Genes In Tissues Research Articles

Genome-wide identification and expression analyses of the pectate lyase (PL) gene family in Fragaria vesca

BackgroundPectate lyase (PL, EC 4.2.2.2), as an endo-acting depolymerizing enzyme, cleaves α-1,4-glycosidic linkages in esterified pectin and involves a broad range of cell wall modifications. However, the knowledge concerning the genome-wide analysis of the PL gene family in Fragaria vesca has not been thoroughly elucidated.ResultsIn this study, sixteen PLs members in F. vesca were identified based on a genome-wide investigation. Substantial divergences existed among FvePLs in gene duplication, cis-acting elements, and tissue expression patterns. Four clusters were classified according to phylogenetic analysis. FvePL6, 8 and 13 in cluster II significantly contributed to the significant expansions during evolution by comparing orthologous PL genes from Malus domestica, Solanum lycopersicum, Arabidopsis thaliana, and Fragaria×ananassa. The cis-acting elements implicated in the abscisic acid signaling pathway were abundant in the regions of FvePLs promoters. The RNA-seq data and in situ hybridization revealed that FvePL1, 4, and 7 exhibited maximum expression in fruits at twenty days after pollination, whereas FvePL8 and FvePL13 were preferentially and prominently expressed in mature anthers and pollens. Additionally, the co-expression networks displayed that FvePLs had tight correlations with transcription factors and genes implicated in plant development, abiotic/biotic stresses, ions/Ca2+, and hormones, suggesting the potential roles of FvePLs during strawberry development. Besides, histological observations suggested that FvePL1, 4 and 7 enhanced cell division and expansion of the cortex, thus negatively influencing fruit firmness. Finally, FvePL1-RNAi reduced leaf size, altered petal architectures, disrupted normal pollen development, and rendered partial male sterility.ConclusionThese results provide valuable information for characterizing the evolution, expansion, expression patterns and functional analysis, which help to understand the molecular mechanisms of the FvePLs in the development of strawberries.

Current concepts of bone grafting in trauma surgery

Bone graft in trauma surgery is commonly used in managing bone defects, non-union, fracture related infections, arthrodesis or to provide structural support in fractures. A variety of bone grafts are made available to the treating physician, which includes autograft, allograft and bone graft substitutes. The future of bone grafting in trauma surgery is exciting with the incorporation of technological advancement such as gene therapy, 3D-printing and tissue engineering. Regardless, there are still limitations to what we understand regarding current bone grafting techniques with conflicting literature on their clinical utility and indication. The aim of this review article therefore is to take a step back and critically evaluate the current concepts of bone grafting in trauma surgery, with special emphasis made on reviewing the types of bone graft, biology of bone graft incorporation and indication for its use in various clinical scenarios.

Functional tumor cell-intrinsic STING, not host STING, drives local and systemic antitumor immunity and therapy efficacy following cryoablation

BackgroundDespite its potential utility in delivering direct tumor killing and in situ whole-cell tumor vaccination, tumor cryoablation produces highly variable and unpredictable clinical response, limiting its clinical utility. The mechanism(s)...

Recent progress in regenerative therapy for damaged salivary glands: From bench to bedside.

For functional restoration of salivary glands (SGs) injured by radiation therapy or Sjögren's syndrome (SS), various experimental approaches, such as gene therapy, tissue engineering, and cell-based therapy, have been proposed. This narrative review summarized recent progresses in research using cell-based therapies, including promising trials that could lead to bench-to-clinic applications. A literature review based on PubMed publications in the last two decades was performed to summarize progresses in cell-based therapies for SG dysfunction. Over 100 experimental studies have shown the therapeutic potential of several types of cells, such as SG stem cells and mesenchymal stem cells, as well as effectively conditioned mononuclear cells, in both radiation injury and SS animal models. These therapies affect to slow fibrosis progression and stimulate tissue regeneration in atrophic glands. However, to date, only a total of seven studies have been developed to the stage of clinical study, showing the safety and preliminary efficacy. To lead the radical effectiveness expected in cell-based therapy, advances in reverse translational research and in innovative experimental research, based on the findings of recent clinical studies, will be critical in the next decade.

Investigating the tissue specificity and prognostic impact of cis-regulatory cancer risk variants.

The tissue-specific incidence of cancers and their genetic basis are poorly understood. Although prior studies have shown global correlation across tissues for cancer risk single-nucleotide polymorphisms (SNPs) identified through genome-wide association studies (GWAS), any shared functional regulation of gene expression on a per SNP basis has not been well characterized. We set to quantify cis-mediated gene regulation and tissue sharing for SNPs associated with eight common cancers. We identify significant tissue sharing for individual SNPs and global enrichment for breast, colorectal, and Hodgkin lymphoma cancer risk SNPs in multiple tissues. In addition, we observe increasing tissue sharing for cancer risk SNPs overlapping with super-enhancers for breast cancer and Hodgkin lymphoma providing further evidence of tissue specificity. Finally, for genes under cis-regulation by breast cancer SNPs, we identify a phenotype characterized by low expression of tumor suppressors and negative regulators of the WNT pathway associated with worse freedom from progression and overall survival in patients who eventually develop breast cancer. Our results introduce a paradigm for functionally annotating individual cancer risk SNPs and will inform the design of future translational studies aimed to personalize assessment of inherited cancer risk across tissues.

Inflammatory profile of keratoconic corneal epithelium

BackgroundRecent studies have presented inflammatory features on keratoconus (KC) and many inflammatory markers are described in the tears of patients with this disease. The KC pathogenesis is still unknown just like the correlation with inflammatory patterns. However, environmental and genetic issues may be part of the progress of KC. In addition, some systemic features, such as allergy and obesity, seem to be related to the progression of KC. Our purpose was to evaluate the neuropeptides vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), chemokines ligand 2 (CCL-2) and 5 (CCL-5), and interleukins 6 (IL-6) and 8 (IL-8) on corneal epithelial cells and blood of patients with KC and in healthy controls. In addition, the neutrophil-to-lymphocyte ratio (NLR) was evaluated to predict inflammation.MethodsThis including prospective observational study included 32 KC patients who underwent corneal crosslinking (CXL) and 32 control patients who underwent photorefractive keratectomy (PRK). Patients’ corneal epithelial cells were removed surgically, and blood (buffy coat) was analyzed. Samples in triplicate were evaluated on rt-PCR for neuropeptides (VIP e NPY), interleukins (IL-6 e IL-8), and chemokines (CCL-2 and CCL-5).ResultsOur study showed statistically higher CCL-5 and IL-8 on corneal epithelial cells in patients with KC. Blood cells were statistically higher in VIP and NPY in the KC group. Interleukin-8 on blood cells was statistically significant in KC’S group; for CCL-2 and CCL-5 they were statistically lower in patients with KC compared with controls. NLR showed no difference between the groups.ConclusionsOur data support the findings of other studies that suggested altering KC status, such as inflammatory corneal disease. The presence of IL-8 in the cornea and blood samples of KC’s group suggested systemic disease with a possible local or repercussion action. Further studies are warranted to elucidate KC pathogenesis and its correlation to systemic disease.

American College of Medical Genetics Issues Guidance on Polygenic Risk Scores.

American College of Medical Genetics Issues Guidance on Polygenic Risk Scores.

The Pitaya Flower Tissue's Gene Differential Expression Analysis between Self-Incompatible and Self-Compatible Varieties for the Identification of Genes Involved in Self-Incompatibility Regulation.

Self-incompatible pitaya varieties have low fruit-setting rates under natural conditions, leading to higher production costs and hindering industrial prosperity. Through transcriptome sequencing, we obtained the 36,900 longest transcripts (including 9167 new transcripts) from 60 samples of flowers. Samples were collected pre- and post-pollination (at 0 h, 0.5 h, 2 h, 4 h, and 12 h) from two varieties of pitaya (self-compatible Jindu No. 1 and self-incompatible Cu Sha). Using the RNA-Seq data and comparison of reference genomes, we annotated 28,817 genes in various databases, and 1740 genes were optimized in their structure for annotation. There were significant differences in the expression of differentially expressed genes (DEGs) in the pitaya stigmas under different pollination types, especially at the late post-pollination stage, where the expression of protease genes increasedal significantly under cross-pollination. We identified DEGs involved in the ribosomal, ubiquitination-mediated, and phyto-signaling pathways that may be involved in pitaya SI regulation. Based on the available transcriptome data and bioinformatics analysis, we tentatively identified HuS-RNase2 as a candidate gynogenetic S gene in the pitaya GSI system.

Different Mouse Models of Nemaline Myopathy Harboring Acta1 Mutations Display Differing Abnormalities Related to Mitochondrial Biology

ACTA1 encodes skeletal muscle-specific α-actin, which polymerizes to form the thin filament of the sarcomere. Mutations in ACTA1 are responsible for approximately 30% of nemaline myopathy (NM) cases. Previous studies of weakness in NM have focused on muscle structure and contractility, but genetic issues alone do not explain the phenotypic heterogeneity observed in patients with NM or NM mouse models. To identify additional biological processes related to NM phenotypic severity, proteomic analysis was performed using muscle protein isolates from wild-type mice in comparison to moderately affected knock-in (KI) Acta1H40Y and the minimally affected transgenic (Tg) ACTA1D286G NM mice. This analysis revealed abnormalities in mitochondrial function and stress-related pathways in both mouse models, supporting an in-depth assessment of mitochondrial biology. Interestingly, evaluating each model in comparison to its wild-type counterpart identified different degrees of mitochondrial abnormality that correlated well with the phenotypic severity of the mouse model. Muscle histology, mitochondrial respiration, electron transport chain function, and mitochondrial transmembrane potential were all normal or minimally affected in the TgACTA1D286G mouse model. In contrast, the more severely affected KI.Acta1H40Y mice displayed significant abnormalities in relation to muscle histology, mitochondrial respirometry, ATP, ADP, and phosphate content, and mitochondrial transmembrane potential. These findings suggest that abnormal energy metabolism is related to symptomatic severity in NM and may constitute a contributor to phenotypic variability and a novel treatment target.

Neural therapy in physiatric settings

Abstract The algorithmic approach modern medicine uses to diagnose and treat illness has helped it spread rapidly and control responsive ailments. On the other hand, a fair number of problems originate from within the person suffering (as opposed to lifestyle or genetic issues). Some of these manifest in ways that take a person through all the constituent investigations and treatments provided by modern medicine only to end up with a diagnosis that is otherwise taken as untreatable. While the clinicians involved are safe, having followed the evidence-based guidelines, the patient continues to live and suffer. Another set of problems prevails in healthcare. While modern medicine can save lives, once that life is saved, very few are aware of what to do next. Most clinicians either do not know what physiatry is, or assume it is physiotherapy. When families ask “What next,” the most common responses are go home and take care of the patient (wash the hands off), do whatever you want (put responsibility on the family), and get some physiotherapy (when not medically supervised is close to quackery). As the health condition (not the person) has been treated as much as possible, these responses are not wrong. Nor are they helpful to the patient/family. A subsection of these issues may be psychosomatic in nature and not controlled with the three mentioned modalities. This is where interventions such as neural therapy can help.

A Study and Analysis of Disease Identification using Genomic Sequence Processing Models: An Empirical Review.

Human gene sequences are considered a primary source of comprehensive information about different body conditions. A wide variety of diseases including cancer, heart issues, brain issues, genetic issues, etc. can be pre-empted via efficient analysis of genomic sequences. Researchers have proposed different configurations of machine learning models for processing genomic sequences, and each of these models varies in terms of their performance & applicability characteristics. Models that use bioinspired optimizations are generally slower, but have superior incremental-performance, while models that use one-shot learning achieve higher instantaneous accuracy but cannot be scaled for larger disease-sets. Due to such variations, it is difficult for genomic system designers to identify optimum models for their application-specific & performance-specific use cases. To overcome this issue, a detailed survey of different genomic processing models in terms of their functional nuances, application-specific advantages, deployment-specific limitations, and contextual future scopes is discussed in this text. Based on this discussion, researchers will be able to identify optimal models for their functional use cases. This text also compares the reviewed models in terms of their quantitative parameter sets, which include, the accuracy of classification, delay needed to classify large-length sequences, precision levels, scalability levels, and deployment cost, which will assist readers in selecting deployment-specific models for their contextual clinical scenarios. This text also evaluates a novel Genome Processing Efficiency Rank (GPER) for each of these models, which will allow readers to identify models with higher performance and low overheads under real-time scenarios.

THE CONSTRUCTION OF HADITH ADDRESSING GENETIC ENGINEERING OF HUMANS

This paper explores positions of hadith and ethics in discussing the genetic engineering of humans by departing from the following questions: a) how do hadith contribute to constructing various aspects of human genetics? b) how did the social context around Prophet Muhammad affect the construction of the hadith? c) how do hadith addressing human genetics relate to scientific development? This paper reveals that the ethics and process of genetic engineering are prescribed in the hadith, illuminating the contextual debates of its time. Issues of genetics that arise in the discourse of human existence, particularly regarding sex and skin color, show a contestation of values related to the position of genetic factors as undeniable. Scientific development provides answers to the increasingly complex and contestatory discourse on genetics and necessitates a paradigm shift in the Muslim community, which often places hadith as a believed and practiced textual truth

Gender effects on autism spectrum disorder: a multi-site resting-state functional magnetic resonance imaging study of transcriptome-neuroimaging.

The gender disparity in autism spectrum disorder (ASD) has been one of the salient features of condition. However, its relationship between the pathogenesis and genetic transcription in patients of different genders has yet to reach a reliable conclusion. To address this gap, this study aimed to establish a reliable potential neuro-marker in gender-specific patients, by employing multi-site functional magnetic resonance imaging (fMRI) data, and to further investigate the role of genetic transcription molecules in neurogenetic abnormalities and gender differences in autism at the neuro-transcriptional level. To this end, age was firstly used as a regression covariate, followed by the use of ComBat to remove the site effect from the fMRI data, and abnormal functional activity was subsequently identified. The resulting abnormal functional activity was then correlated by genetic transcription to explore underlying molecular functions and cellular molecular mechanisms. Abnormal brain functional activities were identified in autism patients of different genders, mainly located in the default model network (DMN) and precuneus-cingulate gyrus-frontal lobe. The correlation analysis of neuroimaging and genetic transcription further found that heterogeneous brain regions were highly correlated with genes involved in signal transmission between neurons' plasma membranes. Additionally, we further identified different weighted gene expression patterns and specific expression tissues of risk genes in ASD of different genders. Thus, this work not only identified the mechanism of abnormal brain functional activities caused by gender differences in ASD, but also explored the genetic and molecular characteristics caused by these related changes. Moreover, we further analyzed the genetic basis of sex differences in ASD from a neuro-transcriptional perspective.

Insights in orthodontic genetic and epigenetic knowledge and its translation in clinical practice

Applying genetic practice to current medicine has become more common and necessary in the prognosis, diagnosis and outcome of a myriad of diseases and disorders. Despite the general awareness of its importance, genetic knowledge still lacks direct application in daily orthodontic practice. The aim was to identify multiple genetic associations with orofacial phenotypes, highlight the importance of genetic influence in orthodontics, and describe challenges and gaps in integrating genetic knowledge in clinical practice. In the process, the influence of environmental factors on orofacial development and treatment is underscored, hence the role of epigenetics in regulating gene expression and tissue remodeling.

Genomic evidence reveals high genetic diversity in a narrowly distributed species and natural hybridization risk with a widespread species in the genus Geodorum

BackgroundUnderstanding genetic diversity is a core issue in conservation genetics. However, previous genetic diversity evaluations of narrowly distributed species have rarely used closely related widespread species as a reference. Furthermore, identifying natural hybridization signals between narrowly and widely distributed sympatric species is of great importance for the development of species conservation programs.MethodsIn this study, population genotyping by sequencing (GBS) was performed for a narrowly distributed species, Geodorum eulophioides (endemic and endangered in Southwest China), and a widespread species, G. densiflorum. A total of 18,490 high-quality single nucleotide polymorphisms (SNPs) were identified at the whole-genome level.ResultsThe results showed that the nucleotide diversity and heterozygosity of G. eulophioides were significantly higher than those of G. densiflorum, confirming that narrowly distributed species can still preserve high genetic diversity. Consistent with taxonomic boundaries, all sampled individuals from the two species were divided into two genetic clusters and showed high genetic differentiation between species. However, in a sympatric population, a few G. eulophioides individuals were detected with genetic components from G. densiflorum, suggesting potential interspecific natural hybridization. This hypothesis was supported by Treemix analysis and hand-hybridization trials. Invasion of the habitat of G. eulophioides invasion by G. densiflorum under anthropogenic disturbance may be the main factor causing interspecific hybridization.ConclusionsTherefore, reducing or avoiding habitat disturbance is a key measure to protect the G. eulophioides populations. This study provides valuable information for future conservation programs for narrowly distributed species.

Definition and conceptual model of genetics literacy: a systematic literature review

Genetic literacy is essential for promoting health and well-being in modern society. Although its importance is increasingly recognised, the definition and crucial dimension to construct a conceptual model are unclear, limiting the possibilities for measurement and comparison intervention. The study aims to review definitions and the conceptual models of genetics literacy and develop a new comprehensive definition and conceptual model based on the discovered dimensions that are relevant in the post-genomic era. We performed a systematic literature review using the Crossref, PubMed, and Scopus databases with Publish or Perish software. An automated content analysis was conducted to identify and develop conceptual model genetics literacy using NVivo 12 software. The review resulted in 10 definitions and 12 conceptual models. Automated content analysis showed that genetic literacy is defined as the ability of an individual to comprehend, use, correlate, assess, and propose genetic information to make arguments, reason, and decide on genetic issues in maintaining or improving the quality of personal and social well-being. Genetic literacy was conceptualised as a set of knowledge, a set of skills or interconnected. The conceptual model of genetics literacy covers two dimensions. i) Knowledge dimension: conceptual (nature of genetic material, transmission, genetic expression, genetic regulation, genetic determinism, genetic technology); sociocultural; epistemic. ii) Skills dimension: argumentation, informal reasoning, and decision-making skills. This definition and conceptual model can serve as a basis for developing interventions and measurements to support regulating, preventing, as well as promoting health and well-being.

A 5-hydroxymethylcytosine-based noninvasive model for ultrasensitive early detection of colorectal advanced adenoma and adenocarcinoma: The METHOD-2 study.

3042 Background: Detection of colorectal tumors at a time when there are more treatment options is associated with better outcomes. This prospective case-control study (NCT03676075) assessed the performance of 5-hydroxymethycytosine (5hmC) biomarkers in circulating cell-free DNA (cfDNA) to detect advanced colorectal adenomas (ADA) or adenocarcinomas (CRC). Methods: This multi-center study enrolled 2,576 participants, including patients with newly diagnosed CRC (n=1,074), ADA (n=356), other solid tumors (n=80), and healthy individuals (HEA) (n=1,066), followed by genome-wide 5hmC profiling using the 5hmC-Seal, a highly sensitive chemical labeling approach. A weighted diagnostic model for CRC (stage I-III) and ADA was developed using the elastic net regularization in a training set of age-, sex-, region-matched samples and validated in independent samples. Results: Distribution of 5hmC in cfDNA reflected gene regulatory relevance and tissue of origin. In an independent validation set of 482 samples, a 96-gene model trained in stage I-III CRC, ADA, and HEA achieved an AUC (area under the curve) of 92.6% (95% CI [confidence interval], 90.7-94.5%) for distinguishing CRC from HEA, regardless of primary location or mutation. This model also showed high capacity for distinguishing ADA from HEA with an AUC of 87.9% as well as cancer-type specificity. Model performance was further confirmed in samples from multiple centers. Functionally, differential 5hmC features associated with CRC and ADA demonstrated relevance to CRC biology, including pathways such as calcium and MAPK signaling. Conclusions: Genome-wide mapping of 5hmC in cfDNA shows promise as a highly sensitive and specific approach to be integrated in a screening program for improving early detection of CRC and high-risk ADA. Clinical trial information: NCT03676075 .

LRBmat: A novel gut microbial interaction and individual heterogeneity inference method for colorectal cancer

The gut microbial community has been shown to play a significant role in various diseases, including colorectal cancer (CRC), which is a major public health concern worldwide. The accurate diagnosis and etiological analysis of CRC are crucial issues. Numerous methods have utilized gut microbiota to address these challenges; however, few have considered the complex interactions and individual heterogeneity of the gut microbiota, which are important issues in genetics and intestinal microbiology, particularly in high-dimensional cases. This paper presents a novel method called Binary matrix based on Logistic Regression (LRBmat) to address these concerns. The binary matrix in LRBmat can directly mitigate or eliminate the influence of heterogeneity, while also capturing information on gut microbial interactions with any order. LRBmat is highly adaptable and can be combined with any machine learning method to enhance its capabilities. The proposed method was evaluated using real CRC data and demonstrated superior classification performance compared to state-of-the-art methods. Furthermore, the association rules extracted from the binary matrix of the real data align well with biological properties and existing literature, thereby aiding in the etiological analysis of CRC.

Predicting molecular mechanisms of hereditary diseases by using their tissue‐selective manifestation

How do aberrations in widely expressed genes lead to tissue‐selective hereditary diseases? Previous attempts to answer this question were limited to testing a few candidate mechanisms. To answer this question at a larger scale, we developed “Tissue Risk Assessment of Causality by Expression” (TRACE), a machine learning approach to predict genes that underlie tissue‐selective diseases and selectivity‐related features. TRACE utilized 4,744 biologically interpretable tissue‐specific gene features that were inferred from heterogeneous omics datasets. Application of TRACE to 1,031 disease genes uncovered known and novel selectivity‐related features, the most common of which was previously overlooked. Next, we created a catalog of tissue‐associated risks for 18,927 protein‐coding genes (https://netbio.bgu.ac.il/trace/). As proof‐of‐concept, we prioritized candidate disease genes identified in 48 rare‐disease patients. TRACE ranked the verified disease gene among the patient's candidate genes significantly better than gene prioritization methods that rank by gene constraint or tissue expression. Thus, tissue selectivity combined with machine learning enhances genetic and clinical understanding of hereditary diseases.

The positive effects of dietary arginine on juvenile hybrid snakehead (Channa maculata♀×Channa argus♂) fed high-carbohydrate diets: Liver inflammation antioxidant response, and glucose metabolism

The aim of this study was to investigate the effects of arginine supplementation on liver morphology, antioxidant capacity, inflammatory response, insulin signaling pathway and glucose metabolism in hybrid snakehead. Five experimental diets (2.31 %, 2.42 %, 2.72 %, 2.92 %, and 3.12 % arginine) were prepared by adding different levels of arginine to the basal diet containing high (27 %) level of carbohydrate. The results showed that the activities of superoxide dismutase (SOD), catalase (CAT), peroxidase (POD) and glutathione peroxidase (GSH-Px) of fish fed with arginine diets were significantly higher than those in control group (p < 0.05), accompanied by the lower malondialdehyde (MDA) content in the same groups (p < 0.05). There were obvious mild inflammatory cell infiltration and increased perihepatic pancreatic space in control group, while the pathological state of the liver was relieved in fish fed with arginine diets. Dietary arginine supplementation resulted in significantly higher glucose metabolism-related genes glucokinase (GK), phosphoenolpyruvate carboxkinase (PEPCK), glycogen synthase (GS) and pyruvate kinase (PK) and insulin signaling pathway key genes insulin receptor subset-1 (IRS-1), protein kinase B (Akt) and phosphoenolpyruvate carboxykinase (PI3K)(p < 0.05). Immune-related genes transforming growth factor β (TGF-β), heat shock protein 70 (HSP70) and heat shock protein 90 (HSP90) were significantly higher in the arginine supplemented diet than in the control group (p < 0.05). Immune-related genes interleukin-8 (IL8), interleukin-1β (IL1β) and tissue tumor necrosis factor-α (TNF-α) in fish fed with arginine diets were significantly lower than those in control group (p < 0.05). In conclusion, dietary arginine can alleviate the adverse effects of high carbohydrate diet on hybrid snakeheads by improving glucose metabolism and enhancing antioxidant, anti-inflammatory and non-specific immune functions.