bluuebunny/crossref_metadata_2025_split huggingface dataset:
Senolytic Combination of Dasatinib and Quercetin Alleviates Intestinal Senescence and Inflammation and Modulates the Gut Microbiome in Aged Mice
Authors: Saccon Tatiana Dandolini , Nagpal Ravinder , Yadav Hariom , Cavalcante Marcelo Borges , Nunes Allancer Divino de Carvalho , Schneider Augusto , Gesing Adam , Hughes Brian , Yousefzadeh Matthew , Tchkonia Tamar , Kirkland James L , Niedernhofer Laura J , Robbins Paul D , Masternak Michal M 
Published: January 2021

Abstract
Cellular senescence contributes to age-related disorders including physical dysfunction, disabilities, and mortality caused by tissue inflammation and damage. Senescent cells accumulate in multiple tissues with aging and at etiological sites of multiple chronic disorders. The senolytic drug combination, Dasatinib plus Quercetin (D+Q), is known to reduce senescent cell abundance in aged mice. However, the effects of long-term D+Q treatment on intestinal senescent cell and inflammatory burden and microbiome composition in aged mice remain unknown. Here, we examine the effect of D+Q on senescence (p16Ink4a and p21Cip1) and inflammation (Cxcl1, Il1β, Il6, Mcp1, and Tnfα) markers in small (ileum) and large (caecum and colon) intestine in aged mice (n = 10) compared to age-matched placebo-treated mice (n = 10). Additionally, we examine microbial composition along the intestinal tract in these mice. D+Q-treated mice show significantly lower senescent cell (p16 and p21 expression) and inflammatory (Cxcl1, Il1β, Il6, Mcp1, and Tnfα expression) burden in small and large intestine compared with control mice. Further, we find specific microbial signatures in ileal, cecal, colonic, and fecal regions that are distinctly modulated by D+Q, with modulation being most prominent in small intestine. Further analyses reveal specific correlation of senescence and inflammation markers with specific microbial signatures. Together, these data demonstrate that the senolytic treatment reduces intestinal senescence and inflammation while altering specific microbiota signatures and suggest that the optimized senolytic regimens might improve health via reducing intestinal senescence, inflammation, and microbial dysbiosis in older subjects.
SPONGEdb: a pan-cancer resource for competing endogenous RNA interactions
Authors: Hoffmann Markus , Pachl Elisabeth , Hartung Michael , Stiegler Veronika , Baumbach Jan , Schulz Marcel H , List Markus 
Published: January 2021

Abstract
microRNAs (miRNAs) are post-transcriptional regulators involved in many biological processes and human diseases, including cancer. The majority of transcripts compete over a limited pool of miRNAs, giving rise to a complex network of competing endogenous RNA (ceRNA) interactions. Currently, gene-regulatory networks focus mostly on transcription factor-mediated regulation, and dedicated efforts for charting ceRNA regulatory networks are scarce. Recently, it became possible to infer ceRNA interactions genome-wide from matched gene and miRNA expression data. Here, we inferred ceRNA regulatory networks for 22 cancer types and a pan-cancer ceRNA network based on data from The Cancer Genome Atlas. To make these networks accessible to the biomedical community, we present SPONGEdb, a database offering a user-friendly web interface to browse and visualize ceRNA interactions and an application programming interface accessible by accompanying R and Python packages. SPONGEdb allows researchers to identify potent ceRNA regulators via network centrality measures and to assess their potential as cancer biomarkers through survival, cancer hallmark and gene set enrichment analysis. In summary, SPONGEdb is a feature-rich web resource supporting the community in studying ceRNA regulation within and across cancer types.
Tracking telomere fusions through crisis reveals conflict between DNA transcription and the DNA damage response
Authors: Liddiard Kate , Grimstead Julia W , Cleal Kez , Evans Anna , Baird Duncan M 
Published: January 2021

AbstractIdentifying attributes that distinguish pre-malignant from senescent cells provides opportunities for targeted disease eradication and revival of anti-tumour immunity. We modelled a telomere-driven crisis in four human fibroblast lines, sampling at multiple time points to delineate genomic rearrangements and transcriptome developments that characterize the transition from dynamic proliferation into replicative crisis. Progression through crisis was associated with abundant intra-chromosomal telomere fusions with increasing asymmetry and reduced microhomology usage, suggesting shifts in DNA repair capacity. Eroded telomeres also fused with genomic loci actively engaged in transcription, with particular enrichment in long genes. Both gross copy number alterations and transcriptional responses to crisis likely underpin the elevated frequencies of telomere fusion with chromosomes 9, 16, 17, 19 and most exceptionally, chromosome 12. Juxtaposition of crisis-regulated genes with loci undergoing de novo recombination exposes the collusive contributions of cellular stress responses to the evolving cancer genome.
Quantity–quality trade-off in the acquisition of token preference by capuchin monkeys (
Sapajus
spp.)
Authors: Quintiero E. , Gastaldi S. , De Petrillo F. , Addessi E. , Bourgeois-Gironde S. 
Published: January 2021

Money represents a cornerstone of human modern economies and how money emerged as a medium of exchange is a crucial question for social sciences. Although non-human primates have not developed monetary systems, they can estimate, combine and exchange tokens. Here, we evaluated quantity–quality trade-offs in token choices in tufted capuchin monkeys as a first step in the investigation of the generalizability of tokens as reinforcers, which is a potentially relevant factor underlying the emergence of money in humans. We measured capuchins' exchange preferences when they were repeatedly provided with 10 units of three token types yielding food combinations varying in quantity and quality. Overall, capuchins maximized their quantitative payoff, preferring tokens associated with a higher food amount, rather than showing violations of rationality. However, some individuals did not maximize their qualitative payoff, possibly because of conditional valuation effects or owing to the choice overload phenomenon, according to which too many options reduce the accuracy of choice. Our study supports the importance of comparative research to finely analyse the multiple components shaping the economic behaviours of other species, possibly to achieve a more comprehensive, evolutionary- and ecologically based understanding of human economic behaviour.
This article is part of the theme issue ‘Existence and prevalence of economic behaviours among non-human primates’.
How animals do business
Authors: de Waal Frans B. M. 
Published: January 2021

The field of comparative behavioural economics investigates decisions about the acquisition and exchange of goods and services. It does so in both humans and other species on the assumption that the cognition and emotions involved have a shared evolutionary background. This preface roughly defines the field and reviews a few selected early studies and concepts to offer a taste of what economic behaviour means in relation to species other than our own.
This article is part of the theme issue ‘Existence and prevalence of economic behaviours among non-human primates’.
Balancing costs and benefits in primates: ecological and palaeoanthropological views
Authors: Garcia Cécile , Bouret Sébastien , Druelle François , Prat Sandrine 
Published: January 2021

Maintaining the balance between costs and benefits is challenging for species living in complex and dynamic socio-ecological environments, such as primates, but also crucial for shaping life history, reproductive and feeding strategies. Indeed, individuals must decide to invest time and energy to obtain food, services and partners, with little direct feedback on the success of their investments. Whereas decision-making relies heavily upon cognition in humans, the extent to which it also involves cognition in other species, based on their environmental constraints, has remained a challenging question. Building mental representations relating behaviours and their long-term outcome could be critical for other primates, but there are actually very little data relating cognition to real socio-ecological challenges in extant and extinct primates. Here, we review available data illustrating how specific cognitive processes enable(d) modern primates and extinct hominins to manage multiple resources (e.g. food, partners) and to organize their behaviour in space and time, both at the individual and at the group level. We particularly focus on how they overcome fluctuating and competing demands, and select courses of action corresponding to the best possible packages of potential costs and benefits in reproductive and foraging contexts.This article is part of the theme issue ‘Existence and prevalence of economic behaviours among non-human primates’.
Conditional valuation for combinations of goods in primates
Authors: Chung Hui-Kuan , Alós-Ferrer Carlos , Tobler Philippe N. 
Published: January 2021

Valuing goods and selecting the one with the highest value forms the basis of adaptive behaviour across species. While it is obvious that the valuation of a given type of goods depends on ownership and availability of that type of goods, the effects of other goods on valuation of the original good are sometimes underappreciated. Yet, goods interact with each other, indicating that the valuation of a given good is conditional on the other goods it is combined with, both in the wild and the laboratory. Here, we introduce conditional valuation in the context of valuing multiple goods and briefly review how human and animal experimentalists can leverage economic tools for the study of interactions among goods. We then review evidence for conditional valuation for combined foods in both human and non-human primates. In the laboratory, non-human primates show increased valuation of certain combinations of foods but decreased valuation of other types of combinations. Thus, similarly to humans, monkeys appear to value combinations of goods in a conditional fashion. Additionally, both humans and monkeys appear to employ similar neural substrates for the valuation of single goods, such as the orbitofrontal cortex. Together, investigations of our evolutionary precursors may provide insights on how we value interacting goods.
This article is part of the theme issue ‘Existence and prevalence of economic behaviours among non-human primates’.
Non-human primates use combined rules when deciding under ambiguity
Authors: Romain A. , Broihanne M-H. , De Marco A. , Ngoubangoye B. , Call J. , Rebout N. , Dufour V. 
Published: January 2021

Decision outcomes in unpredictable environments may not have exact known probabilities. Yet the predictability level of outcomes matters in decisions, and animals, including humans, generally avoid ambiguous options. Managing ambiguity may be more challenging and requires stronger cognitive skills than decision-making under risk, where decisions involve known probabilities. Here we compare decision-making in capuchins, macaques, orangutans, gorillas, chimpanzees and bonobos in risky and ambiguous contexts. Subjects were shown lotteries (a tray of potential rewards, some large, some small) and could gamble a medium-sized food item to obtain one of the displayed rewards. The odds of winning and losing varied and were accessible in the risky context (all rewards were visible) or partially available in the ambiguous context (some rewards were covered). In the latter case, the level of information varied from fully ambiguous (individuals could not guess what was under the covers) to predictable (individuals could guess). None of the species avoided gambling in ambiguous lotteries and gambling rates were high if at least two large rewards were visible. Capuchins and bonobos ignored the covered items and gorillas and macaques took the presence of potential rewards into account, but only chimpanzees and orangutans could consistently build correct expectations about the size of the covered rewards. Chimpanzees and orangutans combined decision rules according to the number of large visible rewards and the level of predictability, a process resembling conditional probabilities assessment in humans. Despite a low sample size, this is the first evidence in non-human primates that a combination of several rules can underlie choices made in an unpredictable environment. Our finding that non-human primates can deal with the uncertainty of an outcome when exchanging one food item for another is a key element to the understanding of the evolutionary origins of economic behaviour.This article is part of the theme issue ‘Existence and prevalence of economic behaviours among non-human primates’.
Economic behaviours among non-human primates
Authors: Bourgeois-Gironde Sacha , Addessi Elsa , Boraud Thomas 
Published: January 2021

Do we have any valid reasons to affirm that non-human primates display economic behaviour in a sufficiently rich and precise sense of the phrase? To address this question, we have to develop a set of criteria to assess the vast array of experimental studies and field observations on individual cognitive and behavioural competences as well as the collective organization of non-human primates. We review a sample of these studies and assess how they answer to the following four main challenges. (i) Do we see any economic organization or institutions emerge among groups of non-human primates? (ii) Are the cognitive abilities, and often biases, that have been evidenced as underlying typical economic decision-making among humans, also present among non-human primates? (iii) Can we draw positive lessons from performance comparisons among primate species, humans and non-humans but also across non-human primate species, as elicited by canonical game-theoretical experimental paradigms, especially as far as economic cooperation and coordination are concerned? And (iv) in which way should we improve models and paradigms to obtain more ecological data and conclusions? Articles discussed in this paper most often bring about positive answers and promising perspectives to support the existence and prevalence of economic behaviours among non-human primates.
This article is part of the theme issue ‘Existence and prevalence of economic behaviours among non-human primates’.
Weakly-Coupled Oscillators with Long-Distance Correlation as a Model of Human Atrial Fibrillation
Authors: Iravanian Shahriar 
Published: January 2021

I.ABSTRACTAtrial Fibrillation (AF) is a chronic, progressive, and heterogeneous disease, which exhibits irregular and chaotic atrial electrical activity. The exact mechanisms of AF have remained elusive. The complexity of the atrial signals, irregular period, and the non-local nature of AF make it very difficult to characterize its spatiotemporal organization. This paper presents a set of data-processing tools to find and evaluate the intracardiac signals in AF based on synchronization theory. Specifically, a graph-theoretical algorithm is developed to prune spurious detections of atrial complexes (spikes). The processing pipeline was applied to 10 intracardiac recordings obtained during ablation procedures in patients with paroxysmal or persistent AF. The AF cases were classified into three main types. Type I (n=3) is defined as the presence of a single driver that dominates both atria and is consistent with the mother rotor hypothesis. The majority of the cases had more than one driver and were classified as types II (n=4) and III (n=3). The drivers, i.e., the interacting organized areas, in type II have significantly different peak frequencies and are only weakly coupled. The drivers in type III have close frequencies, are moderately interacting, and show evidence of transient intermittent phase-locking (intermittency). In addition, a long-distance correlation between channels from the left and right atria was observed. The theory of synchronization is a useful conceptual framework to process and analyze AF and can provide mechanistic insight into AF and the effect of various interventions.
Transcranial magnetic stimulation entrains alpha oscillatory activity in occipital cortex
Authors: Lin Yong-Jun , Shukla Lavanya , Dugué Laura , Valero-Cabré Antoni , Carrasco Marisa 
Published: January 2021

AbstractParieto-occipital alpha rhythms (8-12 Hz) underlie cortical excitability and influence visual performance. Whether the synchrony of intrinsic alpha rhythms in the occipital cortex can be entrained by transcranial magnetic stimulation (TMS) is an open question. We applied 4-pulse, 10-Hz rhythmic TMS to entrain intrinsic alpha oscillators targeting right V1/V2, and tested four predictions with concurrent electroencephalogram (EEG): (1) progressive enhancement of entrainment across time windows, (2) output frequency specificity, (3) dependence on the intrinsic oscillation phase, and (4) input frequency specificity to individual alpha frequency (IAF) in the neural signatures. Two control conditions with an equal number of pulses and duration were arrhythmic-active and rhythmic-sham stimulation. The results confirmed the first three predictions. Rhythmic TMS bursts significantly entrained local neural activity. Near the stimulation site, evoked oscillation amplitude and inter-trial phase coherence (ITPC) were increased for 2 and 3 cycles, respectively, after the last TMS pulse. Critically, ITPC following entrainment positively correlated with IAF rather than with the degree of similarity between IAF and the input frequency (10 Hz). Thus, we entrained alpha-band activity in occipital cortex for ~3 cycles (~300 ms), and IAF predicts the strength of entrained occipital alpha phase synchrony indexed by ITPC.
Structural basis for Potassium transport by KdpFABC
Authors: Sweet Marie E. , Larsen Casper , Zhang Xihui , Schlame Michael , Pedersen Bjørn P. , Stokes David L. 
Published: January 2021

AbstractKdpFABC is an oligomeric K+transport complex in prokaryotes that maintains ionic homeostasis under stress conditions. The complex comprises a channel-like subunit (KdpA) from the Superfamily of K+Transporters and a pump-like subunit (KdpB) from the superfamily of P-type ATPases. Recent structural work has defined the architecture and generated contradictory hypotheses for the transport mechanism. Here, we use substrate analogs to stabilize four key intermediates in the reaction cycle and determine the corresponding structures by cryo-EM. We find that KdpB undergoes conformational changes consistent with other representatives from the P-type superfamily, whereas KdpA, KdpC and KdpF remain static. We observe a series of spherical densities that we assign as K+or water and which define a pathway for K+transport. This pathway runs through an intramembrane tunnel in KdpA and delivers ions to sites in the membrane domain of KdpB. Our structures suggest a mechanism where ATP hydrolysis is coupled to K+transfer between alternative sites in the membrane domain of KdpB, ultimately reaching a low-affinity site where a water-filled pathway allows release of K+to the cytoplasm.
Nitrogen availability drives gene length of dominant prokaryotes and diversity of genes acquiring Nitrogen-species in oceanic systems
Authors: Dlugosch Leon , Poehlein Anja , Wemheuer Bernd , Pfeiffer Birgit , Giebel Helge-A. , Daniel Rolf , Simon Meinhard 
Published: January 2021

AbstractNitrogen (N) is a key element for prokaryotes in the oceans and often limits phytoplankton primary production. An untested option to reduce prokaryotic N-demand under N-limitation is to reduce gene length. Here we show that in the sunlit Atlantic Ocean genes of the prokaryotic microbial communities in the permanently stratified N-limited (sub)tropics are up to 20% shorter than in N-replete regions further south and north. Average gene length (AGL) of major pelagic prokaryotic genera and two virus families correlated positively with nitrate concentrations. Further, the genomic G+C content of 60% of the taxa was lower and the gene repertoire to acquire inorganic and organic N-species higher in N-limited than in N-replete regions. A comparison of the N-demand by reducing gene length or G+C content showed that the former is much more efficient to save N. Our findings introduce a novel and most effective mode of evolutionary adaptation of prokaryotes to save resources including N and energy. They further show an enhanced diversification of genes acquiring N-species and -compounds in N-deplete relative to N-replete regions and thus add important information for a better understanding of the evolutionary adaptation of prokaryotes to N-availability in oceanic systems.
Occurrences of protonated base triples in RNA are determined by their cooperative binding energies and specific functional requirements
Authors: Halder Antarip , Jhunjhunwala Ayush , Bhattacharyya Dhananjay , Mitra Abhijit 
Published: January 2021

AbstractWith wide ranging diversity in their geometries, binding strengths and chemical properties, noncanonical base pairs are equipped to intricately regulate and control the structural dynamics of RNA molecules. Protonation of nucleobases adds to the diversity. Compared to the unprotonated scenario, on one hand they open up new alternatives for base pairing interactions (Class I) while on the other, they modulate the geometry and stability of existing base pairing interactions (Class II). In both cases, compensation of the energetic cost associated with nucleobase protonation at physiological pH, can be understood in terms of protonation induced restructuring of charge distribution. This not only leads to modifications in existing base-base interactions but often also leads to additional stabilizing interactions, resulting in the formation of protonated base triples. Here we report our detailed quantum chemical studies, in conjunction with structural bioinformatics based analysis of RNA crystal and NMR structure datasets, probing into the contribution of such protonated triples in the structural dynamics of RNA. Our studies revealed more than 55 varieties of protonated triples in RNA, some of which occur recurrently within conserved structural motifs present in rRNAs, tRNAs and in other synthetic RNAs. Our studies suggest that high occurrence frequencies are associated with protonated triples which satisfy the specific structural requirements of conserved motifs where they occur. For example, protonated triples with flexible geometries are involved in the formation of tertiary contacts between different distant motifs. Stabilization of protonated base pairs, through the induction of additional energetically cooperative interactions, appears to be another factor. These results provide significant insights into the sequence-structure-function relationships in RNA.
Simultaneous association of grip effort with snack food items does not change preferences
Authors: Aridan Nadav , Schonberg Tom 
Published: January 2021

AbstractEffort is typically considered aversive such that rewards requiring less effort are preferred over identical value rewards that require greater effort, commonly referred to as “effort discounting”. Although effort has been repeatedly shown to be weighed as a cost, there are indications to suggest that under some conditions it may increase preferences. An example for how effort affects preferences is the ‘contrast effect’ were items that follow effort production gain value. In the current study we examined whether the association of grip effort with snack food items would change preferences. In four experiments, we first identified each participant’s individual preferences of snack food items and subjective maximal grip force. We then associated different effort levels with items of similar preference. Finally, we tested for changes in preferences following the effort association. Across the four studies, effort association had no effect on preferences. Using Bayesian analyses, we conclude that simultaneous association of effort does not change preferences in our studies and call for a replication effort of previous findings.