures will diverge quickly at less than one aperture diameter distance away from the coil. To utilize a better depth-focality tradeoff rule and accomplish deep and focused stimulation, a new approach needs to be employed.ObjectivesWe report a new TMS coil design that can deliver deep and spot size adjustable stimulation to deep brain regions.MethodsIn our design, we introduce a magnetic core at the center of a coil to help confine the magnetic field and prevent leakage. We further tilted the wire wrapping angle of the coil to break its ring symmetry and accomplish tunable focusing by adjusting the tilting angle.ResultsBy comparing the electric field decay curves of five types of coils, our results concluded the proposed novel method to improve the coils’ depth-focality profile. Both theoretical calculations and experimental data collectively demonstrated that by using a larger tilting angle, we were able to accomplish a more tightly focused stimulation at any distance away from the coil.ConclusionEnlarging the tilting angle of the coil wire wrapping and applying magnetic core significantly improved the spatial resolution of the field without inducing considerable effect on field decay speed. Our novel TMS coil design plots a new curve in the depth-focality profile with better performance than the existing conventional coil designs in the tradeoff rule.
Complex multi-trait responses to multivariate environmental cues in a seasonal butterfly
Authors: Singh Pragya , van Bergen Erik , Brattström Oskar , Osbaldeston Dave , Brakefield Paul M. , Oostra Vicencio 
Published: September 2019

AbstractDevelopmental plasticity in a seasonal environment allows an organism to optimally match its life-history traits with the fluctuating conditions. This critically relies on abiotic and biotic factors, such as temperature or food quality, that act as environmental cues and predict seasonal transitions. In most seasonal environments, multiple factors vary together, making it crucial to understand their combined effects on an organism’s phenotype. Here, we study plasticity in a multivariate environment in the butterfly Bicyclus anynana that exhibits two distinct seasonal phenotypes. Temperature is an important cue mediating plasticity in this species, but other environmental cues such as larval host plant quality could also be informative since plant quality deteriorates during the transition from wet to dry season in the field. We examine how temperature and host plant quality interact to affect life-history traits. Using a full-factorial design, we expose cohorts of larvae to either poor (old plants) or high (young plants) quality plants at different temperatures. Our results show that plant quality had a temperature and sex-dependent effect on life-history traits. At lower and intermediate temperatures, it decreased body mass and prolonged development time, indicating that poor plant quality acted as a stressor. However, metabolic rates in adults were not affected, indicating that individuals could, at least in part, compensate for stressful juvenile conditions. In contrast, at higher temperatures poor plant quality induced a partial dry-season phenotype, indicating that it may have acted as an environmental cue. Moreover, poor plant quality, particularly in males, also decreased the correlation between life history traits, signifying disrupted phenotypic integration. Our study reveals complex interactive effects of two environmental variables on seasonal plasticity, reflecting differences in their reliability as seasonal cues. This highlights the importance of studying the combined effects of multiple environmental factors to better understand the regulation of phenotypic plasticity in wild.
PrimPol-dependent single-stranded gap formation mediates homologous recombination at bulky DNA adducts
Authors: Piberger Ann Liza , Bowry Akhil , Kelly Richard D W , Walker Alexandra K , Gonzalez Daniel , Bailey Laura J , Doherty Aidan J , Méndez Juan , Morris Joanna R , Bryant Helen E , Petermann Eva 
Published: September 2019

AbstractObstacles on the DNA template can lead to DNA replication fork stalling and genomic rearrangements. RAD51-mediated homologous recombination (HR) can promote restart and repair of stalled forks, but also post-replicative repair once the obstacle has been bypassed. Bulky DNA adducts are important replication-blocking lesions induced by environmental carcinogens, but it is not known whether they activate HR directly at stalled forks, or at gaps left behind ongoing forks. Here we show that in mammalian cells, bulky adducts predominantly induce HR at post-replicative gaps formed by the DNA/RNA primase PrimPol. Using BPDE and other bulky model lesions, we report that RAD51 is not recruited to stalled or collapsed forks, but instead to long gaps formed by PrimPol re-priming activity and resection by MRE11 and EXO1. In contrast, RAD51 loading at DSBs does not require PrimPol. At bulky adducts, PrimPol is required for the induction of sister chromatid exchanges and genetic recombination. Our data support that HR at bulky adducts in mammalian cells involves post-replicative gap repair and define a role for PrimPol in DNA damage tolerance by homologous recombination.
Fertility of Pedicellate Spikelets in Sorghum is Controlled by a Jasmonic Acid Regulatory Module
Authors: Gladman Nicholas , Jiao Yinping , Lee Young Koung , Zhang Lifang , Chopra Ratan , Regulski Michael , Burow Gloria , Hayes Chad , Christensen Shawn A. , Dampanaboina Lavanya , Chen Junping , Burke John , Ware Doreen , Xin Zhanguo 
Published: September 2019

AbstractAs in other cereal crops, the panicles of sorghum (Sorghum bicolor (L.) Moench) comprise two types of floral spikelets (grass flowers). Only sessile spikelets (SSs) are capable of producing viable grains, whereas pedicellate spikelets (PSs) cease development after initiation and eventually abort. Consequently, grain number per panicle (GNP) is lower than the total number of flowers produced per panicle. The mechanism underlying this differential fertility is not well understood. To investigate this issue, we isolated a series of EMS-induced multiseeded (msd) mutants that result in full spikelet fertility, effectively doubling GNP. Previously, we showed that MSD1 is a TCP (Teosinte branched/Cycloidea/PCF) transcription factor that regulates jasmonic acid (JA) biosynthesis, and ultimately floral sex organ development. Here, we show that MSD2 encodes a lipoxygenase (LOX) that catalyzes the first committed step of JA biosynthesis. Further, we demonstrate that MSD1 binds to the promoters of MSD2 and other JA pathway genes. Together, these results show that a JA-induced module regulates sorghum panicle development and spikelet fertility. The findings advance our understanding of inflorescence development and could lead to new strategies for increasing GNP and grain yield in sorghum and other cereal crops.SignificanceThrough a single base pair mutation, grain number can be increased by ~200% in the globally important crop Sorghum bicolor. This mutation affects the expression of an enzyme, MSD2, that catalyzes the jasmonic acid pathway in developing floral meristems. The global gene expression profile in this enzymatic mutant is similar to that of a transcription factor mutant, msd1, indicating that disturbing any component of this regulatory module disrupts a positive feedback loop that occurs normally due to regular developmental perception of jasmonic acid. Additionally, the MSD1 transcription factor is able to regulate MSD2 in addition to other jasmonic acid pathway genes, suggesting that it is a primary transcriptional regulator of this hormone signaling pathway in floral meristems.
Invasion implies substitution in ecological communities with class-structured populations
Authors: Priklopil Tadeas , Lehmann Laurent 
Published: September 2019

AbstractLong-term evolution of quantitative traits is classically and usefully described as the directional change in phenotype due to the recurrent fixation of new mutations. A formal justification for such continual evolution ultimately relies on the “invasion implies substitution”-principle. Here, whenever a mutant allele causing a small phenotypic change can successfully invade a population, the ancestral (or wild-type) allele will be replaced, whereby fostering gradual phenotypic change if the process is repeated. It has been argued that this principle holds in a broad range of situations, including spatially and demographically structured populations experiencing frequency and density dependent selection under demographic and environmental fluctuations. However, prior studies have not been able to account for all aspects of population structure, leaving unsettled the conditions under which the “invasion implies substitution”-principle really holds. In this paper, we start by laying out a program to explore and clarify the generality of the “invasion implies substitution”-principle. Particular focus is given on finding an explicit and functionally constant representation of the selection gradient on a quantitative trait. Using geometric singular perturbation methods, we then show that the “invasion implies substitution”-principle generalizes to well-mixed and scalar-valued polymorphic multispecies ecological communities that are structured into finitely many demographic (or physiological) classes. The selection gradient is shown to be constant over the evolutionary timescale and that it depends only on the resident phenotype, individual growth-rates, population steady states and reproductive values, all of which are calculated from the resident dynamics. Our work contributes to the theoretical foundations of evolutionary ecology.
Parallel clines in native and introduced ragweed populations are likely due to adaptation
Authors: McGoey Brechann V. , Hodgins Kathryn A. , Stinchcombe John R. 
Published: September 2019

AbstractAs introduced species expand their ranges, they often encounter differences in climate which are often correlated with geography. For introduced species, encountering a geographically variable climate sometimes leads to the re-establishment of clines seen in the native range. However, clines can also be caused by neutral processes, and so it is important to gather additional evidence that population differentiation is the result of selection as opposed to non-adaptive processes. Here, we examine phenotypic and genetic differences in ragweed from the native (North America) and introduced (European) ranges. We used a common garden to assess phenotypic differentiation in size and flowering time in ragweed populations. We found significant parallel clines in flowering time in both North America and Europe. Height and branch number had significant clines in North America and, while not statistically significant, the patterns in Europe were the same. We used SNP data to assess population structure in both ranges and to compare phenotypic differentiation to neutral genetic variation. We failed to detect significant patterns of isolation by distance, geographic patterns in population structure, or correlations between the major axes of SNP variation and phenotypes or latitude of origin. We conclude that the clines seen for flowering time and size are most likely the result of adaptation.
Bridging sensory and language theories of dyslexia: towards a multifactorial model
Authors: O’Brien Gabrielle , Yeatman Jason 
Published: September 2019

AbstractCompeting theories of dyslexia posit that reading disability arises from impaired sensory, phonological, or statistical learning mechanisms. Importantly, many theories posit that dyslexia reflects a cascade of impairments emanating from a “core deficit”. Here we collect a battery of psychophysical and language measures in 106 school-aged children to investigate whether dyslexia is best conceptualized under a core-deficit model, or as a disorder with heterogenous origins. Specifically, by capitalizing on the drift diffusion model to separate sensory encoding from task-related influences on performance in a visual motion discrimination experiment, we show that deficits in motion perception, decision making and phonological processing manifest largely independently. Based on statistical models of how variance in reading skill is parceled across measures of sensory encoding, phonological processing and decision-making, our results challenge the notion that a unifying deficit characterizes dyslexia. Instead, these findings indicate a model where reading skill is explained by several distinct, additive predictors, or risk factors, of reading (dis)ability.Research HighlightsOur research provides direct evidence that a single-mechanism, or core-deficit, model of dyslexia cannot account for the range of linguistic and sensory outcomes in children.Individual differences in visual motion processing, perceptual decision making, phonological awareness and rapid naming each account for unique variance in reading skill.Our data support an additive risk-factor model, in which multiple independent dimensions each confer risk for reading difficulties.
Proteasome-mediated protein degradation resets the cell division cycle and triggers ESCRT-III-mediated cytokinesis in an archaeon
Authors: Risa Gabriel Tarrason , Hurtig Fredrik , Bray Sian , Hafner Anne E. , Harker-Kirschneck Lena , Faull Peter , Davis Colin , Papatziamou Dimitra , Mutavchiev Delyan R. , Fan Catherine , Meneguello Leticia , Pulschen Andre Arashiro , Dey Gautam , Culley Siân , Kilkenny Mairi , Pellegrini Luca , de Bruin Robertus A. M. , Henriques Ricardo , Snijders Ambrosius P , Šarić Anđela , Lindås Ann-Christin , Robinson Nick , Baum Buzz 
Published: September 2019

AbstractThe archaeonSulfolobus acidocaldariusis a relative of eukaryotes known to progress orderly through its cell division cycle despite lacking obvious CDK/cyclin homologues. Here, in exploring the mechanisms underpinning archaeal cell division cycle control, we show that the proteasome ofS. acidocaldarius,like its eukaryotic counterpart, regulates the transition from the end of one cell division cycle to the beginning of the next. Further, we identify the archaeal ESCRT-III homologue CdvB as a key target of the proteasome, and show that state-dependent degradation of CdvB triggers archaeal cell division by allowing constriction of a CdvB1:CdvB2 ESCRT-III division ring. These findings suggest an ancient role for proteasome-mediated degradation in resetting the cell division cycle in both archaea and eukaryotes.