bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resynthesis: Marker-based partial reconstruction of elite genotypes in clonally-reproducing plant species
Authors: Eduardo Iban , Alegre Simó , Alexiou Konstantinos G. , Arús Pere 
Published: May 2020

ABSTRACTWe propose a method for marker-based selection of cultivars of clonally-reproducing plant species which keeps the basic genetic architecture of a top-performing cultivar (usually a partly heterozygous genotype), with some agronomically relevant differences (such as production time, product appearance or quality), providing added value to the product or cultivation process. The method is based on selecting a) two complementary nearly-inbred lines from successive selfing generations (ideally only F2 and F3) of large size, that may generate individuals with most of their genome identical to the original cultivar but being homozygous for either of the two component haplotypes in the rest, and b) individuals with such characteristics already occurring in the F2. Option a) allows for introgressing genes from other individuals in one or both of these nearly-inbred lines.Peach, a woody-perennial, clonally-reproduced species, was chosen as a model for a proof of concept of the Resynthesis process due to its biological characteristics: self-compatibility, compact and genetically well-known genome, low recombination rates and relatively short intergeneration time (3-4 years). From 416 F2seedlings from cultivar Sweet Dream (SD), we obtained seven individuals with 76-94% identity with SD, and selected five pairs of complementary lines with average homozygosity of the two parents ≥0.70 such that crossing would produce some individuals highly similar to SD. The application of this scheme to other species with more complex genomes or biological features, including its generalization to F1 hybrids, is discussed.
Rapid Population Decline of the Pillar CoralDendrogyra cylindrusAlong the Florida Reef Tract
Authors: Neely Karen L. , Lewis Cynthia L. 
Published: May 2020

AbstractCoral reefs worldwide are in a state of decline, but the status of populations and stressors for rare species are generally not well documented using broad-scale monitoring protocol. We fate-tracked all known colonies of the pillar coralDendrogyra cylindruson the Florida Reef Tract from 2013 – 2020 to assess the population and document the impacts of chronic and acute stressors. Large average colony size, an absence of juveniles, and large geographic distances between genotypes suggest that the FloridaD. cylindruspopulation has been reproductively extinct for decades. During the study period, low-intensity chronic stressors were balanced by regrowth, while back-to-back years of coral bleaching and thermally-exacerbated disease led to declines that the subsequent years of recovery suggest would take 11 uninterrupted years to overcome. The most recent stressor on Florida’sD. cylindruspopulation is “stony coral tissue loss disease.” Following the appearance of the disease in Florida in 2015, it resulted in unrecoverable losses to theD. cylindruspopulation as tissue, colonies, and whole genotypes were driven to extinction. Losses of 91% of coral tissue, 88% of colonies, and 73% of genotypes between 2014 and early 2020 have led to functional extinction ofD. cylindruson the Florida Reef Tract.
Mechanical Tension in Syndecan-1 is Regulated by Extracellular Mechanical Cues and Fluidic Shear Stress
Authors: Le Victoria , Mei Lei , Voyvodic Peter L. , Zhao Chi , Busch David J. , Stachowiak Jeanne C. , Baker Aaron B. 
Published: May 2020

AbstractThe endothelium plays a central role in regulating vascular homeostasis and is key in determining the response to materials implanted in the vascular system. Endothelial cells are uniquely sensitive to biophysical cues from applied forces and their local cellular microenvironment. The glycocalyx is a layer of proteoglycans, glycoproteins and glycosaminoglycans that lines the luminal surface of the vascular endothelium, interacting directly with the components of the blood and the forces of blood flow. In this work, we examined the changes in mechanical tension of syndecan-1, a cell surface proteoglycan that is an integral part of the glycocalyx, in response to substrate stiffness and fluidic shear stress. Our studies demonstrate that syndecan-1 is mechanically responsive to extracellular mechanical cues and alters its association with cytoskeletal and adhesion-related proteins in response to substrate stiffness and physiological flow.
Converting endogenous genes of the malaria mosquito into simple non-autonomous gene drives for population replacement
Authors: Hoermann Astrid , Tapanelli Sofia , Capriotti Paolo , Masters Ellen K. G. , Habtewold Tibebu , Christophides George K. , Windbichler Nikolai 
Published: May 2020

AbstractGene drives for mosquito population replacement are promising tools for malaria control. However, there is currently no clear pathway for safely testing such tools in endemic countries. The lack of well-characterized promoters for infection-relevant tissues and regulatory hurdles are further obstacles for their design and use. Here we explore how minimal genetic modifications of endogenous mosquito genes can convert them directly into non-autonomous gene drives without disrupting their expression. We co-opted the native regulatory sequences of three midgut-specific loci of the malaria vectorAnopheles gambiaeto host a prototypical antimalarial molecule and guide-RNAs encoded within artificial introns, that support efficient gene drive. We assess the propensity of these modifications to interfere with the development ofPlasmodium falciparumand their effect on fitness. Because of their inherent simplicity and passive mode of drive such traits could form part of an accepted testing pathway of gene drives for malaria eradication.
Mitochondrial fatty acid synthesis coordinates mitochondrial oxidative metabolism
Authors: Nowinski Sara M. , Solmonson Ashley , Rusin Scott F. , Maschek J. Alan , Bensard Claire L. , Fogarty Sarah , Jeong Mi-Young , Lettlova Sandra , Berg Jordan A. , Morgan Jeffrey T. , Ouyang Yeyun , Naylor Bradley C. , Paulo Joao A. , Funai Katsuhiko , Cox James E. , Gygi Steven P. , Winge Dennis R. , Deberardinis Ralph J. , Rutter Jared 
Published: May 2020

AbstractCells harbor two systems for fatty acid synthesis, one in the cytoplasm (catalyzed by fatty acid synthase, FASN) and one in the mitochondria (mtFAS). In contrast to FASN, mtFAS is poorly characterized, especially in higher eukaryotes, with the major product(s), metabolic roles, and cellular function(s) being essentially unknown. Here we show that hypomorphic mtFAS mutants display a severe loss of electron transport chain (ETC) complexes and exhibit compensatory metabolic activities including reductive carboxylation. This effect on ETC complexes appears to be independent of protein lipoylation, the best characterized function of mtFAS, as mutants lacking lipoylation have an intact ETC. Finally, mtFAS impairment blocks the differentiation of skeletal myoblasts in vitro. Together, these data suggest that ETC activity in mammals is profoundly controlled by mtFAS function, thereby connecting anabolic fatty acid synthesis with the oxidation of carbon fuels.
Impact of industrial production system parameters on chicken microbiomes: mechanisms to improve performance and reduceCampylobacter
Authors: McKenna Aaron , Ijaz Umer Zeeshan , Kelly Carmel , Linton Mark , Sloan William T. , Green Brian D. , Lavery Ursula , Dorrell Nick , Wren Brendan W. , Richmond Anne , Corcionivoschi Nicolae , Gundogdu Ozan 
Published: May 2020

AbstractBackgroundThe factors affecting host-pathogen ecology in terms of the microbiome remain poorly studied. Chickens are a key source of protein with gut health heavily dependent on the complex microbiome which has key roles in nutrient assimilation and vitamin and amino acid biosynthesis. The chicken gut microbiome may be influenced by extrinsic production system parameters such asPlacement Birds/m2(stocking density), feed type and additives. Such parameters, in addition to on-farm biosecurity may influence performance and also pathogenic bacterial numbers such asCampylobacter. In this study, three different production systems ‘Normal’ (N), ‘Higher Welfare’ (HW) and ‘Omega-3 Higher Welfare’ (O) were investigated “in a natural environment” at day 7 and day 30 with a range of extrinsic parameters assessing performance in correlation with microbial dynamics andCampylobacterpresence.ResultsOur data identified production system N as significantly dissimilar from production systems HW and O when comparing the prevalence of genera. An increase inPlacement Birds/m2density led to a decrease in environmental pressure influencing the microbial community structure. Prevalence of genera such asEisenbergiellawithin HW and O, and likewiseAlistipeswithin N were representative. These genera have roles directly relating to energy metabolism, amino acid, nucleotide and short chain fatty acid (SCFA) utilisation. Thus, an association exists between consistent and differentiating parameters of the production systems, that affect feed utilisation, advance our knowledge of mechanistic underpinnings, leading to competitive exclusion of genera based on competition for nutrients and other factors.Campylobacterwas identified within specific production system and presence was linked with the increased diversity and increased environmental pressure on microbial community structure. Addition of Omega-3 though did alter prevalence of specific genera, in our analysis did not differentiate itself from HW production system. However, Omega-3 was linked with a positive impact on weight gain.ConclusionsOverall, our results show that microbial communities in different industrial production systems are deterministic in elucidating the underlying biological confounders, and these recommendations are transferable to farm practices and diet manipulation leading to improved performance and better intervention strategies againstCampylobacterwithin the food chain.Graphical Abstract
Mapping fetal brain development based on automated segmentation and 4D brain atlasing
Authors: Li Haotian , Yan Guohui , Luo Wanrong , Liu Tintin , Wang Yan , Liu Ruibin , Zheng Weihao , Zhang Yi , Li Kui , Zhao Li , Limperopoulos Catherine , Zou Yu , Wu Dan 
Published: May 2020

AbstractFetal brain MRI has become an important tool for in utero assessment of brain development and disorders. However, quantitative analysis of fetal brain MRI remains difficult, partially due to the limited tools for automated preprocessing and the lack of normative brain templates. In this paper, we proposed an automated pipeline for fetal brain extraction, super-resolution reconstruction, and fetal brain atlasing to quantitatively map in utero fetal brain development during mid-to-late gestation in a Chinese population. First, we designed a U-net convolutional neural network for automated fetal brain extraction, which achieved an average accuracy of 97%. We then generated a developing fetal brain atlas, using an iterative linear and nonlinear registration approach. Based on the 4D spatiotemporal atlas, we quantified the morphological development of the fetal brain between 23-36 weeks of gestation. The proposed pipeline enabled the fully-automated volumetric reconstruction for clinically available fetal brain MRI data, and the 4D fetal brain atlas provided normative templates for quantitative analysis of potential fetal brain abnormalities, especially in the Chinese population.
Removal of repressive histone marks creates epigenetic memory of recurring heat inArabidopsis
Authors: Yamaguchi Nobutoshi , Matsubara Satoshi , Yoshimizu Kaori , Seki Motohide , Hamada Kouta , Kamitani Mari , Kurita Yuko , Inagaki Soichi , Suzuki Takamasa , Gan Eng-Seng , To Taiko , Kakutani Tetsuji , Nagano Atsushi J. , Satake Akiko , Ito Toshiro 
Published: May 2020

AbstractAcclimation to high temperature increases plants’ tolerance of subsequent lethal high temperatures1-3. Although epigenetic regulation of plant gene expression is well studied, how plants maintain a memory of environmental changes over time remains unclear. Here, we show that JUMONJI (JMJ) proteins4-8, demethylases involved in histone H3 lysine 27 trimethylation (H3K27me3), are necessary forArabidopsis thalianaheat acclimation. Acclimation induces sustained H3K27me3 demethylation at keyHEAT SHOCK PROTEIN(HSP) loci by JMJs, poising theHSPgenes for subsequent activation. Upon sensing heat after a 3-day interval, JMJs directly reactivateHSPgenes. Finally,jmjmutants fail to maintain heat memory under fluctuating field temperature conditions. Our findings of an epigenetic memory mechanism involving histone demethylases may have implications for environmental adaptation of field plants.
SurEau.c : a mechanistic model of plant water relations under extreme drought
Authors: Cochard Hervé , Pimont François , Ruffault Julien , Martin-StPaul Nicolas 
Published: May 2020

SummaryWe describe the operating principle of the detailed version of the soil-plant-atmosphere modelSurEauthat allows, among other things, to predict the risk of hydraulic failure under extreme drought. It is based on the formalization of key physiological processes of plant response to water stress. The hydraulic functioning of the plant is at the core of this model, which focuses on both water flows and water pools using variable hydraulic conductances. The model considers the elementary flow of water from the soil to the atmosphere through different plant organs (roots, trunk branches, leaves and buds) that are described by their symplasm and their apoplasm compartments. Within each organ the flow of water between the apoplasm and the symplasm is also represented; as well as the flow outside the system, from the symplasm of each organ to the atmosphere, through the cuticular conductance. For each organ, the symplasm is described by a pressure volume curves and the apoplasm by the vulnerability curve to cavitation of the xylem. The model can thus compute the loss of conductance caused by cavitation, a leading mechanisms of plant desiccation and drought-induced mortality. Some example simulations are shown to illustrate how the model works.
Silencing of Exosomal miR-181a reverses Pediatric Acute Lymphocytic Leukemia Cell Proliferation
Authors: Haque Shabirul , Vaiselbuh Sarah R. 
Published: May 2020

AbstractExosomes are cell-generated nano-vesicles (30-150 nm) found in most biological fluids. Major components of their cargo are lipids, proteins, RNA, DNA, and non-coding RNAs. Exosomes carry the fingerprint of the parental tumor and as such, may regulate tumor growth, progression and metastasis. We investigated the impact of exosomes on cell proliferation in pediatric acute lymphocytic leukemia and its reversal by silencing of exo-miR-181a.We isolated exosomes from serum of acute lymphocytic leukemia pediatric patients (Exo-PALL) and conditioned medium of leukemic cell lines (Exo-CM) by ultracentrifugation. Gene expression was carried out by q-PCR. We found that Exo-PALL promote cell proliferation in leukemic B cell lines as well as in the control B cell line. This exosome-induced cell proliferation is a precise event with up-regulation of proliferative (PCNA, Ki-67) and pro-survival genes (MCL-1, and BCL2), and suppression of pro-apoptotic genes (BAD, BAX). Exo-PALL and Exo-CM both show over expression of miR-181a compared to controls (Exo-HD). Specific silencing ofexosomalmiR-181a using a miR-181a inhibitor confirms that miR-181a inhibitor treatment reverses Exo-PALL/Exo-CM-induced leukemic cell proliferationin vitro. Altogether, this study suggests that exosomal miR-181a inhibition can be a novel target for growth suppression in pediatric lymphatic leukemia.
Speeding up Inference of Homologous Recombination in Bacteria
Authors: Medina-Aguayo Felipe J , Didelot Xavier , Everitt Richard G 
Published: May 2020

AbstractBacteria reproduce clonally but most species recombine frequently, so that the ancestral process is best captured using an ancestral recombination graph. This graph model is often too complex to be used in an inferential setup, but it can be approximated for example by the ClonalOrigin model. Inference in the ClonalOrigin model is performed via a Reversible-Jump Markov Chain Monte Carlo algorithm, which attempts to jointly explore: the recombination rate, the number of recombination events, the departure and arrival points on the clonal genealogy for each recombination event, and the range of genomic sites affected by each recombination event. However, the Reversible-Jump algorithm usually performs poorly due to the complexity of the target distribution since it needs to explore spaces of different dimensions. Recent developments in Bayesian computation methodology have provided ways to improve existing methods and code, but are not well-known outside the statistics community. We show how exploiting one of these new computational methods can lead to faster inference under the ClonalOrigin model.
Rational design of human cathepsin L with efficient collagenolytic activity
Authors: Choudhury Debi , Biswas Sampa 
Published: May 2020

AbstractCollagens are the main structural components of ECM and collagenolysis is vital for ECM remodelling, which is essential for normal organ homeostasis. Any dysregulation of this process can result in various pathological conditions. The degradation of the interstitial collagens is generally mediated by specific collagenases which are capable of cleaving at specific loci in the collagen triple helix. Lysosomal cysteine cathepsins have general housekeeping as well as some highly specialized functions. Amongst them, human cathepsin K is the only lysosomal cysteine protease which has potent collagenolytic activity against type I collagen. In this study, we have imparted collagenolytic property to another human cysteine protease, cathepsin L, by systematically engineering proline-specificity and GAG-binding surface in the protease. The designed proline-specific mutant shows high specificity for peptidyl substrate containing proline at P2 position but is incapable of cleaving collagen. However, when the proline-specific mutant is further engineered for GAG-binding surface, it can degrade type I collagen in presence of Chondroitin 4-Sulfate (C4-S). We also present high resolution crystal structures of these proline-specific (1.4 Å) and collagen-specific (1.8 Å) mutants. Finally docking studies with prolyl-peptidic substrate (Ala-Gly-Pro-Arg-Ala) at the active site and a GAG molecule (C4-S) at the GAG binding site enables us to identify key structural features responsible for collagenolytic activity of papain-like cysteine proteases. This study provides a rational approach to engineer an efficient collagenase from a human template enzyme which may have various noninvasive therapeutic implications with an expected additional advantage of immuno-compatiblity.
Identification of MAZ as a novel transcription factor regulating erythropoiesis
Authors: Deen Darya , Butter Falk , Holland Michelle L. , Samara Vasiliki , Sloane-Stanley Jacqueline A. , Ayyub Helena , Mann Matthias , Garrick David , Vernimmen Douglas 
Published: May 2020

ABSTRACTErythropoiesis requires a combination of ubiquitous and tissue-specific transcription factors. Here, through DNA affinity purification followed by mass spectrometry, we have identified the widely expressed protein MAZ (Myc-associated zinc finger) as a transcription factor that binds to the promoter of the erythroid-specific human α-globin gene. Genome-wide mapping in primary human erythroid cells revealed that MAZ also occupies active promoters as well as GATA1-bound enhancer elements of key erythroid genes. Consistent with an important role during erythropoiesis, knockdown of MAZ in primary human erythroid cells impairs erythroid differentiation, and genetic variants in theMAZlocus are associated with clinically important human erythroid traits. Taken together, these findings reveal the Zinc-finger transcription factor MAZ to be a previously unrecognised regulator of the erythroid differentiation program.
Increased p53 signaling impairs neural differentiation causing HUWE1-promoted intellectual disabilities
Authors: Aprigliano Rossana , Bradamante Stefano , Mihaljevic Boris , Wang Wei , Fordyce Martin Sarah L. , Bordin Diana L. , Bosshard Matthias , Montaldo Nicola P. , Peng Yunhui , Alexov Emil , Skinner Cindy , Liabakk Nina-Beate , Bjørås Magnar , Schwartz Charles E. , van Loon Barbara 
Published: May 2020

SUMMARYEssential E3 ubiquitin ligase HUWE1 (HECT, UBA and WWE domain containing 1) regulates key factors, as p53. Mutations inHUWE1have been associated with neurodevelopmental X-linked intellectual disabilities (XLIDs), however the pathomechanism at the onset of heterogenous XLIDs remains unknown. In this work, we identify p53 signaling as the process hyperactivated in lymphoblastoid cells from patients with HUWE1-promoted XLIDs. The hiPSCs-based modeling of the severe HUWE1-promoted XLID, the Juberg Marsidi syndrome (JMS), reviled majorly impaired neural differentiation, accompanied by increased p53 signaling. The impaired differentiation results in loss of cortical patterning and overall undergrowth of XLID JMS patient-specific cerebral organoids, thus closely recapitulating key symptoms, as microcephaly. Importantly, the neurodevelopmental potential of JMS hiPSCs is successfully rescued by restoring p53 signaling, upon reduction of p53 levels. In summary, our findings indicate that increased p53 signaling leads to impaired neural differentiation and is the common cause of neurodevelopmental HUWE1-promoted XLIDs.
Do anti-discrimination laws alleviate labour market duality?
Authors: Choi Hoon 
Published: May 2020

PurposeThis paper examines whether and how labour market duality can be alleviated through legislation that prohibits discrimination based on employment type.Design/methodology/approachIn 2007, the Korean government undertook a labour reform banning discriminatory treatment against fixed-term, part-time and dispatched workers. By exploiting a gradual implementation of the anti-discrimination law by firm size targeting a subset of non-regular workers, the paper identifies the treatment effects of the anti-discrimination law, taking a difference-in-difference-in-differences approach.FindingsThe results suggest that the anti-discrimination law significantly increases hourly wages and the probabilities of being covered by national pension, health insurance, and employment insurance for targeted non-regular workers in small firms relative to other workers. Anticipatory behaviours of employers and selective transitions of employees in response to the implementation of the anti-discrimination law do not underlie the estimated effects. The presence of labour unions contributes to reducing gaps in labour conditions between regular workers and targeted non-regular workers.Originality/valueThe main contribution of this paper is to provide empirical evidence on causal impacts of equal pay legislation on the gaps in labour conditions between different categories of workers, using a difference-in-difference-in-differences estimation.