Biomarker screening using integrated bioinformatics for the development of "normal-impaired glucose intolerance-type 2 diabetes mellitus".

Type 2 diabetes mellitus (T2DM) is a progressive disease. We utilized bioinformatics analysis and experimental research to identify biomarkers indicative of the progression of T2DM, aiming for early detection of the disease and timely clinical intervention. Integrating Mfuzz analysis with differential expression analysis, we identified 76 genes associated with the progression of T2DM, which were primarily enriched in signaling pathways such as apoptosis, p53 signaling, and necroptosis. Subsequently, using various analytical methods, including machine learning, we further narrowed down the hub genes to STK17A and CCT5. Based on the hub genes, we calculated the risk score for samples and interestingly found that the score correlated with multiple programmed cell death (PCD) pathways. Animal experiments revealed that the diabetes model exhibited higher levels of MDA and LDH, with lower expression of SOD, accompanied by islet cell apoptosis. In conclusion, our study suggests that during the progression of diabetes, STK17A and CCT5 may contribute to the advancement of the disease by regulating oxidative stress, programmed cell death pathways, and critical signaling pathways such as p53 and MAPK, thereby promoting the death of islet cells. This provides substantial evidence in support of further disease prevention and treatment strategies.

Unveiling the role of differential growth in 3D morphogenesis: An inference method to analyze area expansion rate distribution in biological systems.

The three-dimensional (3D) morphologies of many organs in organisms, such as the curved shapes of leaves and flowers, the branching structure of lungs, and the exoskeletal shape of insects, are formed through surface growth. Although differential growth, a mode of surface growth, has been qualitatively identified as 3D morphogenesis, a quantitative understanding of the mechanical contribution of differential growth is lacking. To address this, we developed a quantitative inference method to analyze the distribution of the area expansion rate, which governs the growth of surfaces into 3D morphology. To validate the accuracy of our method, we tested it on a basic 3D morphology that allowed for the theoretical derivation of the area expansion rate distribution, and then assessed the difference between the predicted outcome and the theoretical solution. We also applied this method to complex 3D shapes and evaluated its accuracy through numerical experiments. The findings of the study revealed a linear decrease in error on a log-log scale with an increase in the number of meshes in both evaluations. This affirmed the reliability of the predictions for meshes that are sufficiently refined. Moreover, we employed our methodology to analyze the developmental process of the Japanese rhinoceros beetle Trypoxylus dichotomus, which is characterized by differential growth regulating 3D morphogenesis. The results indicated a notably high rate of area expansion on the left and right edges of the horn primordium, which is consistent with the experimental evidence of a higher rate of cell division in these regions. Hence, these findings confirm the efficacy of the proposed method in analyzing biological systems.

The role of Wnt, ARL4C, and Sema3A in developmental process and disease pathogenesis.

Various types of tumors, including malignant and benign ones, occur in the oral cavity. These arise from the mucosal epithelium, odontogenic epithelium, and salivary gland. To date, few major driver events in oral tumors have been identified. Accordingly, molecular targets in anti-tumor therapy for oral tumors are lacking. We focused on elucidating the function of aberrantly activated signal transduction related to oral tumor formation, especially in oral squamous cell carcinoma, ameloblastoma, and adenoid cystic carcinoma, which are raised as common oral tumors. Wnt/ß-catenin-dependent pathway is involved in the developmental process, organ homeostasis and disease pathogenesis through regulating various cellular functions by enhancing transcriptional activity. Recently, we identified ADP-ribosylation factor (ARF)-like 4c (ARL4C) and Semaphorin 3A (Sema3A), the expression of which is regulated by Wnt/ß-catenin-dependent pathway, and characterized their functions in the developmental process and tumor formation. This review highlights the recent advances in understanding the roles of Wnt/ß-catenin-dependent pathway, ARL4C and Sema3A, as determined by pathological and experimental studies.

Biological soil crust development affects bacterial communities in the Caragana microphylla community in alpine sandy areas.

Introduction: Biological soil crusts (BSCs) constitute a substantial portion of primary production in dryland ecosystems. They successionally mature to deliver a series of ecosystem services. Bacteria, as an important community in BSCs, play critical roles in maintaining the structure and functions of BSCs. However, the process by which bacterial diversity and community are altered with BSC development is not fully understood. Methods: In this study, amplicons sequencing was used to investigate bacterial diversity and community compositions across five developmental stages of BSCs (bare sand, microbial crusts, algae crusts, lichen crusts, and moss crusts) and their relationship with environmental variables in the Gonghe basin sandy land in Qinghai-Tibet Plateau, northwestern China. Results: The results showed that Proteobacteria, Actinobacteria, Cyanobacteria, Acidobacteria, Bacteroidetes, and Firmicutes were predominant in different developmental stages of BSCs, accounting for more than 77% of the total relative abundance. The phyla of Acidobacteria and Bacteroidetes were abundant in this region. With BSC development, bacterial diversity significantly increased, and the taxonomic community composition significantly altered. The relative abundance of copiotrophic bacteria, such as Actinobacteria, Acidobacteria, Bacteroidetes, Verrucomicrobia, Planctomycetes, and Gemmatimonadetes significantly increased, whereas the relative abundance of oligotrophic bacteria, such as Proteobacteria and Firmicutes significantly decreased. The relative abundance of Cyanobacteria in the algae crusts was significantly higher than that in the other developmental stages (p < 0.05). Conclusion: Variations in bacterial composition suggested that the potential ecological functions of the bacterial community were altered with BSC development. The functions varied from enhancing soil surface stability by promoting soil particle cementation in the early stages to promoting material circulation of the ecosystem by fixing carbon and nitrogen and decomposing litter in the later stages of BSC development. Bacterial community is a sensitive index of water and nutrient alterations during BSC development. SWC, pH value, TC, TOC, TN, NO3 -, TP and soil texture were the primary environmental variables that promoted changes in the bacterial community composition of BSCs.

HPLC-QTRAP-MS-based metabolomics approach investigates the formation mechanisms of meat quality and flavor of Beijing You chicken.

Chicken meat quality and flavor are determined by abundant metabolites. In this study, HPLC-QTRAP-MS-based metabolomic analysis was used to evaluate the characteristic metabolites in the breast muscle of Beijing You chickens aged 56, 98, and 120 days. A total of 544 metabolites in 32 categories were identified, among which amino acids and organic acids were the most abundant. 60 and 55 differential metabolites were identified between 56 and 98 days of age, 98 and 120 days of age, respectively. The content of l-carnitine, l-methionine and 3-hydroxybutyrate increased significantly at 98 or 120 days of age. Arginine biosynthesis, purine metabolism, alanine, aspartic acid, and glutamic acid metabolism were important metabolic pathways that affect chicken meat flavor. This study can help to elucidate the metabolic mechanism of breast muscle during Beijing You chicken development and provide a theoretical reference for the improvement of chicken meat quality and flavor.

Formation and evolution of idiopathic lamellar macular hole-a pilot study.

BACKGROUND: The developmental pathways and subsequent evolutional processes of idiopathic lamellar macular hole (LMH) were studied with spectrum domain optical coherence tomography (SD-OCT). METHODS: Twenty-seven eyes of 26 patients of idiopathic LMH with pre-LMH SD-OCT available were retrospectively reviewed. Relevant OCT parameters and best-corrected visual acuity (BCVA) were collected and analyzed. RESULTS: Four types of developmental pathways of idiopathic LMH were noted. Type 1 (5 cases), involved disruption of a foveal cyst from vitreomacular traction. Type 2 (10 cases), demonstrated rupture of parafoveal cysts or schisis mainly from epiretinal membrane (ERM). In type 3 pathway (5 cases), a central intraretinal cyst formed under tight ERM with subsequent cyst roof dehiscence. Type 4 (7 cases), showed gradual loss of foveal tissue without cystic lesions from ERM traction. There was no statistically significant change in BCVA during LMH formations or subsequent evolutional processes in any types of the developmental pathways. Three cases developed epiretinal proliferation (EP) during evolution, which showed tendency of decrease in BCVA. Among the three cases, one later developed the degenerative configuration. CONCLUSIONS: In summary, four types of tractional developmental pathways of idiopathic LMH were identified. BCVA was relatively stable during LMH formation and follow-up. Deterioration of visual acuity were found in cases that developed EP during evolution. Transformation into degenerative configuration might be possible after LMH formation.

A Dynamical Reconceptualization of Executive-Function Development.

Executive function plays a foundational role in everyday behaviors across the life span. The theoretical understanding of executive-function development, however, is still a work in progress. Doebel proposed that executive-function development reflects skills using control in the service of behavior-using mental content such as knowledge and beliefs to guide behavior in a context-specific fashion. This liberating view contrasts with modular views of executive function. This new view resembles some older dynamic-systems concepts that long ago proposed that behavior reflects the assembly of multiple pieces in context. We dig into this resemblance and evaluate what else dynamic-systems theory adds to the understanding of executive-function development. We describe core dynamic-systems concepts and apply them to executive function-as conceptualized by Doebel-and through this lens explain the multilevel nature of goal-directed behavior and how a capacity to behave in a goal-directed fashion across contexts emerges over development. We then describe a dynamic systems model of goal-directed behavior during childhood and, finally, address broader theoretical implications of dynamic-systems theory and propose new translational implications for fostering children's capacity to behave in a goal-directed fashion across everyday contexts.

Two Sides of the Same Coin: The Roles of KLF6 in Physiology and Pathophysiology.

The Krüppel-like factors (KLFs) family of proteins control several key biological processes that include proliferation, differentiation, metabolism, apoptosis and inflammation. Dysregulation of KLF functions have been shown to disrupt cellular homeostasis and contribute to disease development. KLF6 is a relevant example; a range of functional and expression assays suggested that the dysregulation of KLF6 contributes to the onset of cancer, inflammation-associated diseases as well as cardiovascular diseases. KLF6 expression is either suppressed or elevated depending on the disease, and this is largely due to alternative splicing events producing KLF6 isoforms with specialised functions. Hence, the aim of this review is to discuss the known aspects of KLF6 biology that covers the gene and protein architecture, gene regulation, post-translational modifications and functions of KLF6 in health and diseases. We put special emphasis on the equivocal roles of its full-length and spliced variants. We also deliberate on the therapeutic strategies of KLF6 and its associated signalling pathways. Finally, we provide compelling basic and clinical questions to enhance the knowledge and research on elucidating the roles of KLF6 in physiological and pathophysiological processes.

Dynamics of Gene Co-expression Networks in Time-Series Data: A Case Study in Drosophila melanogaster Embryogenesis.

Co-expression networks tightly coordinate the spatiotemporal patterns of gene expression unfolding during development. Due to the dynamic nature of developmental processes simply overlaying gene expression patterns onto static representations of co-expression networks may be misleading. Here, we aim to formally quantitate topological changes of co-expression networks during embryonic development using a publicly available Drosophila melanogaster transcriptome data set comprising 14 time points. We deployed a network approach which inferred 10 discrete co-expression networks by smoothly sliding along from early to late development using 5 consecutive time points per window. Such an approach allows changing network structure, including the presence of hubs, modules and other topological parameters to be quantitated. To explore the dynamic aspects of gene expression captured by our approach, we focused on regulator genes with apparent influence over particular aspects of development. Those key regulators were selected using a differential network algorithm to contrast the first 7 (early) with the last 7 (late) developmental time points. This assigns high scores to genes whose connectivity to abundant differentially expressed target genes has changed dramatically between states. We have produced a list of key regulators - some increasing (e.g., Tusp, slbo, Sidpn, DCAF12, and chinmo) and some decreasing (Rfx, bap, Hmx, Awh, and mld) connectivity during development - which reflects their role in different stages of embryogenesis. The networks we have constructed can be explored and interpreted within Cytoscape software and provide a new systems biology approach for the Drosophila research community to better visualize and interpret developmental regulation of gene expression.

Full Transcriptomic Response of Pseudomonas aeruginosa to an Inulin-Derived Fructooligosaccharide.

Pseudomonas aeruginosa is an ubiquitous gram-negative opportunistic human pathogen which is not considered part of the human commensal gut microbiota. However, depletion of the intestinal microbiota (Dysbiosis) following antibiotic treatment facilitates the colonization of the intestinal tract by Multidrug-Resistant P. aeruginosa. One possible strategy is based on the use of functional foods with prebiotic activity. The bifidogenic effect of the prebiotic inulin and its hydrolyzed form (fructooligosaccharide: FOS) is well established since they promote the growth of specific beneficial (probiotic) gut bacteria such as bifidobacteria. Previous studies of the opportunistic nosocomial pathogen Pseudomonas aeruginosa PAO1 have shown that inulin and to a greater extent FOS reduce growth and biofilm formation, which was found to be due to a decrease in motility and exotoxin secretion. However, the transcriptional basis for these phenotypic alterations remains unclear. To address this question we conducted RNA-sequence analysis. Changes in the transcript level induced by inulin and FOS were similar, but a set of transcript levels were increased in response to inulin and reduced in the presence of FOS. In the presence of inulin or FOS, 260 and 217 transcript levels, respectively, were altered compared to the control to which no polysaccharide was added. Importantly, changes in transcript levels of 57 and 83 genes were found to be specific for either inulin or FOS, respectively, indicating that both compounds trigger different changes. Gene pathway analyses of differentially expressed genes (DEG) revealed a specific FOS-mediated reduction in transcript levels of genes that participate in several canonical pathways involved in metabolism and growth, motility, biofilm formation, ß-lactamase resistance, and in the modulation of type III and VI secretion systems; results that have been partially verified by real time quantitative PCR measurements. Moreover, we have identified a genomic island formed by a cluster of 15 genes, encoding uncharacterized proteins, which were repressed in the presence of FOS. The analysis of isogenic mutants has shown that genes of this genomic island encode proteins involved in growth, biofilm formation and motility. These results indicate that FOS selectively modulates bacterial pathogenicity by interfering with different signaling pathways.

Connecting the Dots: Finding Continuity Across Visuospatial Tasks and Development.

The study of cognition and its development has long been partitioned into sub-domains, with different tasks designed to assess different constructs and for use during different developmental periods. A central challenge is to understand how a single cognitive system organizes itself across many contexts and developmental periods in which we study it. This article takes a step toward tackling this challenge through a theoretical review of simulations of a dynamic neural field (DNF) model of visuospatial cognitive development. The DNF model simulates basic neurocognitive processes of encoding, maintenance, and long-term memory formation that are coupled to different behavioral systems to generate behaviors required across different tasks used with different age groups. The model simulations reviewed here were initially focused on explaining performance in specific experimental conditions within a developmental period. This article brings to the forefront the larger theoretical goal to understand how a set of basic neurocognitive processes can underlie performance in a wide array of contexts. This review connects behavioral signatures and developmental phenomena from spatial cognition, infant visual exploration, and capacity limits in visual working memory into a single theoretical account of the development of basic visuospatial cognitive processes. Our synthesis yielded three new insights not evident when considering the model simulations in isolation. First, we identified behavior as an emergent product of the neurocognitive processes at work in the model, task context, and development. Second, we show the role of stability of perceptual and memory representations to support behavior within a task and across development. Third, we highlight continuity of ongoing real-time processes at work within and across tasks and over development.

Tinkering and the Origins of Heritable Anatomical Variation in Vertebrates.

Evolutionary change comes from natural and other forms of selection acting on existing anatomical and physiological variants. While much is known about selection, little is known about the details of how genetic mutation leads to the range of heritable anatomical variants that are present within any population. This paper takes a systems-based view to explore how genomic mutation in vertebrate genomes works its way upwards, though changes to proteins, protein networks, and cell phenotypes to produce variants in anatomical detail. The evidence used in this approach mainly derives from analysing anatomical change in adult vertebrates and the protein networks that drive tissue formation in embryos. The former indicate which processes drive variation-these are mainly patterning, timing, and growth-and the latter their molecular basis. The paper then examines the effects of mutation and genetic drift on these processes, the nature of the resulting heritable phenotypic variation within a population, and the experimental evidence on the speed with which new variants can appear under selection. The discussion considers whether this speed is adequate to explain the observed rate of evolutionary change or whether other non-canonical, adaptive mechanisms of heritable mutation are needed. The evidence to hand suggests that they are not, for vertebrate evolution at least.

Reflections on the theoretical contributions and clinical applications of parental insightfulness.

This paper outlines the theoretical antecedents that contextualize parental insightfulness and examines this concept's value in assessing parental functioning and in monitoring treatment progress with parents and young children who experience mental health and relationship problems. As a concept, parental insightfulness provides a much-needed bridge linking important aspects of attachment theory with their psychoanalytic origins, including early contributions that conceptualize parenting as a developmental process that furthers the unfolding capacities of the adult self. The paper examines the compatibility between the dimensions of parental insightfulness and the criteria for a healthy adult sense of self. The empirical body of knowledge generated by the concept of parental insightfulness is briefly reviewed as the basis for using the concept as a valuable tool for the empirical exploration of intrapsychic, interpersonal, and clinical processes in parents and their children.

Characterization of a Potential Ripening Regulator, SlNAC3, from Solanum Lycopersicum.

NAC (for NAM, ATAF1-2, and CUC2) proteins are one of the largest transcription factor families in plants. They have various functions and are closely related to developmental processes of fruits. Tomato (Solanum lycopersicum) is a model plant for studies of fruit growth patterns. In this study, the functional characteristics and action mechanisms of a new NAC-type transcription factor, SlNAC3 (SGN-U568609), were examined to determine its role in tomato development and ripening. The SlNAC3 protein was produced by prokaryotic expression and used to immunize New Zealand white rabbits to obtain a specific polyclonal antibody against SlNAC3. By co-immunoprecipitation and MALDI-TOF-MS assays, we showed that there was an interaction between the SlNAC3 protein and Polygalacturonase-2 (PG-2), which is related to the ripening and softening of fruit. Chromatin immunoprecipitation assays revealed the genome of the highly stress-tolerant Solanum pennellii chromosome 10 (sequence ID, HG975449.1), further demonstrating that SlNAC3 is a negative regulator of drought and salinity stress resistance in tomato, consistent with previous reports. These results indicate that SlNAC3 is not only involved in abiotic stress, but also plays a necessary role in mediating tomato ripening.

Survey of High Throughput RNA-Seq Data Reveals Potential Roles for lncRNAs during Development and Stress Response in Bread Wheat.

Long non-coding RNAs (lncRNAs) are a family of regulatory RNAs that play essential role in the various developmental processes and stress responses. Recent advances in sequencing technology and computational methods enabled identification and characterization of lncRNAs in certain plant species, but they are less known in Triticum aestivum (bread wheat). Herein, we analyzed 52 RNA seq data (>30 billion reads) and identified 44,698 lncRNAs in T. aestivum genome, which were characterized in comparison to the coding sequences (mRNAs). Similar to the mRNAs, lncRNAs were also derived from each sub-genome and chromosome, and showed tissue developmental stage specific and differential expression, as well. The modulated expression of lncRNAs during abiotic stresses like heat, drought, and salt indicated their putative role in stress response. The co-expression of lncRNAs with vital mRNAs including various transcription factors and enzymes involved in Abscisic acid (ABA) biosynthesis, and gene ontology mapping inferred their regulatory roles in numerous biological processes. A few lncRNAs were predicted as precursor (19 lncRNAs), while some as target mimics (1,047 lncRNAs) of known miRNAs involved in various regulatory functions. The results suggested numerous functions of lncRNAs in T. aestivum, and unfolded the opportunities for functional characterization of individual lncRNA in future studies.

Evo-Devo-EpiR: a genome-wide search platform for epistatic control on the evolution of development.

Evo-devo is a theory proposed to study how phenotypes evolve by comparing the developmental processes of different organisms or the same organism experiencing changing environments. It has been recognized that nonallelic interactions at different genes or quantitative trait loci, known as epistasis, may play a pivotal role in the evolution of development, but it has proven difficult to quantify and elucidate this role into a coherent picture. We implement a high-dimensional genome-wide association study model into the evo-devo paradigm and pack it into the R-based Evo-Devo-EpiR, aimed at facilitating the genome-wide landscaping of epistasis for the diversification of phenotypic development. By analyzing a high-throughput assay of DNA markers and their pairs simultaneously, Evo-Devo-EpiR is equipped with a capacity to systematically characterize various epistatic interactions that impact on the pattern and timing of development and its evolution. Enabling a global search for all possible genetic interactions for developmental processes throughout the whole genome, Evo-Devo-EpiR provides a computational tool to illustrate a precise genotype-phenotype map at interface between epistasis, development and evolution.

Implications of Developmental Gene Regulatory Networks Inside and Outside Developmental Biology.

The insight that the genomic control of developmental process is encoded in the form of gene regulatory networks has profound impacts on many areas of modern bioscience. Most importantly, it affects developmental biology itself, as it means that a causal understanding of development requires knowledge of the architecture of regulatory network interactions. Furthermore, it follows that functional changes in developmental gene regulatory networks have to be considered as a primary mechanism for evolutionary process. We here discuss some of the recent advances in gene regulatory network biology and how they have affected our current understanding of development, evolution, and regulatory genomics.

Proteomics and Metabolomics: Two Emerging Areas for Legume Improvement.

The crop legumes such as chickpea, common bean, cowpea, peanut, pigeonpea, soybean, etc. are important sources of nutrition and contribute to a significant amount of biological nitrogen fixation (>20 million tons of fixed nitrogen) in agriculture. However, the production of legumes is constrained due to abiotic and biotic stresses. It is therefore imperative to understand the molecular mechanisms of plant response to different stresses and identify key candidate genes regulating tolerance which can be deployed in breeding programs. The information obtained from transcriptomics has facilitated the identification of candidate genes for the given trait of interest and utilizing them in crop breeding programs to improve stress tolerance. However, the mechanisms of stress tolerance are complex due to the influence of multi-genes and post-transcriptional regulations. Furthermore, stress conditions greatly affect gene expression which in turn causes modifications in the composition of plant proteomes and metabolomes. Therefore, functional genomics involving various proteomics and metabolomics approaches have been obligatory for understanding plant stress tolerance. These approaches have also been found useful to unravel different pathways related to plant and seed development as well as symbiosis. Proteome and metabolome profiling using high-throughput based systems have been extensively applied in the model legume species, Medicago truncatula and Lotus japonicus, as well as in the model crop legume, soybean, to examine stress signaling pathways, cellular and developmental processes and nodule symbiosis. Moreover, the availability of protein reference maps as well as proteomics and metabolomics databases greatly support research and understanding of various biological processes in legumes. Protein-protein interaction techniques, particularly the yeast two-hybrid system have been advantageous for studying symbiosis and stress signaling in legumes. In this review, several studies on proteomics and metabolomics in model and crop legumes have been discussed. Additionally, applications of advanced proteomics and metabolomics approaches have also been included in this review for future applications in legume research. The integration of these "omics" approaches will greatly support the identification of accurate biomarkers in legume smart breeding programs.

Modernization of traditional Chinese medicine is a systematic engineering / 国际中医中药杂志

This article is trying to find out the historical and realistic reasons of the restriction of the process of modernization of traditional Chinese medicine (TCM) from the history of TCM theory and practice of TCM institutional setup and related policies and many other aspects.Then it points out that the TCM in the background of the development of science and technology today is already has the necessary conditions of modernization,but the process can not be succeed overnight,it ought to be a systematic engineering.