bluuebunny/crossref_metadata_2025_split huggingface dataset:
TENT4A non-canonical poly(A) polymerase regulates DNA-damage tolerance via multiple pathways which are mutated in endometrial cancer
Authors: Swain Umakanta , Friedlander Gilgi , Sehrawat Urmila , Sarusi-Portuguez Avital , Rotkopf Ron , Ebert Charlotte , Paz-Elizur Tamar , Dikstein Rivka , Carell Thomas , Geacintov Nicholas , Livneh Zvi 
Published: December 2020

AbstractTENT4A (PAPD7) is a non-canonical poly(A) polymerase, of which little is known. Here we show that TENT4A regulates multiple biological pathways, and focus on its multilayer regulation of translesion DNA synthesis (TLS), in which unrepaired DNA lesions are bypassed by error-prone DNA polymerases. We show that TENT4A regulates mRNA stability and/or translation of DNA polymerase η and RAD18 E3 ligase, which guides the polymerase to replication stalling sites, and monoubiquitinates PCNA, thereby enabling recruitment of error-prone DNA polymerases to damaged DNA sites. Remarkably, in addition to the effect on RAD18 mRNA stability via controlling its poly(A) tail, TENT4A indirectly regulates RAD18 via the tumor suppressor CYLD, and via the long non-coding antisense RNAPAXIP1-AS2, which had no known function. Knocking down the expression ofTENT4AorCYLD, or overexpression ofPAXIP1-AS2led each to reduced amounts of the RAD18 protein and DNA polymerase η, leading to reduced TLS, highlightingPAXIP1-AS2as a new TLS regulator. Bioinformatics analysis revealed that TLS error-prone DNA polymerase genes and theirTENT4A-related regulators are frequently mutated in endometrial cancer genomes, suggesting that TLS is dysregulated in this cancer.
Simple fence modification increases floodplain land movement prospects for freshwater turtles
Authors: Waltham Nathan J. , Schaffer Jason , Perry Justin , Walker Sophie , Nordberg Eric 
Published: December 2020

AbstractFeral pigs predate on freshwater turtles and damage wetland habitats in the process. Installing fences successfully averts access and damage, however, they become a barrier for freshwater turtles requiring land access during migration. We collected 161 turtles (Chelodina rugosa,Emydura subglobosa worrelli, Myuchelys latisternum) from twenty floodplain and riverine wetlands during post-wet (June-August) and late-dry season (November-December) surveys (2015-2018) in northern Australia. Wetlands were either fenced (150 × 150mm square, 1.05m high wire mesh) or not around the wet perimeter. Nine-seven percent of individuals caught in either fenced or unfenced wetlands had a shell carapace width greater than mesh width, of these 44 (46%) were captured inside fenced wetlands, while 50 were caught in unfenced wetlands. The remaining 35 were smaller than 150mm and would easily pass through fence mesh. Sixty-five turtles partook in a fencing manipulative experiment. Turtles with carapace widths wider than mesh often successfully escaped through fences by lifting one side of their shell and passing diagonally. In a second experiment where a piece of vertical wire (1500mmx300mm) was removed, turtles located gates after prospecting and trying to fit through meshing areas that were too small to pass through. Nine-two percent of turtles were able to locate and pass through gates, while 8% failed to locate a gate after 2 hours. Three turtles that did not use gates, and seemed to ‘give up’ and dug into the grass. Gates applied every 4m showed an 83% passage rate, every 2m was 91%, and while every 1m was 100%. Combing field and manipulative experiments revealed that large turtles will prospect and move along a fence until they find suitable passage. Applying turtle gates every 1–4m allows almost 100% passage, and if strategically applied in travel corridors, would minimize the need for large-scale clipping efforts around entire wetlands.
EFFECT OF LAND TENURE ON ADOPTION OF CLIMATE CHANGE ADAPTATION. EVIDENCE FROM MALAWI
Authors: Phiri Horace 
Published: December 2020

ABSTRACTThe definitive aim of this study was to bring to fore the evidence of the importance of tenure considerations in the designing, development, and implementation of climate change programs. This was done by analyzing how land tenure affects the use of adaptation strategies in Malawi. Using secondary data from the Integrated Household Survey (IHS4), a multinomial logit model was fitted to analyze determinants of adoption of climate change adaptation strategies. Land tenure has shown to significantly affect the adoption of the technologies in question. Insecure arrangements such as borrowing and renting land tend to discourage adoption. The proliferation of borrowed or rented in Malawi’s agricultural sector necessitates intervention to encourage adaptation on those farms to avoid land degradation.
Rapid nucleus-scale reorganization of chromatin in neurons enables transcriptional adaptation for memory consolidation
Authors: Peter Manuel , Aschauer Dominik F. , Vaz Pandolfo Renata , Sinning Anne , Grössl Florian , Kargl Dominic , Kraitsy Klaus , Burkard Thomas R. , Luhmann Heiko J. , Haubensak Wulf , Rumpel Simon 
Published: December 2020

AbstractThe interphase nucleus is functionally organized in active and repressed territories defining the transcriptional status of the cell. However, it remains poorly understood how the nuclear architecture of neurons adapts in response to behaviorally relevant stimuli that trigger fast alterations in gene expression patterns. Imaging of fluorescently tagged nucleosomes revealed that pharmacological manipulation of neuronal activityin vitroand auditory cued fear conditioningin vivoinduce nucleus-scale restructuring of chromatin within minutes. Furthermore, the acquisition of auditory fear memory is impaired after infusion of a drug into auditory cortex which blocks chromatin reorganizationin vitro. We propose that active chromatin movements at the nucleus scale act together with local gene-specific modifications to enable transcriptional adaptations at fast time scales. Introducing a transgenic mouse line for photolabeling of histones, we extend the realm of systems available for imaging of chromatin dynamics to living animals.
Agroecosystemic Resilience Index (AgRI): a method to assess agrobiodiversity
Authors: Cleves-Leguízamo José-Alejandro , Youkhana Eva , Toro-Calderon Javier 
Published: December 2020

AbstractAgricultural production systems, subjects of study in agroecology, are non-equilibrium open systems permanently influenced by the action of natural or anthropogenic disturbances or “ripple effects.” Faced with this situation, agroecosystems tend to maintain a state of functional equilibrium in time and space, through an emergent property known asresilience. This concept is related to the dissipative capacity of agroecosystems to interact with the disturbance in such a way as to allow it to preserve its functionality and basic structure, through attenuation of the effect that disturbs the system. The literature reports diverse methods with a variable number of indicators or criteria for the evaluation or analysis of resilience. Many of these present conceptual deficiencies considering that the components of the system have similar characteristics and linear responses, that is, they do not show changes due to the action or nature of the disturbance. In this sense, there is a need to propose a generic method to analyze and evaluate agroecosystemic resilience, through a complex and comprehensive approach that takes into consideration the interaction of physical, biotic, socioeconomic or symbolic components of the system. These interactions are differential (weighted), to facilitate decision-making by the community, farmers, or administrators, regarding adaptations, adjustments or modifications that allow the agroecosystem to maintain its productivity and permanence.
The search for surrogacy in patient derived xenograft mouse trials: glass is less than half full
Authors: Mistry Hitesh B. 
Published: December 2020

AbstractDespite the efforts of many within the drug development and clinical community surrogate biomarkers for patient survival have remained elusive in Oncology. This failure in part is attributable to there being a paucity of clinical trials showing a treatment effect on patient survival. Given this issue an alternative system to explore the surrogacy potential of biomarkers are large preclinical xenograft studies i.e. panel of patient derived xenografts or mouse clinical trials. In this study we explored the surrogacy potential of tumour burden biomarkers, current size of tumour and how its changed, preclinically in a large patient derived xenograft database which contains a diverse number of drugs/treatments (n=61) and xenografts (n=245). We found that of the possible 1830 two-arm mouse trials, 1103 showed a treatment effect on the preclinical end-point, disease progression, (p<0.05). Of these only in 30% did tumour burden markers fully capture the treatment effect on disease progression times i.e. satisfied a key condition for surrogacy. These results highlight that preclinically it is very challenging to find a surrogate marker based purely on measures of tumour burden.
Normal aging affects unconstrained three-dimensional reaching against gravity with reduced vertical precision and increased co-contraction
Authors: Wittenberg George F. , Tian Jing , Kortzorg Nick , Wyers Lore , Van Halewyck Florian , Boisgontier Matthieu P. , Levin Oron , Swinnen Stephan P. , Jonkers Ilse 
Published: December 2020

AbstractReaching for an object in space forms the basis for many activities of daily living and is important in rehabilitation after stroke and in other neurological and orthopedic conditions. It has been the object of motor control and neuroscience research for over a century, but studies often constrain movement to eliminate the effect of gravity or reduce the degrees of freedom. In some studies, aging has been shown to reduce target accuracy, with a mechanism suggested to be impaired corrective movements. We sought first to explore the changes in control of shoulder and elbow joint movements that occur with aging during performance of reaching movements to different target heights with the normal effects of gravity, unconstrained hand movement, and stable target locations. Three-dimensional kinematic data and electromyography were collected in 14 young (25±6 years) and 10 older adults (68±3 years) during second-long reaches to three targets aligned vertically in front of the participants. Older adults took longer to initiate a movement than the young adults and were more variable and inaccurate in their initial and final movements. Target height had greater effect on trajectory curvature variability in older than young adults, with angle variability relative to target position being greater in older adults around the time of peak speed. There were significant age-related differences in use of the multiple degrees of freedom of the upper extremity, with less variability in shoulder abduction in the older group. Muscle activation patterns were similar, except for a higher biceps-triceps co-contraction and tonic levels of some proximal muscle activation. The path length of movements was not affected by age. These results show an age-related deficit in the motor planning and online correction of reaching movements against a predictable force (i.e., gravity). These results will facilitate interpretation of our forthcoming study of transcranial magnetic stimulation effects on the same task in these two populations, and is relevant to any study that seeks to measure the effect of pathological processes on upper extremity motor performance in the elderly.
Evaluating Performance of Drug Repurposing Technologies
Authors: Schuler James , Falls Zackary , Mangione William , Hudson Matthew L. , Bruggemann Liana , Samudrala Ram 
Published: December 2020

AbstractDrug repurposing technologies are growing in number and maturing. However, comparison to each other and to reality is hindered due to lack of consensus with respect to performance evaluation. Such comparability is necessary to determine scientific merit and to ensure that only meaningful predictions from repurposing technologies carry through to further validation and eventual patient use. Here, we review and compare performance evaluation measures for these technologies using version 2 of our shotgun repurposing Computational Analysis of Novel Drug Opportunities (CANDO) platform to illustrate their benefits, drawbacks, and limitations. Understanding and using different performance evaluation metrics ensures robust cross platform comparability, enabling us to continuously strive towards optimal repurposing by decreasing time and cost of drug discovery and development.
Variation in behavior drives multiscale responses to habitat conditions in timber rattlesnakes (Crotalus horridus)
Authors: Hoffman Andrew S. , Tutterow Annalee M. , Gade Meaghan R. , Adams Bryce T. , Peterman William E. 
Published: December 2020

AbstractVariations in both the behavior of wildlife and the scale at which the environment most influences the space use of wild animals (i.e., scale of effect) are critical, but often overlooked in habitat selection modeling. Ecologists have proposed that biological responses happening over longer time frames are influenced by environmental variables at larger spatial scales, but this has rarely been empirically tested. Here, we hypothesized that long-term patterns of behavior (i.e. lasting multiple weeks to months) would be associated with larger scales of effect than more sporadic behaviors. We predicted site use by 43 radio-telemetered timber rattlesnakes (Crotalus horridus) exhibiting four distinct, time-varying behaviors (foraging, digestion, ecdysis, and gestation) using remotely-sensed environmental variables related to forest structure and landscape topography. Among sites used by snakes, warmer temperatures and higher levels of forest disturbance were predictive of behaviors dependent on thermoregulation including gestation and ecdysis while more moderate temperatures and drier, more oak-dominated sites were predictive of foraging. Long-term behaviors were associated with larger spatial scales, supporting our hypothesis that the scale at which habitat selection occurs is linked to the temporal scale of relevant behaviors. Management recommendations based on single-scale models of habitat use that do not account for fine-scale variations in behavior may obscure the importance of potentially limiting habitat features needed for infrequent behaviors that are critically important for growth and reproduction of this and related species.
Unusual predominance of maintenance DNA methylation in Spirodela polyrhiza
Authors: Harkess Alex , Bewick Adam J. , Lu Zefu , Fourounjian Paul , Messing Joachim , Michael Todd P. , Schmitz Robert J. , Meyers Blake C. 
Published: December 2020

Abstract5-methylcytosine (5mC) is a modified base often described as necessary for the proper regulation of genes and transposons and for the maintenance of genome integrity in plants. However, the extent of this dogma is limited by the current phylogenetic sampling of land plant species diversity. Here, we report that a monocot plant, Spirodela polyrhiza, has lost CG gene body methylation, genome-wide CHH methylation, and the presence or expression of several genes in the highly conserved RNA-directed DNA methylation (RdDM) pathway. It has also lost the CHH methyltransferase CHROMOMETHYLASE 2. Consequently, the transcriptome is depleted of 24-nucleotide, heterochromatic, small interfering RNAs that act as guides for the deposition of 5mC to RdDM-targeted loci in all other currently sampled angiosperm genomes. Although the genome displays low levels of genome-wide 5mC primarily at LTR retrotransposons, CG maintenance methylation is still functional. In contrast, CHG methylation is weakly maintained even though H3K9me2 is present at loci dispersed throughout the euchromatin and highly enriched at regions likely demarcating pericentromeric regions. Collectively, these results illustrate that S. polyrhiza is maintaining CG and CHG methylation mostly at repeats in the absence of small RNAs. S. polyrhiza reproduces rapidly through clonal propagation in aquatic environments, which we hypothesize may enable low levels of maintenance methylation to persist in large populations.Significance StatementDNA methylation is a widespread chromatin modification that is regularly found in all plant species. By examining one aquatic duckweed species, Spirodela polyrhiza, we find that it has lost highly conserved genes involved in methylation of DNA at sites often associated with repetitive DNA, and within genes, however DNA methylation and heterochromatin is maintained during cell division at other sites. Consequently, small RNAs that normally guide methylation to silence repetitive DNA like retrotransposons are diminished. Despite the loss of a highly conserved methylation pathway, and the reduction of small RNAs that normally target repetitive DNA, transposons have not proliferated in the genome, perhaps due in part to the rapid, clonal growth lifestyle of duckweeds.
Electrical synaptic transmission requires a postsynaptic scaffolding protein
Authors: Lasseigne Abagael M. , Echeverry Fabio A. , Ijaz Sundas , Michel Jennifer Carlisle , Martin E. Anne , Marsh Audrey J. , Trujillo Elisa , Marsden Kurt C. , Pereda Alberto E. , Miller Adam C. 
Published: December 2020

SUMMARYElectrical synaptic transmission relies on neuronal gap junctions containing channels constructed by Connexins. While at chemical synapses neurotransmitter-gated ion channels are critically supported by scaffolding proteins, it is unknown if channels at electrical synapses require similar scaffold support. Here we investigated the functional relationship between neuronal Connexins and Zonula Occludens 1 (ZO1), an intracellular scaffolding protein localized to electrical synapses. Using model electrical synapses in zebrafish Mauthner cells, we demonstrated that ZO1 is required for robust synaptic Connexin localization, but Connexins are dispensable for ZO1 localization. Disrupting this hierarchical ZO1/Connexin relationship abolishes electrical transmission and disrupts Mauthner-cell-initiated escape responses. We found that ZO1 is asymmetrically localized exclusively postsynaptically at neuronal contacts where it functions to assemble intercellular channels. Thus, forming functional neuronal gap junctions requires a postsynaptic scaffolding protein. The critical function of a scaffolding molecule reveals an unanticipated complexity of molecular and functional organization at electrical synapses.
Methodological Insights Theory development in qualitative management control: revisiting the roles of triangulation and generalization
Authors: Sridharan V.G. 
Published: December 2020

PurposeThis research paper seeks to advance the techniques of “within-paradigm” triangulation and theoretical generalization adopted in qualitative field studies for new theory development in management control.Design/methodology/approachUsing the evidence gleaned from three positivist case studies along with some published interpretivist studies, this paper identifies three triangulation approaches and links them with three forms of theoretical generalization in qualitative field studies.FindingsWhile the “literal” approach to triangulation has its place in the extant literature, this study finds that two other approaches, labeled “convergent” and “normative” triangulation, which are relevant in many circumstances to link multiple pieces of evidence in order to build credible explanations. In theory development, while the extant forms of theoretical generalization (constructive and contextual) are useful for identifying new solutions for both practical and theoretical concerns, this paper finds that a third form, namely “transposed” logic, is relevant in identifying new control problems that can benefit by adopting the observed unusual solutions.Originality/valueWithin triangulation, while the extant literature endorses the role of literal triangulation in obtaining consistent evidence, including how verifying inconsistent responses helps improve the validity of the obtained evidence, this paper advances two new triangulation approaches that can enrich the extant literature. Within theoretical generalization, while the extant literature deems constructive and contextual forms as “rhetoric”, this paper (1) expands their status to “logic” by clarifying their theoretical purpose and (2) introduces one new form, namely “transposed” logic that helps identify a generalizable range of management control problems that can adopt the observed unusual solution.
Quantum-like modelling in game theory: Quo Vadis? A brief review
Authors: Patra Sudip , Ghose Partha 
Published: December 2020

Purpose
The current paper is a brief review of the emerging field of quantum-like modelling in game theory. This paper aims to explore several quantum games, which are superior compared to their classical counterparts, which means either they give rise to superior Nash equilibria or they make the game fairer. For example, quantum Prisoners Dilemma generates Pareto superior outcomes as compared to defection outcome in the famous classical case. Again, a quantum-like version of cards game can make the game fairer, increasing the chance of winning of players who are disadvantaged in the classical case. This paper explores all the virtues of simple quantum games, also highlighting some findings of the authors as regards Prisoners Dilemma game.

Design/methodology/approach
As this is a general review paper, the authors have not demonstrated any specific mathematical method, rather explored the well-known quantum probability framework, used for designing quantum games. They have a short appendix which explores basic structure of Hilbert space representation of human decision-making.

Findings
Along with the review of the extant literature, the authors have also highlighted some new findings for quantum Prisoners Dilemma game. Specifically, they have shown in the earlier studies (which are referred to here) that a pure quantum entanglement set up is not needed for designing better games, even a weaker condition, which is classical entanglement is sufficient for producing Pareto improved outcomes.

Research limitations/implications
Theoretical research, with findings and implications for future game designs, it has been argued that it is not always needed to have true quantum entanglement for superior Nash Equilibria.

Originality/value
The main purpose here is to raise awareness mainly in the social science community about the possible applications of quantum-like game theory paradigm. The findings related to Prisoners Dilemma game are, however, original.
Sense of coherence as influencing information sharing at the workplace
Authors: Heinström Jannica , Ahmad Farhan , Huvila Isto , Ek Stefan 
Published: December 2020

PurposeThis study introduces sense of coherence (SOC) as a factor in information sharing at the workplace.Design/methodology/approachData were collected by a survey conducted on 311 respondents in a multinational organization, and analyzed using partial least square structural equation modelling.FindingsSOC influenced information sharing both directly and indirectly as mediated by trust and employee learning orientation. Trust, moreover, influenced receiving information more strongly than sending it, while employee learning orientation more strongly affected sending information.Originality/valueThe findings underline the importance of a holistic understanding of information sharing, including individual differences and employee well-being.