bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tuning cell motility via cell tension with a mechanochemical cell migration model
Authors: Tao K. , Wang J. , Kuang X. , Wang W. , Liu F. , Zhang L. 
Published: November 2019

AbstractCell migration is orchestrated by a complicated mechanochemical system. However, few cell migration models take account of the coupling between a biochemical network and mechanical factors. Here, we construct a mechanochemical cell migration model to study the cell tension effect on cell migration. Our model incorporates the interactions between Rac-GTP, Rac-GDP, F-actin, myosin, and cell tension, and it is based on phase field approach hence very convenient in describing the cell shape change. This model captures common features of cell polarization, cell shape change, and cell migration modes. It shows cell tension inhibits migration ability monotonically when cells are applied with persistent external stimuli. On the other hand, if random internal noise is significant, the regulation of cell tension exerts a non-monotonic effect on cell migration. As the elevation of cell tension impedes the formation of multiple protrusions hence enhances the streamline position of the cell body. Therefore the migration ability could be maximized at intermediate cell tension under random internal noise. These model predictions are consistent with our singlecell experiments and other experimental results.Statement of significanceCell migration plays a vital role in many biological processes such as tumor metastasis. It is a complicated process regulated by dynamic coupling between the biochemical network and mechanical forces. However, few cell migration models take account of both factors. Here, we construct a mechanochemical cell migration model to study how cell migration is regulated by cell tension. Our model predicts that cell tension not only inhibits cell movement under persistent external stimuli but also prompts cell migration under random internal noise when cell tension is low. Therefore an optimized cell tension could maximize the migration ability under random internal noise. We further confirmed these model predictions are consistent with our single-cell experiments and other published experimental results.
Translational regulation of Pmt1 and Pmt2 by Bfr1 affects unfolded protein O-mannosylation
Authors: Castells-Ballester Joan , Rinis Natalie , Kotan Ilgin , Gal Lihi , Bausewein Daniela , Kats Ilia , Zatorska Ewa , Kramer Günter , Bukau Bernd , Schuldiner Maya , Strahl Sabine 
Published: November 2019

ABSTRACTO-mannosylation is implicated in protein quality control inSaccharomyces cerevisiaedue to the attachment of mannose to serine and threonine residues of un- or misfolded proteins in the endoplasmic reticulum (ER). This process also designated as unfolded protein O-mannosylation (UPOM) that ends futile folding cycles and saves cellular resources is mainly mediated by protein O-mannosyltransferases Pmt1 and Pmt2. Here we describe a genetic screen for factors that influence O-mannosylation in yeast, using slow-folding GFP as a reporter. Our screening identifies the RNA binding protein brefeldin A resistance factor 1 (Bfr1) that has not been linked to O-mannosylation and ER protein quality control before. We find that Bfr1 affects O-mannosylation through changes in Pmt1 and Pmt2 protein abundance, but has no effect onPMT1andPMT2transcript levels, mRNA localization to the ER membrane or protein stability. Ribosome profiling reveals that Bfr1 is a crucial factor for Pmt1 and Pmt2 translation thereby affecting unfolded protein O-mannosylation. Our results uncover a new level of regulation of protein quality control in the secretory pathway.
Proximate causes of infertility and embryo mortality in captive zebra finches
Authors: Pei Yifan , Forstmeier Wolfgang , Wang Daiping , Martin Katrin , Rutkowska Joanna , Kempenaers Bart 
Published: November 2019

AbstractSome species show high rates of reproductive failure, which is puzzling because natural selection works against such failure in every generation. Hatching failure is common in both captive and wild zebra finches (Taeniopygia guttata), yet little is known about its proximate causes. Here we analyze data on reproductive performance (fate of >23,000 eggs) based on up to 14 years of breeding of four captive zebra finch populations. We find that virtually all aspects of reproductive performance are negatively affected by inbreeding (mean r = -0.117), by an early-starting, age-related decline (mean r = -0.132), and by poor early-life nutrition (mean r = - 0.058). However, these effects together explain only about 3% of the variance in infertility, offspring mortality, fecundity and fitness. In contrast, individual repeatability of different fitness components varied between 15% and 50%. As expected, we found relatively low heritability in fitness components (median: 7% of phenotypic, and 29% of individually repeatable variation). Yet, some of the heritable variation in fitness appears to be maintained by antagonistic pleiotropy (negative genetic correlations) between male fitness traits and female and offspring fitness traits. The large amount of unexplained variation suggests a potentially important role of local dominance and epistasis, including the possibility of segregating genetic incompatibilities.
Catalytic inhibition of H3K9me2 writers disturbs epigenetic marks during bovine nuclear reprogramming
Authors: Sampaio RV , Sangalli JR , De Bem THC , Ambrizi DR , del Collado M , Bridi A , Ávila ACFCM , Macabelli CH , Oliveira LJ , da Silveira JC , Chiaratti MR , Perecin F , Bressan FF , Smith LC , Ross PJ , Meirelles FV 
Published: November 2019

AbstractOrchestrated events, including extensive changes in epigenetic marks, allow a somatic nucleus to become totipotent after transfer into an oocyte, a process termed nuclear reprogramming. Recently, several strategies have been applied in order to improve reprogramming efficiency, mainly focused on removing repressive epigenetic marks such as histone methylation from the somatic nucleus. Herein we used the specific and non-toxic chemical probe UNC0638 to inhibit the catalytic activity of the histone metyltransferases EHMT1 and EHMT2. Either the donor cell (before reconstruction) or the early embryo was exposed to the probe to assess its effect on developmental rates and epigenetic marks. First, we showed that the treatment of bovine fibroblasts with UNC0638 did mitigate the levels of H3K9me2. Moreover, H3K9me2 levels were decreased in cloned embryos regardless of treating either donor cells or early embryos with UNC0638. Additional epigenetic marks such as H3K9me3, 5mC, and 5hmC were also affected by the UNC0638 treatment. Therefore, the use of UNC0638 did diminish the levels of H3K9me2 and H3K9me3 in SCNT-derived blastocysts, but this was unable to improve their preimplantation development. These results indicate that the specific reduction of H3K9me2 by inhibiting EHMT1/2 causes diverse modifications to the chromatin during early development, suggesting an intense epigenetic crosstalk during nuclear reprogramming.
Exposure during embryonic development to Roundup® Power 2.0 affects lateralization, level of activity and growth, but not defensive behaviour of marsh frog tadpoles
Authors: Bolis Alessandro , Gazzola Andrea , Pellitteri-Rosa Daniele , Colombo Anita , Bonfanti Patrizia , Bellati Adriana 
Published: November 2019

ABSTRACTAs glyphosate-based herbicides, sold under the commercial name Roundup®, represent the most used herbicides in the world, contamination of the freshwater environment by glyphosate has become a widespread issue. In Italy, glyphosate was detected in half of the surface waters monitoring sites and its concentrations were higher than environmental quality standards in 24.5% of them. It can last from days to months in water, leading to exposure for aquatic organisms and specifically to amphibians’ larvae that develop in shallow water bodies with proven effects to development and behaviour. In this study, we tested the effects of a 96h exposure during embryonic development of marsh frog’s tadpoles to three ecologically relevant Roundup® Power 2.0 concentrations. As expected, given the low concentrations tested, no mortality was observed. Morphological measurements highlighted a reduction in the total length in tadpoles exposed to 7.6 mg a.e./L, while an increase was observed at lower concentrations of 0.7 and 3.1 mg a.e./L compared to control group. Tadpoles raised in 7.6 mg a.e./L also showed a smaller tail membrane than those raised in the control solution. Regarding behaviour, we tested tadpoles in two different sessions (Gosner stages 25 and 28/29) for lateralization, antipredator response and basal activity. Lower intensity of lateralization was detected in tadpoles raised at the highest Roundup® concentration in the first session of observation, while no significant difference among treatments was observed in the second one. In both sessions, effects of glyphosate embryonic exposure on antipredator response, measured as the proportional change in activity after the injection of tadpole-fed predator (Anax imperator) cue, were not detected. Tadpoles exposed during embryonic development to Roundup® exhibited lower basal activity than the control group, with the strongest reduction for the 7.6 mg a.e./L treatment. Our results reinforce the concern of glyphosate contamination impact on amphibians.
Estimating Genetic Inheritance in Case-control Studies
Authors: Li Na , Zhu Jiayan , Li Zhengbang 
Published: November 2019

AbstractCase-control genetic association study is an efficient tool to search for the deleterious genetic variants predispose to human complex diseases, where the additive mode of inheritance is commonly assumed. However, how the genetic variants influence the occurrence of a certain disease is impossible to know beforehand. We show numerically that the existing procedures using the Hardy-Weinberg equilibrium test to choose the genetic model might be inconsistent. We propose a new method to choose the genetic model by adopting co-dominant code for risk allele and logistic regression model. Extensive computer simulation results demonstrate superiorities of the new method. Applications to six single nucleotide polymorphisms(SNPs) for breast cancer and eight SNPs for Type 2 Diabetes further show good performances of proposed method. In order to specify a genetic model for an allele, our method has some merits and is consistent as sample size is large. We propose to apply our method in related fields.
A Multiple-trait Bayesian Variable Selection Regression Method for Integrating Phenotypic Causal Networks in Genome-Wide Association Studies
Authors: Wang Zigui , Chapman Deborah , Morota Gota , Cheng Hao 
Published: November 2019

ABSTRACTBayesian regression methods that incorporate different mixture priors for marker effects are used in multi-trait genomic prediction. These methods can also be extended to genome-wide association studies (GWAS). In multiple-trait GWAS, incorporating the underlying causal structures among traits is essential for comprehensively understanding the relationship between genotypes and traits of interest. Therefore, we develop a GWAS methodology, SEM-BayesCΠ, which, by applying the structural equation model (SEM), can be used to incorporate causal structures into a multi-trait Bayesian regression method using mixture priors. The performance of SEM-BayesCΠ was demonstrated by comparing its GWAS results with those from multi-trait BayesCΠ. Through the inductive causation (IC) algorithm, three potential causal structures were inferred of 0.9 highest posterior density (HPD) interval. SEM-BayesCΠ provides a more comprehensive understanding of the genotype-phenotype mapping than multi-trait BayesCΠ by performing GWAS based on indirect, direct and overall marker effects. The software tool JWAS offers open-source routines to perform these analyses.
The Reissner Fiber is Highly Dynamic in vivo and Controls Morphogenesis of the Spine
Authors: Troutwine Benjamin , Gontarz Paul , Minowa Ryoko , Monstad-Rios Adrian , Konjikusic Mia J. , Sepich Diane S. , Kwon Ronald Y. , Solnica-Krezel Lilianna , Gray Ryan S. 
Published: November 2019

SummarySpine morphogenesis requires the integration of multiple musculoskeletal tissues with the nervous system. Cerebrospinal fluid (CSF) physiology is important for development and homeostasis of the central nervous system and its disruption has been linked to scoliosis in zebrafish [1, 2]. Suspended in the CSF is an enigmatic glycoprotein thread called the Reissner fiber, which is secreted from the subcomissural organ (SCO) in the brain and extends caudally through the central canal to where it terminates at the base of the spinal cord. In zebrafish,scospondinnull mutants are unable to assemble the Reissner fiber and fail to extend a straight body axis during embryonic development [3]. Here, we describe zebrafish hypomorphic missense alleles, which assemble the Reissner fiber and straighten the body axis during early embryonic development, yet progressively lose the fiber, concomitant with the emergence of body curvature, alterations in neuronal gene expression, and scoliosis in adults. Using an endogenously taggedscospondin-GFPzebrafish knock-in line, we directly visualized Reissner fiber dynamics during the normal development and during the progression of scoliosis, and demonstrate that the Reissner fiber is critical for the morphogenesis of the spine. Our study establishes a framework for future investigations of mechanistic roles of the Reissner fiber including its dynamic properties, molecular interactions, and how these processes are involved in the regulation of spine morphogenesis and scoliosis.HighlightsHypomorphic mutations in zebrafishscospondinresult in progressive scoliosisThe disassembly of the Reissner fiber inscospondinhypomorphic mutants results in the strong upregulation of neuronal receptors and synaptic transport componentsAn endogenous fluorescent knock-in allele ofscospondinreveals dynamic properties of the Reissner fiber during zebrafish developmentLoss of the Reissner fiber during larval development is a common feature of zebrafish scoliosis models
To composite or replicate: how sampling method and protocol differences alter stream bioassessment metrics
Authors: Tronstad Lusha , Wilmot Oliver , Thornbrugh Darren , Hotaling Scott 
Published: November 2019

AbstractAquatic invertebrates are excellent indicators of ecosystem quality; however, choosing a sampling method can be difficult. Each method and associated protocol has advantages and disadvantages, and finding the approach that minimizes biases yet fulfills management objectives is crucial. To test the effects of both sampling methods and sample handling – i.e., to composite samples or leave them as replicates – we collected aquatic invertebrates from the Niobrara River at Agate Fossil Beds National Monument, Nebraska using three methods and two sample handling protocols. We compared aquatic invertebrate assemblages collected with a Hester-Dendy multi-plate sampler, Hess sampler and a D-frame dipnet. We calculated six common bioassessment metrics from composite (combined) and replicate (separate) samples. Hess samples contained the highest taxonomic richness (capturing 77% of all taxa observed) and dipnet samples the least (47%). Hester-Dendy samples had the greatest proportion of Ephemeroptera, and Ephemeroptera, Plecoptera and Trichoptera (EPT). Dipnet samples had the lowest evenness values. In terms of sample handling, composite samples had inflated richness, diversity and evenness compared to replicate samples, but bioassessment metrics calculated from proportions or averages (i.e. Hilsenhoff’s Biotic Index and the proportion of EPT taxa) did not differ between them. The proportion of invertebrate groups from composite samples were not statistically different among sampling methods, but several groups differed between replicate samples collected by different methods. Ultimately, we recommend collecting replicate samples with a Hess sampler when the goal of the study is to detect ecosystem change, among locations or differences in variables of interest.
A Division of Labor in the Recruitment and Topological Organization of a Bacterial Morphogenic Complex
Authors: Caccamo Paul D. , Jacq Maxime , VanNieuwenhze Michael S. , Brun Yves V. 
Published: November 2019

SummaryBacteria come in an array of shapes and sizes, but the mechanisms underlying diverse morphologies are poorly understood. The peptidoglycan (PG) cell wall is the primary determinant of cell shape. At the molecular level, morphological variation often results from the regulation of enzymes involved in cell elongation and division. These enzymes are spatially controlled by cytoskeletal scaffolding proteins, that both recruit and organize the PG synthesis complex. How then do cells define alternative morphogenic processes that are distinct from cell elongation and division? To address this, we have turned to the specific morphotype of Alphaproteobacterial stalks. Stalk synthesis is a specialized form of zonal growth, which requires PG synthesis in a spatially constrained zone to extend a thin cylindrical projection of the cell envelope. The morphogen SpmX defines the site of stalk PG synthesis, but SpmX is a PG hydrolase. How then does a non-cytoskeletal protein, SpmX, define and constrain PG synthesis to form stalks? Here we report that SpmX and the bactofilin BacA act in concert to regulate stalk synthesis in Asticcacaulis biprosthecum. We show that SpmX recruits BacA to the site of stalk synthesis. BacA then serves as a stalk-specific topological organizer for PG synthesis activity, including its recruiter SpmX, at the base of the stalk. In the absence of BacA, cells produce “pseudostalks” that are the result of unconstrained PG synthesis. Therefore, the protein responsible for recruitment of a morphogenic PG remodeling complex, SpmX, is distinct from the protein that topologically organizes the complex, BacA.
Evaluating the efficacy of multiple myeloma cell lines as models for patient tumors via transcriptomic correlation analysis
Authors: Sarin Vishesh , Yu Katharine , Ferguson Ian D. , Gugliemini Olivia , Nix Matthew A. , Hann Byron C. , Sirota Marina , Wiita Arun P. 
Published: November 2019

AbstractMultiple myeloma (MM) cell lines are routinely used to model the disease. However, a long-standing question is how well these cell lines truly represent tumor cells in patients. Here, we employ a recently-described method of transcriptional correlation profiling to compare similarity of 66 MM cell lines to 779 newly-diagnosed MM patient tumors. We found that individual MM lines differ significantly with respect to patient tumor representation, with median R ranging from 0.35-0.54. ANBL-6 was the “best” line, markedly exceeding all others (p < 2.2e-16). Notably, some widely-used cell lines (RPMI-8226, U-266) scored poorly in our patient similarity ranking (48 and 52 of 66, respectively). Lines cultured with interleukin-6 showed significantly improved correlations with patient tumor (p = 9.5e-4). When common MM genomic features were matched between cell lines and patients, only t(4;14) and t(14;16) led to increased transcriptional correlation. To demonstrate utility of our top-ranked line for preclinical studies, we showed that intravenously-implanted ANBL-6 proliferates in hematopoietic organs in immunocompromised mice. Overall, our large-scale quantitative correlation analysis, utilizing emerging datasets, provides a resource informing the MM community of cell lines that may be most reliable for modeling patient disease while also elucidating biological differences between cell lines and tumors.
Wnt Regulation: Exploring Axin-Disheveled interactions and defining mechanisms by which the SCF E3 ubiquitin ligase is recruited to the destruction complex
Authors: Schaefer Kristina N. , Pronobis Mira , Williams Clara E. , Zhang Shiping , Bauer Lauren , Goldfarb Dennis , Yan Feng , Major M. Ben , Peifer Mark 
Published: November 2019

AbstractWnt signaling plays key roles in embryonic development and adult stem cell homeostasis, and is altered in human cancer. Signaling is turned on and off by regulating stability of the effector β-catenin. The multiprotein destruction complex binds and phosphorylates β-catenin, and transfers it to the SCF-TrCP E3-ubiquitin ligase, for ubiquitination and destruction. Wnt signals act though Dishevelled to turn down the destruction complex, stabilizing β-catenin. Recent work clarified underlying mechanisms, but important questions remain. We explore β-catenin transfer from the destruction complex to the E3 ligase, and test models suggesting Dishevelled and APC2 compete for association with Axin. We find that Slimb/TrCP is a dynamic component of the destruction complex biomolecular condensate, while other E3 proteins are not. Recruitment requires Axin and not APC, and Axin’s RGS domain plays an important role. We find that elevating Dishevelled levels inDrosophilaembryos has paradoxical effects, promoting the ability of limiting levels of Axin to turn off Wnt signaling. When we elevate Dishevelled levels, it forms its own cytoplasmic puncta, but these do not recruit Axin. SIM imaging in mammalian cells suggests that this may result by promoting Dishevelled: Dishevelled interactions at the expense of Dishevelled:Axin interactions when Dishevelled levels are high.
Chromosome-level assembly of Drosophila bifasciata reveals important karyotypic transition of the X chromosome
Authors: Bracewell Ryan , Tran Anita , Chatla Kamalakar , Bachtrog Doris 
Published: November 2019

ABSTRACTThe Drosophila obscura species group is one of the most studied clades of Drosophila and harbors multiple distinct karyotypes. Here we present a de novo genome assembly and annotation of D. bifasciata, a species which represents an important subgroup for which no high-quality chromosome-level genome assembly currently exists. We combined long-read sequencing (Nanopore) and Hi-C scaffolding to achieve a highly contiguous genome assembly approximately 193Mb in size, with repetitive elements constituting 30.1% of the total length. Drosophila bifasciata harbors four large metacentric chromosomes and the small dot, and our assembly contains each chromosome in a single scaffold, including the highly repetitive pericentromere, which were largely composed of Jockey and Gypsy transposable elements. We annotated a total of 12,821 protein-coding genes and comparisons of synteny with D. athabasca orthologs show that the large metacentric pericentromeric regions of multiple chromosomes are conserved between these species. Importantly, Muller A (X chromosome) was found to be metacentric in D. bifasciata and the pericentromeric region appears homologous to the pericentromeric region of the fused Muller A-AD (XL and XR) of pseudoobscura/affinis subgroup species. Our finding suggests a metacentric ancestral X fused to a telocentric Muller D and created the large neo-X (Muller A-AD) chromosome ∼15 MYA. We also confirm the fusion of Muller C and D in D. bifasciata and show that it likely involved a centromere-centromere fusion.