Miracle-dz/UniFAR-FTUs huggingface dataset:
Detecting selection with a genetic cross

Significance Natural selection is the force that underlies the spectacular adaptations of all organisms to their environments. However, not all traits are under selection; a key question is which traits have been shaped by selection, as opposed to the random drift of neutral traits. Here, I develop a test of selection on quantitative traits that can be applied to almost any genetic cross between divergent populations or species. The test is robust to a wide range of potential confounders and has greater power to detect selection than existing tests. Applied to empirical data, the test reveals widespread selection in both domesticated and wild species, allowing selection to be detected more easily and powerfully than previously possible. Distinguishing which traits have evolved under natural selection, as opposed to neutral evolution, is a major goal of evolutionary biology. Several tests have been proposed to accomplish this, but these either rely on false assumptions or suffer from low power. Here, I introduce an approach to detecting selection that makes minimal assumptions and only requires phenotypic data from ∼10 individuals. The test compares the phenotypic difference between two populations to what would be expected by chance under neutral evolution, which can be estimated from the phenotypic distribution of an F2 cross between those populations. Simulations show that the test is robust to variation in the number of loci affecting the trait, the distribution of locus effect sizes, heritability, dominance, and epistasis. Comparing its performance to the QTL sign test—an existing test of selection that requires both genotype and phenotype data—the new test achieves comparable power with 50- to 100-fold fewer individuals (and no genotype data). Applying the test to empirical data spanning over a century shows strong directional selection in many crops, as well as on naturally selected traits such as head shape in Hawaiian Drosophila and skin color in humans. Applied to gene expression data, the test reveals that the strength of stabilizing selection acting on mRNA levels in a species is strongly associated with that species’ effective population size. In sum, this test is applicable to phenotypic data from almost any genetic cross, allowing selection to be detected more easily and powerfully than previously possible.
Description of Bacillus thuringiensis wratislaviensis (H‐47), a new serotype originating from WrocŁaw (Poland), and other soil isolates from the same area

Twenty‐four Bacillus thuringienis (Bt) strains were isolated and examined in respect of serotype, plasmid content crystal‐composing proteins and insecticidal activity. Strains PO1–PO11 and PO14–PO15 were recognized as B. thuringiensis kurstaki H3a3b3c. The strains PO12 and PO13 were found to share a common novel antigen determining the new serotype H‐47, and were designated as serovar wratislaviensis. Further investigations showed that all strains carried multiple plasmids (for example six different large plasmids in PO12 strain) and formed crystals composed of either two proteins, 135·8 kDa and 66·2 kDa (strains PO1–PO11 and PO14–PO24), or on protein, 66·2 kDa (strains PO12 and PO13). Preliminary toxicity tests with crude suspensions of spores and crystals showed rather low activity (<50% mortality) against fruitfly larvae and nymphs of cockroaches and high toxic effects (up to 90% mortality) against house fly larvae.
Growth and Yield Performance of Jerusalem Artichoke Clones in a Semiarid Region of China

This study investigated biomass yield and growth characteristics of 26 Jerusalem artichoke (Helianthus tuberosus L.) clones and assessed it as a bioenergy crop for a semiarid region of the Loess Plateau in China. Genotype, year, and genotype ´ year interaction contributed to differences in crop development, growth characteristics, and biomass yields (dry matter). Generally, biomass yields in 2011 were lower than in 2008, mainly due to a more severe soil moisture deficit in 2011. Shoot and tuber biomass yields (STBY) ranged from 18.9 to 35.0 Mg ha–1 in 2008 and from 16.1 to 24.8 Mg ha–1 in 2011. Clones HUB-2 and BJ-4 produced the highest shoot biomass yield (SBY), amounting to 31.3 and 25.6 Mg ha–1, respectively, in the wetter year but higher drought sensitivity. Clones HUN-2, SD-2, and SHH-1 produced the second highest SBY, which varied between 14.3 and 20.1 Mg ha–1. Clones GZ-1, HEN-1, HUB-1, IM-1, and SX-2 are recommended for tuber production and produced tuber yields >8 Mg ha–1 in both seasons. Clones SD-2 and SHH-1 exhibited drought sensitivity indices
Trends and determinants of prelacteal feeding in Turkey: analysis of 2003–2018 demographic and health surveys

Abstract Objective: The aim of the current study is to analyse the trends, determinants of prelacteal feeding (PLF) and its relations with the mode of delivery among infants <24 months over the years 2003–2018. Design: We pooled data from Turkey Demographic and Health Surveys (TDHS). The key outcome variable was PLF. Factors associated with PLF were analysed by using complex sample multiple logistic regression analysis, separately and merged database. Setting: TDHS in 2003, 2008, 2013 and 2018. Participants: Mother–infant dyads (n 4942). Results: PLF rates fluctuated between 29·3 and 41·4 %. The most common types of PLF were infant formula (61·1 %) followed by sugar/glucose water (24·9 %) and plain water (9·3 %). PLF rate was 1·51 times higher (95 % CI 1·28, 1·78) in cases delivered by caesarean section as compared with those delivered by vaginal route. According to the initiation time of breast-feeding after delivery, the most significant absolute change in PLF rate was observed within 1 h (10·9 % increase). Delayed initiation of breast-feeding was associated with significantly higher odds of PLF compared with the first hour (1 to < 2 h: adjusted OR (AOR) 1·29, 95 % CI 1·04, 1·61; 2–23 h: AOR 1·73, 95 % CI 1·42, 2·11; ≥24 h: AOR 11·37, 95 % CI 8·81, 14·69). Conclusions: To eliminate suboptimal breast-feeding practices, counselling on breast-feeding and delivery type during antenatal visits, postnatal breast-feeding support and social support should be provided to all mothers and families.
Mechanotransduction and Stiffness-Sensing: Mechanisms and Opportunities to Control Multiple Molecular Aspects of Cell Phenotype as a Design Cornerstone of Cell-Instructive Biomaterials for Articular Cartilage Repair

Since material stiffness controls many cell functions, we reviewed the currently available knowledge on stiffness sensing and elucidated what is known in the context of clinical and experimental articular cartilage (AC) repair. Remarkably, no stiffness information on the various biomaterials for clinical AC repair was accessible. Using mRNA expression profiles and morphology as surrogate markers of stiffness-related effects, we deduced that the various clinically available biomaterials control chondrocyte (CH) phenotype well, but not to equal extents, and only in non-degenerative settings. Ample evidence demonstrates that multiple molecular aspects of CH and mesenchymal stromal cell (MSC) phenotype are susceptible to material stiffness, because proliferation, migration, lineage determination, shape, cytoskeletal properties, expression profiles, cell surface receptor composition, integrin subunit expression, and nuclear shape and composition of CHs and/or MSCs are stiffness-regulated. Moreover, material stiffness modulates MSC immuno-modulatory and angiogenic properties, transforming growth factor beta 1 (TGF-β1)-induced lineage determination, and CH re-differentiation/de-differentiation, collagen type II fragment production, and TGF-β1- and interleukin 1 beta (IL-1β)-induced changes in cell stiffness and traction force. We then integrated the available molecular signaling data into a stiffness-regulated CH phenotype model. Overall, we recommend using material stiffness for controlling cell phenotype, as this would be a promising design cornerstone for novel future-oriented, cell-instructive biomaterials for clinical high-quality AC repair tissue.
Adversarial Recurrent Time Series Imputation

For the real-world time series analysis, data missing is a ubiquitously existing problem due to anomalies during data collecting and storage. If not treated properly, this problem will seriously hinder the classification, regression, or related tasks. Existing methods for time series imputation either impose too strong assumptions on the distribution of missing data or cannot fully exploit, even simply ignore, the informative temporal dependencies and feature correlations across different time steps. In this article, inspired by the idea of conditional generative adversarial networks, we propose a generative adversarial learning framework for time series imputation under the condition of observed data (as well as the labels, if possible). In our model, we employ a modified bidirectional RNN structure as the generator G, which is aimed at generating the missing values by taking advantage of the temporal and nontemporal information extracted from the observed time series. The discriminator D is designed to distinguish whether each value in a time series is generated or not so that it can help the generator to make an adjustment toward a more authentic imputation result. For an empirical verification of our model, we conduct imputation and classification experiments on several real-world time series data sets. The experimental results show an eminent improvement compared with state-of-the-art baseline models.
Transcription factor CncC potentially regulates the expression of multiple detoxification genes that mediate indoxacarb resistance in Spodoptera litura

The xenobiotic transcription factor cap ‘n’ collar isoform C (CncC) is considered the central regulator of antioxidant and detoxification genes. Previous research indicated that CncC regulates three‐phase enzymes responsible for insecticide resistance. In this study, the SlituCncC gene from Spodoptera litura was obtained and characterized. Quantitative polymerase chain reaction (qPCR) analysis showed that SlituCncC was expressed in all developmental stages and tissues, but was highly expressed in 3rd‐ and 4th‐instar larvae, and in the Malpighian tubule, fat body, and midgut. In addition, SlituCncC was up‐regulated and more highly induced with indoxacarb treatment in the indoxacarb‐resistant strains compared with the susceptible strain. RNA interference‐mediated gene silencing of SlituCncC significantly increased mortality of S. litura when exposed to indoxacarb. Furthermore, comparative transcriptome analysis showed that 842 genes were down‐regulated and 127 genes were up‐regulated in SlituCncC knockdown S. litura. Further analysis indicated that 18 three‐phase enzymes were identified in the down‐regulated genes, of which seven were associated with indoxacarb resistance in S. litura. qPCR analysis confirmed that expression of six of these seven genes was consistent with RNA sequencing data. All six detoxification genes were induced by indoxacarb, and the expression patterns were similar to that of SlituCncC. Finally, the CncC–Maf binding site was predicted in all six gene promoters. This study indicates that the transcription factor SlituCncC may regulate multiple detoxification genes that mediate indoxacarb resistance in S. litura.
Gap junctions amplify TRPV4 activation-initiated cell injury via modification of intracellular Ca2+ and Ca2+-dependent regulation of TXNIP

ABSTRACT The elevated intracellular Ca2+ and oxidative stress are well-reported mechanisms behind renal tubular epithelial injury initiated by various insults. Given that TRPV4 and connexin43 (Cx43) channels are activated by a wide range of stimuli and regulate both intracellular Ca2+ and redox status, we speculated an involvement of these channels in renal tubular cell injury. Here, we tested this possibility and explored the potential underlying mechanisms. Our results demonstrated that exposure of renal tubular epithelial cells to aminoglycoside G418 led to cell death, which was attenuated by both TRPV4 and gap junction (Gj) inhibitor. Activation of TRPV4 caused cell damage, which was associated with an early increase in Cx43 expression and function. Inhibition of Cx43 with chemical inhibitor or siRNA largely prevented TRPV4 activation-induced cell damage. Further analysis revealed that TRPV4 agonists elicited a rise in intracellular Ca2+ and caused a Ca2+-dependent elevation in TXNIP (a negative regulator of the antioxidant thioredoxin). In the presence of Gj inhibitor, however, these effects of TRPV4 were largely prevented. The depletion of intracellular Ca2+ with Ca2+ chelator BAPTA-AM or downregulation of TXNIP with siRNA significantly alleviated TRPV4 activation-initiated cell injury. Collectively, our results point to a critical involvement of TRPV4/Cx43 channel interaction in renal tubular cell injury through mechanisms involving a synergetic induction of intracellular Ca2+ and oxidative stress. Channel interactions could be an important mechanism underlying cell injury. Targeting channels could have therapeutic potential for the treatment of acute tubular cell injury.
Pattern in the Root Epidermis: An Interplay of Diffusible Signals and Cellular Geometry

Abstract The epidermis of roots is composed of hair and non-hair cells. Patterning of this epidermis results from spatially regulated differentiation of these cell types. Root epidermal development in vascular plants may be divided into three broad groups based on the mode of hair development; Type 1: any cell in the epidermis can form a root hair; Type 2: the smaller product of an asymmetric cell division forms a root hair; Type 3: the epidermis is organized into discrete files of hair and non-hair cells. The Arabidopsis root epidermis is composed of discrete files of hair and non-hair cells (Type 3). Genetic and physiological evidence indicates that ethylene is a positive regulator of hair cell development. Genes with opposite roles in the development of hair cells in the shoot (trichomes) and hair cells in the root have been identified. Plants with presumptive loss of function alleles in the TRANSPARENT TESTA GLABRA (TTG) or GLABRA2 ( GL2 ) genes are devoid of trichomes indicating that these genes are positive regulators of trichome development. The development of supernumerary root hair cells in these mutant backgrounds illustrates that these genes are also negative regulators of root hair cell development. A model that explains the spatial pattern of epidermal cell differentiation implicates ethylene or its precursor 1-amino-1-cyclopropane carboxylate as a diffusible signal. Possible roles for the TTG and GL2 genes in relation to the ethylene signal are discussed.
β3, a novel auxiliary subunit for the voltage‐gated sodium channel, is expressed preferentially in sensory neurons and is upregulated in the chronic constriction injury model of neuropathic pain

Adult dorsal root ganglia (DRG) have been shown to express a wide range of voltage‐gated sodium channel α‐subunits. However, of the auxiliary subunits, β1 is expressed preferentially in only large‐ and medium‐diameter neurons of the DRG while β2 is absent in all DRG cells. In view of this, we have compared the distribution of β1 in rat DRG and spinal cord with a novel, recently cloned β1‐like subunit, β3. In situ hybridization studies demonstrated high levels of β3 mRNA in small‐diameter c‐fibres, while β1 mRNA was virtually absent in these cell types but was expressed in 100% of large‐diameter neurons. In the spinal cord, β3 transcript was present specifically in layers I/II (substantia gelatinosa) and layer X, while β1 mRNA was expressed in all laminae throughout the grey matter. Since the pattern of β3 expression in DRG appears to correlate with the TTX‐resistant voltage‐gated sodium channel subunit PN3, we co‐expressed the two subunits in Xenopus oocytes. In this system, β3 caused a 5‐mV hyperpolarizing shift in the threshold of activation of PN3, and a threefold increase in the peak current amplitude when compared with PN3 expressed alone. On the basis of these results, we examined the expression of β‐subunits in the chronic constriction injury model of neuropathic pain. Results revealed a significant increase in β3 mRNA expression in small‐diameter sensory neurons of the ipsilateral DRG. These results show that β3 is the dominant auxiliary sodium channel subunit in small‐diameter neurons of the rat DRG and that it is significantly upregulated in a model of neuropathic pain.
In vitro Approaches to Extending the Host-range of Agrobacterium for Plant Transformation

Modifications of co-cultivation conditions can lead to successful gene transfer to species once thought beyond the host-range of Agrobacterium, including a number of monocots. Hence, when defining the host-range of Agrobacterium, distinction must be made between host-range for pathogenecity (oncogenicity) and host-range for transformation. Important factors in determining the ability of Agrobacterium to transfer DNA to the plant genome include genetic, physiological and physical components of the bacterium × plant interaction.
Pathogenesis of Osteoarthritis: Risk Factors, Regulatory Pathways in Chondrocytes, and Experimental Models

As the most common chronic degenerative joint disease, osteoarthritis (OA) is the leading cause of pain and physical disability, affecting millions of people worldwide. Mainly characterized by articular cartilage degradation, osteophyte formation, subchondral bone remodeling, and synovial inflammation, OA is a heterogeneous disease that impacts all component tissues of the articular joint organ. Pathological changes, and thus symptoms, vary from person to person, underscoring the critical need of personalized therapies. However, there has only been limited progress towards the prevention and treatment of OA, and there are no approved effective disease-modifying osteoarthritis drugs (DMOADs). Conventional treatments, including non-steroidal anti-inflammatory drugs (NSAIDs) and physical therapy, are still the major remedies to manage the symptoms until the need for total joint replacement. In this review, we provide an update of the known OA risk factors and relevant mechanisms of action. In addition, given that the lack of biologically relevant models to recapitulate human OA pathogenesis represents one of the major roadblocks in developing DMOADs, we discuss current in vivo and in vitro experimental OA models, with special emphasis on recent development and application potential of human cell-derived microphysiological tissue chip platforms.
Group Sparse Joint Non-Negative Matrix Factorization on Orthogonal Subspace for Multi-Modal Imaging Genetics Data Analysis

With the development of multi-model neuroimaging technology and gene detection technology, the efforts of integrating multi-model imaging genetics data to explore the virulence factors of schizophrenia (SZ) are still limited. To address this issue, we propose a novel algorithm called group sparse of joint non-negative matrix factorization on orthogonal subspace (GJNMFO). Our algorithm fuses single nucleotide polymorphism (SNP) data, function magnetic resonance imaging (fMRI) data and epigenetic factors (DNA methylation) by projecting three-model data into a common basis matrix and three different coefficient matrices to identify risk genes, epigenetic factors and abnormal brain regions associated with SZ. Specifically, we introduce orthogonal constraints on the basis matrix to discard unimportant features in the row of coefficient matrices. Since imaging genetics data have rich group information, we draw into group sparse on three coefficient matrices to make the extracted features more accurate. Both the simulated and real Mind Clinical Imaging Consortium (MCIC) datasets are performed to validate our approach. Simulation results show that our algorithm works better than other competing methods. Through the experiments of MCIC datasets, GJNMFO reveals a set of risk genes, epigenetic factors and abnormal brain functional regions, which have been verified to be both statistically and biologically significant.
SSKM_Succ: A Novel Succinylation Sites Prediction Method Incorporating K-Means Clustering With a New Semi-Supervised Learning Algorithm

Protein succinylation is a type of post-translational modification (PTM) that occurs on lysine sites and plays a key role in protein conformation regulation and cellular function control. When training in computational method, it is difficult to designate negative samples because of the uncertainty of non-succinylation lysine sites, and if not handled properly, it may affect the performance of computational models dramatically. Therefore, we propose a new semi-supervised learning method to identify reliable non-succinylation lysine sites as negative samples. This method, named SSKM_Succ, also employs K-means clustering to divide data into 5 clusters. Besides, information of proximal PTMs and three kinds of sequence features (grey pseudo amino acid composition, K-space and position-special amino acid propensity) are utilized to formulate protein. Then, we perform a two-step feature selection to remove redundant features and construct the optimization model for each cluster. Finally, support vector machine is applied to construct a prediction model for each cluster. Promising results are obtained by this method with an accuracy of 80.18 percent for succinylation sites on the independent testing dataset. Meanwhile, we compare the result with other existing tools, and it shows that our method is promising for predicting succinylation sites. Through analysis, we further verify that succinylated protein has potential effects on amino acid degradation and fatty acid metabolism, and speculate that protein succinylation may be closely related to neurodegenerative diseases. The code of SSKM_Succ is available on the web https://github.com/yangyq505/SSKM_Succ. git.
Effect of α-Interferon, 17β-Estradiol, and Tamoxifen on Estrogen Receptor Concentration and Cell Cycle Kinetics of MCF 7 Cells

The interaction of alpha-interferon, 17 beta-estradiol, and tamoxifen on estrogen receptor content, growth fraction, proliferative rate, and total protein synthesis of MCF 7 cells was investigated under culture conditions (minus phenol red and at low concentrations of "stripped" fetal calf serum) allowing for direct stimulation of proliferation by estrogens. Exposure to estradiol alone resulted in a decrease of estrogen receptor content as measured by immunoassay, an increase of the proportion of cells in S phase, and increases in cell proliferation as well as total protein synthesis. alpha-Interferon treatment resulted in cell cycle arrest with reduced proliferation, an increase of estrogen receptor content, but a decrease in the rate of total protein synthesis. Pretreatment with alpha-interferon inhibited the estrogen induced stimulation of cell growth as well as the associated decrease of estrogen receptor content. Tamoxifen treatment resulted in decreased cell proliferation and decrease of estrogen receptor content and of total protein synthesis. These results suggest that the estrogen receptor concentration of MCF 7 cells is growth fraction related. Pretreatment with alpha-interferon enhanced the inhibitory effect of tamoxifen on cell proliferation while preventing the tamoxifen induced reduction of estrogen receptor content. The synergistic effect of alpha-interferon and tamoxifen are most marked following 72 h pretreatment with interferon, when the maximum interferon induced increase of estrogen receptor concentration is evident. The mechanism is thus due probably to an increase of cellular receptor as a ligand for tamoxifen binding and suggests a possible role for the clinical use of interferons combined with tamoxifen.