Miracle-dz/UniFAR-FTUs huggingface dataset:
Genome-wide quantitative trait loci mapping on Verticillium wilt resistance in 300 chromosome segment substitution lines from Gossypium hirsutum × Gossypium barbadense

Cotton Verticillium wilt (VW) is a devastating disease seriously affecting fiber yield and quality, and the most effective and economical prevention measure at present is selection and extension of Gossypium varieties harboring high resistant VW. However, multiple attempts to improve the VW resistance of the most widely cultivated Upland cotton have brought in little significant progress, and it seems necessary and urgent to develop Chromosome segment substitution lines (CSSLs) for merging the superior genes related with high yield and wide adaptation from G. hirsutum and VW resistance and excellent fiber quality from G. barbadense. In this study, 300 CSSLs were chosen from the developed BC5F3:5 CSSLs constructed by G. hirsutum CCRI36 and G. barbadense Hai1 to conduct quantitative trait locus (QTL) mapping on VW resistance, and a total of 53 QTLs relevant to VW disease index (DI) were identified together with the phenotypic data of 2 years investigations in two fields with two replications per year. All the QTLs were distributed on 20 chromosomes with phenotypic variation of 3.74-11.89%, of which 29 stable ones were consistent in at least two environments. Based on Meta-analysis on the 53 QTLs, 43 novel ones were identified, while 10 ones consistent to previously identified QTLs. Meanwhile, 32 QTL hotspot regions were detected, including 15 ones were novel. This study concentrates on QTL identification and screening hotspot region related with VW in the 300 CSSLs, which lay a solid platform not only for revealing the genetic and molecular mechanisms of VW resistance, but also for further fine mapping, gene cloning and molecular designing in breeding program for resistant cotton varieties.
Adhesion-mediated mechanosignaling forces mitohormesis

Mitochondria control eukaryotic cell fate by producing the energy needed to support life and the signals required to execute programmed cell death. The biochemical milieu is known to affect mitochondrial function and contribute to the dysfunctional mitochondrial phenotypes implicated in cancer and the morbidities of ageing. However, the physical characteristics of the extracellular matrix are also altered in cancer and in aging tissues. We demonstrate that cells sense the physical properties of the extracellular matrix and activate a mitochondrial stress response that adaptively tunes mitochondrial function via SLC9A1-dependent ion exchange and HSF1-dependent transcription. Overall, our data indicate that adhesion-mediated mechanosignaling may play an unappreciated role in the altered mitochondrial functions observed in aging and cancer. Graphical Abstract
Sex differences in neural correlates of age-related episodic memory decline

Aging is associated with episodic memory decline and alterations in memory-related brain function. However, it remains unclear if age-related memory decline is associated with similar patterns of brain aging in women and men. Here, we used task fMRI to investigate sex differences in neural correlates of episodic encoding and retrieval of spatial contextual details, and whether the effect of age on memory-related brain function was similar in women compared to men. We obtained fMRI scans in 41 women and 41 men, between the ages of 21 to 76 years, during spatial context encoding and retrieval. We observed no significant sex difference in retrieval accuracy. We conducted a brain-behaviour multivariate PLS analysis of the fMRI data. Both sexes activated dorsal and lateral prefrontal cortex (PFC), inferior parietal cortex (IPC) and left parahippocampal gyrus (PHG) at encoding and this supported subsequent memory performance. There were sex differences in retrieval activity in these same regions, and in lateral occipital-temporal and ventrolateral PFC. In addition, sex differentially impact the effect of age on PFC, IPC, PHG, lateral occipital-temporal and ventrolateral PFC activity. Overall, our findings suggest that the neural correlates of age-related spatial context memory decline differ in women compared to men.
Anti-microbial activity of potential probiotic lactic acid bacteria against Methicillin-Resistant Staphylococcus Aureus (MRSA)

Lactic acid bacteria (LAB)are the essential ingredients in probiotic foods, intestinal microflora, and dairy products able to cope up and exist in diverse environmental ranges. Samples were collected using sterile test tubes and transported to a laboratory in the icebox for further biochemical characterization. Gram test and catalase activity were examined after microscopically distinct colonies were sub-cultured to pure colonies based on standard gram and catalase test protocols. Subsequently, these bacteria were characterized for their ability to grow at various salt concentrations (5%,10%, and15%) and temperature gradients (15°C, 30°C, 45°C). Acid-tolerance was analyzed by growing the colonies in MRS broth adjusted to acidic pH (pH 3) and pH 7.2 (control). Bile tolerance of LAB isolates was assayed by growing in 0.3% bile-supplemented MRS agar. Bile salt hydrolase (BSH) activity was studied by growing 10 μl of the prepared overnight culture on BSH screening media containing MRS agar plate supplemented with bile salts. The LAB isolates were checked for antimicrobial activity by agar well diffusion assay. All isolates found gram-positive, catalase-negative and non-motile, convex elevation and entire margin. All LAB isolates were able to grow at 5-10% Nacl concentration, whereas moderately grow at 10% concentration but rarely grow at 15% Nacl concentration. BCM2, BBM3 and BGM1 record the highest acidic resistance viability percentage 94.9%, 92.7%, and 91.8% respectively. BCM3 has the lowest acidic resistance with a viable percentage of 87.4%. BBM1 records the highest bile tolerance activity whereas BCM2 has the lowest bile tolerance. All isolates were found BSH positive. The study reveals LAB isolates showed a putative probiotic potential. Article highlights LAB are the main ingredients of probiotic products commercially available in the market nowadays. To effectively functioning the host gastrointestinal tract probiotics, need to have certain criteria like acid and bile tolerance this study reveals Acid tolerance activity of LAB isolated from bovine milk Bile tolerance activity of LAB isolated from bovine milk Bile salt hydrolase (BSH) activity of LAB isolates Antimicrobial activity of LAB against MRSA
Leptin Receptors in RIP-Cre25Mgn neurons Mediate Anti-Dyslipidemia Effects of Leptin in Insulin-Deficient Male Mice

Leptin is a potent endocrine hormone produced by adipose tissue and regulates a broad range of metabolism including glucose and lipid metabolism, with and without insulin. It is evident that central leptin signaling can lower hyperglycemia in insulin-deficient rodents via multiple mechanisms including restoration of dyslipidemia. However, the specific neurons that regulate these glucose-lowering and anti-dyslipidemia effects of leptin remain unidentified. Here we report that leptin receptors (LEPRs) in neurons expressing Cre recombinase driven by a short fragment of a promoter region of Ins2 gene (RIP-Cre25Mgn neurons) are required for central leptin signaling to reverse hyperglycemia and dyslipidemia in insulin-deficient mice. Ablation of LEPRs in RIP-Cre25Mgn neurons completely blocks glucose-lowering effects of leptin in insulin-deficient mice. Further investigations reveal that insulin-deficient mice lacking LEPRs in RIP-Cre25Mgn neurons (RIP-CreΔLEPR mice) exhibit greater lipid levels in blood and liver compared to wild-type controls, and that leptin injection into the brain does not suppress dyslipidemia in insulin-deficient RIP-CreΔLEPR mice. Leptin administration into the brain combined with acipimox, which lowers blood lipids by suppressing triglyceride lipase activity, can restore normal glycemia in insulin-deficient RIP-CreΔLEPR mice, suggesting that excess circulating lipids are a driving-force of hyperglycemia in insulin-deficient RIP-CreΔLEPR mice. Collectively, our data demonstrate that LEPRs in RIP-Cre25Mgn neurons significantly contribute to glucose-lowering effects of leptin in an insulin-independent manner by suppression of dyslipidemia.
Controlling the Growth of the Skin Commensal Staphylococcus epidermidis Using d-Alanine Auxotrophy

The skin microbiome is rich in opportunities for novel therapeutics for skin diseases, and synthetic biology offers the advantage of providing novel functionality or therapeutic benefit to live biotherapeutic products. The development of novel bacterial strains whose growth can be controlled without the use of antibiotics or genetic elements conferring antibiotic resistance enables modulation of therapeutic exposure and improves safety. This study presents the design and in vitro evidence of a skin commensal whose growth can be controlled through d-alanine. The basis of this strain will support future clinical studies of this strain in humans. ABSTRACT Using live microbes as therapeutic candidates is a strategy that has gained traction across multiple therapeutic areas. In the skin, commensal microorganisms play a crucial role in maintaining skin barrier function, homeostasis, and cutaneous immunity. Alterations of the homeostatic skin microbiome are associated with a number of skin diseases. Here, we present the design of an engineered commensal organism, Staphylococcus epidermidis, for use as a live biotherapeutic product (LBP) candidate for skin diseases. The development of novel bacterial strains whose growth can be controlled without the use of antibiotics or genetic elements conferring antibiotic resistance enables modulation of therapeutic exposure and improves safety. We therefore constructed an auxotrophic strain of S. epidermidis that requires exogenously supplied d-alanine. The S. epidermidis NRRL B-4268 Δalr1 Δalr2 Δdat strain (SEΔΔΔ) contains deletions of three biosynthetic genes: two alanine racemase genes, alr1 and alr2 (SE1674 and SE1079), and the d-alanine aminotransferase gene, dat (SE1423). These three deletions restricted growth in d-alanine-deficient medium, pooled human blood, and skin. In the presence of d-alanine, SEΔΔΔ colonized and increased expression of human β-defensin 2 in cultured human skin models in vitro. SEΔΔΔ showed a low propensity to revert to d-alanine prototrophy and did not form biofilms on plastic in vitro. These studies support the potential safety and utility of SEΔΔΔ as a live biotherapeutic strain whose growth can be controlled by d-alanine. IMPORTANCE The skin microbiome is rich in opportunities for novel therapeutics for skin diseases, and synthetic biology offers the advantage of providing novel functionality or therapeutic benefit to live biotherapeutic products. The development of novel bacterial strains whose growth can be controlled without the use of antibiotics or genetic elements conferring antibiotic resistance enables modulation of therapeutic exposure and improves safety. This study presents the design and in vitro evidence of a skin commensal whose growth can be controlled through d-alanine. The basis of this strain will support future clinical studies of this strain in humans.
Noise-Correlation Is Modulated by Reward Expectation in the Primary Motor Cortex Bilaterally During Manual and Observational Tasks in Primates

Reward modulation is represented in the motor cortex (M1) and could be used to implement more accurate decoding models to improve brain computer interfaces (BCIs) (Zhao et al. 2018). Analyzing trial-to-trial noise-correlations between neural units in the presence of rewarding (R) and non-rewarding (NR) stimuli adds to our understanding of cortical network dynamics. We utilized Pearson’s correlation coefficient to measure shared variability between simultaneously recorded units (32 – 112) and found significantly higher noise-correlation and positive correlation between the populations’ signal- and noise-correlation during NR trials as compared to R trials. This pattern is evident in data from two non-human primates (NHPs) during single-target center out reaching tasks, both manual and action observation versions. We conducted mean matched noise-correlation analysis in order to decouple known interactions between event triggered firing rate changes and neural correlations. Isolated reward discriminatory units demonstrated stronger correlational changes than units unresponsive to reward firing rate modulation, however the qualitative response was similar, indicating correlational changes within the network as a whole can serve as another information channel to be exploited by BCIs that track the underlying cortical state, such as reward expectation, or attentional modulation. Reward expectation and attention in return can be utilized with reinforcement learning towards autonomous BCI updating.
Revealing dynamic protein acetylation across subcellular compartments.

Protein acetylation is a widespread post-translational modification implicated in many cellular processes. Recent advances in mass spectrometry have enabled the cataloging of thousands of sites throughout the cell, however identifying regulatory acetylation marks have proven to be a daunting task. Knowledge of the kinetics and stoichiometry of site-specific acetylation are important factors to uncover function. Here, an improved method of quantifying acetylation stoichiometry was developed and validated, providing a detailed landscape of dynamic acetylation stoichiometry within cellular compartments. The dynamic nature of site-specific acetylation in response to serum stimulation was revealed. In two distinct human cell lines, growth factor stimulation led to site-specific, temporal acetylation changes, revealing diverse kinetic profiles that clustered into several groups. Overlap of dynamic acetylation sites among two different human cell lines suggested similar regulatory control points across major cellular pathways that include splicing, translation, and protein homeostasis. Rapid increases in acetylation on protein translational machinery suggest a positive regulatory role under pro-growth conditions. Lastly, higher median stoichiometry was observed in cellular compartments where active acetyltransferases are well-described. Datasets can be accessed through ProteomExchange via the MassIVE repository (ProteomExchange: PXD014453; MassIVE: MSV000084029).
Large-scale interpretation of chemical-genetic interaction profiles using a genetic interaction network

Genetic interactions provide a key for interpreting the functional information contained in chemical-genetic interaction profiles. However, they have remained underutilized in this capacity across recent chemical-genetic interaction screening efforts and their ability to interpret chemical-genetic interaction profiles on a large scale has not been tested. We developed a method, which we refer to as CG-TARGET (Chemical Genetic Translation via A Reference Genetic nETwork), that integrates the data from large-scale chemical-genetic interaction screens with genetic interaction data to predict the biological processes perturbed by compounds. CG-TARGET compared favorably to a standard enrichment approach across a variety of benchmarks, achieving similar performance on measures of accuracy and substantial improvement in the ability to control the false discovery rate of its predictions. We found that one-third to one-half of gene mutants in the data contribute to the highest-confidence biological process predictions and that these contributions overwhelmingly come from negative chemical-genetic interactions. This method was used to prioritize over 1500 out of over 13,000 compounds for further study in a recently-completed chemical-genetic interaction screen in Saccharomyces cerevisiae, enabling the rapid functional annotation of unknown compounds to biological processes through targeted biological validations. We present here a detailed characterization of the method and further biological validations to demonstrate the utility of genetic interactions in the interpretation of chemical-genetic interaction profiles and the effectiveness of our implementation of this concept.
Subject-independent decoding of affective states using functional near-infrared spectroscopy

Affective decoding is the inference of human emotional states using brain signal measurements. This approach is crucial to develop new therapeutic approaches for psychiatric rehabilitation, such as affective neurofeedback protocols. To reduce the training duration and optimize the clinical outputs, an ideal clinical neurofeedback could be trained using data from an independent group of volunteers before being used by new patients. Here, we investigated if this subject-independent design of affective decoding can be achieved using functional near-infrared spectroscopy (fNIRS) signals from frontal and occipital areas. For this purpose, a linear discriminant analysis classifier was first trained in a dataset (49 participants, 24.65±3.23 years) and then tested in a completely independent one (20 participants, 24.00±3.92 years). Significant balanced accuracies between classes were found for positive vs. negative (64.50±12.44%, p<0.01) and negative vs. neutral (67.75±14.45%, p<0.01) affective states discrimination during a passive elicitation condition consisting in viewing affective-loaded images. For an active elicitation condition, in which volunteers were instructed to recollect personal affective experiences, significant accuracy was found for positive vs. neutral affect classification (71.00±17.93%, p<0.01). In this last case, only three fNIRS channels were enough to discriminate between neutral and positive affective states. Our results highlight fNIRS as a feasible technique for subject-independent affective decoding, reaching significant classification accuracies of affective states using only a few but biologically relevant features.
Reprogramming the endogenous type III-A CRISPR-Cas system for genome editing, RNA interference and CRISPRi screening in Mycobacterium tuberculosis

Mycobacterium tuberculosis (M.tb) causes the current leading infectious disease. Examination of the functional genomics of M.tb and development of drugs and vaccines are hampered by the complicated and time-consuming genetic manipulation techniques for M.tb. Here, we reprogrammed M.tb endogenous type III-A CRISPR-Cas10 system for simple and efficient gene editing, RNA interference and screening via simple delivery of a plasmid harboring a mini-CRISPR array, thereby avoiding the introduction of exogenous proteins and minimizing proteotoxicity. We demonstrated that M.tb genes were efficiently and specifically knocked-in/out by this system, which was confirmed by whole-genome sequencing. This system was further employed for single and simultaneous multiple-gene RNA interference. Moreover, we successfully applied this system for genome-wide CRISPR interference screening to identify the in-vitro and intracellular growth-regulating genes. This system can be extensively used to explore the functional genomics of M.tb and facilitate the development of new anti-Mycobacterial drugs and vaccines. Summary Tuberculosis caused by Mycobacterium tuberculosis (M.tb) is the current leading infectious disease affecting more than ten million people annually. To dissect the functional genomics and understand its virulence, persistence, and antibiotics resistance, a powerful genome editing tool and high-throughput screening methods are desperately wanted. Our study developed an efficient and a robust tool for genome editing and RNA interference in M.tb using its endogenous CRISPR cas10 system. Moreover, the system has been successfully applied for genome-wide CRISPR interference screening. This tool could be employed to explore the functional genomics of M.tb and facilitate the development of anti-M.tb drugs and vaccines.
CryoSIM: super-resolution 3D structured illumination cryogenic fluorescence microscopy for correlated ultrastructural imaging

Rapid cryo-preservation of biological specimens is the gold standard for visualising cellular structures in their true structural context. However, current commercial cryo-fluorescence microscopes are limited to low resolutions. To fill this gap, we have developed cryoSIM, a microscope for 3D super-resolution fluorescence cryo-imaging for correlation with cryo electron microscopy or cryo soft X-ray tomography. We provide the full instructions for replicating the instrument mostly from off-the-shelf components and accessible, user-friendly open source Python control software. Therefore, cryoSIM democratises the ability to detect molecules using super-resolution fluorescence imaging of cryo-preserved specimens for correlation with their cellular ultrastructure.
The chromatin remodeler LSH controls genome-wide cytosine hydroxymethylation

TET proteins convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), leading to a dynamic epigenetic state of DNA that can influence transcription. While TET proteins have been associated with either epigenetic repression or activation complexes, the overall understanding of the molecular mechanisms involved in TET-mediated regulation of gene transcription still remains limited. Here, we show that TET proteins interact with lymphoid-specific helicase (LSH), a chromatin remodeling factor belonging to the SNF2 super family. Lsh knock-out leads to a significant reduction of 5-hydroxymethylation global level in mouse embryonic fibroblasts (MEFs) and in embryonic stem cells (ESC). Whole genome sequencing of 5hmC in wild-type versus Lsh knock-out MEFs and ESCs showed that in absence of Lsh, some regions of the genome gain 5hmC while others lose it, with not much effect on gene expression. We further show that 5hmC modifications upon Lsh loss is not a direct consequence of 5mC decrease, as differentially hydroxymethylated regions (DhMR) did not overlap with DMR (differentially methylated regions), underlying that these modifications occurred at different genomic loci. Altogether, our results suggest that LSH is a key regulator of 5hmC in both MEFs and ESC and that TET proteins rely on specific factors to establish genome-wide 5hmC patterns.