bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Cdc14 phosphatase controls resolution of recombination intermediates and crossover formation during meiosis
Authors: Alonso-Ramos Paula , Álvarez-Melo David , Strouhalova Katerina , Pascual-Silva Carolina , Garside George B. , Arter Meret , Bermejo Teresa , Grigaitis Rokas , Wettstein Rahel , Fernández-Díaz Marta , Matos Joao , Geymonat Marco , San-Segundo Pedro A. , Carballo Jesús A. 
Published: March 2019

AbstractMeiotic defects derived from incorrect DNA repair during gametogenesis can lead to mutations, aneuploidies and infertility. Coordinated resolution of meiotic recombination intermediates is required for crossover formation, ultimately necessary for accurate completion of both rounds of chromosome segregation. Numerous master kinases orchestrate the correct assembly and activity of the repair machinery. Although much less is known, reversal of phosphorylation events in meiosis must also be key to coordinate the timing and functionality of repair enzymes. Cdc14 is an evolutionarily conserved phosphatase required for the dephosphorylation of multiple CDK1 targets. Mutations that inactivate this phosphatase lead to meiotic failure, but until now it was unknown if Cdc14 plays a direct role in meiotic recombination. Here, we show that elimination of Cdc14 leads to severe defects in the processing and resolution of recombination intermediates, causing a drastic depletion of crossovers when other repair pathways are compromised. We also show that Cdc14 is required for correct activity and localization of the Holliday Junction resolvase Yen1/GEN1. We reveal that Cdc14 regulates Yen1 activity from meiosis I onwards, and this function is essential for crossover resolution in the absence of other repair pathways. We also demonstrate that Cdc14 and Yen1 are required to safeguard sister chromatid segregation during the second meiotic division, a late action that is independent of the earlier role in crossover formation. Thus, this work uncovers previously undescribed functions of Cdc14 in the regulation of meiotic recombination.
Electrospray Surface Charge Describes Protein Molecular Motion
Authors: Chalk Rod , Borkowska Oktawia , Azeez Kamal Abdul , Oerum Stephanie , Born Petra , Gileadi Opher , Burgess-Brown Nicola 
Published: March 2019

AbstractThe electrospray mass/charge distribution for a protein is an instantaneous measurement of surface areas during the transition from liquid to gas phase. Protonation is dependent upon surface area and surface area is related to protein folding under all conditions. M/z distributions for proteins and protein analogues all with different degrees of entropy were compared. Rigid dipeptide self-assemblies of any size possess a single m/z, whereas protein always displays multiple m/z distributions. Native proteins have narrow, defined m/z distributions, while denatured proteins and synthetic homopolypetides possess the widest possible m/z distributions. These observations are consistent with dynamic changes in surface area resulting from molecular motion.
A Bayesian method using sparse data to estimate penetrance of disease-associated genetic variants
Authors: Kroncke Brett M. , Smith Derek K. , Glazer Andrew M. , Roden Dan M. , Blume Jeffrey D. 
Published: March 2019

AbstractPurposeA major challenge in genomic medicine is how to best predict risk of disease from rare variants discovered in Mendelian disease genes but with limited phenotypic data. We have recently used Bayesian methods to show thatin vitrofunctional measurements and computational pathogenicity classification of variants in the cardiac geneSCN5Acorrelate with rare arrhythmia penetrance. We hypothesized that similar predictors could be used to impute variant-specific penetrance prior probabilities.MethodsFrom a review of 756 publications, we developed a pattern mixture algorithm, based on a Bayesian Beta-Binomial model, to generateSCN5Avariant-specific penetrance priors for the heart arrhythmia Brugada syndrome (BrS).ResultsThe resulting priors correlate with mean BrS penetrance posteriors (cross validated R2= 0.41).SCN5Avariant function and structural context provide the most information predictive of BrS penetrance. The resulting priors are interpretable as equivalent to the observation of affected and unaffected carriers.ConclusionsBayesian estimates of penetrance can efficiently integrate variant-specific data (e.g. functional, structural, and sequence) to accurately estimate disease risk attributable to individual variants. We suggest this formulation of penetrance is quantitative, probabilistic, and more precise than, but consistent with, discrete pathogenicity classification approaches.
In vivoglucose imaging in multiple model organisms with an engineered single-wavelength sensor
Authors: Keller Jacob P. , Marvin Jonathan S. , Lacin Haluk , Lemon William C. , Shea Jamien , Kim Soomin , Lee Richard T. , Koyama Minoru , Keller Philipp J. , Looger Loren L. 
Published: March 2019

AbstractGlucose is arguably the most important molecule in metabolism, and its mismanagement underlies diseases of vast societal import, most notably diabetes. Although glucose-related metabolism has been the subject of intense study for over a century, tools to track glucose in living organisms with high spatio-temporal resolution are lacking. We describe the engineering of a family of genetically encoded glucose sensors with high signal-to-noise ratio, fast kinetics and affinities varying over four orders of magnitude (1 µM to 10 mM). The sensors allow rigorous mechanistic characterization of glucose transporters expressed in cultured cells with high spatial and temporal resolution. Imaging of neuron/glia co-cultures revealed ∼3-fold higher glucose changes in astrocytes versus neurons. In larvalDrosophilacentral nervous system explants, imaging of intracellular neuronal glucose suggested a novel rostro-caudal transport pathway in the ventral nerve cord neuropil, with paradoxically slower uptake into the peripheral cell bodies and brain lobes. In living zebrafish, expected glucose-related physiological sequelae of insulin and epinephrine treatments were directly visualized in real time. Additionally, spontaneous muscle twitches induced glucose uptake in muscle, and sensory- and pharmacological perturbations gave rise to large but enigmatic changes in the brain. These sensors will enable myriad experiments, most notably rapid, high-resolution imaging of glucose influx, efflux, and metabolism in behaving animals.
Noroviruses subvert the core stress granule component G3BP1 to promote viral VPg-dependent translation
Authors: Hosmillo Myra , Lu Jia , McAllaster Michael R. , Eaglesham James B. , Wang Xinjie , Emmott Edward , Domingues Patricia , Chaudhry Yasmin , Fitzmaurice Timothy J , Tung Matthew K.H. , Panas Marc , McInerney Gerald , Locker Nicholas , Willen Craig B. , Goodfellow Ian 
Published: March 2019

AbstractKnowledge of the host factors required for norovirus replication has been hindered by the challenges associated with culturing human noroviruses. We have combined proteomic analysis of the viral translation and replication complexes with a CRISPR screen, to identify host factors required for norovirus infection. The core stress granule component G3BP1 was identified as a host factor essential for efficient human and murine norovirus infection, demonstrating a conserved function across theNorovirusgenus. Furthermore, we show that G3BP1 functions in the novel paradigm of viral VPg-dependent translation initiation, contributing to the assembly of translation complexes on the VPg-linked viral positive sense RNA genome by facilitating 40S recruitment. Our data suggest that G3BP1 functions by providing viral RNA a competitive advantage over capped cellular RNAs, uncovering a novel function for G3BP1 in the life cycle of positive sense RNA viruses and identifying the first host factor with pan-norovirus pro-viral activity.
Nuclear Genome Size is Positively Correlated with Mean LTR Insertion Date in Fern and Lycophyte Genomes
Authors: Baniaga Anthony E. , Barker Michael S. 
Published: March 2019

AbstractNuclear genome size is highly variable in vascular plants. The composition of long terminal repeat retrotransposons (LTRs) is a chief mechanism of long term change in the amount of nuclear DNA. Compared to flowering plants, little is known about LTR dynamics in ferns and lycophytes. Drawing upon the availability of recently sequenced fern and lycophyte genomes we investigated these dynamics and placed them in the context of vascular plants. We found that similar to seed plants, mean LTR insertion dates were strongly correlated with haploid nuclear genome size. Fern and lycophyte species with small genomes such as those of the heterosporousSelaginellaand members of the Salviniaceae had recent mean LTR insertion dates, whereas species with large genomes such as homosporous ferns had old mean LTR insertion dates intermediate between angiosperms and gymnosperms. This pattern holds despite methylation and life history differences in ferns and lycophytes compared to seed plants, and our results are consistent with other patterns of structural variation in fern and lycophyte genomes.
Deciphering the ‘m6A code’ via quantitative profiling of m6A at single-nucleotide resolution
Authors: Garcia-Campos Miguel Angel , Edelheit Sarit , Toth Ursula , Shachar Ran , Nir Ronit , Lasman Lior , Brandis Alexander , Hanna Jacob H. , Rossmanith Walter , Schwartz Schraga 
Published: March 2019

AbstractN6-methyladenosine (m6A) is the most abundant modification on mRNA, and is implicated in critical roles in development, physiology and disease. The ability to map m6A using immunoprecipitation-based approaches has played a critical role in dissecting m6A functions and mechanisms of action. Yet, these approaches are of limited specificity, unknown sensitivity, and unable to quantify m6A stoichiometry. These limitations have severely hampered our ability to unravel the factors determining where m6A will be deposited, to which levels (the ‘m6A code’), and to quantitatively profile m6A dynamics across biological systems. Here, we used the RNase MazF, which cleaves specifically at unmethylated RNA sites, to develop MASTER-seq for systematic quantitative profiling of m6A sites at 16-25% of all m6A sites at single nucleotide resolution. We established MASTER-seq for orthogonal validation andde novodetection of m6A sites, and for tracking of m6A dynamics in yeast gametogenesis and in early mammalian differentiation. We discover that antibody-based approaches severely underestimate the number of m6A sites, and that both the presence of m6A and its stoichiometry are ‘hard-coded’ via a simple and predictable code within the extended sequence composition at the methylation sites. This code accounts for ~50% of the variability in methylation levels across sites, allows excellentde novoprediction of methylation sites, and predicts methylation acquisition and loss across evolution. We anticipate that MASTER-seq will pave the path towards a more quantitative investigation of m6A biogenesis and regulation in a wide variety of systems, including diverse cell types, stimuli, subcellular components, and disease states.
The exhaustive genomic scan approach, with an application to rare-variant association analysis
Authors: Kanoungi George , Nothnagel Michael , Becker Tim , Drichel Dmitriy 
Published: March 2019

AbstractRegion-based genome-wide scans are usually performed by use of a priori chosen analysis regions. Such an approach will likely miss the region comprising the strongest signal and, thus, may result in increased type II error rates and decreased power. Here, we propose a genomic exhaustive scan approach that analyzes all possible subsequences and does not rely on a prior definition of the analysis regions. As a prime instance, we present a computationally ultra-efficient implementation using the rare-variant collapsing test for phenotypic association, the genomic exhaustive collapsing scan (GECS). Our implementation allows for the identification of regions comprising the strongest signals in large, genome-wide rare-variant association studies while controlling the family-wise error rate via permutation. Application of GECS to two genomic data sets revealed several novel significantly associated regions for age-related macular degeneration and for schizophrenia. Our approach also offers a high potential for genome-wide scans for selection, methylation and other analyses.
Colony entropy - Allocation of goods in ant colonies
Authors: Greenwald Efrat , Eckmann Jean-Pierre , Feinerman Ofer 
Published: March 2019

AbstractAllocation of goods is a key feature in defining the connection between the individual and the collective scale in any society. Both the process by which goods are to be distributed, and the resulting allocation to the members of the society may affect the success of the population as a whole. One of the most striking natural examples of a highly successful cooperative society is the ant colony which often acts as a single superorganism. In particular, each individual within the ant colony has a “communal stomach” which is used to store and share food with the other colony members by mouth to mouth feeding. Sharing food between communal stomachs allows the colony as a whole to get its food requirements and, more so, allows each individual within the colony to reach its nutritional intake target. The vast majority of colony members do not forage independently but obtain their food through secondary interactions in which food is exchanged between individuals. The global effect of this exchange is not well understood. To gain better understanding into this process we used fluorescence imaging to measure how the collected food is distributed and homogenized within aCamponotus sanctusant colony. Using entropic measures to quantify food-blending, we show that while collected food flows into all parts of the colony it homogenizes only partly. We show that mixing is controlled by the ants’ interaction rule in which only a fraction of the maximal potential is actually transferred. This rule leads to a robust blending process:i.e., neither the exact food volume that is transferred, nor the interaction schedule are essential to generate the global outcome. Finally, we show how the ants’ interaction rules may optimize a trade-off between fast dissemination and efficient mixing.Author summaryWe study how food is distributed in colonies of ants. Food collected by a small fraction of ants is distributed throughout the colony through a series of mouth-to-mouth interactions.An interesting interplay exists between food dissemination and food mixing within the colony. High levels of dissemination are important as they ensure that any food type is available to any ant. On the other hand, high dissemination induces mixing and this reduces the required variety of nutritional choices within the colony.Tracking fluorescent-labelled food and interpreting the results within concepts of information theory, we show that food collected by each forager reaches almost every ant in the colony. Nonetheless, it is not homogenized across workers, resulting in a limited level of mixing.We suggest that the difference in food mixture held by each individuals can provide ants the potential to control their nutritional intake by interacting with different partners.
Frontal cortex tracks surprise separately for different sensory modalities but engages a common inhibitory control mechanism
Authors: Wessel Jan R. , Huber David E. 
Published: March 2019

AbstractThe brain constantly generates predictions about the environment to guide action. Unexpected events lead to surprise and can necessitate the modification of ongoing behavior. Surprise can occur for any sensory domain, but it is not clear how these separate surprise signals are integrated to affect motor output. By applying a trial-to-trial Bayesian surprise model to human electroencephalography data recorded during a cross-modal oddball task, we tested whether there are separate predictive models for different sensory modalities (visual, auditory), or whether expectations are integrated across modalities such that surprise in one modality decreases surprise for a subsequent unexpected event in the other modality. We found that while surprise was represented in a common frontal signature across sensory modalities (the fronto-central P3 event-related potential), the single-trial amplitudes of this signature more closely conformed to a model with separate surprise terms for each sensory domain. We then investigated whether surprise-related fronto-central P3 activity indexes the rapid inhibitory control of ongoing behavior after surprise, as suggested by recent theories. Confirming this prediction, the fronto-central P3 amplitude after both auditory and visual unexpected events was highly correlated with the fronto-central P3 found after stop-signals (measured in a separate stop-signal task). Moreover, surprise-related and stopping-related activity loaded onto the same component in a cross-task independent components analysis. Together, these findings suggest that medial frontal cortex maintains separate predictive models for different sensory domains, but engages a common mechanism for inhibitory control of behavior regardless of the source of surprise.Author summarySurprise is an elementary cognitive computation that the brain performs to guide behavior. We investigated how the brain tracks surprise across different senses: Do unexpected sounds make subsequent unexpected visual stimuli less surprising? Or does the brain maintain separate expectations of environmental regularities for different senses? We found that the latter is the case. However, even though surprise was separately tracked for auditory and visual events, it elicited a common signature over frontal cortex in both sensory domains. Importantly, we observed the same neural signature when actions had to be stopped after non-surprising stop-signals in a motor inhibition task. This suggests that this signature reflects a rapid interruption of ongoing behavior when our surroundings do not conform to our expectations.
Comeback workout: QM practices and the health and fitness industry
Authors: Cha Wonsuk 
Published: March 2019

PurposeThe purpose of this paper is to provide a theoretical model for the relationship between quality management (QM) practices and the health and fitness industry through two competencies, including relational competence (RC) and technical competence (TC).Design/methodology/approachDrawing from the resource-based view and the relational competence theory, this paper seeks a further understanding of the conceptual link between QM practices and the health and fitness industry.FindingsThis paper proposes that RC and TC will positively mediate the relationship between QM practices and customers’ behavioral intentions to use the health and fitness service.Research limitations/implicationsThis paper provides an integrated perspective to the health and fitness industry. More specifically, this paper suggests that QM practices can be applicable to customers’ behavioral intentions to use the health and fitness service. This paper also provides a solid conceptual foundation through which managers in the health and fitness industry put more effort in developing the relationship with customers. An empirical investigation might be needed for future study.Practical implicationsThis paper suggests that managers and employees in the health and fitness industry need to provide a sustained and consistent effort into maintaining the interaction with customers. This paper also suggests that the use of QM practices can be related to customer perception (e.g. boosting behavioral intentions toward service providers) and can provide sustainable competitive advantage in the health and fitness industry.Originality/valueThis paper extends current understanding of QM practices and the health and fitness industry by providing a conceptual framework regarding how QM practices are related to the health and fitness industry through RC and TC.
Why do “teeth” need “voice”? The case of anti‐corruption agencies in three Australian states
Authors: Ankamah Samuel Siebie 
Published: March 2019

AbstractInteractions between horizontal accountability agencies (e.g., anti‐corruption agencies [ACAs]) and social accountability actors (e.g., journalists, civil society activists, and complainants/whistleblowers) are recognized as important to horizontal agencies’ performance, but the reason(s) is not clear. This study therefore explores why horizontal accountability agencies need social accountability actors in performing their functions. The study analyses data from 30 key stakeholders in Australia, including ACAs staff members, social accountability actors, and other observers to report on the specific support roles social actors play to ACAs’ activities and operations. Through the conceptual lens of social accountability, evidence show that social actors play four key types of support roles to ACAs’ activities and operations: activate ACAs’ investigations; “amplify” ACAs’ operations; guard ACAs’ activities and operations; and defend ACAs’ independence and powers. These findings support the need for interactions and, also, affirm the potential for research into how these support roles can better be provided for effective anti‐corruption outcomes. The research is of value to public accountability agencies in Australia, and internationally.
Military‐style fitness boot camps: contested resources in accounting for fatness
Authors: Gimlin Debra , Buckingham Alan 
Published: March 2019

AbstractIn this article, we examine the social management of fatness via an analysis of 4 years of participant‐observation in military‐style fitness boot camps and interviews with camp participants, trainers and organisers/owners. We begin by focusing on popular imagery of the ‘boot camp’. The boot camp model takes various forms; yet, whether it involves civilian participants, as on reality television shows, or the imagined military ones of films, the boot camp model emphasises the re‐fashioning of the individual via the disciplining of bodies and selves. Such constructions of boot camps were employed by our respondents to lay claim to identities which highlight their hard work, strength of character, fundamental ‘goodness’ and self‐discipline, as those qualities are demonstrated through the body – even though participants’ actual bodies change little at camp. Such meanings stand in direct contradiction to broader social constructions of fatness and participants’ own negative perceptions of fat people. Moreover, even within the camps themselves, such identity claims are contested, both by camp trainers and by slimmer and ‘fitter’ attendees. These counterclaims are grounded in ideas about the characterological implications of the fat body, beliefs about the purpose of boot camp and notions of the body's capacity for change.