Miracle-dz/UniFAR-FTUs huggingface dataset:
The rate of spontaneous mutations in yeast deficient for MutSβ function

Mutations in simple sequence repeat loci underlie many inherited disorders in humans, and are increasingly recognized as important determinants of natural phenotypic variation. In eukaryotes, mutations in these sequences are primarily repaired by the MutSβ mismatch repair complex. To better understand the role of this complex in mismatch repair and the determinants of simple sequence repeat mutation predisposition, we performed mutation accumulation in yeast strains with abrogated MutSβ function. We demonstrate that mutations in simple sequence repeat loci in the absence of mismatch repair are primarily deletions. We also show that mutations accumulate at drastically different rates in short (<8 bp) and longer repeat loci. These data lend support to a model in which the mismatch repair complex is responsible for repair primarily in longer simple sequence repeats.
Variations of photosynthetic N-use efficiency through plant phylogeny in relation 2 to mesophyll cell wall thickness 3

Photosynthetic nitrogen-use efficiency (PNUE) varied greatly among C 3 34 species. Previous studies suggested that PNUE patterns in spermatophyta are 35 characterized in relation to leaf mass per area (LMA) and explained by the LMA- 36 mediated tradeoffs between N allocation to cell walls and Rubisco and mesophyll 37 conductance (g m ). However, morpho-physiological mechanisms and interrelationships 38 shaping PNUE remain unclear at an evolutionary time scale. Here, we compiled a 39 novel large matrix of leaf morpho-anatomical and physiological traits in 679 C 3 40 species from bryophytes to angiosperm to further understand the complexity of 41 interrelationships underlying PNUE variations. We found that LMA, mesophyll cell 42 wall thickness (T cwm ), Rubisco N allocation fraction (P R ), and g m together interpreted 43 83% of PNUE variations, 65% of which were explained by P R and g m . Paired-trait 44 correlation analysis and path analysis indicated a weak correlation between PNUE 45 and LMA, while the paired PNUE–T cwm correlation was strong. There were positively 46 interactive effects of P R and g m on PNUE. The effects of P R on PNUE were species- 47 dependent on g m ; that is, the P R contribution on PNUE was massively greater in high- 48 g m species than that in low-g m ones. The P R was inversely proportional to T cwm which 49 was similar to the g m –T cwm relationship (p < 0.01). Additionally, g m was positively 50 regulated by chloroplast surface area exposed to intercellular airspace per unit leaf 51 mass (S c ) (p < 0.01). Collectively, coordinated changes in P R and g m connecting T cwm 52 suggested the T cwm -mediated complex physiology mechanisms controlling the PNUE 53 across contrasting plant groups. 54 55 56 57 the rate (V cmax ), the maximum rate (J max ), stomatal limitation on photosynthesis (l s ), mesophyll limitation on photosynthesis (l m ), biochemical limitation on photosynthesis (l b ), and (L temp ). photosynthetic coordination theory originally proposed by Caemmerer further developed by Maire et al in 31 individual C 3 species, et al Smith et al and Harrison et al regional vegetation studies states that photosynthesis tends to be co-limited by electron transport and carboxylation under average environmental conditions, thus maximizing potential resource use for growth and reproduction. The photosynthetic coordination quantitative predicting P m mol m –2 s –1 ), suggesting stronger mesophyll limitation on photosynthesis; vice verse , stronger biochemical limitation on photosynthesis was evident in species with high g m > 0.001 mol g –1 s –1 . These results suggested stronger
The direct and indirect pathways of the basal ganglia antagonistically influence cortical activity and perceptual decisions

The striatum, input nucleus of the basal ganglia, receives topographically organized input from the cortex and gives rise to the direct and indirect pathways with antagonistic effects on the output of the basal ganglia. We optogenetically stimulated the direct and indirect pathways in mice and measured their influence on perceptual decisions and neuronal activity in the cortex. In a task in which mice had to detect a visual stimulus, unilateral direct-pathway stimulation increased the probability of lick responses to the non-stimulated side and increased cortical activity globally. In contrast, indirect-pathway stimulation increased the probability of licks to the stimulated side and decreased activity in visual cortical areas. To probe the possible role of the two pathways in working memory, we trained the mice to report the location of a stimulus with licking one of two spouts, after a memory delay. Direct-pathway stimulation prior to and during the memory delay enhanced both the neural representation of a contralateral visual stimulus and the number of contraversive choices, whereas indirect-pathway stimulation had the opposite effects, in accordance with an antagonistic influence of the direct and indirect pathways on licking direction. Our results demonstrate how these two pathways influence perceptual decisions and working memories, and modify activity in the cerebral cortex. One sentence summary Visuomotor transformations are influenced antagonistically by the direct and indirect pathways of the basal ganglia during visual detection and working memory tasks
Vibrio type III secretion system 2 is not restricted to the Vibrionaceae and encodes differentially distributed repertoires of effector proteins

Vibrio parahaemolyticus is the leading cause of seafood-borne gastroenteritis worldwide. A distinctive feature of the O3:K6 pandemic clone, and its derivatives, is the presence of a second, phylogenetically distinct, Type III Secretion System (T3SS2) encoded within the genomic island VPaI-7. The T3SS2 allows the delivery of effector proteins directly into the cytosol of infected eukaryotic cells to subvert key host cell processes, critical for V. parahaemolyticus to colonize and cause disease. Furthermore, the T3SS2 also increases the environmental fitness of V. parahaemolyticus in its interaction with bacterivorous protists; hence it has been proposed that it contributed to the global oceanic spread of the pandemic clone. Several reports have identified T3SS2-related genes in Vibrio and non-Vibrio species, suggesting that the T3SS2 gene cluster is not restricted to the Vibrionaceae and can mobilize through horizontal gene transfer events. In this work, we performed a large-scale genomic analysis to determine the phylogenetic distribution of the T3SS2 gene cluster and its repertoire of effector proteins. We identified putative T3SS2 gene clusters in 1130 bacterial genomes from 8 bacterial genera, 5 bacterial families and 47 bacterial species. A hierarchical clustering analysis allowed us to define 6 T3SS2 subgroups (I-VI) with different repertoires of effector proteins, redefining the concepts of T3SS2 core and accessory effector proteins. Finally, we identified a subset of T3SS2 gene clusters (subgroup VI) that lack most T3SS2 effector proteins described to date and provided a list of 10 novel effector candidates for this subgroup through bioinformatic analysis. Collectively, our findings indicate that the T3SS2 extends beyond the Vibrionaceae family and suggest that different effector protein repertories could have a differential impact on the pathogenic potential and environmental fitness of each bacteria that have acquired the Vibrio T3SS2 gene cluster. DATA SUMMARY All genome sequences used in this study were downloaded from the National Center for Biotechnology Information (NCBI) RefSeq or GenBank databases (See Table S1 for accession numbers). Files for the T3SS2 reconstructed phylogenetic tree (Newick tree and MSA fasta file), hierarchical clustering data analysis file from MORPHEUS, Table S1 with genome accession numbers and all the data of the absence/presence of T3SS2-related components, and Table S2 with the prediction of novel effector proteins are available as part of the online Supporting Dataset at the Zenodo data repository (https://doi.org/10.5281/zenodo.7016552). The T3SS2 phylogenetic tree can be interactively visualized in https://itol.embl. de/tree/19016190125374711626959067#
Landscape configurations determining the genetic structure of the Yellow-Spotted Amazon River Turtle (Podocnemis unifilis) in Brazilian Amazonia

Context Waterfalls and rapids of Amazon basin have been suggested as causing the speciation and genetic structure of many freshwater species, including turtles. The species behavior affects the way waterfalls and rapids limit gene flow. The Yellow-spotted River Turtle (Podocnemis unifilis), a widely distributed and endangered Amazonian turtle, does not show the habit to migrate long distances for breeding or eating, but has a complex geographic pattern of genetic variation. Objectives Here, we investigate isolation by distance and by resistance of P. unifilis. We analyzed if the species ecological niche and waterfalls explain the genetic distance in Brazilian Amazonia. Methods We evaluated the P. unifilis spatial distribution of genetic variability and diversity using the control region of mitochondrial DNA. We tested the hypotheses of isolation either by distance and resistance through an integrative approach using genetic, geographic, and ecological data. We created a resistance matrix using species niche modeling. We compared the explanation power of geographical distance (both linear and in-water distance) and resistance distance on genetic distance (ΦST fixation index) using multiple regressions and Mantel tests. Results We found a high genetic diversity and pattern of genetic structure proved to be geographically complex. The population structure followed some watersheds but also showed structuring within different rivers. We found that landscape resistance better explains genetic distance than linear and in-water distance. Conclusions The resistance of the landscape influences the displacement of individuals by aquatic, vegetational, biological, and geomorphological variables, and efforts to species conservation need to be applied throughout its distribution considering landscape genetics.
Inaccurate fossil placement does not compromise tip-dated divergence times

Time-scaled phylogenies underpin the interrogation of evolutionary processes across deep timescales, as well as attempts to link these to Earth’s history. By inferring the placement of fossils and using their ages as temporal constraints, tip dating under the fossilised-birth death (FBD) process provides a coherent prior on divergence times. At the same time, it also links topological and temporal accuracy, as incorrectly placed fossil terminals should misinform divergence times. This could pose serious issues for obtaining accurate node ages, yet the interaction between topological and temporal error has not been thoroughly explored. We simulate phylogenies and associated morphological datasets using methodologies that incorporate evolution under selection, and are benchmarked against empirical datasets. We find that datasets of moderate sizes (300 characters) and realistic levels of missing data generally succeed in inferring the correct placement of fossils on a constrained extant backbone topology, and that true node ages are usually contained within Bayesian posterior distributions. While increased fossil sampling improves the accuracy of inferred ages, topological and temporal errors do not seem to be linked: analyses in which fossils resolve less accurately do not exhibit elevated errors in node age estimates. At the same time, divergence times are systematically biased, a pattern that stems from a mismatch between the FBD prior and the shape of our simulated trees. While these results are encouraging, suggesting even fossils with uncertain affinities can provide useful temporal information, they also emphasise that paleontological information cannot overturn discrepancies between model priors and the true diversification history.
Dispersal inference from population genetic variation using a convolutional neural network

The geographic nature of biological dispersal shapes patterns of genetic variation over landscapes, making it possible to infer properties of dispersal from genetic variation data. Here we present an inference tool that uses geographically distributed genotype data in combination with a convolutional neural network to estimate a critical population parameter: the mean per-generation dispersal distance. Using extensive simulation, we show that our deep learning approach is competitive with or outperforms state-of-the-art methods, particularly at small sample sizes. In addition, we evaluate varying nuisance parameters during training—including population density, demographic history, habitat size, and sampling area—and show that this strategy is effective for estimating dispersal distance when other model parameters are unknown. Whereas competing methods depend on information about local population density or accurate identification of identity-by-descent tracts, our method uses only single-nucleotide-polymorphism data and the spatial scale of sampling as input. Strikingly, and unlike other methods, our method does not use the geographic coordinates of the genotyped individuals. These features make our method, which we call “disperseNN”, a potentially valuable new tool for estimating dispersal distance in non-model systems with whole genome data or reduced representation data. We apply disperseNN to 12 different species with publicly available data, yielding reasonable estimates for most species. Importantly, our method estimated consistently larger dispersal distances than mark-recapture calculations in the same species, which may be due to the limited geographic sampling area covered by some mark-recapture studies. Thus genetic tools like ours complement direct methods for improving our understanding of dispersal.
Data Fusion by Matrix Completion for Exposome Target Interaction Prediction

Human exposure to toxic chemicals presents a huge health burden and disease risk. Key to understanding chemical toxicity is knowledge of the molecular target(s) of the chemicals. Because a comprehensive safety assessment for all chemicals is infeasible due to limited resources, a robust computational method for discovering targets of environmental exposures is a promising direction for public health research. In this study, we implemented a novel matrix completion algorithm named coupled matrix-matrix completion (CMMC) for predicting exposome-target interactions, which exploits the vast amount of accumulated data regarding chemical exposures and their molecular targets. Our approach achieved an AUC of 0.89 on a benchmark dataset generated using data from the Comparative Toxicogenomics Database. Our case study with bisphenol A (BPA) and its analogues shows that CMMC can be used to accurately predict molecular targets of novel chemicals without any prior bioactivity knowledge. Overall, our results demonstrate the feasibility and promise of computational predicting environmental chemical-target interactions to efficiently prioritize chemicals for further study.
CLINICAL AND LABORATORY STUDIES ON EMACIATION AND ILL-THRIFTINESS IN CATTLE AT ASWAN GOVERNORATE

Cattle has an economic importance in Aswan governorate, hence it considered the main source of income for most farmers. Emaciation in cattle was the main complain mentioned by many cattle breeders. The aim of the present work is to evaluate the relation between emaciation as a clinical sign and the haematological and biochemical parameters in blood serum of cattle. 160 emaciated Cows, 1- > 5 years old and 20 clinically healthy cows selected from 19 villages at Edfu district constitute the basis of this work. The clinical examination of emaciated cows revealed poor body condition, debility, alopecia, rough dry hair coat and pale mucous membrane. Faecal examination of the emaciated cows revealed the presence of fasciola gigantica (8 2cases), paramhistomum cervi (13 cases), eggs and/or larvae of gastrointestinal nematodes (56 cases). All values of total erythrocytes count, haemogloloin, packed cells volume and total leucocytes count were decreased in all emaciated cows at all ages. Marked drop in values of these parameters were recorded in parasitic emaciated cases. Marked drop with slight variations in the values of blood serum Ca, P, Mg, Cu and Zn was recorded in all emaciated animals whether parasitic or non-parasitic (infested). Significant decrease in total serum protein and albumin was recorded in the emaciated cows. Marked rise in blood serum values of AST and ALT in animals with emaciation irrespective of ages or parasitic infestation, was noticed.
Edinburgh Research Explorer Caveat Venditor - Crowded Exits!

Crowded exits arise in stocks where short-sellers hold large positions relative to normal trading volume, and when a catalyst prompts short-sellers to cover their positions rapidly and simultaneously. The temporary excess of demand for stock relative to normal trading volume leads to upward pressure on the stock price. Using a commercial stock lending database for up to 681 stocks listed on the London Stock Exchange from 1 st Sep 2003 to 31 st May 2007, we find that crowded exits are associated with positive abnormal returns of up to 27% over a period of 60 days. This result is both statistically and economically significant. New, long-only investors would generally find it difficult to exploit this finding by buying into crowded exits, as by definition these are illiquid positions; however, incumbent short-sellers, unable to readily cover their positions, suffer losses. We infer that short-sellers thus face an important indirect constraint on short-selling in the form of crowded exits.
Accounting flexibility and managers' forecast behavior prior to seasoned equity offerings

This study examines the effect of accounting flexibility on managers’ forecasting behavior prior to seasoned equity offerings (SEOs). Although SEO firms have a strong incentive to convey optimistic information to boost the pre-SEO stock price, they also face enhanced litigation risk arising from SEO-related regulations. Thus, I hypothesize that managers will release positive news through their forecasts (relative to the prevailing analyst consensus) prior to an SEO only if they have the accounting flexibility to manage subsequent reported earnings to meet or exceed their forecasts. I find that managers with greater accounting flexibility are more likely to issue a forecast prior to the SEO and that their forecasts are more likely to convey positive news and are more specific. Furthermore, I find no effect of accounting flexibility for non-SEO control firms or for non-SEO periods. My results suggest that when managers experience a tension between the incentive for voluntary disclosure and high litigation risk, accounting flexibility is an important factor that determines their forecasting behavior. JEL classification: M41; G32; G14
Supplementary Online Materials for Computational and Neurobiological Foundations of Leadership Decisions

Decisions as diverse as committing soldiers to the battlefield or picking a school for your child share a basic attribute: assuming responsibility for the outcome of others. This responsibility is inherent in the roles of prime ministers and generals, as well as in the more quotidian roles of firmmanagers, schoolteachers, and parents. Here we identify the underlying behavioral, computational, and neurobiologicalmechanisms that determine the choice to assume responsibility over others. Leaders must take responsibility for others and affect the well-being of individuals, organizations, and nations. We identify the effects of responsibility on leaders’ choices at the behavioral and neurobiological level and document the widespread existence of responsibility aversion, i.e., a reduced willingness to make decisions if the welfare of others is at stake. In mechanistic terms, basic preferences towards risk, losses and ambiguity do not explain responsibility aversion which, instead, is driven by a second-order cognitive process reflecting an increased demand for certainty about the best choice when others’ welfare is affected. Finally, models estimating levels of information flow between brain regions processing separate choice components, provide the first step in understanding the neurobiological basis of individual variability in responsibility aversion and leadership scores. We identify and characterize the computations and neural mechanisms underlying choices to lead. DOI: https://doi.org/10.1126/science.aat0036 Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-153022 Journal Article Accepted Version Originally published at: Edelson, Micah G; Polania, Rafael; Ruff, Christian C; Fehr, Ernst; Hare, Todd A (2018). Computational and neurobiological foundations of leadership decisions. Science, 361(6401):online. DOI: https://doi.org/10.1126/science.aat0036
Is physician online information sharing always beneficial to patient education? An attention perspective

Aims With the development of information technology, online health platforms and physician online information sharing play an important role in public health management and patient education. Is physician online information sharing always beneficial to patient education? From the attention perspective, this study aims to explore how physician online information sharing influences patient education, considering the contingent roles of physician online reputation and offline expertise. Methods A 6-month panel data of 61,566 physician-month observations from an online health platform in China was used to tested the proposed hypotheses. Considering the inefficiency and estimated bias of the ordinary least squares regression model, this study conducted the fixed models to test the direct and moderating effects. Results The results indicate that physician online information sharing is positively related to potential patient education, while the relationship between physician online information sharing and realized patient education is an inverted U-shape. Physician online reputation enhances the positive relationship between physician online information sharing and potential patient education, but physician offline expertise weakens the abovementioned relationship. In addition, physician offline expertise flattens the curvilinear effect of physician online information sharing on realized patient education. Conclusion This study contributes to the literature about attention theory and information sharing for patient education, and provides implications for practice.
How does mindfulness relate to benign/malicious envy? The mediating role of resilience, internal locus of control and self-esteem

The present study aimed to explore the roles of resilience, internal locus of control, and self-esteem in the link between mindfulness and benign/malicious envy (BE/ME). Nine hundred ninety-one participants (299 males, 692 females; mean age = 19.05 ± 1.54) completed a survey that assessed mindfulness, internal locus of control, resilience, self-esteem, and BE/ME. The results suggest that resilience, internal locus of control, and self-esteem independently mediate the relationship between mindfulness and BE/ME. Additionally, “internal locus of control → resilience” and “self-esteem → resilience” play chain mediating roles in the relationship between mindfulness and BE/ME. Namely, mindfulness is positively associated with resilience via improving internal control and self-esteem, thereby inhibiting malicious envy and promoting benign envy. The present study advances our knowledge of the mindfulness reperceiving theory, and thus provides a new explanation for the inhibition of negative emotions from the perspective of resilience, internal locus of control, and self-esteem.