Genetics and Molecular Biology最新文献

Integrative network analysis (INA) is important for identifying gene modules or epigenetically regulated molecular pathways in diseases. This study evaluated the effect of excessive gestational weight gain (EGWG) on INA of differentially methylated regions, maternal metabolism and offspring growth. Brazilian women from "The Araraquara Cohort Study" with adequate pre-pregnancy body mass index were divided into EGWG (n=30) versus adequate gestational weight gain (AGWG, n=45) groups. The methylome analysis was performed on maternal blood using the Illumina MethylationEPIC BeadChip. Fetal-neonatal growth was assessed by ultrasound and anthropometry, respectively. Maternal lipid and glycemic profiles were investigated. Maternal triglycerides-TG (p=0.030) and total cholesterol (p=0.014); fetus occipito-frontal diameter (p=0.005); neonate head circumference-HC (p=0.016) and thoracic perimeter (p=0.020) were greater in the EGWG compared to the AGWG group. Multiple linear regression analysis showed that maternal DNA methylation was associated with maternal TG and fasting insulin, fetal abdominal circumference, and fetal and neonate HC. The DMRs studied were enriched in 142 biological processes, 21 molecular functions,and 17 cellular components with terms directed for the fatty acids metabolism. Three DMGMs were identified:COL3A1, ITGA4 and KLRK1. INA targeted chronic diseases and maternal metabolism contributing to an epigenetic understanding of the involvement of GWG in maternal metabolism and fetal-neonatal growth.

Photosynthetic phosphoenolpyruvate carboxylase (PEPC) catalyses the irreversible carboxylation of phosphoenolpyruvate (PEP), producing oxaloacetate (OAA). This enzyme catalyses the first step of carbon fixation in C4 photosynthesis, contributing to the high photosynthetic efficiency of C4 plants. PEPC is also involved in replenishing tricarboxylic acid cycle intermediates, such as OAA, being involved in the C/N balance. In plants, PEPCs are classified in two types: bacterial type (BTPC) and plant-type (PTPC), which includes photosynthetic and non-photosynthetic PEPCs. During C4 evolution, photosynthetic PEPCs evolved independently. C4 PEPCs evolved to be highly expressed and active in a spatial-specific manner. Their gene expression pattern is also regulated by developmental cues, light, circadian clock as well as adverse environmental conditions. However, the gene regulatory networks controlling C4 PEPC gene expression, namely its cell-specificity, are largely unknown. Therefore, after an introduction to the evolution of PEPCs, this review aims to discuss the current knowledge regarding the transcriptional regulation of C4 PEPCs, focusing on cell-specific and developmental expression dynamics, light and circadian regulation, as well as response to abiotic stress. In conclusion, this review aims to highlight the evolution, transcriptional regulation by different signals and importance of PEPC in C4 photosynthesis and its potential as tool for crop improvement.

Latin America (LatAm) has a rich and historically significant role in delineating both novel and well-documented genetic disorders. However, the ongoing advancements in the field of human genetics pose challenges to the relatively slow adaption of LatAm in the field. Here, we describe past and present contributions of LatAm to the discovery of novel genetic disorders, often referred as novel gene-disease associations (NGDA). We also describe the current methodologies for discovery of NGDA, taking into account the latest developments in genomics. We provide an overview of opportunities and challenges for NGDA research in LatAm considering the steps currently performed to identify and validate such associations. Given the multiple and diverse needs of populations and countries in LatAm, it is imperative to foster collaborations amongst patients, indigenous people, clinicians and scientists. Such collaborative effort is essential for sustaining and enhancing the LatAm´s contributions to the field of NGDA.

Mucopolysaccharidosis type IIIB (MPS IIIB) is caused by deficiency of alpha-N-acetylglucosaminidase, leading to storage of heparan sulphate. The disease is characterized by intellectual disability and hyperactivity, among other neurological and somatic features. Here we studied retrospective data from a total of 19 MPS IIIB patients from Brazil, aiming to evaluate disease progression. Mean age at diagnosis was 7.2 years. Speech delay was one of the first symptoms to be identified, around 2-3 years of age. Behavioral alterations include hyperactivity and aggressiveness, starting around age four. By the end of the first decade, patients lost acquired abilities such as speech and ability to walk. Furthermore, as disease progresses, respiratory, cardiovascular and joint abnormalities were found in more than 50% of the patients, along with organomegaly. Most common cause of death was respiratory problems. The disease progression was characterized in multiple systems, and hopefully these data will help the design of appropriate clinical trials and clinical management guidelines.

Butyrate is a promising candidate for an antitumoral drug, as it promotes cancer cell apoptosis and reduces hormone receptor activity, while promoting differentiation and proliferation in normal cells. However, the effects of low-dose butyrate on breast cancer cell cultures are unclear. We explored the impact of sub-therapeutic doses of butyrate on estrogen receptor alpha (ERα) transcriptional activity in MCF-7 cells, using RT-qPCR, Western blot, wound-healing assays, and chromatin immunoprecipitation. Our results showed that sub-therapeutic doses of sodium butyrate (0.1 - 0.2 mM) increased the transcription of ESR1, TFF1, and CSTD genes, but did not affect ERα protein levels. Moreover, we observed an increase in cell migration in wound-healing assays. ChIP assays revealed that treatment with 0.1 mM of sodium butyrate resulted in estrogen-independent recruitment of ERα at the pS2 promoter and loss of NCoR. Appropriate therapeutic dosage of butyrate is essential to avoid potential adverse effects on patients' health, especially in the case of estrogen receptor-positive breast tumors. Sub-therapeutic doses of butyrate may induce undesirable cell processes, such as migration due to low-dose butyrate-mediated ERα activation. These findings shed light on the complex effects of butyrate in breast cancer and provide insights for research in the development of antitumoral drugs.

ABT737 is used as a specific BCL2 inhibitor, which can treat papillary thyroid carcinoma (PTC). However, the effect of ABT737 on PTC cell apoptosis is limited. Moreover, BCL2 inhibition causes the activation of Beclin1-dependent autophagy. Our study aimed to explore the effects of autophagy and Beclin1 on ABT737 efficacy in PTC. The experimental data showed that ABT737 synchronously enhanced autophagic activity and apoptosis level in PTC cells. ABT737 also promoted the dissociation of BCL2-Beclin1 and BCL2-Bax complexes. Autophagy inhibitors, Bafilomycin A1 and 3-MA, enhanced the inhibitory effect of ABT737 on the survival and function in PTC cells. Consistently, autophagy inhibition with Beclin1 pharmacological inhibitor (spautin-1) also enhanced the efficacy of ABT737. Additionally, ABT737 at low-dose promoted LC3 conversion in PTC cells, and did not affect PTC cell apoptosis and survival. However, The efficacy of low-dose of ABT737 in PTC cell apoptosis and survival was displayed with the addition of Bafilomycin A1, 3-MA or spautin-1. In conclusion, the limited role of ABT737 in PTC cell apoptosis is attributed to its promoting effect on Beclin1-dependent autophagy. Therefore, autophagy inhibition based on Beclin1 downregulation can enhance the sensitivity of PTC cells to ABT737-induced death.

Olive flounder (Paralichthys olivaceus), a popular aquaculture species, is plagued by the disease scuticociliatosis caused by Miamiensis avidus, which has a high mortality rate and is typically treated with chemicals such as formalin and hydrogen peroxide. However, Carpesii fructus extract has shown potential as a natural therapeutic agent by reducing the motility of M. avidus. However, despite its potential importance, the effect of the extract on fish metabolism remains unknown. In this study, the effect of Carpesii fructus extract and formalin on fish metabolism was analysed by whole transcriptome analysis in the liver of P. olivaceus. A total of 37,796 transcripts were generated and differential expression genes (DEGs) were identified in the liver of P. olivaceus treated with Carpesii fructus extract or formalin. In addition, functional analysis of DEGs between treatment groups was presented using Gene Ontology. These results will be crucial for the study of scuticociliatosis in various fish species, including P. olivaceus, and for the development of therapeutic agents for other diseases.

Bougainvillea is a popular ornamental plant. Although Bougainvillea is abundant in germplasm resources, cultivars and flower colors, there is no rare blue colour varieties, due to the absence of delphinidin-based anthocyanins. This study analyzed the Bougainvillea leaf and bract transcriptome to select hosts of genetic transformation that would be suitable for the accumulation of delphinidin. A total of 36 gigabyte (GB) of raw data was obtained by transcriptome sequencing, with 4,058 significantly differentially expressed genes, including 1,854 upregulated and 2,204 downregulated genes. Annotation of these genes was performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. Through annotation, two CHS genes, one F3H gene, one DFR gene, and one F3'H gene involved in the delphinidin biosynthesis pathway were identified. The expression levels of these genes and total flavonoid content in the bracts of six Bougainvillea varieties were examined through quantitative real-time PCR and spectrophotometry, respectively. Through the comprehensive evaluation based on membership function method, the suitable host order for a blue-hued Bougainvillea transgene is Singapore White>Elizabeth Angus>Ratana Yellow>China Beauty>Orange King>Brilliant Variegata. Thus, Singapore White variety was the most appropriate transgene host for blue-hued Bougainvillea. The results of this study provide a reference for the directed breeding of blue-hued Bougainvillea.

Prostate cancer (PCA) is the second most common type of cancer in the world. Nevertheless, diagnosis is still based on nonspecific methods, or invasive methods which makes clinical decision and diagnosis difficult, generating risk of both underdiagnosis and overdiagnosis. Given the high prevalence, morbidity and mortality of PCA, new strategies are needed for its diagnosis. A review of the literature on available biomarkers for PCA was performed, using the following terms: prostate cancer AND marker OR biomarker. The search was carried out in Pubmed, Science Direct, Web of Science and Clinical Trial. A total of 35 articles were used, and PHI (Prostate Health Index) and the 4Kscore tests were identified as the best well-established serum markers. These tests are based on the evaluation of expression levels of several molecules. For analysis of urine samples, Progensa, ExoDXProstate, and Mi Prostate Score Urine Test are available. All these tests have the potential to help diagnosis, avoiding unnecessary biopsies, but they are used only in association with digital rectal examination and PSA level data. The search for biomarkers that can help in the diagnosis and therapeutic management of PCA is still in its initial phase, requiring more efforts for an effective clinical application.

Transposable elements are repetitive and mobile DNA segments that can be found in virtually all organisms investigated to date. Their complex structure and variable nature are particularly challenging from the genomic annotation point of view. Many softwares have been developed to automate and facilitate TEs annotation at the genomic level, but they are highly heterogeneous regarding documentation, usability and methods. In this review, we revisited the existing software for TE genomic annotation, concentrating on the most often used ones, the methodologies they apply, and usability. Building on the state of the art of TE annotation software we propose best practices and highlight the strengths and weaknesses from the available solutions.