bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-site phosphorylation of the TOPBP1 ATR Activation Domain propels ATR signaling during the response to DNA breaks
Authors: Senebandith Holly , Ruis Kenna , Montales Katrina , Huynh Oanh , Jami-Alahmadi Yasaman , Wohlschlegel James A. , Michael W. Matthew 
Published: September 2022

AbstractTOPBP1 is a BRCT domain-containing scaffold protein that plays important roles in a diverse array of cellular processes, including DNA damage signaling, DNA repair, DNA replication, and mRNA transcription. For DNA damage signaling, TOPBP1 activates the crucial damage response kinase ATR and this occurs during replication stress as well as during a DNA double-strand break response. ATR signaling allows cells to survive genotoxic issues and represents a formidable barrier to transformation to a tumorigenic state. Despite its importance to genome stability, the biochemical mechanism for how TOPBP1 activates ATR is not fully understood. TOPBP1 uses a discrete domain, termed the ATR activation domain, to stimulate ATR kinase. Recent work has shown that the AAD must be in a multimeric state to activate ATR. Other work has shown that phosphorylation of the AAD on serine 1131 (in Xenopus) is important for its function, and some have suggested that this is linked to the formation of TOPBP1 condensates during a DNA damage response. In this study we examine AAD phosphorylation in detail and we report three important new findings. One, S1131 phosphorylation promotes ATR activation in a manner independent of condensate formation and is instead linked to promoting multimerization of the AAD. Two, we identify a novel sight of AAD phosphorylation, on T1098, and show that is required for ATR activation. Three, we identify additional, candidate phosphorylation sites, some of which fit the consensus for casein kinase 2, and we show that casein kinase 2 activity is required for the AAD to perform its function. These studies show that multi-site phosphorylation of the AAD is an important component of the mechanism by which TOPBP1 activates ATR.
Genetic factors influence behavioural repeatability in juvenile poison frogs
Authors: Sonnleitner Ria , Alanen Emmi , Fouilloux Chloe , Valkonen Janne K. , Rojas Bibiana 
Published: September 2022

AbstractIndividual behaviour is a combination of previous experiences and genetic factors whose interaction can be adaptively adjusted to respond to changes in the surrounding environment. Understanding the continuity of behaviours both within and among individuals can help us disentangle the ecological and evolutionary significance underlying patterns of aggression, activity, boldness, and cooperation. In this study, we examined whether there is repeatability in the activity levels of juvenile dyeing poison frogs (Dendrobates tinctorius). This tropical species, known for its striking coloration and skin toxins, changes upon metamorphosis from an aquatic to a terrestrial habitat where individuals must immediately become active foragers to acquire their chemical defences. We did not find individual behaviour to be repeatable, however, we detected repeatability in activity at the family level, suggesting that behavioural variation may be explained, at least partially, by genetic factors in addition to a common environment. The assumption that activity level is very important for the survival of individuals after metamorphosis is supported by our results in that genetic factors seem to play a role in the formation of activity level. Further experiments are needed to investigate to what extent other areas of the individuals’ lives are affected by the respective activity levels, and what significance this has for the survival of a population.
Evolutionary analysis reveals the role of a non-catalytic domain of peptidyl arginine deiminase 2 in transcriptional regulation
Authors: Villanueva-Cañas José Luis , Fernandez-Fuentes Narcis , Saul Dominik , Kosinsky Robyn Laura , Teyssier Catherine , Rogalska Malgorzata Ewa , Pérez Ferran Pegenaute , Oliva Baldomero , Notredame Cedric , Beato Miguel , Sharma Priyanka 
Published: September 2022

AbstractPeptidyl arginine deiminases (PADIs) catalyze protein citrullination, a post-translational conversion of arginine to citrulline. The most widely expressed member of this family, PADI2, regulates cellular processes that impact several diseases. We hypothesized that we could gain new insights into PADI2 function through a systematic evolutionary and structural analysis. Here, we identify 20 positively selected PADI2 residues, 16 of which are structurally exposed and maintain PADI2 interactions with cognate proteins. Many of these selected residues reside in non-catalytic regions of PADI2. We validate the importance of a prominent loop in the middle domain that encompasses PADI2 L162, a residue under positive selection. This site is essential for interaction with the transcription elongation factor (P-TEFb) and mediates active transcription of the oncogenesc-MYC, andCCNB1,as well as impacting cellular proliferation. These insights could be key to understanding and addressing the role of the PADI2c-MYCaxis in cancer progression.Significance StatementHere we use a systematic evolutionary analysis to identify positively selected residues in the non-catalytic domain of PADI2 and link the positive selection of key residues to a role in transcription. Specifically, a structurally exposed loop in the PADI2 middle domain encompasses the positively selected residue L162 which is linked to transcription and cellular proliferation. This loop contributes to PADI2 interaction with the P-TEFb complex and cellular proliferation. Our results showcase the utility of combining evolutionary and experimental approaches to dissect the evolution of essential functional processes.
The Vap33/Eph/Vav/Cdc42 complex confers temporal specification to the outgrowth of primary dendrites in Drosophila neurons
Authors: Kamiyama Daichi , Nishida Yuri , Kamiyama Rie , Fitch Miyuki , Chihara Takahiro 
Published: September 2022

SUMMARYThe formation of primary dendrites (dendritogenesis) significantly affects the overall orientation and coverage of dendritic arborization, limiting the number and types of inputs a neuron can receive. Previously we reported how a Drosophila motoneuron spatially controls the positioning of dendritogenesis through the Dscam1/Dock/Pak1 pathway; however, how the neuron defines the timing of this process remains elusive. Here we show that the Eph receptor tyrosine kinase provides a temporal cue. We find that, at the onset of dendritogenesis, the Eph receptor recruits the Rho Family GEF Vav to the intracellular domain of Eph, which transiently activates the Cdc42 family of small GTPase. We also show that vap33 (vesicle-associated membrane protein-associated protein) mutants exhibit defects in Cdc42 activation and dendritic outgrowth, indicating Vap33 may play an upstream role in Eph signaling. Together, our result and previous studies argue that the formation of primary dendrites requires the proximity of active Cdc42 and membrane-anchored Pak1 driven by collaborative action between two distinct signaling complexes, Vap33/Eph/Vav and Dscam1/Dock. Signal integration from multiple input pathways would represent a general mechanism for the spatiotemporal precision of dendrite branch formation.
Totem: a user-friendly tool for clustering-based inference of tree-shaped trajectories from single-cell data
Authors: Smolander Johannes , Junttila Sini , Elo Laura L 
Published: September 2022

AbstractSingle-cell RNA-sequencing enables cell-level investigation of cell differentiation, which can be modelled using trajectory inference methods. While tremendous effort has been put into designing these methods, inferring accurate trajectories automatically remains difficult. Therefore, the standard approach involves testing different trajectory inference methods and picking the trajectory giving the most biologically sensible model. As the default parameters are often suboptimal, their tuning requires methodological expertise. We introduce Totem, an open-source, easy-to-use R package designed to facilitate inference of tree-shaped trajectories from single-cell data. Totem generates a large number of clustering results, estimates their topologies as minimum spanning trees, and uses them to measure the connectivity of the cells. Besides automatic selection of an appropriate trajectory, cell connectivity enables to visually pinpoint branching points and milestones relevant to the trajectory. Furthermore, testing different trajectories with Totem is fast, easy, and does not require in-depth methodological knowledge.
Plant and prokaryotic TIR domains generate distinct cyclic ADPR NADase products
Authors: Bayless Adam M. , Chen Sisi , Ogden Sam C. , Xu Xiaoyan , Sidda John D. , Manik Mohammad K. , Li Sulin , Kobe Bostjan , Ve Thomas , Song Lijiang , Grant Murray , Wan Li , Nishimura Marc T. 
Published: September 2022

AbstractToll/interleukin-1 receptor (TIR) domain proteins function in cell death and immunity. In plants and bacteria, TIR domains are enzymes that produce isomers of cyclic ADPR (cADPR) as putative immune signaling molecules. The identity and functional conservation of cADPR isomer signals is unclear. A previous report found that a plant TIR could cross-activate the prokaryotic Thoeris TIR-immune system, suggesting the conservation of plant and prokaryotic TIR-immune signals. Here, we generate auto-active Thoeris TIRs and test the converse hypothesis: do prokaryotic Thoeris TIRs also cross-activate plant TIR-immunity? Using in planta and in vitro assays, we find that Thoeris and plant TIRs generate overlapping sets of cADPR isomers, and further clarify how plant and Thoeris TIRs activate the Thoeris system via producing 3’cADPR. This study demonstrates that the TIR-signaling requirements for plant and prokaryotic immune systems are distinct and that TIRs across kingdoms generate a diversity of small molecule products.
Probabilistic 3D-modelling of genomes and genomic domains by integrating high-throughput imaging and Hi-C using machine learning
Authors: Castillo David , Mendieta-Esteban Julen , Marti-Renom Marc A. 
Published: September 2022

AbstractAmong the existing techniques for interrogating the genome structure, Hi-C assays have become the most performed experiments and constitute the majority of the publicly available datasets. As a result, there is a continuous demand to create and improve algorithms and methods to assist the scientific community in the interpretation of Hi-C experimental data. Here we introduce probabilistic TADbit (pTADbit), a new approach that combines Deep Learning and restraint-based modelling to infer the three-dimensional (3D) structure of genome and genomic domains interrogated by Hi-C experiments. pTADbit uses thousands of microscopy-based distances between genomic loci to train a neural network model that aims at predicting the population distribution of the spatial distance between two genomic loci based solely on their Hi-C interaction frequency. pTADbit produces more accurate chromatin models compared to the original TADbit as well as other available 3D modeling methods, while drastically reducing the required computation time. The resulting ensemble of models not only agree consistently with independent measures obtained by imaging experiments but also better capture the heterogeneity of the cell population. The development of pTADbit lays the basis for the integration of data produced from high-throughput imaging assays into the 3D modelling genomes and genomic domains.
Monkey dorsolateral prefrontal cortex represents abstract visual sequences during a no-report task
Authors: Rodriguez Nadira Yusif , McKim Theresa H. , Basu Debaleena , Ahuja Aarit , Desrochers Theresa M. 
Published: September 2022

AbstractMonitoring sequential information is an essential component of our daily lives. Many of these sequences are abstract, in that they do not depend on the individual stimuli, but do depend on an ordered set of rules (e.g., chop then stir when cooking). Despite the ubiquity and utility of abstract sequential monitoring, little is known about its neural mechanisms. Human rostrolateral prefrontal cortex (RLPFC) exhibits specific increases in neural activity (i.e., “ramping”) during abstract sequences. Monkey dorsolateral prefrontal cortex (DLPFC) has been shown to represent sequential information in motor (not abstract) sequence tasks, and contains a sub-region, area 46, with homologous functional connectivity to human RLPFC. To test the prediction that area 46 may represent abstract sequence information, and do so with parallel dynamics to those found in humans, we conducted functional magnetic resonance imaging (fMRI) in monkeys. When monkeys performed no-report abstract sequence viewing, we found that left and right area 46 responded to abstract sequential changes. Interestingly, responses to rule and number changes overlapped in right area 46 and left area 46 exhibited responses to abstract sequence rules with changes in ramping activation, similar to that observed in humans. Together, these results indicate that monkey DLPFC monitors abstract visual sequential information, potentially with a preference for different dynamics in the two hemispheres. More generally, these results show that abstract sequences are represented in functionally homologous regions across monkeys and humans.Significance StatementDaily, we complete sequences that are “abstract” because they depend on an ordered set of rules (e.g., chop then stir when cooking) rather than the identity of individual items. Little is known about how the brain tracks, or monitors, this abstract sequential information. Based on previous human work showing abstract sequence related dynamics in an analogous area, we tested if monkey dorsolateral prefrontal cortex (DLPFC), specifically area 46, represents abstract sequential information using awake monkey fMRI. We found that area 46 responded to abstract sequence changes, with a preference for more general responses on the right and dynamics similar to humans on the left. These results suggest that abstract sequences are represented in functionally homologous regions across monkeys and humans.
The Geometric Evolution of Aortic Dissections: Predicting Surgical Success using Fluctuations in Integrated Gaussian Curvature
Authors: Khabaz Kameel , Yuan Karen , Pugar Joseph , Jiang David , Sankary Seth , Dhara Sanjeev , Kim Junsung , Kang Janet , Nguyen Nhung , Cao Kathleen , Washburn Newell , Bohr Nicole , Lee Cheong Jun , Kindlmann Gordon , Milner Ross , Pocivavsek Luka 
Published: September 2022

AbstractClinical imaging modalities are a mainstay of modern disease management, but the full utilization of imaging-based data remains elusive. Aortic disease is defined by anatomic scalars quantifying aortic size, even though aortic disease progression initiates complex shape changes. We present an imaging-based geometric descriptor, inspired by fundamental ideas from topology and soft-matter physics that captures dynamic shape evolution. The aorta is reduced to a two-dimensional mathematical surface in space whose geometry is fully characterized by the local principal curvatures. Disease causes deviation from the smooth bent cylindrical shape of normal aortas, leading to a family of highly heterogeneous surfaces of varying shapes and sizes. To deconvolute changes in shape from size, the shape is characterized using integrated Gaussian curvature or total curvature. The fluctuation in total curvature (δK) across aortic surfaces captures heterogeneous morphologic evolution by characterizing local shape changes. We discover that aortic morphology evolves with a power-law defined behavior with rapidly increasingδKforming the hallmark of aortic disease. DivergentδKis seen for highly diseased aortas indicative of impending topologic catastrophe or aortic rupture. We also show that aortic size (surface area or enclosed aortic volume) scales as a generalized cylinder for all shapes. Classification accuracy for predicting aortic disease state (normal, diseased with successful surgery, and diseased with failed surgical outcomes) is92.8 ±1.7%. The analysis ofδKcan be applied on any three-dimensional geometric structure and thus may be extended to other clinical problems of characterizing disease through captured anatomic changes.
Quaker accountability regimes: the case of the Richardson family networks, 1840–1914
Authors: McLean Tom , McGovern Tom , Slack Richard , McLean Malcolm 
Published: September 2022

PurposeThis paper aims to explore the development of the accountability ideals and practices of Quaker industrialists during the period 1840–1914.Design/methodology/approachThe research employs a case study approach and draws on the extensive archives of Quaker industrialists in the Richardson family networks, British Parliamentary Papers and the Religious Society of Friends together with relevant contemporary and current literature.FindingsFriends shed their position as Enemies of the State and obtained status and accountabilities undifferentiated from those of non-Quakers. The reciprocal influences of an increasingly complex business environment and radical changes in religious beliefs and practices combined to shift accountabilities from the Quaker Meeting House to newly established legal accountability mechanisms. Static Quaker organisation structures and accountability processes were ineffective in a rapidly changing world. Decision-making was susceptible to the domination of the large Richardson family networks in the Newcastle Meeting House. This research found no evidence of Quaker corporate social accountability through action in the Richardson family networks and it questions the validity of this concept. The motivations underlying Quakers’ personal philanthropy and social activism were multiple and complex, extending far beyond accountabilities driven by religious belief.Originality/valueThis research has originality and value as a study of continuity and change in Quaker accountability regimes during a period that encompassed fundamental changes in Quakerism and its orthopraxy, and their business, social and political environments.
The macroeconomic effect of COVID-induced economic policy uncertainty in Nigeria: a DSGE approach
Authors: Adeiza Adams , Oye Queen Esther , Alege Philip O. 
Published: September 2022

PurposeThis study examined the macroeconomic effects of COVID-19-induced economic policy uncertainty (EPU) in Nigeria. The study considered the effects of three related shocks: EPU, COVID-19 and correlated economic policy uncertainty and COVID-19 shock.Design/methodology/approachFirst, the study presented VAR evidence that fiscal and monetary policy uncertainty depresses real output. Thereafter, a nonlinear DSGE model with second-moment fiscal and monetary policy shocks was solved using the third-order Taylor approximation method.FindingsThe authors found that EPU shock is negligible and expansionary. By contrast, COVID-19 shocks have strong contractionary effects on the economy. The combined shocks capturing the COVID-19-induced EPU shock were ultimately recessionary after an initial expansionary effect. The implication is that the COVID-19 pandemic-induced EPU adversely impacted macroeconomic outcomes in Nigeria in a non-trivial manner.Practical implicationsThe result shows the importance of policies to cushion the effect of uncertain fiscal and monetary policy path in the aftermath of COVID-19.Originality/valueThe originality of the paper lies in examining the impact of COVID-19 induced EPU in the context of a developing economy using the DSGE methodology.
Design of temperature-based adaptive refresh circuit for 2T array memory
Authors: Yin Wanjun , Jiang Lin-na 
Published: September 2022

Purpose
The purpose of this paper through the redundant monitoring unit reflecting the real-time temperature change of the array, an adaptive refresh circuit based on temperature is designed.

Design/methodology/approach
This paper proposed a circuit design for temperature-adaptive refresh with a fixed refresh frequency of traditional memory, high refresh power consumption at low temperature and low refresh frequency at high temperature.

Findings
Adding a metal oxide semiconductor (MOS) redundancy monitoring unit consistent with the storage unit to the storage bank can monitor the temperature change of the storage bank in real time, so that temperature-based memory adaptive refresh can be implemented.

Originality/value
According to the characteristics that the data holding time of dynamic random access memory storage unit decreases with the increase of temperature, a MOS redundant monitoring unit which is consistent with the storage unit is added to the storage array with the 2T storage unit as the core.
Workers' well-being and job performance in the context of COVID-19: a sector-specific approach
Authors: Boulet Maude , Parent-Lamarche Annick 
Published: September 2022

PurposeThe main objective of this study is to scrutinize the relationship between workers' well-being and job performance across sectors during the first lockdown. The authors also aim to examine the indirect effects of satisfaction with work-life balance, reopening of schools after closure, workload and teleworking on performance through well-being.Design/methodology/approachThe authors used a sample of 447 Canadian workers collected online during the first lockdown to perform a series of structural equation models.FindingsThe results show that workers' well-being increases job performance and satisfaction with work-life balance has a positive indirect effect on job performance through well-being in all sectors. This finding suggests that workers' well-being mediates the relationship between satisfaction with work-life balance and performance. However, the reopening of schools, increased workload and teleworking do not have universal effects across sectors.Practical implicationsAll organizations should implement human resources (HR) practices that promote workers' well-being and family-friendly workplaces, especially during the pandemic. Conversely, teleworking has a sector-specific effect that must be considered when implemented.Originality/valueThis study stands out by strengthening the bridge between workers' well-being and job performance. The effects of well-being and satisfaction with work-life balance on job performance are universal, while the impact of reopening of schools, increased workload and teleworking are sector-specific.