bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNF169 limits 53BP1 deposition at DSBs to stimulate single-strand annealing repair
Authors: An Liwei , Dong Chao , Li Junshi , Chen Jie , Yuan Jingsong , Huang Jun , Chan Kui Ming , Yu Cheng-han , Huen Michael S. Y. 
Published: August 2018

Significance
53BP1 restrains DNA end resection, and its dosage imbalance upsets DNA double-strand break (DSB) repair pathway choice. Here, by monitoring 53BP1 distribution on DSB-flanking chromatin, we have established a dose-dependent role of the RING finger protein RNF169 in limiting 53BP1 DSB deposition. Moreover, we found that forced expression of RNF169 overcomes 53BP1 activity and stimulates mutagenic DSB repair via the single-strand annealing pathway. Our findings suggest that aberrant expression of RNF169 may represent a deleterious factor in DSB repair control and in maintenance of genome stability.
JUM is a computational method for comprehensive annotation-free analysis of alternative pre-mRNA splicing patterns
Authors: Wang Qingqing , Rio Donald C. 
Published: August 2018

Significance
Alternative pre-mRNA splicing (AS) is a critical gene regulatory mechanism to produce diverse, tissue-specific, and functionally distinct protein profiles in eukaryotes to maintain normal cellular functions. Aberrant AS patterns are constantly associated with many human diseases, including cancer. The exceptional complexity of AS imposes a major challenge to analyzing AS across various tissues and cell types. Here we present a computational algorithm to profile and quantitate tissue-specific AS profiles from RNA-sequencing data without any prior knowledge of the host transcriptome. The junction usage model shows consistent superior performance in both specificity and sensitivity compared with other currently available AS analysis methods, and can be readily applied to a wide range of RNA samples from different organisms for accurate and comprehensive analyses of AS.
Deep mutational scanning of hemagglutinin helps predict evolutionary fates of human H3N2 influenza variants
Authors: Lee Juhye M. , Huddleston John , Doud Michael B. , Hooper Kathryn A. , Wu Nicholas C. , Bedford Trevor , Bloom Jesse D. 
Published: August 2018

Significance
A key goal in the study of influenza virus evolution is to forecast which viral strains will persist and which ones will die out. Here we experimentally measure the effects of all amino acid mutations to the hemagglutinin protein from a human H3N2 influenza strain on viral growth in cell culture. We show that these measurements have utility for distinguishing among viral strains that do and do not succeed in nature. Overall, our work suggests that new high-throughput experimental approaches may be useful for understanding virus evolution in nature.
Discovery of fissionogenic Cs and Ba capture five years after Oklo reactor shutdown
Authors: Groopman Evan E. , Willingham David G. , Meshik Alex P. , Pravdivtseva Olga V. 
Published: August 2018

Significance
The Oklo natural nuclear reactors provide a wealth of information regarding the migration and retention of fission products in nuclear wastes. Radioactive volatile and gaseous elements easily escape from reactor fuel into the environment without proper containment. Cesium, in particular, represents a significant environmental and health hazard. Here, we used an isotope imaging system to identify the location of sequestered fissionogenic Cs and Ba in Oklo. Cesium and Ba were captured in Ru metal/sulfide aggregates shortly after reactor criticality ceased. These elements were otherwise nearly completely lost from the reactor. We have further discovered the most depleted natural U on Earth, indicating that these fission products were retained in the most active region of the reactor.
The consequences of cavity creation on the folding landscape of a repeat protein depend upon context
Authors: Jenkins Kelly A. , Fossat Martin J. , Zhang Siwen , Rai Durgesh K. , Klein Sean , Gillilan Richard , White Zackary , Gerlich Grayson , McCallum Scott A. , Winter Roland , Gruner Sol M. , Barrick Doug , Royer Catherine A. 
Published: August 2018

SignificanceExtant protein sequences are the result of evolutionary pressure. Eliminating core packing interactions by mutation, regardless of position, generally results in similar perturbations to global stability. In contrast, we find that cavity creation has highly varied consequences for a protein folding landscape, depending upon the context in which the cavities are introduced. These observations have implications for interpreting evolutionary adaptation, as it is likely that proteins have evolved to exhibit optimal levels of conformational heterogeneity and dynamics. These results should also inform protein engineering efforts, as they provide insight into how sequence can modulate the population of functionally important excited states, as well as states that lead to secondary, undesirable reactions such as oligomerization, aggregation, surface activity, and phase separation.
Phosphoinositides control the localization of HOPS subunit VPS41, which together with VPS33 mediates vacuole fusion in plants
Authors: Brillada Carla , Zheng Jiameng , Krüger Falco , Rovira-Diaz Eliezer , Askani Jana Christin , Schumacher Karin , Rojas-Pierce Marcela 
Published: August 2018

Significance
Plant vacuoles are essential organelles and occupy up to 90% of the cell volume. Their roles include regulation of stomata movements, protein storage in seeds, gravity sensing, and ion homeostasis. Vacuole or lysosome fusion in eukaryotes is mediated by two multisubunit complexes, SNARE and homotypic fusion and vacuolar protein sorting (HOPS), but only the SNARE complex is well characterized in plants. Here, we show that, similar to other eukaryotes, HOPS mediates vacuole fusion in plants by interaction with SNAREs and that the HOPS subunit VPS33 and the SNARE protein SYP22 display the sites for interaction between these complexes. In contrast to other eukaryotes, however, plant HOPS recruitment to liposomes is inhibited by phosphoinositides, which appear to define strict rules for regulating fusion and fragmentation of dynamic vacuoles.
Structural and mechanistic analysis of the arsenate respiratory reductase provides insight into environmental arsenic transformations
Authors: Glasser Nathaniel R. , Oyala Paul H. , Osborne Thomas H. , Santini Joanne M. , Newman Dianne K. 
Published: August 2018

Significance
Microbial arsenate respiration enhances the mobility of arsenic and contributes to the poisoning of tens of millions of people worldwide. Our ability to quantitatively predict how microbial activities shape arsenic geochemistry depends on a detailed understanding of how the enzymes that catalyze arsenate reduction work under environmentally relevant conditions. The structural and kinetic findings of the Arr enzyme complex reported here both help rationalize its extracytoplasmic localization and allow us to predict that the rate of arsenate release from minerals likely constrains its activity in sedimentary environments. Moreover, this work illustrates that engineering environmental bacteria to overexpress their native proteins can be straightforward, a strategy that may advance the study of enzymes that are challenging to express in traditional hosts.
Mre11 complex links sister chromatids to promote repair of a collapsed replication fork
Authors: Zhu Min , Zhao Hongchang , Limbo Oliver , Russell Paul 
Published: August 2018

Significance
When replication forks collapse at single-strand DNA breaks, the resulting single-ended DNA double-strand breaks (seDSBs) are repaired by sister chromatid recombination (SCR). The Mre11–Rad50–Nbs1 (MRN) protein complex and CtIP/Ctp1 nucleolytically resect the seDSB to initiate SCR, but MRN was also proposed to promote SCR by tethering the seDSB to the unbroken sister chromatid. Here, we show that MRN sequentially localizes with the seDSB and sister chromatid during SCR. Provision of an intrachromosomal repair template alleviates the requirement for the nonnucleolytic function of MRN in repair of a collapsed replication fork. Zinc-coordinating “hooks” in Rad50 that are linchpins for MRN intercomplexes are essential for SCR. These studies support the MRN tethering hypothesis.
Designing antiphase boundaries by atomic control of heterointerfaces
Authors: Wang Zhen , Guo Hangwen , Shao Shuai , Saghayezhian Mohammad , Li Jun , Fittipaldi Rosalba , Vecchione Antonio , Siwakoti Prahald , Zhu Yimei , Zhang Jiandi , Plummer E. W. 
Published: August 2018

Significance
The mechancial and transport properties of every material are intimately coupled to the generation and formation of defects. In many systems, the nucleation process of defects is highly unpredictable due to the multiple coexisting nucleation mechanisms. A strategy to design and manipulate defect nucleation and formation can improve our understanding and in principle lead to the ability to control performance. Here we present a simple approach of designing 2D defects—named antiphase boundaries—using an atomic-controlled high-quality interface. These defects have a well-defined origin, location, and nucleation mechanism. Via advanced synthesis technology, atomically resolved electron microscopy, and theory, we reveal that these defects display distinctive properties such as physical merging and antipolar structural phases to potentially achieve memory devices.
Maternal Folic Acid Supplementation During Pregnancy Promotes Neurogenesis and Synaptogenesis in Neonatal Rat Offspring
Authors: Wang Xinyan , Li Wen , Li Zhenshu , Ma Yue , Yan Jing , Wilson John X , Huang Guowei 
Published: August 2018

Abstract
Maternal folic acid supplementation during pregnancy is associated with improved cognitive performances in offspring. However, the effect of supplementation on offspring’s neurogenesis and synaptogenesis is unknown, and whether supplementation should be continued throughout pregnancy is controversial. In present study, 3 groups of female rats were fed a folate-normal diet, folate-deficient diet, or folate-supplemented diet from 1 week before mating until the end of pregnancy. A fourth group fed folate-normal diet from 1 week before mating until mating, then fed folate-supplemented diet for 10 consecutive days, then fed folate-normal diet until the end of pregnancy. Offspring were sacrificed on postnatal day 0 for measurement of neurogenesis and synaptogenesis by immunofluorescence and western blot. Additionally neural stem cells (NSCs) were cultured from offspring’s hippocampus for immunocytochemical measurement of their rates of proliferation and neuronal differentiation. The results demonstrated that maternal folic acid supplementation stimulated hippocampal neurogenesis by increasing proliferation and neuronal differentiation of NSCs, and also enhanced synaptogenesis in cerebral cortex of neonatal offspring. Hippocampal neurogenesis was stimulated more when supplementation was continued throughout pregnancy instead of being limited to the periconceptional period. In conclusion, maternal folic acid supplementation, especially if continued throughout pregnancy, improves neurogenesis and synaptogenesis in neonatal offspring.
Measuring and understanding individual differences in cognition
Authors: Boogert Neeltje J. , Madden Joah R. , Morand-Ferron Julie , Thornton Alex 
Published: August 2018

Individuals vary in their cognitive performance. While this variation forms the foundation of the study of human psychometrics, its broader importance is only recently being recognized. Explicitly acknowledging this individual variation found in both humans and non-human animals provides a novel opportunity to understand the mechanisms, development and evolution of cognition. The papers in this special issue highlight the growing emphasis on individual cognitive differences from fields as diverse as neurobiology, experimental psychology and evolutionary biology. Here, we synthesize this body of work. We consider the distinct challenges in quantifying individual differences in cognition and provide concrete methodological recommendations. In particular, future studies would benefit from using multiple task variants to ensure they target specific, clearly defined cognitive traits and from conducting repeated testing to assess individual consistency. We then consider how neural, genetic, developmental and behavioural factors may generate individual differences in cognition. Finally, we discuss the potential fitness consequences of individual cognitive variation and place these into an evolutionary framework with testable hypotheses. We intend for this special issue to stimulate researchers to position individual variation at the centre of the cognitive sciences.This article is part of the theme issue ‘Causes and consequences of individual differences in cognitive abilities’.
Linking personality and cognition: a meta-analysis
Authors: Dougherty Liam R. , Guillette Lauren M. 
Published: August 2018

In the past decade, several conceptual papers have linked variation in animal personality to variation in cognition, and recent years have seen a flood of empirical studies testing this link. However, these results have not been synthesized in a quantitative way. Here, we systematically search the literature and conduct a phylogenetically controlled meta-analysis of empirical papers that have tested the relationship between animal personality (exploration, boldness, activity, aggression and sociability) and cognition (initial learning/reversal speed, number of correct choices/errors after standard training). We find evidence for a small but significant relationship between variation in personality and variation in learning across species in the absolute scale; however, thedirectionof this relationship is highly variable and when both positive and negative effect sizes are considered, the average effect size does not differ significantly from zero. Importantly, this variation among studies is not explained by differences in personality or learning measure, or taxonomic grouping. Further, these results do not support current hypotheses suggesting that that fast-explorers are fast-learners or that slow-explorers perform better on tests of reversal learning. Rather, we find evidence that bold animals are faster learners, but only when boldness is measured in response to a predator (or simulated predator) and not when boldness is measured by exposure to a novel object (or novel food). Further, although only a small sub-sample of papers reported results separately for males and females, sex explained a significant amount of variation in effect size. These results, therefore, suggest that, while personality and learning are indeed related across a range of species, the direction of this relationship is highly variable. Thus further empirical work is needed to determine whether there are important moderators of this relationship.This article is part of the theme issue ‘Causes and consequences of individual differences in cognitive abilities’.
Comparative psychometrics: establishing what differs is central to understanding what evolves
Authors: Völter Christoph J. , Tinklenberg Brandon , Call Josep , Seed Amanda M. 
Published: August 2018

Cognitive abilities cannot be measured directly. What we can measure is individual variation in task performance. In this paper, we first make the case for why we should be interested in mapping individual differences in task performance onto particular cognitive abilities: we suggest that it is crucial for examining the causes and consequences of variation both within and between species. As a case study, we examine whether multiple measures of inhibitory control for non-human animals do indeed produce correlated task performance; however, no clear pattern emerges that would support the notion of a common cognitive ability underpinning individual differences in performance. We advocate a psychometric approach involving a three-step programme to make theoretical and empirical progress: first, we need tasks that reveal signature limits in performance. Second, we need to assess the reliability of individual differences in task performance. Third, multi-trait multi-method test batteries will be instrumental in validating cognitive abilities. Together, these steps will help us to establish what varies between individuals that could impact their fitness and ultimately shape the course of the evolution of animal minds. Finally, we propose executive functions, including working memory, inhibitory control and attentional shifting, as a sensible starting point for this endeavour.This article is part of the theme issue ‘Causes and consequences of individual differences in cognitive abilities’.
Stress hormones, social associations and song learning in zebra finches
Authors: Boogert Neeltje J. , Lachlan Robert F. , Spencer Karen A. , Templeton Christopher N. , Farine Damien R. 
Published: August 2018

The use of information provided by others is a common short-cut adopted to inform decision-making. However, instead of indiscriminately copying others, animals are often selective in what, when and whom they copy. How do they decide which ‘social learning strategy’ to use? Previous research indicates that stress hormone exposure in early life may be important: while juvenile zebra finches copied their parents' behaviour when solving novel foraging tasks, those exposed to elevated levels of corticosterone (CORT) during development copied only unrelated adults. Here, we tested whether this switch in social learning strategy generalizes to vocal learning. In zebra finches, juvenile males often copy their father's song; would CORT-treated juveniles in free-flying aviaries switch to copying songs of other males? We found that CORT-treated juveniles copied their father's song less accurately as compared to control juveniles. We hypothesized that this could be due to having weaker social foraging associations with their fathers, and found that sons that spent less time foraging with their fathers produced less similar songs. Our findings are in line with a novel hypothesis linking early-life stress and social learning: early-life CORT exposure may affect social learning indirectly as a result of the way it shapes social affiliations.
This article is part of the theme issue ‘Causes and consequences of individual differences in cognitive abilities’.
Identification and Ranking of Recurrent Neo-Epitopes in Cancer
Authors: Blanc Eric , Holtgrewe Manuel , Dhamodaran Arunraj , Messerschmidt Clemens , Willimsky Gerald , Blankenstein Thomas , Beule Dieter 
Published: August 2018

AbstractImmune escape is one of the hallmarks of cancer and several new treatment approaches attempt to modulate and restore the immune system’s capability to target cancer cells. At the heart of the immune recognition process lies antigen presentation from somatic mutations. These neo-epitopes are emerging as attractive targets for cancer immunotherapy and new strategies for rapid identification of relevant candidates have become a priority. We carefully screen TCGA data sets for recurrent somatic amino acid exchanges and apply MHC class I binding predictions. We propose a method for in silico selection and prioritization of candidates which have a high potential for neo-antigen generation and are likely to appear in multiple patients. While the percentage of patients carrying a specific neo-epitope and HLA-type combination is relatively small, the sheer number of new patients leads to surprisingly high reoccurence numbers. We identify 769 epitopes which are expected to occur in 77629 patients per year. While our candidate list will definitely contain false positives, the results provide an objective order for wet-lab testing of reusable neo-epitopes. Thus recurrent neo-epitopes may be suitable to supplement existing personalized T cell treatment approaches with precision treatment options.
Meiotic drive of female-inherited supernumerary chromosomes in a pathogenic fungus
Authors: Habig Michael , Kema Gert H.J. , Stukenbrock Eva H. 
Published: August 2018

AbstractMeiosis is a key cellular process of sexual reproduction involving the pairing of homologous sequences. In many species however, meiosis can also involve the segregation of supernumerary chromosomes, which can lack a homolog. How these unpaired chromosomes undergo meiosis is largely unknown. In this study we investigated chromosome segregation during meiosis in the haploid fungusZymoseptoria triticithat possesses a large complement of supernumerary chromosomes. We used isogenic whole chromosome deletion strains to compare meiotic transmission of chromosomes when paired and unpaired. Unpaired chromosomes inherited from the male parent as well as paired supernumerary chromosomes showed Mendelian inheritance. In contrast, unpaired chromosomes inherited from the female parent showed non-Mendelian inheritance but were amplified and transmitted to all meiotic products. We concluded that the supernumerary chromosomes ofZ. triticishow a meiotic drive and propose an additional feedback mechanism during meiosis which initiates amplification of unpaired female-inherited chromosomes.
No single, stable 3D representation can explain pointing biases in a spatial updating task
Authors: Vuong Jenny , Fitzgibbon Andrew W. , Glennerster Andrew 
Published: August 2018

AbstractPeople are able to keep track of objects as they navigate through space, even when objects are out of sight. This requires some kind of representation of the scene and of the observer’s location but the form this representation might take is debated. We tested the accuracy and reliability of observers’ estimates of the visual direction of previously-viewed targets. Participants viewed 4 objects from one location, with binocular vision and small head movements giving information about the 3D locations of the objects. Without any further sight of the targets, participants walked to another location and pointed towards them. All the conditions were tested in an immersive virtual environment and some were also carried out in a real scene. Participants made large, consistent pointing errors that are poorly explained by any consistent 3D representation. Instead, if a 3D representation is to account for the data it would need to be one where the target boxes were squashed, almost into a plane, quite far away from the true location of the boxes and in different places depending on the orientation of the obscuring wall at the moment the participant points. In short, our data show that the mechanisms for updating visual direction of unseen targets are not based on a stable 3D model of the scene, even a distorted one.