Showing papers in "Genes in 2022"
TL;DR: The cuproptosis-related gene signature could serve as a potential prognostic predictor for ccRCC patients and may offer novel insights into the cancer treatment.
Abstract: Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of renal cell carcinoma, which is characterized by metabolic reprogramming. Cuproptosis, a novel form of cell death, is highly linked to mitochondrial metabolism and mediated by protein lipoylation. However, the clinical impacts of cuproptosis-related genes (CRGs) in ccRCC largely remain unclear. In the current study, we systematically evaluated the genetic alterations of cuproptosis-related genes in ccRCC. Our results revealed that CDKN2A, DLAT, DLD, FDX1, GLS, PDHA1 and PDHB exhibited differential expression between ccRCC and normal tissues (|log2(fold change)| > 2/3 and p < 0.05). Utilizing an iterative sure independence screening (SIS) method, we separately constructed the prognostic signature of CRGs for predicting the overall survival (OS) and progression-free survival (PFS) in ccRCC patients. The prognostic score of CRGs yielded an area under the curve (AUC) of 0.658 and 0.682 for the prediction of 5-year OS and PFS, respectively. In the Kaplan−Meier survival analysis of OS, a higher risk score of cuproptosis-related gene signature was significantly correlated with worse overall survival (HR = 2.72 (2.01–3.68), log-rank p = 1.76 × 10−7). Patients with a higher risk had a significantly shorter PFS (HR = 2.83 (2.08–3.85), log-rank p = 3.66 × 10−7). Two independent validation datasets (GSE40435 (N = 101), GSE53757 (N = 72)) were collected for meta-analysis, suggesting that CDKN2A (log2(fold change) = 1.46, 95%CI: 1.75–2.35) showed significantly higher expression in ccRCC tissues while DLAT (log2(fold change) = −0.54, 95%CI: −0.93–−0.15) and FDX1 (log2(fold change) = −1.01, 95%CI: −1.61–−0.42) were lowly expressed. The expression of CDKN2A and FDX1 in ccRCC was also significantly associated with immune infiltration levels and programmed cell death protein 1 (PD-1) expression (CDKN2A: r = 0.24, p = 2.14 × 10−8; FDX1: r = −0.17, p = 1.37 × 10−4). In conclusion, the cuproptosis-related gene signature could serve as a potential prognostic predictor for ccRCC patients and may offer novel insights into the cancer treatment.
136 citations
TL;DR: The crosstalk of melatonin with other phytohormones such as auxins, gibberellic acids, cytokinins, ethylene, and salicylic acid under normal and stressful conditions suggest that phytomelatonin is a key player in crop improvement and biotic and abiotic stress regulation.
Abstract: Melatonin was discovered in plants in the late nineties, but its role, signaling, and crosstalk with other phytohormones remain unknown. Research on melatonin in plants has risen dramatically in recent years and the role of this putative plant hormone under biotic and abiotic stress conditions has been reported. In the present review, we discuss the main functions of melatonin in the growth and development of plants, its role under abiotic stresses, such as water stress (waterlogging and drought), extreme temperature (low and high), salinity, heavy metal, and light-induced stress. Similarly, we also discuss the role of melatonin under biotic stresses (antiviral, antibacterial, and antifungal effects). Moreover, the present review meticulously discusses the crosstalk of melatonin with other phytohormones such as auxins, gibberellic acids, cytokinins, ethylene, and salicylic acid under normal and stressful conditions and reports melatonin receptors and signaling in plants. All these aspects of melatonin suggest that phytomelatonin is a key player in crop improvement and biotic and abiotic stress regulation.
24 citations
TL;DR: How functional mitochondria help cancer cells’ survival in the harsh tumor microenvironment, immune evasion, progression, and treatment resistance is described and how targeting mitochondria may improve oncological outcomes is explained.
Abstract: Like living organisms, cancer cells require energy to survive and interact with their environment. Mitochondria are the main organelles for energy production and cellular metabolism. Recently, investigators demonstrated that cancer cells can hijack mitochondria from immune cells. This behavior sheds light on a pivotal piece in the cancer puzzle, the dependence on the normal cells. This article illustrates the benefits of new functional mitochondria for cancer cells that urge them to hijack mitochondria. It describes how functional mitochondria help cancer cells’ survival in the harsh tumor microenvironment, immune evasion, progression, and treatment resistance. Recent evidence has put forward the pivotal role of mitochondria in the metabolism of cancer stem cells (CSCs), the tumor components responsible for cancer recurrence and metastasis. This theory highlights the mitochondria in cancer biology and explains how targeting mitochondria may improve oncological outcomes.
23 citations
TL;DR: This review highlights the relevance of studying brain-enriched miRNAs, the mechanisms underlying their regulation of target gene expression, their dysregulation leading to progressive neurodegeneration, and their potential for biomarker marker and therapeutic intervention.
Abstract: Neurodegenerative diseases originate from neuronal loss in the central nervous system (CNS). These debilitating diseases progress with age and have become common due to an increase in longevity. The National Institute of Environmental Health Science’s 2021 annual report suggests around 6.2 million Americans are living with Alzheimer’s disease, and there is a possibility that there will be 1.2 million Parkinson’s disease patients in the USA by 2030. There is no clear-cut universal mechanism for identifying neurodegenerative diseases, and therefore, they pose a challenge for neurobiology scientists. Genetic and environmental factors modulate these diseases leading to familial or sporadic forms. Prior studies have shown that miRNA levels are altered during the course of the disease, thereby suggesting that these noncoding RNAs may be the contributing factor in neurodegeneration. In this review, we highlight the role of miRNAs in the pathogenesis of neurodegenerative diseases. Through this review, we aim to achieve four main objectives: First, we highlight how dysregulation of miRNA biogenesis led to these diseases. Second, we highlight the computational or bioinformatics tools required to identify the putative molecular targets of miRNAs, leading to biological molecular pathways or mechanisms involved in these diseases. Third, we focus on the dysregulation of miRNAs and their target genes leading to several neurodegenerative diseases. In the final section, we highlight the use of miRNAs as potential diagnostic biomarkers in the early asymptomatic preclinical diagnosis of these age-dependent debilitating diseases. Additionally, we discuss the challenges and advances in the development of miRNA therapeutics for brain targeting. We list some of the innovative strategies employed to deliver miRNA into target cells and the relevance of these viral and non-viral carrier systems in RNA therapy for neurodegenerative diseases. In summary, this review highlights the relevance of studying brain-enriched miRNAs, the mechanisms underlying their regulation of target gene expression, their dysregulation leading to progressive neurodegeneration, and their potential for biomarker marker and therapeutic intervention. This review thereby highlights ways for the effective diagnosis and prevention of these neurodegenerative disorders in the near future.
23 citations
TL;DR: This study strongly suggests that the CYP11A1, CYP17A 1, and CYP19A1 genes might significantly enhance the probability of developing PCOS with infertility.
Abstract: Polycystic ovary syndrome is a multifactorial condition associated with reproductive and endocrine organs and might cause infertility and metabolic abnormalities in childbearing age. PCOS seems to be a multifactorial disorder resulting from the combination of several genetic and environmental factors. Little research has been conducted to date on the impact of polymorphisms in infertility. We aim to review the appearance of polymorphisms in females of diverse ethnicities and their effect on infertility in the population with polycystic ovary syndrome. There have been numerous reports of the importance of the steroidogenesis pathway and genetic variants in PCOS pathogenesis. The most important genes that play a role in the aetiology of PCOS are CYP11A1, CYP17A1, and CYP19A1. We evaluated the occurrence of polymorphisms in various ethnicities in the CYP11A1, CYP17A1, and CYP19A1 genes and their efficacy on increasing PCOS risk with infertility. Our findings revealed that polymorphisms in various ethnicities are associated with the risk of PCOS with infertility. Although conflicting results regarding CYP11A1, CYP17A1, and CYP19A1 polymorphisms and their influence on PCOS with infertility have been reported in a small number of papers, the authors feel this may be attributable to the sample size and ethnic composition of the examined populations. In conclusion, our study strongly suggests that the CYP11A1, CYP17A1, and CYP19A1 genes might significantly enhance the probability of developing PCOS with infertility.
23 citations
TL;DR: It is highlighted that monogenic Parkinson’s disease is influenced by ethnicity and geographical differences, reinforcing the need for global efforts to pool large numbers of patients and identify novel candidate genes.
Abstract: Parkinson’s disease may be caused by a single pathogenic variant (monogenic) in 5–10% of cases, but investigation of these disorders provides valuable pathophysiological insights. In this review, we discuss each genetic form with a focus on genotype, phenotype, pathophysiology, and the geographic and ethnic distribution. Well-established Parkinson’s disease genes include autosomal dominant forms (SNCA, LRRK2, and VPS35) and autosomal recessive forms (PRKN, PINK1 and DJ1). Furthermore, mutations in the GBA gene are a key risk factor for Parkinson’s disease, and there have been major developments for X-linked dystonia parkinsonism. Moreover, atypical or complex parkinsonism may be due to mutations in genes such as ATP13A2, DCTN1, DNAJC6, FBXO7, PLA2G6, and SYNJ1. Furthermore, numerous genes have recently been implicated in Parkinson’s disease, such as CHCHD2, LRP10, TMEM230, UQCRC1, and VPS13C. Additionally, we discuss the role of heterozygous mutations in autosomal recessive genes, the effect of having mutations in two Parkinson’s disease genes, the outcome of deep brain stimulation, and the role of genetic testing. We highlight that monogenic Parkinson’s disease is influenced by ethnicity and geographical differences, reinforcing the need for global efforts to pool large numbers of patients and identify novel candidate genes.
20 citations
TL;DR: This review focuses on progress in the study of m1A methyltransferases,m1A demethylases and m1a-dependent RNA-binding proteins and highlights the biological mechanisms and functions of m 1A RNA modification, as well as its association with human disease.
Abstract: N1-methyladenosine (m1A) is a prevalent and reversible post-transcriptional RNA modification that decorates tRNA, rRNA and mRNA. Recent studies based on technical advances in analytical chemistry and high-throughput sequencing methods have revealed the crucial roles of m1A RNA modification in gene regulation and biological processes. In this review, we focus on progress in the study of m1A methyltransferases, m1A demethylases and m1A-dependent RNA-binding proteins and highlight the biological mechanisms and functions of m1A RNA modification, as well as its association with human disease. We also summarize the current understanding of detection approaches for m1A RNA modification.
19 citations
TL;DR: In this article , the major differences between M1-like and M2-like macrophages, their associated metabolic pathways, and their roles in atherosclerosis are discussed.
Abstract: The implication of the heterogeneous spectrum of pro- and anti-inflammatory macrophages (Macs) has been an important area of investigation over the last decade. The polarization of Macs alters their functional phenotype in response to their surrounding microenvironment. Macs are the major immune cells implicated in the pathogenesis of atherosclerosis. A hallmark pathology of atherosclerosis is the accumulation of pro-inflammatory M1-like macrophages in coronary arteries induced by pro-atherogenic stimuli; these M1-like pro-inflammatory macrophages are incapable of digesting lipids, thus resulting in foam cell formation in the atherosclerotic plaques. Recent findings suggest that the progression and stability of atherosclerotic plaques are dependent on the quantity of infiltrated Macs, the polarization state of the Macs, and the ratios of different types of Mac populations. The polarization of Macs is defined by signature markers on the cell surface, as well as by factors in intracellular and intranuclear compartments. At the same time, pro- and anti-inflammatory polarized Macs also exhibit different gene expression patterns, with differential cellular characteristics in oxidative phosphorylation and glycolysis. Macs are reflective of different metabolic states and various types of diseases. In this review, we discuss the major differences between M1-like Macs and M2-like Macs, their associated metabolic pathways, and their roles in atherosclerosis.
19 citations
TL;DR: The de novo assembly and annotation of the complete chloroplast genome of wax gourd with 156,758 bp is reported, suggesting a difference in genome size, gene duplication and deletion, and the presence of pseudogenes.
Abstract: Benincasa hispida (wax gourd) is an important Cucurbitaceae crop, with enormous economic and medicinal importance. Here, we report the de novo assembly and annotation of the complete chloroplast genome of wax gourd with 156,758 bp in total. The quadripartite structure of the chloroplast genome comprises a large single-copy (LSC) region with 86,538 bp and a small single-copy (SSC) region with 18,060 bp, separated by a pair of inverted repeats (IRa and IRb) with 26,080 bp each. Comparison analyses among B. hispida and three other species from Benincaseae presented a significant conversion regarding nucleotide content, genome structure, codon usage, synonymous and non-synonymous substitutions, putative RNA editing sites, microsatellites, and oligonucleotide repeats. The LSC and SSC regions were found to be much more varied than the IR regions through a divergent analysis of the species within Benincaseae. Notable IR contractions and expansions were observed, suggesting a difference in genome size, gene duplication and deletion, and the presence of pseudogenes. Intronic gene sequences, such as trnR-UCU–atpA and atpH–atpI, were observed as highly divergent regions. Two types of phylogenetic analysis based on the complete cp genome and 72 genes suggested sister relationships between B. hispida with the Citrullus, Lagenaria, and Cucumis. Variations and consistency with previous studies regarding phylogenetic relationships are discussed. The cp genome of B. hispida provides valuable genetic information for the detection of molecular markers, research on taxonomic discrepancies, and the inference of the phylogenetic relationships of Cucurbitaceae.
17 citations
TL;DR: Clinical features and genetic diagnosis of diseases caused by mutations in the gene encoding valosin-containing protein (VCP/p97), the functionally diverse AAA-ATPase, and genetic counselling implications of VCP-MSP are reviewed.
Abstract: In this work, we review clinical features and genetic diagnosis of diseases caused by mutations in the gene encoding valosin-containing protein (VCP/p97), the functionally diverse AAA-ATPase. VCP is crucial to a multitude of cellular functions including protein quality control, stress granule formation and clearance, and genomic integrity functions, among others. Pathogenic mutations in VCP cause multisystem proteinopathy (VCP-MSP), an autosomal dominant, adult-onset disorder causing dysfunction in several tissue types. It can result in complex neurodegenerative conditions including inclusion body myopathy, frontotemporal dementia, amyotrophic lateral sclerosis, or combinations of these. There is also an association with other neurodegenerative phenotypes such as Alzheimer-type dementia and Parkinsonism. Non-neurological presentations include Paget disease of bone and may also include cardiac dysfunction. We provide a detailed discussion of genotype-phenotype correlations, recommendations for genetic diagnosis, and genetic counselling implications of VCP-MSP.
16 citations
TL;DR: In this review, the basic principle of alternative splicing is concluded and how splicing isoforms affect physiological activities through specific disease examples are shown.
Abstract: Alternative splicing of pre-mRNA is a key mechanism for increasing the complexity of proteins in humans, causing a diversity of expression of transcriptomes and proteomes in a tissue-specific manner. Alternative splicing is regulated by a variety of splicing factors. However, the changes and errors of splicing regulation caused by splicing factors are strongly related to many diseases, something which represents one of this study’s main interests. Further understanding of alternative splicing regulation mediated by cellular factors is also a prospective choice to develop specific drugs for targeting the dynamic RNA splicing process. In this review, we firstly concluded the basic principle of alternative splicing. Afterwards, we showed how splicing isoforms affect physiological activities through specific disease examples. Finally, the available treatment methods relative to adjusting splicing activities have been summarized.
TL;DR: The aim is to be able to initiate the production of enough dystrophin to change the rate of progression and create a clinical shift towards the better in Duchenne muscular dystrophy.
Abstract: Molecular treatments for Duchenne muscular dystrophy (DMD) are already in clinical practice. One particular means is exon skipping, an approach which has more than 15 years of background. There are several promising clinical trials based on earlier works. The aim is to be able to initiate the production of enough dystrophin to change the rate of progression and create a clinical shift towards the better. Some of these molecules already have received at least conditional approval by health authorities; however, we still need new accumulating data.
TL;DR: This review summarizes the current state of development of N-terminal antisense and gene therapies for DMD, mainly focusing on exon-skipping therapy for duplications and deletions, as well as microdystrophin therapy.
Abstract: Duchenne muscular dystrophy (DMD) is a fatal genetic disease affecting children that is caused by a mutation in the gene encoding for dystrophin. In the absence of functional dystrophin, patients experience progressive muscle deterioration, leaving them wheelchair-bound by age 12 and with few patients surviving beyond their third decade of life as the disease advances and causes cardiac and respiratory difficulties. In recent years, an increasing number of antisense and gene therapies have been studied for the treatment of muscular dystrophy; however, few of these therapies focus on treating mutations arising in the N-terminal encoding region of the dystrophin gene. This review summarizes the current state of development of N-terminal antisense and gene therapies for DMD, mainly focusing on exon-skipping therapy for duplications and deletions, as well as microdystrophin therapy.
TL;DR: It was demonstrated that this four-gene signature was a better prognostic factor than clinical factors such as age and stage of disease and that their high expression was associated with a lower risk of death.
Abstract: Lung adenocarcinoma (LUAD) is often diagnosed at an advanced stage, so it is necessary to identify potential biomarkers for the early diagnosis and prognosis of LUAD. In our study, a gene co-expression network was constructed using weighted gene co-expression network analysis (WGCNA) in order to obtain the key modules and genes correlated with LUAD prognosis. Four hub genes (HLF, CHRDL1, SELENBP1, and TMEM163) were screened out using least absolute shrinkage and selection operator (LASSO)–Cox regression analysis; then, a prognostic model was established for predicting overall survival (OS) based on these four hub genes..Furthermore, the prognostic values of this four-gene signature were verified in four validation sets (GSE26939, GSE31210, GSE72094, and TCGA-LUAD) as well as in the GEPIA database. To assess the prognostic values of hub genes, receiver operating characteristic (ROC) curves were constructed and a nomogram was created. We found that a higher expression of four hub genes was associated with a lower risk of patient death. In a training set, it was demonstrated that this four-gene signature was a better prognostic factor than clinical factors such as age and stage of disease. Moreover, our results revealed that these four genes were suppressor factors of LUAD and that their high expression was associated with a lower risk of death. In summary, we demonstrated that this four-gene signature could be a potential prognostic factor for LUAD patients. These findings provide a theoretical basis for exploring potential biomarkers for LUAD prognosis prediction in the future.
TL;DR: BPA’s ability to alter oxidative stress in oocytes and, to a lesser extent, in sperm is supported, however, BPS and BPF likely act through different mechanisms.
Abstract: Bisphenol A (BPA) and its analogs, bisphenol S (BPS) and bisphenol F (BPF), might impact fertility by altering oxidative stress pathways. Here, we hypothesize that bisphenols-induced oxidative stress is responsible for decreased gamete quality. In both female (cumulus-oocyte-complexes—COCs) and male (spermatozoa), oxidative stress was measured by CM-H2DCFDA assay and key ROS scavengers (SOD1, SOD2, GPX1, GPX4, CAT) were quantified at the mRNA and protein levels using qPCR and Western blot (COCs)/immunofluorescence (sperm). Either gamete was treated in five groups: control, vehicle, and 0.05 mg/mL of BPA, BPS, or BPF. Our results show elevated ROS in BPA-treated COCs but decreased production in BPS- and BPF-treated spermatozoa. Additionally, both mRNA and protein expression of SOD2, GPX1, and GPX4 were decreased in BPA-treated COCs (p < 0.05). In sperm, motility (p < 0.03), but not morphology, was significantly altered by bisphenols. SOD1 mRNA expression was significantly increased, while GPX4 was significantly reduced. These results support BPA’s ability to alter oxidative stress in oocytes and, to a lesser extent, in sperm. However, BPS and BPF likely act through different mechanisms.
TL;DR: The roles of lncRNAs in regulating the angiogenic switch are reviewed and their potential use as both prognostic biomarkers and targets for the development of future therapies are discussed.
Abstract: Angiogenesis is one of the hallmarks of cancer, and the establishment of new blood vessels is vital to allow for a tumour to grow beyond 1–2 mm in size. The angiogenic switch is the term given to the point where the number or activity of the pro-angiogenic factors exceeds that of the anti-angiogenic factors, resulting in the angiogenic process proceeding, giving rise to new blood vessels accompanied by increased tumour growth, metastasis, and potential drug resistance. Long noncoding ribonucleic acids (lncRNAs) have been found to play a role in the angiogenic switch by regulating gene expression, transcription, translation, and post translation modification. In this regard they play both anti-angiogenic and pro-angiogenic roles. The expression levels of the pro-angiogenic lncRNAs have been found to correlate with patient survival. These lncRNAs are also potential drug targets for the development of therapies that will inhibit or modify tumour angiogenesis. Here we review the roles of lncRNAs in regulating the angiogenic switch. We cover specific examples of both pro and anti-angiogenic lncRNAs and discuss their potential use as both prognostic biomarkers and targets for the development of future therapies.
TL;DR: This study made use of scientometric methods, particularly document co-citation analysis (DCA), to systematically review literature on ASD genetic research from 2018 to 2022, and revealed that recent literature on ASD genetic research can be broadly organised into 12 major clusters representing various sub-topics.
Abstract: Genetic research in Autism Spectrum Disorder (ASD) has progressed tremendously in recent decades. Dozens of genetic loci and hundreds of alterations in the genetic sequence, expression, epigenetic transformation, and interactions with other physiological and environmental systems have been found to increase the likelihood of developing ASD. There is therefore a need to represent this wide-ranging yet voluminous body of literature in a systematic manner so that this information can be synthesised and understood at a macro level. Therefore, this study made use of scientometric methods, particularly document co-citation analysis (DCA), to systematically review literature on ASD genetic research from 2018 to 2022. A total of 14,818 articles were extracted from Scopus and analyzed with CiteSpace. An optimized DCA analysis revealed that recent literature on ASD genetic research can be broadly organised into 12 major clusters representing various sub-topics. These clusters are briefly described in the manuscript and potential applications of this study are discussed.
TL;DR: The baker’s yeast Saccharomyces cerevisiae has become a powerful model in ecology and evolutionary biology and exhibit hallmark differences in sexuality, heterozygosity, gene copy number variation, horizontal gene transfer and introgression events, and maltose utilization ability.
Abstract: The baker’s yeast Saccharomyces cerevisiae has become a powerful model in ecology and evolutionary biology. A global effort on field survey and population genetics and genomics of S. cerevisiae in past decades has shown that the yeast distributes ubiquitously in nature with clearly structured populations. The global genetic diversity of S. cerevisiae is mainly contributed by strains from Far East Asia, and the ancient basal lineages of the species have been found only in China, supporting an ‘out-of-China’ origin hypothesis. The wild and domesticated populations are clearly separated in phylogeny and exhibit hallmark differences in sexuality, heterozygosity, gene copy number variation (CNV), horizontal gene transfer (HGT) and introgression events, and maltose utilization ability. The domesticated strains from different niches generally form distinct lineages and harbor lineage-specific CNVs, HGTs and introgressions, which contribute to their adaptations to specific fermentation environments. However, whether the domesticated lineages originated from a single, or multiple domestication events is still hotly debated and the mechanism causing the diversification of the wild lineages remains to be illuminated. Further worldwide investigations on both wild and domesticated S. cerevisiae, especially in Africa and West Asia, will be helpful for a better understanding of the natural and domestication histories and evolution of S. cerevisiae.
TL;DR: In this article , the salt tolerance of 200 diverse flax accessions during the germination stage was evaluated, and then the Genome-Wide Association Study (GWAS) was carried out based on the relative germination rate (RGR), relative shoot length (RSL) and relative root length (RRL), whereby quantitative trait loci (QTLs) related to salt tolerance were identified.
Abstract: Soil salinization seriously affects the growth and distribution of flax. However, there is little information about the salt tolerance of flax. In this study, the salt tolerance of 200 diverse flax accessions during the germination stage was evaluated, and then the Genome-wide Association Study (GWAS) was carried out based on the relative germination rate (RGR), relative shoot length (RSL) and relative root length (RRL), whereby quantitative trait loci (QTLs) related to salt tolerance were identified. The results showed that oil flax had a better salt tolerance than fiber flax. A total of 902 single nucleotide polymorphisms (SNPs) were identified on 15 chromosomes. These SNPs were integrated into 64 QTLs, explaining 14.48 to 29.38% (R2) of the phenotypic variation. In addition, 268 candidate genes were screened by combining previous transcriptome data and homologous gene annotation. Among them, Lus10033213 is a single-point SNP repeat mapping gene, which encodes a Glutathione S-transferase (GST). This study is the first to use GWAS to excavate genes related to salt tolerance during the germination stage of flax. The results of this study provide important information for studying the genetic mechanism of salt tolerance of flax, and also provide the possibility to improve the salt tolerance of flax.
TL;DR: This study identified an ancient DNA extraction protocol that resulted in the recovery of significantly more human mtDNA fragments than protocols previously used in casework, and utilizing single-stranded rather than double-Stranded library preparation resulted in increased attainment of reportable mtDNA profiles.
Abstract: The integration of massively parallel sequencing (MPS) technology into forensic casework has been of particular benefit to the identification of unknown military service members. However, highly degraded or chemically treated skeletal remains often fail to provide usable DNA profiles, even with sensitive mitochondrial (mt) DNA capture and MPS methods. In parallel, the ancient DNA field has developed workflows specifically for degraded DNA, resulting in the successful recovery of nuclear DNA and mtDNA from skeletal remains as well as sediment over 100,000 years old. In this study we use a set of disinterred skeletal remains from the Korean War and World War II to test if ancient DNA extraction and library preparation methods improve forensic DNA profiling. We identified an ancient DNA extraction protocol that resulted in the recovery of significantly more human mtDNA fragments than protocols previously used in casework. In addition, utilizing single-stranded rather than double-stranded library preparation resulted in increased attainment of reportable mtDNA profiles. This study emphasizes that the combination of ancient DNA extraction and library preparation methods evaluated here increases the success rate of DNA profiling, and likelihood of identifying historical remains.
TL;DR: A common wheat genotype, Aus27352 from Yugoslavia, showed resistance to currently predominating Australian pathotypes of the wheat leaf rust pathogen as discussed by the authors , which was temporarily named LrAW2.
Abstract: Breeding for leaf rust resistance has been successful worldwide and is underpinned by the discovery and characterisation of genetically diverse sources of resistance. An English scientist, Arthur Watkins, collected pre-Green Revolution wheat genotypes from 33 locations worldwide in the early part of the 20th Century and this collection is now referred to as the ‘Watkins Collection’. A common wheat genotype, Aus27352 from Yugoslavia, showed resistance to currently predominating Australian pathotypes of the wheat leaf rust pathogen. We crossed Aus27352 with a leaf rust susceptible wheat selection Avocet S and a recombinant inbred line (RIL) F6 population of 200 lines was generated. Initial screening at F3 generation showed monogenic segregation for seedling response to leaf rust in Aus27352. These results were confirmed by screening the Aus27352/Avocet S RIL population. The underlying locus was temporarily named LrAW2. Bulked segregant analysis using the 90K Infinium SNP array located LrAW2 in the long arm of chromosome 2B. Tests with molecular markers linked to two leaf rust resistance genes, Lr50 and Lr58, previously located in chromosome 2B, indicated the uniqueness of LrAW2 and it was formally designated Lr82. Kompetitive allele-specific polymerase chain reaction assays were developed for Lr82-linked SNPs. KASP_22131 mapped 0.8 cM proximal to Lr82 and KASP_11333 was placed 1.2 cM distal to this locus. KASP_22131 showed 91% polymorphism among a set of 89 Australian wheat cultivars. We recommend the use of KASP_22131 for marker assisted pyramiding of Lr82 in breeding programs following polymorphism check on parents.
TL;DR: The study revealed that native genetic resistance to FAW is quantitative in nature and is controlled by many loci with minor effects.
Abstract: The recent invasion, rapid spread, and widescale destruction of the maize crop by the fall armyworm (FAW; Spodoptera frugiperda (J.E. Smith)) is likely to worsen the food insecurity situation in Africa. In the present study, a set of 424 maize lines were screened for their responses to FAW under artificial infestation to dissect the genetic basis of resistance. All lines were evaluated for two seasons under screen houses and genotyped with the DArTseq platform. Foliar damage was rated on a scale of 1 (highly resistant) to 9 (highly susceptible) and scored at 7, 14, and 21 days after artificial infestation. Analyses of variance revealed significant genotypic and genotype by environment interaction variances for all traits. Heritability estimates for leaf damage scores were moderately high and ranged from 0.38 to 0.58. Grain yield was negatively correlated with a high magnitude to foliar damage scores, ear rot, and ear damage traits. The genome-wide association study (GWAS) revealed 56 significant marker–trait associations and the predicted functions of the putative candidate genes varied from a defense response to several genes of unknown function. Overall, the study revealed that native genetic resistance to FAW is quantitative in nature and is controlled by many loci with minor effects.
TL;DR: The molecular changes linked to epigenetic and epitranscriptomic dysregulation in prostate cancer and the role that alterations to DNA and RNA modifications play in the initiation and progression of prostate cancer are summarized.
Abstract: The initiation of prostate cancer has been long associated with DNA copy-number alterations, the loss of specific chromosomal regions and gene fusions, and driver mutations, especially those of the Androgen Receptor. Non-mutational events, particularly DNA and RNA epigenetic dysregulation, are emerging as key players in tumorigenesis. In this review we summarize the molecular changes linked to epigenetic and epitranscriptomic dysregulation in prostate cancer and the role that alterations to DNA and RNA modifications play in the initiation and progression of prostate cancer.
TL;DR: This review will provide an overview of the recent developments in gemcitabine prodrugs and their effectiveness in treating cancerous tumors.
Abstract: Gemcitabine is a nucleoside analog that has been used widely as an anticancer drug for the treatment of a variety of conditions, including ovarian, bladder, non-small-cell lung, pancreatic, and breast cancer. However, enzymatic deamination, fast systemic clearance, and the emergence of chemoresistance have limited its efficacy. Different prodrug strategies have been explored in recent years, seeking to obtain better pharmacokinetic properties, efficacy, and safety. Different drug delivery strategies have also been employed, seeking to transform gemcitabine into a targeted medicine. This review will provide an overview of the recent developments in gemcitabine prodrugs and their effectiveness in treating cancerous tumors.
TL;DR: The most efficient cleaning strategies for cell-free DNA were the different sodium hypochlorite solutions and Trigene®, for which a maximum of 0.3% DNA was recovered on all three surfaces.
Abstract: Decontamination strategies and their efficiencies are crucial when performing routine forensic analysis, and many factors influence the choice of agent to use. In this study, the effects of ten different cleaning strategies were evaluated to compare their ability to remove contaminating DNA molecules. Cell-free DNA or blood was deposited on three surfaces (plastic, metal, and wood) and decontaminated with various treatments. The quantities of recovered DNA, obtained by swabbing the surfaces after cleaning using the different strategies, was analyzed by real-time PCR. Large differences in the DNA removal efficiencies were observed between different cleaning strategies, as well as between different surfaces. The most efficient cleaning strategies for cell-free DNA were the different sodium hypochlorite solutions and Trigene®, for which a maximum of 0.3% DNA was recovered on all three surfaces. For blood, a maximum of 0.8% of the deposited DNA was recovered after using Virkon® for decontamination. The recoveries after using these cleaning strategies correspond to DNA from only a few cells, out of 60 ng of cell-free DNA or thousands of deposited blood cells.
TL;DR: This univariate analysis confirms the potential of systemic inflammation indexes in patients with glioblastoma, while the multivariate analysis verifies the prognostic value of NPW/LM and NPM/L.
Abstract: Background. Systemic immunity and inflammation indexes (SI) derived from blood cells have gained increasing attention in clinical oncology as potential biomarkers that are associated with survival. Materials and methods. We tested 12 different SI using blood tests from patients with isocitrate dehydrogenase 1 and 2 wild-type glioblastomas, treated with radio-chemotherapy. The primary endpoint was their overall survival. Results. A total of 77 patients, comprising 43 males and 34 females, with a median age of 64 years (age range 26–84), who were treated between October 2010 and July 2020, were included in the present analysis (approved by a local ethics committee). In the univariate Cox regression analysis, all the indexes except two showed a statistically significant impact on OS. In the multivariate Cox regression analysis, neutrophil × platelet × leukocyte/(lymphocyte × monocyte) (NPW/LM) and neutrophil × platelet × monocyte/lymphocyte (NPM/L) maintained their statistically significant impact value. Conclusions. This univariate analysis confirms the potential of systemic inflammation indexes in patients with glioblastoma, while the multivariate analysis verifies the prognostic value of NPW/LM and NPM/L.
TL;DR: Cis-acting elements analysis showed that WAK/WAKL might be involved in plant growth and development, plant response to abiotic stress and hormones, andGene expression pattern analysis indicated that most WAK-like kinase genes in J. regia might play a role in the development of leaves and be involvement in plant response in biotic stress.
Abstract: Wall-associated kinase (WAK) and WAK-like kinase (WAKL) are receptor-like kinases (RLKs), which play important roles in signal transduction between the cell wall and the cytoplasm in plants. WAK/WAKLs have been studied in many plants, but were rarely studied in the important economic walnut tree. In this study, 27 and 14 WAK/WAKL genes were identified in Juglans regia and its wild related species Juglans mandshurica, respectively. We found tandem duplication might play a critical role in the expansion of WAK/WAKL gene family in J. regia, and most of the WAK/WAKL homologous pairs underwent purified selection during evolution. All WAK/WAKL proteins have the extracellular WAK domain and the cytoplasmic protein kinase domain, and the latter was more conserved than the former. Cis-acting elements analysis showed that WAK/WAKL might be involved in plant growth and development, plant response to abiotic stress and hormones. Gene expression pattern analysis further indicated that most WAK/WAKL genes in J. regia might play a role in the development of leaves and be involved in plant response to biotic stress. Our study provides a new perspective for the evolutionary analysis of gene families in tree species and also provides potential candidate genes for studying WAK/WAKL gene function in walnuts.
TL;DR: The importance of evaluating extraction and normalization for reliable miRNA analysis and how miRNA detection accuracy, especially from plasma, can be improved are described and explored.
Abstract: MicroRNAs (miRNAs) are promising molecules that can regulate gene expression, and their expression level and type have been associated with early diagnosis, targeted therapy, and prognosis of various diseases. Therefore, analysis of miRNA in the plasma or serum is useful for the discovery of biomarkers and the diagnosis of implicated diseases to achieve potentially unprecedented progress in early treatment. Numerous methods to improve sensitivity have recently been proposed and confirmed to be valuable in miRNA detection. Specifically, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) is an effective and common method for sensitive and specific analysis of miRNA from biological fluids, such as plasma or serum. Despite this, the application of qRT-PCR is limited, as it can be affected by various contaminants. Therefore, extraction studies have been frequently conducted to maximize the extracted miRNA amount while simultaneously minimizing contaminants. Moreover, studies have evaluated extraction efficiency and normalization of the extracted sample. However, variability in results among laboratories still exists. In this review, we aimed to summarize the factors influencing the qualification and quantification of miRNAs in the plasma using qRT-PCR. Factors influencing reliable analysis of miRNA using qRT-PCR are described in detail. Additionally, we aimed to describe the importance of evaluating extraction and normalization for reliable miRNA analysis and to explore how miRNA detection accuracy, especially from plasma, can be improved.
TL;DR: In this paper , the authors investigated within-population prediction accuracies using the baseline M1 model and two reaction norm models (M2 and M3) with three random cross-validation (CV1, CV2, and CV0) schemes.
Abstract: Some studies have investigated the potential of genomic selection (GS) on stripe rust, leaf rust, Fusarium head blight (FHB), and leaf spot in wheat, but none of them have assessed the effect of the reaction norm model that incorporated GE interactions. In addition, the prediction accuracy on common bunt has not previously been studied. Here, we investigated within-population prediction accuracies using the baseline M1 model and two reaction norm models (M2 and M3) with three random cross-validation (CV1, CV2, and CV0) schemes. Three Canadian spring wheat populations were evaluated in up to eight field environments and genotyped with 3158, 5732, and 23,795 polymorphic markers. The M3 model that incorporated GE interactions reduced residual variance by an average of 10.2% as compared with the main effect M2 model and increased prediction accuracies on average by 2-6%. In some traits, the M3 model increased prediction accuracies up to 54% as compared with the M2 model. The average prediction accuracies of the M3 model with CV1, CV2, and CV0 schemes varied from 0.02 to 0.48, from 0.25 to 0.84, and from 0.14 to 0.87, respectively. In both CV2 and CV0 schemes, stripe rust in all three populations, common bunt and leaf rust in two populations, as well as FHB severity, FHB index, and leaf spot in one population had high to very high (0.54-0.87) prediction accuracies. This is the first comprehensive genomic selection study on five major diseases in spring wheat.
TL;DR: In this article , a total of 5324 single nucleotide polymorphisms associated with parthenocarpy were detected in a Genome-wide association study (GWAS) of cucumber lines, from which six loci, including two novel loci (Pfs1.1 and Pfs4.1), were identified.
Abstract: Parthenocarpy is an important agronomic trait in cucumber (Cucumis sativus L.) production. However, the systematic identification of parthenocarpic germplasms from national gene banks for cucumber improvement remains an international challenge. In this study, 201 cucumber lines were investigated, including different ecotypes. The percentages of parthenocarpic fruit set (PFS) and parthenocarpic fruit expansion (PFE) were evaluated in three experiments. In natural populations, the PFS rates fit a normal distribution, while PFE rates showed a skewed distribution, suggesting that both PFS and PFE rates are typical quantitative traits. Genetic analysis showed that parthenocarpy in different ecotypes was inherited in a similar incompletely dominant manner. A total of 5324 single nucleotide polymorphisms (SNPs) associated with parthenocarpy were detected in a Genome-wide association study (GWAS) of parthenocarpy in the 31 cucumber lines, from which six parthenocarpic loci, including two novel loci (Pfs1.1 and Pfs4.1), were identified. Consequently, fifteen of the elite lines that were screened presented relatively stronger parthenocarpy ability (PFS > 90%, PFE > 50%), among which six cucumber lines (18007s, 18008s, 18022s, 18076s, 18099s, and 18127s) exhibited weak first-fruit inhibition. Three lines (18011s, 18018s, and 18019s) were screened for super ovary parthenocarpy, which showed more attractive performance. Four low-temperature-enhanced parthenocarpy lines (18018s, 18022s, 18029s, and 18012s) were identified, which were suited for breeding for counter-season production. Our approaches could help increase efficiency and lead to parthenocarpy improvements for modern cucumber cultivars.