Genome-wide Identification, Evolutionary and Functional Analyses of Kfb Family Members in Potato

Background: Kelch repeat F-box (KFB) proteins play vital roles in the regulation of multitudinous biochemical and physiological processes in plants, including growth and development, stress response and secondary metabolism. Multiple KFBs have been characterized in various plant species, but this family members have not been systematically identified and analyzed in potato. Results: Genome and transcriptome analyses of StKFB gene family were conducted to dissect the structure, evolution and function of the KFBs in Solanum tuberosum L. Totally, 44 StKFB members were identified and were classified into 5 groups according to their structural and phylogenetic features. The chromosomal localization analysis showed that the 44 StKFB genes were located on 12 chromosomes. Among these genes, two pairs of genes (StKFB15/16 and StKFB40/41) were predicted to be tandemly duplicated genes, and one pair of genes (StKFB15/29) was segmentally duplicated genes. The syntenic analysis showed that the KFBs in potato were closely related to the KFBs in tomato and pepper. Expression profiles of StKFBs in 13 different tissues and in potato plants with different treatments uncovered distinct spatial expression patterns of these genes and their potential roles in response to various stresses. Transcriptomic and qRT-PCR analyses of StKFBs deciphered that multiple StKFB genes were differentially expressed in three colored potato tubers. Genes that were highly expressed in yellow fleshed tubers (Jin-16) and were lowly expressed in the red- (Red Rose-2) or purple-fleshed (Xisen-8) tubers, such as StKFB07, StKFB15, StKFB23, StKFB29 and StKFB44, may negatively regulate anthocyanin biosynthesis.Conclusions: This study reports the structure, evolution and expression characteristics of the KFB family in potato. These findings set the stage for further study of functional mechanisms of StKFBs, and also provide candidate genes for potato genetic improvement.

Genome-wide meta-analysis of phytosterols reveals five novel loci and a detrimental effect on coronary atherosclerosis

Phytosterol serum concentrations are under tight genetic control. The relationship between phytosterols and coronary artery disease (CAD) is controversially discussed. We perform a genome-wide meta-analysis of 32 phytosterol traits reflecting resorption, cholesterol synthesis and esterification in six studies with up to 9758 subjects and detect ten independent genome-wide significant SNPs at seven genomic loci. We confirm previously established associations at ABCG5/8 and ABO and demonstrate an extended locus heterogeneity at ABCG5/8 with different functional mechanisms. New loci comprise HMGCR, NPC1L1, PNLIPRP2, SCARB1 and APOE. Based on these results, we perform Mendelian Randomization analyses (MR) revealing a risk-increasing causal relationship of sitosterol serum concentrations and CAD, which is partly mediated by cholesterol. Here we report that phytosterols are polygenic traits. MR add evidence of both, direct and indirect causal effects of sitosterol on CAD.

Neuro-anatomical and neuro-molecular markers in salience network and their integration in machine learning-based prediction of cognitive dysfunction in mild cognitive impairment

Recent studies indicate disrupted functional mechanisms of salience network regions, especially right anterior insula (RAI), left AI (LAI), and anterior cingulate cortex (ACC), in mild cognitive impairment (MCI). However, the underlying neuro-anatomical and neuro-molecular mechanisms in these regions are not clearly understood yet. It is also unknown whether integration of multi-modal neuro-anatomical and neuro-molecular markers could predict cognitive impairment better in MCI. Herein we quantified neuro-anatomical volumetric markers via structural magnetic resonance imaging (sMRI) and neuro-molecular amyloid markers via positron emission tomography with Pittsburgh compound B (PET PiB) in SN regions of MCI (n = 33) and healthy controls (n = 27). We found that neuro-anatomical markers are significantly reduced while neuro-molecular markers are significantly elevated in SN nodes of MCI compared to healthy controls (p < 0.05). These altered markers in MCI patients were associated with their worse cognitive performance (p < 0.05). Our machine learning-based modeling further suggested that the integration of multi-modal markers predicts cognitive impairment in MCI superiorly compared to using single modality-specific markers. Overall, these findings shed light on the underlying neuro-anatomical volumetric and neuro-molecular amyloid alterations in SN regions and show the significance of multi-modal markers integration approach in better predicting cognitive impairment in MCI.

A functional view reveals substantial predictability of pollinator-mediated selection

A predictive understanding of adaptation to changing environments hinges on a mechanistic understanding of the extent and causes of variation in natural selection. Estimating variation in selection is difficult due to the complex relationships between phenotypic traits and fitness, and the uncertainty associated with individual selection estimates. Plant-pollinator interactions provide ideal systems for understanding variation in selection and its predictability, because both the selective agents (pollinators) and the process linking phenotypes to fitness (pollination) are generally known. Through examples from the pollination literature, I discuss how explicit consideration of the functional mechanisms underlying trait-performance relationships can clarify the relationship between traits and fitness, and how variation in the ecological context that generates selection can help disentangle biologically important variation in selection from sampling variation. I then evaluate the predictability of variation in pollinator-mediated selection through a survey, reanalysis, and synthesis of results from the literature. The synthesis demonstrates that pollinator-mediated selection often varies substantially among trait functional groups, as well as in time and space. Covariance between patterns of selection and ecological variables provides additional support for the biological importance of observed selection, but the detection of such covariance depends on careful choice of relevant predictor variables as well as consideration of quantitative measurements and their meaning, an aspect often neglected in selection studies.

Accelerated Methods of Determining Wheat Genotypes Primary Resistance to Extreme Temperatures

Several morphological and functional mechanisms determine the resistance of plants to extreme temperatures. Depending on the specificity of mechanisms of action, we divided them into two groups: (1) the mechanisms that ensure the avoidance/reduction of the exposure dose; (2) functional mechanisms which increase plant resistance and ability to recover damages caused by stress through regulation metabolic and genes expression activity. We developed theoretical and practical methods to appreciate the contribution of parameters from both groups on the primary and adaptive resistance of different wheat genotypes. This problem became more complicated because some properties are epigenetically inherited and can influence genotypes’ primary (initial) resistance to stressors. The article describes results obtained by the accelerated determination of the initial resistance of wheat (Triticum aestivum L.) genotypes to temperature stress and the prospects for their implementation in the selection and development of methods for rational choosing wheat varieties for cultivation under specific environmental conditions.

Single Molecule Analysis of differential functional mechanisms of MtRecG while being exposed to variants of stalled replication-fork

Helicases are motor proteins involved in multiple activities to carry out manipulation of the nucleic acids for efficient gene regulation. In case of roadblocks that can lead the replication machinery to get halted, a complex molecular surveillance system utilizing helicases as its key player ensures the halted fork to resume its duplication process. RecG, belonging to the category of Superfamily-2 plays a vital role in rescuing different kinds of stalled fork. Here, through adoption of single-molecule techniques we have attempted to probe the DNA unwinding features by RecG and tried to capture several stages of genetic rearrangement. An elevated processivity of RecG has been observed for the kinds of stalled fork where progression of lagging daughter strand is ahead than that of the leading strand. Through precise alteration of its function in terms of unwinding, depending upon the substrate DNA, RecG catalyzes the formation of Holliday junction from a stalled fork DNA. In summary, we have featured that RecG adopts asymmetric mode of locomotion to unwind the lagging daughter strand to facilitate Holliday junction creation which acts as a suitable intermediate for recombinational repair pathway.

Identification and verification of the molecular mechanisms and prognostic values of the cadherin gene family in gastric cancer

While cadherin (CDH) genes are aberrantly expressed in cancers, the functions of CDH genes in gastric cancer (GC) remain poorly understood. The clinical significance and molecular mechanisms of CDH genes in GC were assessed in this study. Data from a total of 1226 GC patients included in The Cancer Genome Atlas (TCGA) and Kaplan–Meier plotter database were used to independently explore the value of CDH genes in clinical application. The TCGA RNA sequencing dataset was used to explore the molecular mechanisms of CDH genes in GC. Using enrichment analysis tools, CDH genes were found to be related to cell adhesion and calcium ion binding in function. In TCGA cohort, 12 genes were found to be differentially expressed between GC para-carcinoma and tumor tissue. By analyzing GC patients in two independent cohorts, we identified and verified that CDH2, CDH6, CDH7 and CDH10 were significantly associated with a poor GC prognosis. In addition, CDH2 and CDH6 were used to construct a GC risk score signature that can significantly improve the accuracy of predicting the 5-year survival of GC patients. The GSEA approach was used to explore the functional mechanisms of the four prognostic CDH genes and their associated risk scores. It was found that these genes may be involved in multiple classic cancer-related signaling pathways, such as the Wnt and phosphoinositide 3-kinase signaling pathways in GC. In the subsequent CMap analysis, three small molecule compounds (anisomycin, nystatin and bumetanide) that may be the target molecules that determine the risk score in GC, were initially screened. In conclusion, our current study suggests that four CDH genes can be used as potential biomarkers for GC prognosis. In addition, a prognostic signature based on the CDH2 and CDH6 genes was constructed, and their potential functional mechanisms and drug interactions explored.

Evaluation of the Function of Probiotics, Emphasizing the Role of their Binding to the Intestinal Epithelium in the Stability and their Effects on the Immune System

Due to the importance of using cost-effective methods for therapeutic purposes, the function of probiotics as safe microorganisms and the study of their relevant functional mechanisms have recently been in the spotlight. Finding the mechanisms of attachment and stability and their beneficial effects on the immune system can be useful in identifying and increasing the therapeutic effects of probiotics. In this review, the functional mechanisms of probiotics were comprehensively investigated. Relevant articles were searched in scientific sources, documents, and databases, including PubMed, NCBI, Bactibace, OptiBac, and Bagel4. The most important functional mechanisms of probiotics and their effects on strengthening the epithelial barrier, competitive inhibition of pathogenic microorganisms, production of antimicrobials, binding and interaction with the host, and regulatory effects on the immune system were discussed.In this regard, the attachment of probiotics to the epithelium is very important because the prerequisite for their proper functioning is to establish a proper connection to the epithelium. Therefore, more attention should be paid to the binding effect of probiotics, including sortase A, a significant factor involved in the expression of sortase-dependent proteins (SDP), on their surface as mediators of intestinal epithelial cell binding. In general, by investigating the functional mechanisms of probiotics, it was concluded that the mechanism by which probiotics regulate the immune system and adhesion capacity can directly and indirectly have preventive and therapeutic effects on a wide range of diseases. However, further study of these mechanisms requires extensive research on various aspects.

Multipopulational transcriptome analysis of post-weaned beef cattle at arrival further validates candidate biomarkers for predicting clinical bovine respiratory disease

Bovine respiratory disease (BRD) remains the leading infectious disease in post-weaned beef cattle. The objective of this investigation was to contrast the at-arrival blood transcriptomes from cattle derived from two distinct populations that developed BRD in the 28 days following arrival versus cattle that did not. Forty-eight blood samples from two populations were selected for mRNA sequencing based on even distribution of development (n = 24) or lack of (n = 24) clinical BRD within 28 days following arrival; cattle which developed BRD were further stratified into BRD severity cohorts based on frequency of antimicrobial treatment: treated once (treated_1) or treated twice or more and/or died (treated_2+). Sequenced reads (~ 50 M/sample, 150 bp paired-end) were aligned to the ARS-UCD1.2 bovine genome assembly. One hundred and thirty-two unique differentially expressed genes (DEGs) were identified between groups stratified by disease severity (healthy, n = 24; treated_1, n = 13; treated_2+, n = 11) with edgeR (FDR ≤ 0.05). Differentially expressed genes in treated_1 relative to both healthy and treated_2+ were predicted to increase neutrophil activation, cellular cornification/keratinization, and antimicrobial peptide production. Differentially expressed genes in treated_2+ relative to both healthy and treated_1 were predicted to increase alternative complement activation, decrease leukocyte activity, and increase nitric oxide production. Receiver operating characteristic (ROC) curves generated from expression data for six DEGs identified in our current and previous studies (MARCO, CFB, MCF2L, ALOX15, LOC100335828 (aka CD200R1), and SLC18A2) demonstrated good-to-excellent (AUC: 0.800–0.899; ≥ 0.900) predictability for classifying disease occurrence and severity. This investigation identifies candidate biomarkers and functional mechanisms in at arrival blood that predicted development and severity of BRD.