bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Genomic Selection Models for Exploring Predictive Ability of Complex Traits in Breeding Programs
Authors: Merrick Lance F. , Carter Arron H. 
Published: April 2021

AbstractTraits with a complex unknown genetic architecture are common in breeding programs. However, they pose a challenge for selection due to a combination of complex environmental and pleiotropic effects that impede the ability to create mapping populations to characterize the trait’s genetic basis. One such trait, seedling emergence of wheat (Triticum aestivumL.) from deep planting, presents a unique opportunity to explore the best method to use and implement GS models to predict a complex trait. 17 GS models were compared using two training populations, consisting of 473 genotypes from a diverse association mapping panel (DP) phenotyped from 2015-2019 and the other training population consisting of 643 breeding lines phenotyped in 2015 and 2020 in Lind, WA with 40,368 markers. There were only a few significant differences between GS models, with support vector machines reaching the highest accuracy of 0.56 in a single breeding line trial using cross-validations. However, the consistent moderate accuracy of cBLUP and other parametric models indicates no need to implement computationally demanding non-parametric models for complex traits. There was an increase in accuracy using cross-validations from 0.40 to 0.41 and independent validations from 0.10 to 0.17 using diversity panels lines to breeding lines. The environmental effects of complex traits can be overcome by combining years of the same populations. Overall, our study showed that breeders can accurately predict and implement GS for a complex trait by using parametric models within their own breeding programs with increased accuracy as they combine training populations over the years.
Rapid global phaseout of animal agriculture has the potential to stabilize greenhouse gas levels for 30 years and offset 68 percent of CO2emissions this century
Authors: Eisen Michael B. , Brown Patrick O. 
Published: April 2021

AbstractAnimal agriculture contributes significantly to global warming through ongoing emissions of the potent greenhouse gases methane and nitrous oxide, and displacement of biomass carbon on the land used to support livestock. However, because estimates of the magnitude of the effect of ending animal agriculture often focus on only one factor, the full potential benefit of a more radical change remains underappreciated. Here we quantify the full “climate opportunity cost” of current global livestock production, by modeling the combined, long-term effects of emission reductions and biomass recovery that would be unlocked by a phaseout of animal agriculture. We show that, even in the absence of any other emission reductions, persistent drops in atmospheric methane and nitrous oxide levels, and slower carbon dioxide accumulation, following a phaseout of livestock production would, through the end of the century, have the same cumulative effect on the warming potential of the atmosphere as a 25 gigaton per year reduction in anthropogenic CO2emissions, providing half of the net emission reductions necessary to limit warming to 2°C. The magnitude and rapidity of these potential effects should place the reduction or elimination of animal agriculture at the forefront of strategies for averting disastrous climate change.Significance StatementThe use of animals to produce food has a negative impact on the climate, but the benefits of a global switch to a plant based diet are underappreciated. We show that the global warming impact, through the rest of this century, of eliminating greenhouse gas emissions from livestock and allowing native ecosystems to regrow on the land currently used to house and feed livestock, would be equivalent to a 68% reduction in carbon dioxide emissions. We hope putting clearer numbers on the “climate opportunity cost” of our continued use of animals as food technology will help policymakers and the public properly prioritize dietary change as a climate defense strategy.Declaration of Conflict of InterestPatrick Brown is the founder and CEO of Impossible Foods, a company developing alternatives to animals in food-production. Michael Eisen is an advisor to Impossible Foods. Both are shareholders in the company and thus stand to benefit financially from reduction of animal agriculture.
The dominant axes of lifetime behavioral variation in honey bees
Authors: Smith Michael L , Davidson Jacob D , Wild Benjamin , Dormagen David M , Landgraf Tim , Couzin Iain D 
Published: April 2021

AbstractInsect colonies are decentralized systems that employ task allocation, whereby individuals undertake different roles to fulfil colony needs, such as honey bee “nurses”, “nest workers”, and “foragers”. However, the extent to which individuals can be well-classified by discrete “roles”, how they change behavior from day-to-day, over entire lifetimes, and with environmental conditions, is poorly understood. Using long-term automated tracking of over 4,200 individually-identified beesApis mellifera, we use behavioral metrics to quantify and compare behavior. We show that individuals exhibit behavioral variation along two dominant axes that represent nest substrate use and movement within the nest. Across lifetimes, we find that individuals differ in foraging onset, and that certain bees exhibit lifelong consistencies in their movement patterns. Furthermore, we examine a period of sudden nectar availability where the honey stores tripled over 6 days, and see that the colony exhibits a distributed shift in activity that did not require a large-scale colony reorganization. Our quantitative approach shows how collective units differ over days and lifetimes, and how sources of variation and variability contribute to the colony’s robust yet flexible response.
Scalable, methanol-free manufacturing of the SARS-CoV-2 receptor binding domain in engineeredKomagataella phaffii
Authors: Dalvie Neil C. , Biedermann Andrew M. , Rodriguez-Aponte Sergio A. , Naranjo Christopher A. , Rao Harish D. , Rajurkar Meghraj P. , Lothe Rakesh R. , Shaligram Umesh S. , Johnston Ryan S. , Crowell Laura E. , Castelino Seraphin , Tracey Mary Kate , Whittaker Charles A. , Love J. Christopher 
Published: April 2021

AbstractPrevention of COVID-19 on a global scale will require the continued development of high-volume, low-cost platforms for the manufacturing of vaccines to supply on-going demand. Vaccine candidates based on recombinant protein subunits remain important because they can be manufactured at low costs in existing large-scale production facilities that use microbial hosts likeKomagataella phaffii(Pichia pastoris). Here, we report an improved and scalable manufacturing approach for the SARS-CoV-2 spike protein receptor binding domain (RBD); this protein is a key antigen for several reported vaccine candidates. We genetically engineered a manufacturing strain ofK. phaffiito obviate the requirement for methanol-induction of the recombinant gene. Methanol-free production improved the secreted titer of the RBD protein by >5x by alleviating protein folding stress. Removal of methanol from the production process enabled scale up to a 1,200 L pre-existing production facility. This engineered strain is now used to produce an RBD-based vaccine antigen that is currently in clinical trials and could be used to produce other variants of RBD as needed for future vaccines.
Folding of VemP into translation-arresting secondary structure is driven by the ribosome exit tunnel
Authors: Kolář Michal H. , Nagy Gabor , Kunkel John , Vaiana Sara M. , Bock Lars V. , Grubmüller Helmut 
Published: April 2021

AbstractThe ribosome is a fundamental biomolecular complex responsible for protein production in cells. Nascent proteins emerge from the ribosome through a tunnel, where they may interact with the tunnel walls or small molecules such as antibiotics. These interactions can cause translational arrest with notable physiologic consequences. Here, we studied the arrest caused by the regulatory peptide VemP, which is known to form anα-helix in the ribosome tunnel near the peptidyl transferase center under specific conditions. We used all-atom molecular dynamics simulations of the entire ribosome and circular dichroism spectroscopy to study the driving forces of helix formation and how VemP causes the translational arrest. To that aim, we compared VemP dynamics in the ribosome tunnel with its dynamics in solution. We show that the VemP sequence has a low helical propensity in water and that the propensity is higher in more hydrophobic solvents. We propose that helix formation within the ribosome is driven by the tunnel environment and that a portion of VemP acts as an anchor. This anchor might slow down VemP progression through the tunnel enabling theα-helix formation, which causes the elongation arrest.
Alterations in chromosome spatial compartmentalization classify prostate cancer progression
Authors: Martin Rebeca San , Das Priyojit , Marques Renata Dos Reis , Xu Yang , McCord Rachel Patton 
Published: April 2021

AbstractProstate cancer aggressiveness and metastatic potential are influenced by gene expression, genomic aberrations, and cellular morphology. These processes are in turn dependent in part on the 3D structure of chromosomes, packaged inside the nucleus. Using chromosome conformation capture (Hi-C), we conducted a systematic genome architecture comparison on a cohort of cell lines that model prostate cancer progression, ranging from normal epithelium to bone metastasis. Here, we describe how chromatin compartmentalization identity (A-open vs. B-closed) changes with progression: specifically, we find that 48 gene clusters switch from the B to the A compartment, including androgen receptor, WNT5A, and CDK14. These switches could prelude transcription activation and are accompanied by changes in the structure, size, and boundaries of the topologically associating domains (TADs). Further, compartmentalization changes in chromosome 21 are exacerbated with progression and may explain, in part, the genesis of the TMPRSS2-ERG translocation: one of the main drivers of prostate cancer. These results suggest that discrete, 3D genome structure changes play a deleterious role in prostate cancer progression.SummaryThrough a systematic analysis of chromosome conformation capture in a cohort of cells that model cancer progression, San Martin et.al. find that rearrangement of the 3D genome structure in prostate cancer is a potential mechanism for disease exacerbation and that genome-wide compartment identity can classify cancer according to progression.
Linking Population Dynamics to Microbial Kinetics for Hybrid Modeling of Engineered Bioprocesses
Authors: Cheng Zhang , Yao Shiyun , Yuan Heyang 
Published: April 2021

AbstractMechanistic and data-driven models have been developed to provide predictive insights into the design and optimization of engineered bioprocesses. These two modeling strategies can be combined to form hybrid models to address the issues of parameter identifiability and prediction interpretability. Herein, we developed a novel and robust hybrid modeling strategy by incorporating microbial population dynamics into model construction. The hybrid model was constructed using bioelectrochemical systems (BES) as a platform system. We collected 77 samples from 13 publications, in which the BES were operated under diverse conditions, and performed holistic processing of the 16S rRNA amplicon sequencing data. Community analysis revealed core populations composed of putative electroactive taxaGeobacter, Desulfovibrio, Pseudomonas, andAcinetobacter. Primary Bayesian networks were trained with the core populations and environmental parameters, and directed Bayesian networks were trained by defining the operating parameters to improve the prediction interpretability. Both networks were validated with Bray-Curtis similarly, relative root-mean-square error (RMSE), and a null model. The hybrid model was developed by first building a three-population mechanistic component and subsequently feeding the estimated microbial kinetic parameters into network training. The hybrid model generated a simulated community that shared a Bray-Curtis similarity of 72% with the actual microbial community and an average relative RMSE of 7% for individual taxa. When examined with additional samples that were not included in network training, the hybrid model achieved accurate prediction of current production with a relative error-based RMSE of 0.8 and outperformed the data-driven models. The genomics-enabled hybrid modeling strategy represents a significant step toward robust simulation of a variety of engineered bioprocesses.
Genome-Wide Association Studies and Genomic Selection for Grain Protein Content Stability in a Nested Association Mapping Population of Spring Wheat
Authors: Sandhu Karansher S. , Mihalyov Paul D. , Lewien Megan J. , Pumphrey Michael O. , Carter Arron H. 
Published: April 2021

AbstractGrain protein content (GPC) is controlled by complex genetic systems and their interactions, and is an important quality determinant for hard spring wheat as it has a positive effect on bread and pasta quality. GPC is variable among genotypes and strongly influenced by environment. Thus, understanding the genetic control of wheat GPC and identifying genotypes with improved stability is an important breeding goal. The objectives of this research were to identify genetic backgrounds with less variation for GPC across environments and identify quantitative trait loci (QTLs) controlling the stability of GPC. A spring wheat nested association mapping (NAM) population of 650 recombinant inbred lines (RIL) derived from 26 diverse founder parents crossed to one common parent, ‘Berkut’, was phenotyped over three years of field trials (2014-2016). Genomic selection models were developed and compared based on prediction of GPC and GPC stability. After observing variable genetic control of GPC within the NAM population, seven RIL families displaying reduced marker-by-environment interaction were selected based on a stability index derived from Finlay-Wilkinson regression. A genome-wide association study identified seven significant QTLs for GPC stability with a Bonferroni-adjustedPvalue <0.05. This study also demonstrated that genome-wide prediction of GPC with ridge regression best linear unbiased estimates reached up tor= 0.69. Genomic selection can be used to apply selection pressure for GPC and improve genetic gain for GPC.
A soil-binding polysaccharide complex released from root hairs functions in rhizosheath formation
Authors: Galloway Andrew F. , Akhtar Jumana , Burak Emma , Marcus Susan E. , Field Katie J. , Dodd Ian C. , Knox Paul 
Published: April 2021

SUMMARYTo elucidate factors involved in rhizosheath formation, wild type (WT) barley (Hordeum vulgareL. cv. Pallas) and a root hairless mutant,bald root barley(brb), were investigated with a combination of physiological, biochemical and immunochemical assays. When grown in soil, WT barley roots bound ∼5-fold more soil thanbrbper unit root length. High molecular weight (HMW) polysaccharide exudates ofbrbroots had less soil-binding capacity than those of WT root exudates. Carbohydrate and glycan monoclonal antibody analyses of HMW polysaccharide exudates indicated differing glycan profiles. Relative to WT plants, root exudates ofbrbhad reduced signals for arabinogalactan-protein (AGP), extensin and heteroxylan epitopes thanbrb. In contrast, thebrbroot exudate contained ∼25-fold more detectable xyloglucan epitope relative to WT. Epitope detection chromatography indicated that the increased detection of xyloglucan inbrbexudates was due to enhanced abundance of a neutral polymer. Exudate preparations frombrbhad decreased amounts of an acidic form of xyloglucan associated with root-hair located glycoprotein and heteroxylan epitopes and with soil-binding properties. Therefore, in addition to physically structuring soil particles, root hairs facilitate rhizosheath formation by releasing a soil-binding polysaccharide complex.One sentence summaryThe root exudate of a root hairless mutant of barley, relative to wild type, has an altered pattern of polysaccharide epitopes and lesser amounts of an acidic soil-binding polysaccharide complex.
MiR-212-3p functions as a tumor suppressor gene in group 3 medulloblastoma via targeting Nuclear Factor I/B (NFIB)
Authors: Perumal Naveenkumar , Kanchan Ranjana K. , Doss David , Bastola Noah , Atri Pranita , Venkata Ramakanth C. , Thapa Ishwor , Vengoji Raghupathy , Maurya Shailendra K. , Klinkebiel David , Talmon Geoffrey A. , Nasser Mohd W. , Batra Surinder K. , Mahapatra Sidharth 
Published: April 2021

ABSTRACTBackgroundMedulloblastoma (MB), the most frequent malignant pediatric brain tumor, is subdivided into four primary subgroups, wingless-type (WNT), sonic hedgehog (SHH), group 3, and group 4. Haploinsufficiency of chromosome 17p13.3 and c-Myc amplification distinguish high-risk group 3 tumors associated with rapid metastasis, recurrence and early mortality. We sought to identify the role of miR-212-3p, which resides on chromosome 17p13.3, in the pathophysiology of group 3 MB.MethodsWe first determined miR-212-3p expression in group 3 MB using several publicly-available datasets with confirmatory studiesin vitro. We then identified epigenetic regulation by studying methylation and HDAC modifications along the promoter region. We used two systems for expression restoration, i.e. transient transfection or stable induction, to delineate miR-212-3p’s tumor suppressive and biochemical properties via assays assessing cancer proliferation, migration, invasion, colony formation, along with cell cycle and apoptosis analyses. We then compared MB and miR target databases to isolate a putative target whose biochemical and oncogenic properties were similarly elucidated using either transient silencing of target expression or stable induction of miR-212-3p.ResultsRNA expression analyses revealed dramatically reduced miR-212-3p levels in group 3 tumors and cell lines mainly through epigenetic silencing via histone modifications. Restoring miR-212-3p expression reducedin vitrocancer cell proliferation, migration, colony formation, and wound healing. Elevated miR-212-3p levels shifted c-Myc phosphorylation (from serine-62 to threonine-58), triggering destabilization and degradation; concurrently, its pro-apoptotic binding partners, i.e., Bin-1 and P19ARF, were upregulated with subsequent elevated apoptotic signals. Using a combination of transcriptomic data and dual luciferase assay, we isolated an oncogenic target of miR-212-3p, i.e. NFIB, a nuclear transcription factor implicated in metastasis and recurrence in various cancers. Increased expression of NFIB was confirmed in group 3 tumors, with poor survival shown in high-expressing patients. Transient NFIB silencingin vitroreduced cancer cell proliferation, colony formation, migration, and invasion. Concurrently, in group 3 MB cells, reduced medullosphere formation along with decreased expression of stem cell markers (Nanog, Oct4, Sox2, CD133) were noted.ConclusionThese results substantiate the tumor-suppressive role of miR-212-3p in group 3 MB and provide a potential therapeutic oncogenic target implicated in metastasis and tumor recurrence.
A Scribble-E-cadherin complex controls daughter cell patterning by multiple mechanisms
Authors: Chann Anchi S. , Chen Ye , Kinwel Tanja , Humbert Patrick O. , Russell Sarah M. 
Published: April 2021

AbstractThe fate of the two daughter cells is intimately connected to their positioning, which is in turn regulated by cell junction remodelling and orientation of the mitotic spindle. How multiple cues are integrated to dictate the ultimate patterning of daughters is not clear. Here, we identify novel mechanisms of regulation of daughter positioning in single MCF10A cells. The polarity protein, Scribble, links E-cadherin to NuMA and Arp2/3 signalling for sequential roles in daughter positioning. First Scribble transmits cues from E-cadherin localised in retraction fibres to control orientation of the mitotic spindle. Second, Scribble re-locates to the junction between the two daughters to allow a new E-cadherin-based-interface to form between them, influencing the width of the nascent daughter-daughter junction, generation of filopodia and subsequent cell patterning. Thus, E-cadherin and Scribble dynamically relocate to different intracellular sites during cell division to orient the mitotic spindle and control placement of the daughter cells after cell division.
SARS-CoV-2 RNA load in the lower respiratory tract, viral RNAemia and N-antigenemia in critically ill adult COVID-19 patients: relationship with biomarkers of disease severity
Authors: Olea Beatriz , Albert Eliseo , Torres Ignacio , Gozalvo-Rovira Roberto , Carbonell Nieves , Ferreres José , Poujois Sandrine , Costa Rosa , Colomina Javier , Rodríguez Jesús , Luisa Blasco María , Navarro David 
Published: April 2021

ABSTRACTBackgroundLittle is known about the comparative kinetics of SARS-CoV-RNA load in the lower respiratory tract and in blood compartment in patients admitted to the intensive care unit, and how these relate to biomarkers of COVID-19 severity.MethodsSeventy-three consecutive critically ill COVID-19 patients (median age, 65 years) were recruited. Serial lower respiratory tract (n=165) and plasma (n=340) specimens were collected. RT-PCR and lateral flow immunochromatography assay were used for SARS-CoV-2 RNA quantitation and N protein detection in plasma, respectively. Serum levels of inflammatory and tissue-damage biomarkers in paired specimens were analyzed.ResultsSARS-CoV-RNA was detected in the lower respiratory tract of most patients (92%). Viral RNAemia and N-antigenemia were documented in 35.6% and 40.1% of patients, respectively. Viral RNAemia and N-antigenemia cleared at a faster rate than SARS-CoV-2 RNA in tracheal aspirates (TA). SARS-CoV-2 RNA load was higher (P<0.001) in TA than in plasma, and correlated significantly (Rho, 0.41; P<0.001). A modest correlation was found between SARS-CoV-2 RNA load in TA and plasma and levels of ferritin and lactose dehydrogenase (Rho≤0.3; P≤0.008) in paired serum specimens. Neither the dynamics of SARS-CoV-2 RNA load in TA and plasma, nor N-antigenemia detection rate differed between surviving and deceased patients. Yet, a trend towards a higher mortality was seen in patients with viral RNAemia (OR; 2.82; 95% CI, 0.94-8.47; P=0.06).ConclusionNeither SARS-CoV-2 replication rate in the lower respiratory tract nor its presence in the blood appeared to critically impact on survival in ICU COVID-19 patients.SUMMARYSARS-CoV-2 RNA load in the lower respiratory tract and plasma and N-antigenemia followed different kinetics, correlated modestly with serum levels of inflammatory and tissue-damage biomarkers and lymphopenia and did not appear to increase overall mortality risk in critically ill adult COVID-19 patients.