Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic Diversity and Signatures of Selection for Thermal Stress in Cattle and Other Two Bos Species Adapted to Divergent Climatic Conditions

Understanding the biological mechanisms of climatic adaptation is of paramount importance for the optimization of breeding programs and conservation of genetic resources. The aim of this study was to investigate genetic diversity and unravel genomic regions potentially under selection for heat and/or cold tolerance in thirty-two worldwide cattle breeds, with a focus on Chinese local cattle breeds adapted to divergent climatic conditions, Datong yak (Bos grunniens; YAK), and Bali (Bos javanicus) based on dense SNP data. In general, moderate genetic diversity levels were observed in most cattle populations. The proportion of polymorphic SNP ranged from 0.197 (YAK) to 0.992 (Mongolian cattle). Observed and expected heterozygosity ranged from 0.023 (YAK) to 0.366 (Sanhe cattle; SH), and from 0.021 (YAK) to 0.358 (SH), respectively. The overall average inbreeding (±SD) was: 0.118 ± 0.028, 0.228 ± 0.059, 0.194 ± 0.041, and 0.021 ± 0.004 based on the observed versus expected number of homozygous genotypes, excess of homozygosity, correlation between uniting gametes, and runs of homozygosity (ROH), respectively. Signatures of selection based on multiple scenarios and methods (FST, HapFLK, and ROH) revealed important genomic regions and candidate genes. The candidate genes identified are related to various biological processes and pathways such as heat-shock proteins, oxygen transport, anatomical traits, mitochondrial DNA maintenance, metabolic activity, feed intake, carcass conformation, fertility, and reproduction. This highlights the large number of biological processes involved in thermal tolerance and thus, the polygenic nature of climatic resilience. A comprehensive description of genetic diversity measures in Chinese cattle and YAK was carried out and compared to 24 worldwide cattle breeds to avoid potential biases. Numerous genomic regions under positive selection were detected using three signature of selection methods and candidate genes potentially under positive selection were identified. Enriched function analyses pinpointed important biological pathways, molecular function and cellular components, which contribute to a better understanding of the biological mechanisms underlying thermal tolerance in cattle. Based on the large number of genomic regions identified, thermal tolerance has a complex polygenic inheritance nature, which was expected considering the various mechanisms involved in thermal stress response.
Combination of Genome-Wide Association Study and QTL Mapping Reveals the Genetic Architecture of Fusarium Stalk Rot in Maize

Stalk rot causes significant yield loss in maize worldwide. The breeding of resistant variety is a potential way to effectively control the disease. This study aims to dissect resistance genes for maize stalk rot caused by Fusarium graminearum using an integrated gene mapping method. A diversity panel of 165 inbred lines and an F2 population from the hybridization of CDMA66 and Huangzao 4 were used as materials. The 165 inbred lines were clustered into four subgroups, of which tropical materials are in the majority. Through combining disease severity index (DSI) and single nucleotide polymorphisms (SNPs) of Maize 50K chip and 20K, genome-wide association analysis (GWAS) revealed 34 SNPs that were significantly associated with stalk rot in maize (P < 0.001). These SNPs were distributed on chromosomes 1, 3, 4, 6, 8, and 10, of which the loci on chromosomes 4 and 8 were confirmed by the mapped QTLs for stalk rot. Finally, candidate genes were identified including GRMZM2G082709 which encoded NAC domain-containing protein and thioredoxin reductase (GRMZM5G841142). However, LRR receptor-like serine/threonine-protein kinase (GRMZM2G080041) was down-regulated after inoculation. These SNPs and candidate genes identified would provide essential information for resistant gene cloning and molecular breeding of anti-stalk rot variety in maize.
What Do I Talk About When I Talk About Smart Contracts? Open Challenges in Smart Contracts

Contracts regulate most of our professional and personal life: they enable modern society to operate. The term “Smart Contract,” coined in 1994 by Nick Szabo, means different things to different people. This editorial perspective explores the meanings of the term “smart contract” and the challenges about the legality of “smart contracts. ” We are familiar with contracts written in natural language, yet our relationships with smart contracts is yet to be defined. The advent of blockchain technology seems to have accelerated the development and the opportunities for the adoption of smart contracts. The purpose of this editorial is to create an interdisciplinary section where computer scientists and members of the legal profession participate in a constructive debate around smart contracts to positively influence future development.
Word Entropy-Based Approach to Detect Highly Variable Genetic Markers for Bacterial Genotyping

Genotyping methods are used to distinguish bacterial strains from one species. Thus, distinguishing bacterial strains on a global scale, between countries or local districts in one country is possible. However, the highly selected bacterial populations (e.g., local populations in hospital) are typically closely related and low diversified. Therefore, currently used typing methods are not able to distinguish individual strains from each other. Here, we present a novel pipeline to detect highly variable genetic segments for genotyping a closely related bacterial population. The method is based on a degree of disorder in analyzed sequences that can be represented by sequence entropy. With the identified variable sequences, it is possible to find out transmission routes and sources of highly virulent and multiresistant strains. The proposed method can be used for any bacterial population, and due to its whole genome range, also non-coding regions are examined.
In-game Social Interaction and Gaming Disorder: A Perspective From Online Social Capital

Background and Aims: Social interaction in the online games has been found to predict gaming disorder, but little research has examined the mechanism of this association. Drawing on the social capital theory, the present study investigated the mediating role of online social capital on the relationship between in-game social interaction and gaming disorder and the moderating role of alienation on the relationship between online social capital and gaming disorder. Methods: A sample of 457 Chinese massively multiplayer online role-playing game gamers was recruited to complete the In-game Social Interaction Questionnaire, Online Social Capital Scale, Alienation Scale, and Pathological Gaming Scale. Results: The results showed that online social capital was a mediator in the relationship between in-game social interaction and gaming disorder. Moreover, for individuals with low alienation, the effect of online social capital on gaming disorder was weaker than for those with high alienation. Conclusions: The present study provides new insight into the complex processes involved in the effect of in-game social interaction on gaming disorder, and the results have important theoretical and practical implications.
Phenotypic Resemblance to Neuropsychiatric Disorder and Altered mRNA Profiles in Cortex and Hippocampus Underlying IL15Rα Knockout

Background Previous studies of the functions of IL15Rα have been limited to immune activities and skeletal muscle development. Immunological factors have been identified as one of the multiple causes of psychosis, and neurological symptoms have been described in IL15Rα knockout (KO) mice. Seeking to explore possible mechanisms for this in the IL15Rα–/– mouse brain, we analyzed gene expression patterns in the cortex and hippocampus using the RNA-seq technique. Methods IL15Rα KO mice were generated and littermate wildtype (WT) mice were used as a control group. A Y-maze was used to assess behavior differences between the two groups. The cortex and hippocampus of 3-month-old male mice were prepared and RNA-seq and transcriptome analysis were performed by gene set enrichment analysis (GSEA). Results Compared with the WT group, IL15Rα KO animals showed higher speed in the novel arm and more entrance frequency in the old arm in the Y-maze experiment. GSEA indicated that 18 pathways were downregulated and 13 pathways upregulated in both cortex and hippocampus from the GO, KEGG, and Hallmark gene sets. The downregulated pathways formed three clusters: respiratory chain and electron transport, regulation of steroid process, and skeletal muscle development. Conclusion IL15Rα KO mice exhibit altered expression of multiple pathways, which could affect many functions of the brain. Lipid biosynthesis and metabolism in the central nervous system (CNS) should be investigated to provide insights into the effect of IL15Rα on psychosis in this murine model.
Do Conceptual Innovations Facilitate Transformative Change? The Case of Biodiversity Governance

This paper explores to what extent and in what ways conceptual innovations matter for biodiversity governance. A three-step analysis is employed, starting with identifying theoretical insights on how concepts matter for transformative change. These insights provide a lens for examining the academic debate on the Ecosystem Services concept and for identifying critical conceptual challenges related to transformative change. Finally, how the concept is used and valued in policy practice is explored through an empirical study of policy practitioners in Sweden. Based on this investigation we conclude that the ES concept holds important but restricted properties for transformative change. The ES concept provides new meanings in the form of economic valuation of nature, but these remain highly contested and difficult to practice; ES function as a boundary object, but poorly integrates social analysis and, in practice engages professionals, rather than resulting in more inclusive public participation; and ES function performatively by reflecting a technocratic ideal and raising awareness rather than targeting fundamental political challenges. Finally, the paper returns to the general questions of how conceptual innovations can generate transformative change and argues that in the continued work of conceptually developing the Nature's Contribution to People, researchers and practitioners need to pay close attention to interpretive frames, political dimensions, and institutional structures, necessitating a strong role for social analysis in this process of conceptual innovation.
Convective drying of medicinal, aromatic and spice plants: a review

Purpose of review: Convective drying with hot air is the most common way to preserve medicinal and aromatic plants. The choice of the optimal drying air temperature is a central economic and ecological criterion. This review compiles experimental studies in terms of models for drying kinetics and losses of active ingredients during drying at different drying conditions. Main findings: Most experimental studies focused on species with essential oils as active ingredients, revealing increasing essential-oil losses with increasing temperature. However, there are differences in temperature sensitivity between species. To describe drying kinetics in most studies the Page model was used. However, as relative humidity of drying air is commonly neglected in the model, drying kinetics of bulks cannot be described. Directions for future research: Experiments with a range of drying air temperatures have to be performed for further medicinal, aromatic and spice plant species. As common reference for calculating losses of active ingredients the content in fresh material should be analysed. Over-drying has to be prevented in drying experiments and analyses of active ingredients should be repeated after a storage period of several months. Furthermore, bulk models are needed to estimate drying processes that are relevant in practice.
The Shared Use of Extended Phenotypes Increases the Fitness of Simulated Populations

Extended phenotypes are manifestations of genes that occur outside of the organism that possess those genes. In spite of their widespread occurrence, the role of extended phenotypes in evolutionary biology is still a matter of debate. Here, we explore the indirect effects of extended phenotypes, especially their shared use, in the fitness of simulated individuals and populations. A computer simulation platform was developed in which different populations were compared regarding their ability to produce, use, and share extended phenotypes. Our results show that populations that produce and share extended phenotypes outrun populations that only produce them. A specific parameter in the simulations, a bonus for sharing extended phenotypes among conspecifics, has a more significant impact in defining which population will prevail. All these findings strongly support the view, postulated by the extended fitness hypothesis (EFH) that extended phenotypes play a significant role at the population level and their shared use increases population fitness. Our simulation platform is available at https://github.com/guilherme-araujo/gsop-dist.
Modulation of Neuronal Potassium Channels During Auditory Processing

The extraction and localization of an auditory stimulus of interest from among multiple other sounds, as in the ‘cocktail-party’ situation, requires neurons in auditory brainstem nuclei to encode the timing, frequency, and intensity of sounds with high fidelity, and to compare inputs coming from the two cochleae. Accurate localization of sounds requires certain neurons to fire at high rates with high temporal accuracy, a process that depends heavily on their intrinsic electrical properties. Studies have shown that the membrane properties of auditory brainstem neurons, particularly their potassium currents, are not fixed but are modulated in response to changes in the auditory environment. Here, we review work focusing on how such modulation of potassium channels is critical to shaping the firing pattern and accuracy of these neurons. We describe how insights into the role of specific channels have come from human gene mutations that impair localization of sounds in space. We also review how short-term and long-term modulation of these channels maximizes the extraction of auditory information, and how errors in the regulation of these channels contribute to deficits in decoding complex auditory information.
Unraveling the Sclerotinia Basal Stalk Rot Resistance Derived From Wild Helianthus argophyllus Using a High-Density Single Nucleotide Polymorphism Linkage Map

Basal stalk rot (BSR), caused by the fungus Sclerotinia sclerotiorum, is a serious disease of sunflower (Helianthus annuus L.) in the humid temperate growing areas of the world. BSR resistance is quantitative and conditioned by multiple genes. Our objective was to dissect the BSR resistance introduced from the wild annual species Helianthus argophyllus using a quantitative trait loci (QTL) mapping approach. An advanced backcross population (AB-QTL) with 134 lines derived from the cross of HA 89 with a H. argophyllus Torr. and Gray accession, PI 494573, was evaluated for BSR resistance in three field and one greenhouse growing seasons of 2017–2019. Highly significant genetic variations (p < 0.001) were observed for BSR disease incidence (DI) in all field screening tests and disease rating and area under the disease progress curve in the greenhouse. The AB-QTL population and its parental lines were genotyped using the genotyping-by-sequencing method. A genetic linkage map spanning 2,045.14 cM was constructed using 3,110 SNP markers mapped on 17 sunflower chromosomes. A total of 21 QTL associated with BSR resistance were detected on 11 chromosomes, each explaining a phenotypic variation ranging from 4.5 to 22.6%. Of the 21 QTL, eight were detected for BSR DI measured in the field, seven were detected for traits measured in the greenhouse, and six were detected from both field and greenhouse tests. Thirteen of the 21 QTL had favorable alleles from the H. argophyllus parent conferring increased BSR resistance.
Detection of Mycobacterium avium ssp. paratuberculosis in Cultures From Fecal and Tissue Samples Using VOC Analysis and Machine Learning Tools

Analysis of volatile organic compounds (VOCs) is a novel approach to accelerate bacterial culture diagnostics of Mycobacterium avium subsp. paratuberculosis (MAP). In the present study, cultures of fecal and tissue samples from MAP-infected and non-suspect dairy cattle and goats were explored to elucidate the effects of sample matrix and of animal species on VOC emissions during bacterial cultivation and to identify early markers for bacterial growth. The samples were processed following standard laboratory procedures, culture tubes were incubated for different time periods. Headspace volume of the tubes was sampled by needle trap-micro-extraction, and analyzed by gas chromatography-mass spectrometry. Analysis of MAP-specific VOC emissions considered potential characteristic VOC patterns. To address variation of the patterns, a flexible and robust machine learning workflow was set up, based on random forest classifiers, and comprising three steps: variable selection, parameter optimization, and classification. Only a few substances originated either from a certain matrix or could be assigned to one animal species. These additional emissions were not considered informative by the variable selection procedure. Classification accuracy of MAP-positive and negative cultures of bovine feces was 0.98 and of caprine feces 0.88, respectively. Six compounds indicating MAP presence were selected in all four settings (cattle vs. goat, feces vs. tissue): 2-Methyl-1-propanol, 2-methyl-1-butanol, 3-methyl-1-butanol, heptanal, isoprene, and 2-heptanone. Classification accuracies for MAP growth-scores ranged from 0.82 for goat tissue to 0.89 for cattle feces. Misclassification occurred predominantly between related scores. Seventeen compounds indicating MAP growth were selected in all four settings, including the 6 compounds indicating MAP presence. The concentration levels of 2,3,5-trimethylfuran, 2-pentylfuran, 1-propanol, and 1-hexanol were indicative for MAP cultures before visible growth was apparent. Thus, very accurate classification of the VOC samples was achieved and the potential of VOC analysis to detect bacterial growth before colonies become visible was confirmed. These results indicate that diagnosis of paratuberculosis can be optimized by monitoring VOC emissions of bacterial cultures. Further validation studies are needed to increase the robustness of indicative VOC patterns for early MAP growth as a pre-requisite for the development of VOC-based diagnostic analysis systems.
Cytotoxic and Pro-Apoptotic Effects of a Sub-Toxic Concentration of Fluvastatin on OVCAR3 Ovarian Cancer Cells After its Optimized Formulation to Melittin Nano-Conjugates

Fluvastatin (FLV) is a hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor often used to lower total and low-density lipoprotein (LDL) cholesterol and for the prevention of adverse cardiovascular events. This drug as well as melittin (MEL), the major component of honeybee venom (Apis mellifera), has shown antineoplastic activity, then representing promising approaches for cancer therapy. However, adverse effects related to the use of FLV and MEL have been reported and very few studies have been carried out to obtain an optimized formulation allowing for combining the two drugs and then maximizing the anticancer activity, then minimizing the needed dosage. In the present study, an optimized formulation in terms of minimized particle size and maximized zeta potential was investigated for its cytotoxic potential in human OVCAR3 ovarian cancer cells. FLV-MEL nano-conjugates, containing a sub-toxic concentration of drug, demonstrated an improved cytotoxic potential (IC50 = 2.5 µM), about 18-fold lower, compared to the free drug (IC50 = 45.7 µM). Cell cycle analysis studies demonstrated the significant inhibition of the OVCAR3 cells proliferation exerted by FLV-MEL nano-conjugates compared to all the other treatments, with a higher percentage of cells accumulating on G2/M and pre-G1 phases, paralleled by lower percentage of cells in G0/G1 and S phases. The synergistic antineoplastic activity of FLV and MEL combined in the optimized formula was also showed by the marked pronecrotic and pro-apoptotic activities, the latter mediated by the modulation of BAX/BCL-2 ratio in favor of BAX. Our optimized FLV-MEL formulation might therefore represents a novel path for the development of specific and more effective antineoplastic drugs directed against ovarian cancer.
Predicting cross-tissue hormone–gene relations using balanced word embeddings

Motivation Large volumes of biomedical literature present an opportunity to build whole-body human models comprising both within-tissue and across-tissue interactions among genes. Current studies have mostly focused on identifying within-tissue or tissue-agnostic associations, with a heavy emphasis on associations among disease, genes and drugs. Literature mining studies that extract relations pertaining to inter-tissue communication, such as between genes and hormones, are solely missing. Results We present here a first study to identify from literature the genes involved in inter-tissue signaling via a hormone in the human body. Our models BioEmbedS and BioEmbedS-TS respectively predict if a hormone-gene pair is associated or not, and whether an associated gene is involved in the hormone’s production or response. Our models are classifiers trained on word embeddings that we had carefully balanced across different strata of the training data such as across production vs. response genes of a hormone (or) well-studied vs. poorly-represented hormones in the literature. Model training and evaluation are enabled by a unified dataset called HGv1 of ground-truth associations between genes and known endocrine hormones that we had compiled. Our models not only recapitulate known gene mediators of tissue-tissue signaling (e.g., at average 70.4% accuracy for BioEmbedS), but also predicts novel genes involved in inter-tissue communication in humans. Furthermore, the species-agnostic nature of our ground-truth HGv1 data and our predictive modeling approach, demonstrated concretely using human data and generalized to mouse, hold much promise for future work on elucidating inter-tissue signaling in other multi-cellular organisms. Availability Proposed HGv1 dataset along with our models’ predictions, and the associated code to reproduce this work are available respectively at https://cross-tissue-signaling.herokuapp. com/, and https://github.com/BIRDSgroup/BioEmbedS. Contact nmanik@cse.iitm. ac.in