bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantifying the Influence of Mutation Detection on Tumour Subclonal Reconstruction
Authors: Liu Lydia Y. , Bhandari Vinayak , Salcedo Adriana , Espiritu Shadrielle M. G. , Morris Quaid D. , Kislinger Thomas , Boutros Paul C. 
Published: September 2018

AbstractWhole-genome sequencing can be used to estimate subclonal populations in tumours and this intra-tumoural heterogeneity is linked to clinical outcomes. Many algorithms have been developed for subclonal reconstruction, but their variabilities and consistencies are largely unknown. We evaluated sixteen pipelines for reconstructing the evolutionary histories of 293 localized prostate cancers from single samples, and eighteen pipelines for the reconstruction of 10 tumours with multi-region sampling. We show that predictions of subclonal architecture and timing of somatic mutations vary extensively across pipelines. Pipelines show consistent types of biases, with those incorporating SomaticSniper and Battenberg preferentially predicting homogenous cancer cell populations and those using MuTect tending to predict multiple populations of cancer cells. Subclonal reconstructions using multi-region sampling confirm that single-sample reconstructions systematically underestimate intra-tumoural heterogeneity, predicting on average fewer than half of the cancer cell populations identified by multi-region sequencing. Overall, these biases suggest caution in interpreting specific architectures and subclonal variants.
An ABC method for whole-genome sequence data: inferring paleolithic and neolithic human expansions
Authors: Jay Flora , Boitard Simon , Austerlitz Frédéric 
Published: September 2018

AbstractSpecies generally undergo a complex demographic history, consisting, in particular, of multiple changes in population size. Genome-wide sequencing data are potentially highly informative for reconstructing this demographic history. A crucial point is to extract the relevant information from these very large datasets. Here we designed an approach for inferring past demographic events from a moderate number of fully sequenced genomes. Our new approach uses Approximate Bayesian Computation (ABC), a simulation-based statistical framework that allows (i) identifying the best demographic scenario among several competing scenarios, and (ii) estimating the best-fitting parameters under the chosen scenario. ABC relies on the computation of summary statistics. Using a cross-validation approach, we showed that statistics such as the lengths of haplotypes shared between individuals, or the decay of linkage disequilibrium with distance, can be combined with classical statistics (eg heterozygosity, Tajima’s D) to accurately infer complex demographic scenarios including bottlenecks and expansion periods. We also demonstrated the importance of simultaneously estimating the genotyping error rate. Applying our method on genome-wide human-sequence databases, we finally showed that a model consisting in a bottleneck followed by a Paleolithic and a Neolithic expansion was the most relevant for Eurasian populations.
Dominance in dogs as rated by owners corresponds to ethologically valid markers of dominance
Authors: Kubinyi Enikő , Wallis Lisa J 
Published: September 2018

AbstractDominance is well defined in ethology, debated in psychology, and is often unclear among the dog owning public and in the press. However, to date, no study has examined how owners perceive dominance in dogs, and what different behaviours and personality types are used to describe dominant and subordinate individuals. A questionnaire study was launched to investigate the external validity of owner-derived estimates of dominance in dog dyads sharing the same household (N = 1151). According to the owners, dogs rated as dominant (87%) have priority access to resources (resting place, food, and rewards), undertake certain tasks (defend and lead the group, bark more), display dominance (win fights, lick the other’s mouth less, and mark over the other’s urine), share certain personality traits (smarter, more aggressive and impulsive), and are older than their partner dog (all p < 0.0001). An age-related hypothesis has been suggested to explain dominance in dogs, but we found that dog age did not explain the occurrence of dominance-related behaviours over the owners’ estimate of dominance status. Results suggest that owner-derived reports of dominance ranks of dogs living in multi-dog households correspond to ethologically valid behavioural markers of dominance. Size and physical condition were unrelated to the perceived dominance. Surprisingly, in mixed-sex dyads, females were more frequently rated as dominant than males, which might correspond to a higher proportion of neutered females in this subgroup. For future studies that wish to allocate dominance status using owner report, we offer a novel survey.
Insulin Producing Cells Monitor the Cold and Compensate the Cold-Induced Sleep in Drosophila
Authors: Zhang Xu O. , Cui Xinyue , Zhu Dikai 
Published: September 2018

AbstractSleep is regulated by environmental factors including temperature, but the neural circuits that receive the sensory signal and mediate the regulation remain unclear. We examined how cold could influence Drosophila sleep patterns and its neural mechanism. The results showed that Drosophila has more sleep duration, less sleep latency and deeper sleep depth under cold condition. We identified the Insulin-producing Cells (IPCs) can be activated by cold, and receive the cold signal from the 11216 cold-sensing neuron without a direct synaptic connection. Elevation of IPCs’ sensitivity to cold impairs the sleep-promoting effect of cold while blocking of IPCs enhance the effect mostly on sleep circadian, suggesting that the cold activated IPCs have a compensative role in sleep regulation. Our finding revealed a potential neural circuit that help maintain sleep circadian in detrimental environment and may give new insight to the complicated sleep regulation mechanism.
The NSL complex mediated nucleosome landscape is required to maintain transcription fidelity and suppression of transcription noise
Authors: Lam Kin Chung , Chung Ho-Ryun , Semplicio Giuseppe , Bhardwaj Vivek , Iyer Shantanu S. , Holz Herbert , Georgiev Plamen , Akhtar Asifa 
Published: September 2018

AbstractNucleosomal organization at gene promoters is critical for transcription, with a nucleosome-depleted region (NDR) at transcription start sites (TSSs) being required for transcription initiation. How NDR and the precise positioning of the +1 nucleosome is maintained on active genes remains unclear. Here, we report that the Drosophila Non-Specific Lethal (NSL) complex is necessary to maintain this stereotypical nucleosomal organization at promoters. Upon NSL1 depletion, nucleosomes invade the NDRs at TSSs of NSL-bound genes. NSL complex member NSL3 binds to TATA-less promoters in a sequence-dependent manner. The NSL complex interacts with the NURF chromatin remodeling complex and is necessary and sufficient to recruit NURF to target promoters. The NSL complex is not only essential for transcription but is required for accurate TSS selection for genes with multiple TSSs. Further, loss of NSL complex leads to an increase in transcriptional noise. Thus, the NSL complex establishes a canonical nucleosomal organization that enables transcription and determines TSS fidelity.
Efficient transposon mutagenesis mediated by an IPTG-controlled conditional suicide plasmid
Authors: Naorem Santa S. , Han Jin , Zhang Stephanie Y. , Zhang Junyi , Graham Lindsey B. , Song Angelou , Smith Cameron V. , Rashid Fariha , Guo Huatao 
Published: September 2018

AbstractBackgroundTransposon mutagenesis is highly valuable for bacterial genetic and genomic studies. The transposons are usually delivered into host cells through conjugation or electroporation of a suicide plasmid. However, many bacterial species cannot be efficiently conjugated or transformed for transposon saturation mutagenesis. For this reason, temperature-sensitive (ts) plasmids have also been developed for transposon mutagenesis, but prolonged incubation at high temperatures to induce ts plasmid loss can be harmful to the hosts and lead to enrichment of mutants with adaptive genetic changes. In addition, the ts phenotype of a plasmid is often strain- or species-specific, as it may become non-ts or suicidal in different bacterial species.ResultsWe have engineered several conditional suicide plasmids that have a broad host range and whose loss is IPTG-controlled. One construct, which has the highest stability in the absence of IPTG induction, was then used as a curable vector to deliver hyperactive miniTn5 transposons for insertional mutagenesis. Our analyses show that these new tools can be used for efficient and regulatable transposon mutagenesis in Escherichia coli, Acinetobacter baylyi and Pseudomonas aeruginosa. In P. aeruginosa PAO1, we have used this method to generate a Tn5 insertion library with an estimated diversity of ~108, which is ~2 logs larger than the best transposon insertional library of PAO1 and related Pseudomonas strains previously reported.ConclusionWe have developed a number of IPTG-controlled conditional suicide plasmids. By exploiting one of them for transposon delivery, a highly efficient and broadly useful mutagenesis system has been developed. As the assay condition is mild, we believe that our methodology will have broad applications in microbiology research.
Cell-Type Switches Induced by Stochastic Histone Modification Inheritance
Authors: Huang Rongsheng , Lei Jinzhi , Pei-Yuan Zhou 
Published: September 2018

ABSTRACTCell plasticity is important for tissue developments during which somatic cells may switch between distinct states. Genetic networks to yield multistable states are usually required to yield multiple states, and either external stimuli or noise in gene expressions are trigger signals to induce cell-type switches between the states. In many biological systems, cells show highly plasticity and can switch between different state spontaneously, but maintaining the dynamic equilibrium of the cell population. Here, we considered a mechanism of spontaneous cell-type switches through the combination between gene regulation network and stochastic epigenetic state transitions. We presented a mathematical model that consists of a standard positive feedback loop with changes of histone modifications during with cell cycling. Based on the model, nucleosome state of an associated gene is a random process during cell cycling, and hence introduces an inherent noise to gene expression, which can automatically induce cell-type switches in cell cycling. Our model reveals a simple mechanism of spontaneous cell-type switches through a stochastic histone modification inheritance during cell cycle. This mechanism is inherent to the normal cell cycle process, and is independent to the external signals.
Bayesian Inference of Other Minds Explains Human Choices in Group Decision Making
Authors: Khalvati Koosha , Park Seongmin A. , Mirbagheri Saghar , Philippe Remi , Sestito Mariateresa , Dreher Jean-Claude , Rao Rajesh P. N. 
Published: September 2018

AbstractTo make decisions in a social context, humans have to predict the behavior of others, an ability that is thought to rely on having a model of other minds known as theory of mind. Such a model becomes especially complex when the number of people one simultaneously interacts is large and the actions are anonymous. Here, we show that in order to make decisions within a large group, humans employ Bayesian inference to model the “mind of the group,” making predictions of others’ decisions while also considering the effects of their own actions on the group as a whole. We present results from a group decision making task known as the Volunteers Dilemma and demonstrate that a Bayesian model based on partially observable Markov decision processes outperforms existing models in quantitatively explaining human behavior. Our results suggest that in group decision making, rather than acting based solely on the rewards received thus far, humans maintain a model of the group and simulate the group’s dynamics into the future in order to choose an action as a member of the group.
PERK Signaling Regulates Extracellular Proteostasis of an Amyloidogenic Protein During Endoplasmic Reticulum Stress
Authors: Romine Isabelle C. , Wiseman R. Luke 
Published: September 2018

ABSTRACTThe PERK arm of the unfolded protein response (UPR) regulates cellular proteostasis and survival in response to endoplasmic reticulum (ER) stress. However, the impact of PERK signaling on extracellular proteostasis is poorly understood. We define how PERK signaling influences extracellular proteostasis during ER stress using a conformational reporter of the secreted amyloidogenic protein transthyretin (TTR). We show that inhibiting PERK signaling impairs ER stress-dependent secretion of destabilized TTR by increasing its ER retention in chaperone-bound complexes. Interestingly, PERK inhibition promotes the ER stress-dependent secretion of TTR in non-native conformations that accumulate extracellularly as soluble oligomers. Pharmacologic or genetic TTR stabilization partially restores secretion of native TTR tetramers. However, PERK inhibition still increases the ER stress-dependent secretion of TTR in non-native conformations under these conditions, indicating that the conformation of stable secreted proteins can also be affected by inhibiting PERK. Our results define a role for PERK in regulating extracellular proteostasis during ER stress and indicate that genetic or aging-related alterations in PERK signaling can exacerbate ER stress-related imbalances in extracellular proteostasis implicated in diverse diseases.
Quantitative study of the somitogenetic wavefront in zebrafish
Authors: Zhang Weiting , Ducos Bertrand , Delagrange Marine , Vriz Sophie , Bensimon David 
Published: September 2018

ABSTRACTA quantitative description of the molecular networks that sustain morphogenesis is one of the challenges of developmental biology. Specifically, a molecular understanding of the segmentation of the antero-posterior axis in vertebrates has yet to be achieved. This process known as somitogenesis is believed to result from the interactions between a genetic oscillator and a posterior-moving determination wavefront. Here we quantitatively study and perturb the network in zebrafish that sustains this wavefront and compare our observations to a model whereby the wavefront is due to a switch between stable states resulting from reciprocal negative feedbacks of Retinoic Acid (RA) on the activation of ERK and of ERK on RA synthesis. This model quantitatively accounts for the near linear shortening of the post-somitic mesoderm (PSM) in response to the observed exponential decrease during somitogenesis of the mRNA concentration of a morphogen (Fgf8). It also accounts for the observed dynamics of the PSM when the molecular components of the network are perturbed. The generality of our model and its robustness allows for its test in other model organisms.
Co-translation drives the assembly of mammalian nuclear multisubunit complexes
Authors: Kamenova Ivanka , Mukherjee Pooja , Conic Sascha , Mueller Florian , El-Saafin Farrah , Bardot Paul , Garnier Jean-Marie , Dembele Doulaye , Capponi Simona , Timmers H.T. Marc , Vincent Stéphane D. , Tora László 
Published: September 2018

AbstractCells dedicate significant energy to build proteins often organized in multiprotein assemblies with tightly regulated stoichiometries. As genes encoding proteins assembling in the same multisubunit complexes are dispersed in the genome of eukaryotes, it is unclear how multisubunit complexes assemble. We show that mammalian nuclear transcription complexes (TFIID, TREX-2 and SAGA) composed of a large number of subunits but lacking precise architectural details are built co-translationally. We demonstrate that the dimerization domains and their positions in the interacting subunits determine the co-translational assembly pathway (simultaneous or sequential). Our results indicate that protein translation and complex assembly are linked in building mammalian multisubunit complexes and suggest that co-translational assembly is a general principle in mammalian cells to avoid non-specific interactions and protein aggregation. These findings will significantly advance structural biology by defining endogenous co-translational building blocks in the architecture of multisubunit complexes.
Arabidopsis Class I Formin FH1 Relocates Between Membrane Compartments During Root Cell Ontogeny And Associates With Plasmodesmata
Authors: Oulehlová Denisa , Kollárová Eva , Cifrová Petra , Pejchar Přemysl , Žárský Viktor , Cvrčková Fatima 
Published: September 2018

AbstractFormins are evolutionarily conserved eukaryotic proteins engaged in actin nucleation and other aspects of cytoskeletal organization. Angiosperms have two formin clades with multiple paralogs; typical plant Class I formins are integral membrane proteins that can anchor cytoskeletal structures to membranes. For the main Arabidopsis housekeeping Class I formin, FH1 (At3g25500), plasmalemma localization was documented in heterologous expression and overexpression studies. We previously showed that loss of FH1 function increases cotyledon epidermal pavement cell shape complexity via modification of actin and microtubule organization and dynamics. Here we employ transgenic Arabidopsis expressing green fluorescent protein-tagged FH1 (FH1-GFP) from its native promoter to investigatein vivobehaviour of this formin using advanced microscopy techniques. The fusion protein is functional, since its expression complements thefh1loss-of-function mutant phenotype. Accidental overexpression of FH1-GFP results in a decrease in trichome branch number, whilefh1mutation has the opposite effect, indicating a general role of this formin in controlling cell shape complexity. Consistent with previous reports, FH1-GFP associates with membranes. However, the protein exhibits surprising actin- and secretory pathway-dependent dynamic localization and relocates between cellular endomembranes and the plasmalemma during cell division and differentiation in root tissues, with transient tonoplast localization at the transition/elongation zones border. FH1-GFP also accumulates in actin-rich regions of cortical cytoplasm and associates with plasmodesmata in both the cotyledon epidermis and root tissues. Together with previous reports from metazoan systems, this suggests that formins might have an ancestral role at cell-cell junctions.
The Dlg-module and clathrin-mediated endocytosis regulate EGFR signaling and cyst cell-germline coordination in theDrosophilatestis
Authors: Papagiannouli Fani , Berry Cameron Wynn , Fuller Margaret T. 
Published: September 2018

SUMMARYTissue homeostasis and repair relies on proper communication of stem cells and their differentiating daughters with the local tissue microenvironment. In theDrosophilamale germline adult stem cell lineage, germ cells proliferate and progressively differentiate enclosed in supportive somatic cyst cells, forming a small organoid, the functional unit of differentiation. Here we show that cell polarity and vesicle trafficking influence signal transduction in cyst cells, with profound effects on the germ cells they enclose. Our data suggest that both the cortical components Dlg, Scrib, Lgl and the clathrin-mediated endocytic (CME) machinery downregulate EGFR signaling. Knockdown ofdlg, scrib, lglor CME components in cyst cells resulted in germ cell death, similar to increased signal transduction via the EGFR, while lowering EGFR or downstream signaling components rescued the defects. This work provides new insights on how cell polarity and endocytosis cooperate to regulate signal transduction and sculpt developing tissues.
Deacetylation of catalytic lysine in CDK1 is essential for Cyclin-B binding and cell cycle
Authors: Deota Shaunak , Rathnachalam Sivasudhan , Namrata Kanojia , Boob Mayank , Fulzele Amit , Radhika S , Ganguli Shubhra , Balaji Chinthapalli , Kaypee Stephanie , Vishwakarma Krishna Kant , Kundu Tapas Kumar , Bhandari Rashna , de Peredo Anne Gonzalez , Mishra Mithilesh , Venkatramani Ravindra , Kolthur-Seetharam Ullas 
Published: September 2018

AbstractCyclin-dependent-kinases (CDKs) are essential for cell cycle progression. While dependence of CDK activity on Cyclin levels is established, molecular mechanisms that regulate their binding are less studied. Here, we show that CDKl:Cyclin-B interactions are regulated by acetylation, which was hitherto unknown. We demonstrate that cell cycle dependent acetylation of the evolutionarily conserved catalytic lysine in CDK1 or eliminating its charge state abrogates Cyclin-B binding. Opposing activities of SIRT1 and P300 regulate acetylation, which marks a reserved pool of CDK1. Our high resolution structural analyses into the formation of kinase competent CDK1: Cyclin-B complex have unveiled long-range effects of catalytic lysine in configuring the CDK1 interface for Cyclin-B binding. Cells expressing acetylation mimic mutant of Cdc2 in yeast are arrested in G2 and fail to divide. Thus, by illustrating cell cycle dependent deacetylation as a determinant of CDK1:Cyclin-B interaction, our results redefine the current model of CDK1 activation and cell cycle progression.