Miracle-dz/UniFAR-FTUs huggingface dataset:
Rhizosphere Microbial Community Structure Is Selected by Habitat but Not Plant Species in Two Tropical Seagrass Beds

Rhizosphere bacterial community structures and their determining drivers have been studied in a variety of marine and freshwater ecosystems for a range of plant species. However, there is still limited information about the influence of habitat on microbial communities in seagrass beds. This study aimed to determine which factors (habitat and plant species) have crucial roles on the rhizospheric bacteria associated with two tropical seagrass species (Thalassia hemprichii and Enhalus acoroides) that are dominant at Xincun Bay and Tanmen Harbor in Hainan Island, South China. Using Illumina HiSeq sequencing, we observed substantial differences in the bacterial richness, diversity, and relative abundances of taxa between the two habitats, which were characterized differently in sediment type and nutrient status. Rhizospheric bacteria from sandy sediment at the eutrophic Xincun Bay were dominated by Desulfobacteraceae and Helicobacteraceae, which are primarily involved in sulfate cycling, whereas rhizosphere microbes from the reef flat at oligotrophic Tanmen Harbor were dominated by Vibrionaceae and Woeseiaceae, which may play important roles in nitrogen and carbon fixing. Additionally, we speculated that host-specific effects of these two seagrass species may be covered under nutrient-rich conditions and in mixed community patches, emphasizing the importance of the nutrient status of the sediment and vegetation composition of the patches. In addition, our study confirmed that Proteobacteria was more adapted to the rhizosphere environment than to low-carbon conditions that occurred in bulk sediment, which was primarily dominated by well-known fermentative bacteria in the phylum Firmicutes.
Performance Improvement of Near-Infrared Spectroscopy-Based Brain-Computer Interface Using Regularized Linear Discriminant Analysis Ensemble Classifier Based on Bootstrap Aggregating

Ensemble classifiers have been proven to result in better classification accuracy than that of a single strong learner in many machine learning studies. Although many studies on electroencephalography-brain-computer interface (BCI) used ensemble classifiers to enhance the BCI performance, ensemble classifiers have hardly been employed for near-infrared spectroscopy (NIRS)-BCIs. In addition, since there has not been any systematic and comparative study, the efficacy of ensemble classifiers for NIRS-BCIs remains unknown. In this study, four NIRS-BCI datasets were employed to evaluate the efficacy of linear discriminant analysis ensemble classifiers based on the bootstrap aggregating. From the analysis results, significant (or marginally significant) increases in the bitrate as well as the classification accuracy were found for all four NIRS-BCI datasets employed in this study. Moreover, significant bitrate improvements were found in two of the four datasets.
Incorporating Genome-Wide Association Mapping Results Into Genomic Prediction Models for Grain Yield and Yield Stability in CIMMYT Spring Bread Wheat

Untangling the genetic architecture of grain yield (GY) and yield stability is an important determining factor to optimize genomics-assisted selection strategies in wheat. We conducted in-depth investigation on the above using a large set of advanced bread wheat lines (4,302), which were genotyped with genotyping-by-sequencing markers and phenotyped under contrasting (irrigated and stress) environments. Haplotypes-based genome-wide-association study (GWAS) identified 58 associations with GY and 15 with superiority index Pi (measure of stability). Sixteen associations with GY were “environment-specific” with two on chromosomes 3B and 6B with the large effects and 8 associations were consistent across environments and trials. For Pi, 8 associations were from chromosomes 4B and 7B, indicating ‘hot spot’ regions for stability. Epistatic interactions contributed to an additional 5–9% variation on average. We further explored whether integrating consistent and robust associations identified in GWAS as fixed effects in prediction models improves prediction accuracy. For GY, the model accounting for the haplotype-based GWAS loci as fixed effects led to up to 9–10% increase in prediction accuracy, whereas for Pi this approach did not provide any advantage. This is the first report of integrating genetic architecture of GY and yield stability into prediction models in wheat.
Myeloid Cells Enriched for a Dendritic Cell Population From People Living With HIV Have Altered Gene Expression Not Restored by Antiretroviral Therapy

Antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infections has been designed to optimize CD4 T-cell survival and limit HIV replication. Cell types other than CD4 T cells such as monocytes/macrophage, dendritic cells, and granulocytes (collectively known as myeloid cells), are generally not considered in the development of ART protocols. Myeloid dendritic cells (mDCs) are the most potent inducers of CD4 T-cell activation and central to the regulation of immune responses. mDCs in the blood are decreased in number, altered in function, and implicated in promoting HIV latency in people living with HIV (PLWH). We found that cells enriched for mDC in PLWH had transcriptional changes compared to mDC from HIV uninfected individuals, some of which were not completely restored by ART. In contrast, other mDC functions such as interleukin-1 signaling and type I interferon pathways were restored by ART. Some of the transcriptional changes in mDC not completely reversed by ART were enriched in genes that are classically associated with cells of the monocyte/macrophage lineage, but new single-cell RNA sequencing studies show that they are also expressed by a subset of mDC. A cellular enzyme, acyloxyacyl hydrolase (AOAH), important for lipopolysaccharide (LPS) detoxification, had increased transcription in mDC of PLWH, not restored by ART. It is possible that one reason ART is not completely successful in PLWH is the failure to phenotypically change the mDCs. Thus, inability of ART to be completely effective might involve myeloid cells and the failure to restore mDC function as measured by gene transcription. We suggest that mDC and myeloid cells should be considered in future combination ART development.
Skewed X-Chromosome Inactivation and Compensatory Upregulation of Escape Genes Precludes Major Clinical Symptoms in a Female With a Large Xq Deletion

In mammalian females, X-chromosome inactivation (XCI) acts as a dosage compensation mechanism that equalizes X-linked genes expression between homo- and heterogametic sexes. However, approximately 12–23% of X-linked genes escape from XCI, being bi-allelic expressed. Herein, we report on genetic and functional data from an asymptomatic female of a Fragile X syndrome family, who harbors a large deletion on the X-chromosome. Array-CGH uncovered that the de novo, terminal, paternally originated 32 Mb deletion on Xq25-q28 spans 598 RefSeq genes, including escape and variable escape genes. Androgen receptor (AR) and retinitis pigmentosa 2 (RP2) methylation assays showed extreme skewed XCI ratios from both peripheral blood and buccal mucosa, silencing the abnormal X-chromosome. Surprisingly, transcriptome-wide analysis revealed that escape and variable escape genes spanning the deletion are mostly upregulated on the active X-chromosome, precluding major clinical/cognitive phenotypes in the female. Metaphase high count, hemizygosity concordance for microsatellite markers, and monoallelic expression of genes within the deletion suggest the absence of mosaicism in both blood and buccal mucosa. Taken together, our data suggest that an additional protective gene-by-gene mechanism occurs at the transcriptional level in the active X-chromosome to counterbalance detrimental phenotype effects of large Xq deletions.
The Arabidopsis Proteins AtNHR2A and AtNHR2B Are Multi-Functional Proteins Integrating Plant Immunity With Other Biological Processes

AtNHR2A (Arabidopsis thaliana nonhost resistance 2A) and AtNHR2B (Arabidopsis thaliana nonhost resistance 2B) are two proteins that participate in nonhost resistance, a broad-spectrum mechanism of plant immunity that protects plants against the majority of potential pathogens. AtNHR2A and AtNHR2B are localized to the cytoplasm, chloroplasts, and other subcellular compartments of unknown identity. The multiple localizations of AtNHR2A and AtNHR2B suggest that these two proteins are highly dynamic and versatile, likely participating in multiple biological processes. In spite of their importance, the specific functions of AtNHR2A and AtNHR2B have not been elucidated. Thus, to aid in the functional characterization of these two proteins and identify the biological processes in which these proteins operate, we used immunoprecipitation coupled with mass spectrometry (IP-MS) to identify proteins interacting with AtNHR2A and AtNHR2B and to generate their interactome network. Further validation of three of the identified proteins provided new insights into specific pathways and processes related to plant immunity where AtNHR2A and AtNHR2B participate. Moreover, the comprehensive analysis of the AtNHR2A- and AtNHR2B-interacting proteins using published empirical information revealed that the functions of AtNHR2A and AtNHR2B are not limited to plant immunity but encompass other biological processes.
Suppression of Arabidopsis Mediator Subunit-Encoding MED18 Confers Broad Resistance Against DNA and RNA Viruses While MED25 Is Required for Virus Defense

Mediator subunits play key roles in numerous physiological pathways and developmental processes in plants. Arabidopsis Mediator subunits, MED18 and MED25, have previously been shown to modulate disease resistance against fungal and bacterial pathogens through their role in jasmonic acid (JA) signaling. In this study, Arabidopsis mutant plants of the two Mediator subunits, med18 and med25, were tested against three ssRNA viruses and one dsDNA virus belonging to four different families: Turnip mosaic virus (TuMV), Cauliflower mosaic virus (CaMV), Alternanthera mosaic virus (AltMV), and Cucumber mosaic virus (CMV). Although both subunits are utilized in JA signaling, they occupy different positions (Head and Tail domain, respectively) in the Mediator complex and their absence affected virus infection differently. Arabidopsis med18 plants displayed increased resistance to RNA viral infection and a trend against the DNA virus, while med25 mutants displayed increased susceptibility to all viruses tested at 2 and 14 days post inoculations. Defense marker gene expression profiling of mock- and virus-inoculated plants showed that med18 and med25 mutants exhibited an upregulated SA pathway upon virus infection at 2 dpi for all viruses tested. JA signaling was also suppressed in med18 plants after virus infection, independent of which virus infected the plants. The upregulation of SA signaling and suppression of JA signaling in med18 may have led to more targeted oxidative burst and programmed cell death to control viruses. However, the susceptibility exhibited by med25 mutants suggests that other factors, such as a weakened RNAi pathway, might play a role in the observed susceptibility. We conclude that MED18 and MED25 have clear and opposite effects on accumulation of plant viruses. MED18 is required for normal virus infection, while MED25 is important for defense against virus infection. Results from this study provide a better understanding of the role of Mediator subunits during plant-virus interactions, viral disease progression and strategies to develop virus resistant plants.
miR-424 Promotes Bovine Adipogenesis Through an Unconventional Post-Transcriptional Regulation of STK11

Adipose tissue is the largest energy reservoir and secretory organ in the animal body, and is essential for maintaining normal physiological functions and metabolic balance. MicroRNAs regulate the process of adipogenic differentiation through post-transcriptional regulatory mechanisms. In the present study, miR-424 was upregulated during bovine adipocyte differentiation both in vivo and in vitro. The overexpression and interference of miR-424 exhibited the positive regulatory role in the differentiation of bovine adipocytes. Furthermore, miR-424 directly binds to the three prime untranslated region (3' UTR) of serine/threonine kinase 11 (STK11, also called LKB1), a master upstream gene in the AMP-activated protein kinase (AMPK) cascade, and up-regulates its expression. Functional studies showed that the knockdown of STK11 attenuated the pro-adipogenic effect of miR-424. Post-transcriptional regulation of STK11 by miR-424 was mediated potentially in an RNA binding protein (RBP) binding site-dependent manner. In conclusion, our study shows that miR-424 promotes bovine adipogenesis through an unconventional post-transcriptional regulation of STK11, which may serve as a potential target for the regulation of bovine adipogenesis and the improvement of livestock breeding efficiency.
Post-translational Modifications of the Peptidyl-Prolyl Isomerase Pin1

The peptidyl-prolyl cis/trans isomerase (PPIase) Pin1 is a unique enzyme that only binds to Ser/Thr-Pro peptide motifs after phosphorylation and regulates the conformational changes of the bond. The Pin1-catalyzed isomerization upon phosphorylation can have profound effects on substrate biological functions, including their activity, stability, assembly, and subcellular localization, affecting its role in intracellular signaling, transcription, and cell cycle progression. The functions of Pin1 are regulated by post-translational modifications (PTMs) in many biological processes, which include phosphorylation, ubiquitination, SUMOylation and oxidation. Phosphorylation of different Pin1 sites regulates Pin1 enzymatic activity, binding ability, localization, and ubiquitination by different kinases under various cellular contexts. Moreover, SUMOylation and oxidation have been shown to downregulate Pin1 activity. Although Pin1 is tightly regulated under physiological conditions, deregulation of Pin1 PTMs contributes to the development of human diseases including cancer and Alzheimer’s disease (AD). Therefore, manipulating the PTMs of Pin1 may be a promising therapeutic option for treating various human diseases. In this review, we focus on the molecular mechanisms of Pin1 regulation by PTMs and the major impact of Pin1 PTMs on the progression of cancer and AD.
Significance of MEF2C and RUNX3 Regulation for Endochondral Differentiation of Human Mesenchymal Progenitor Cells

Guiding progenitor cell development between chondral versus endochondral pathways is still an unachieved task of cartilage neogenesis, and human mesenchymal progenitor cell (MPC) chondrogenesis is considered as a valuable model to better understand hypertrophic development of chondrocytes. Transcription factors Runx2, Runx3, and Mef2c play prominent roles for chondrocyte hypertrophy during mouse development, but little is known on the importance of these key fate-determining factors for endochondral development of human MPCs. The aim of this study was to unravel the regulation of RUNX2, RUNX3, and MEF2C during MPC chondrogenesis, the pathways driving their expression, and the downstream hypertrophic targets affected by their regulation. RUNX2, RUNX3, and MEF2C gene expression was differentially regulated during chondrogenesis of MPCs, but remained low and unregulated when non-hypertrophic articular chondrocytes were differentiated under the same conditions. RUNX3 and MEF2C mRNA and protein levels rose in parallel to hypertrophic marker upregulation, but surprisingly, RUNX2 gene expression changed only by trend and RUNX2 protein remained undetectable. While RUNX3 expression was driven by TGF-β and BMP signaling, MEF2C responded to WNT-, BMP-, and Hedgehog-pathway inhibition. MEF2C but not RUNX3 levels correlated significantly with COL10A1, IHH, and IBSP gene expression when hypertrophy was attenuated. IBSP was a downstream target of RUNX3 and MEF2C but not RUNX2 in SAOS-2 cells, underlining the capacity of RUNX3 and MEF2C to stimulate osteogenic marker expression in human cells. Conclusively, RUNX3 and MEF2C appeared more important than RUNX2 for human endochondral MPC chondrogenesis. Pathways altering the speed of chondrogenesis (FGF, TGF-β, BMP) affected RUNX2 or RUNX3, while pathways changing hypertrophy (WNT, PTHrP/HH) regulated mainly MEF2C. Taken together, reduction of MEF2C levels is a new goal to shift human cartilage neogenesis toward the chondral pathway.
Deficient Decision Making in Pathological Gamblers Correlates With Gray Matter Volume in Medial Orbitofrontal Cortex

Individuals suffering from pathological gambling (PG) show impaired decision making, but it is still not clear how this impairment is related to other traits and neuroanatomical characteristics. In this study, we investigated how the influence of PG on decision making (1) is connected to different impulsivity facets and (2) how it is related to gray matter volume (GMV) in various brain regions. Twenty-eight diagnosed PG patients and 23 healthy controls completed the cups task to measure decision making. In this task, participants had to decide between safe and risky options, which varied in expected value (EV) between risk advantageous, equal EV, and risk disadvantageous choices. A delay discounting task and the Barrant Impulsiveness Scale were applied to assess multiple impulsivity facets. In addition, structural magnetic resonance images were acquired. In comparison to the control group PG patients demonstrated more deficits in decision making, indicated by less EV sensitivity, but there was no significant difference in number of overall risky choices. Also, PG patients showed increased impulsivity in nearly every dimension. Results revealed (1) a positive correlation between decision making impairments and non-planning impulsivity but no significant relation to other impulsivity facets. Although we found no GMV differences between PG patients and controls, (2) a regions of interest analysis showed a correlation between medial orbitofrontal GMV and EV sensitivity in PG patients. Our findings showed that (1) the association between decision making and impulsivity can also be found in PG patients, but only for certain impulsivity facets. This suggests that it is essential to consider measuring different dimensions, when investigating impulsivity in a PG sample. Secondly, our findings revealed that (2) dysfunctional decision making—particularly the component of risk evaluation—is related to decreased GMV in the medial orbitofrontal cortex, a brain region concerned with processing of rewards. Interestingly, we did not find more risky choices for PG patients, and thus, we assume that decision making deficits in PG are primarily related to risk evaluation, not risk seeking, which is in line with our GMV findings.
Identification of Whole-Genome Significant Single Nucleotide Polymorphisms in Candidate Genes Associated With Serum Biochemical Traits in Chinese Holstein Cattle

A genome-wide association study (GWAS) was conducted on 23 serum biochemical traits in Chinese Holstein cattle. The experimental population consisted of 399 cattle, each genotyped by a commercial bovine 50K SNP chip, which had 49,663 SNPs. After data cleaning, 41,092 SNPs from 361 Holstein cattle were retained for GWAS. The phenotypes were measured values of serum measurements of these animals that were taken at 11 days after parturition. Two statistical models, a fixed-effect linear regression model (FLM) and a mixed-effect linear model (MLM), were used to estimate the association effects of SNPs. Genome-wide significant and suggestive thresholds were set up to be 1.22E−06 and 2.43E−06, respectively. In the Chinese Holstein population, FLM identified 81 genome-wide significant (0.05/41,092 = 1.22E−06) SNPs associated with 11 serum traits. Among these SNPs, five SNPs (BovineHD0100005950, ARS-BFGL-NGS-115158, BovineHD1500021175, BovineHD0800028900, and BTB-00442438) were also identified by the MLM to have genome-wide suggestive effects on CHE, DBIL, and LDL. Both statistical models pinpointed two SNPs that had significant effects on the Holstein population. The SNP BovineHD0800028900 (located near the gene LOC101903458 on chromosome 8) was identified to be significantly associated with serum high- and low-density lipoprotein (HDL and LDL), whereas BovineHD1500021175 (located in 73.4Mb on chromosome 15) was an SNP significantly associated with total bilirubin and direct bilirubin (TBIL and DBIL). Further analyses are needed to identify the causal mutations affecting serum traits and to investigate the correlation of effects for loci associated with fatty liver disease in dairy cattle.
Engineering light-controllable CAR T cells for cancer immunotherapy

Light-sensitive regulators were engineered to control genetic induction of CAR expression in T cells for cancer immunotherapy. T cells engineered to express chimeric antigen receptors (CARs) can recognize and engage with target cancer cells with redirected specificity for cancer immunotherapy. However, there is a lack of ideal CARs for solid tumor antigens, which may lead to severe adverse effects. Here, we developed a light-inducible nuclear translocation and dimerization (LINTAD) system for gene regulation to control CAR T activation. We first demonstrated light-controllable gene expression and functional modulation in human embryonic kidney 293T and Jurkat T cell lines. We then improved the LINTAD system to achieve optimal efficiency in primary human T cells. The results showed that pulsed light stimulations can activate LINTAD CAR T cells with strong cytotoxicity against target cancer cells, both in vitro and in vivo. Therefore, our LINTAD system can serve as an efficient tool to noninvasively control gene activation and activate inducible CAR T cells for precision cancer immunotherapy.
Subfunctionalization of phytochrome B1/B2 leads to differential auxin and photosynthetic responses

Abstract Gene duplication and polyploidization are genetic mechanisms that instantly add genetic material to an organism's genome. Subsequent modification of the duplicated material leads to the evolution of neofunctionalization (new genetic functions), subfunctionalization (differential retention of genetic functions), redundancy, or a decay of duplicated genes to pseudogenes. Phytochromes are light receptors that play a large role in plant development. They are encoded by a small gene family that in tomato is comprised of five members: PHYA, PHYB1, PHYB2, PHYE, and PHYF. The most recent gene duplication within this family was in the ancestral PHYB gene. Using transcriptome profiling, co‐expression network analysis, and physiological and molecular experimentation, we show that tomato SlPHYB1 and SlPHYB2 exhibit both common and non‐redundant functions. Specifically, PHYB1 appears to be the major integrator of light and auxin responses, such as gravitropism and phototropism, while PHYB1 and PHYB2 regulate aspects of photosynthesis antagonistically to each other, suggesting that the genes have subfunctionalized since their duplication.