DNA methylation meta-analysis confirms the division of the genome into two functional groups

Based on a meta-analysis of human genome methylation data, we tested a theoretical model in which aging is explained by the redistribution of limited resources in cells between two main tasks of the organism: its self-sustenance based on the function of the housekeeping gene group (HG) and functional differentiation, provided by the (IntG) integrative gene group. A meta-analysis of methylation of 100 genes, 50 in the HG group and 50 in IntG, showed significant differences ( p<0.0001) between our groups in the level of absolute methylation values of genes bodies and its promoters. We showed a reliable decrease of absolute methylation values in IntG with rising age in contrast to HG, where this level remained constant. The one-sided decrease in methylation in the IntG group is indirectly confirmed by the dispersion data analysis, which also decreased in the genes of this group. The imbalance between HG and IntG in methylation levels suggests that this IntG-shift is a side effect of the ontogenesis grownup program and the main cause of aging. The theoretical model of functional genome division also suggests the leading role of slow dividing and post mitotic cells in triggering and implementing the aging process.

ARF small GTPases in the developmental function mediated by ARF regulators GNOM and VAN3

ARF small GTPases are molecular switches acting in intracellular trafficking. Their cycles of activity are controlled by regulators, ARF Guanine nucleotide Exchange Factors (ARF-GEFs) and ARF GTPase Activating Proteins (ARF-GAPs). The ARF-GEF GNOM (GN) and the ARF-GAP VAN3 share a prominent function in auxin-mediated developmental patterning, but the ARFs which they might control were not identified. We conducted a loss-of-function and localization-based screening of the ARF/ARF-LIKE gene family in Arabidopsis thaliana with the primary aim of identifying functional partners of GN and VAN3, while extending the limited understanding of this gene group as a whole. We identified a function of ARLA1 in branching angle control. Mutants lacking the variably localized ARLB1, ARFB1, ARFC1, ARFD1, and ARF3, even in high order combinations, do not exhibit any evident phenotypes. Loss of function arfa1 phenotypes support a major role of ARFA1 in growth and development overall, but patterning defects typical to gn loss of function are not found. ARFA1 are not localized at the plasma membrane, where GN and VAN3 carry out developmental patterning function according to current models. Taken together, putative ARF partners of GN and VAN3 in developmental patterning cannot be conclusively identified.

Drosophila DAxud1: A New Element in Transcriptional Pausing Complex Stabilization

BackgroundA rapid transcriptional response under an acute stimulus is common in all cellular systems and is an adaptation that allows tolerance to environmental changes. A gene group that has been studied because of its fast response and cytoprotective effects are the hsp genes (encodingHeat Shock Proteins(HSPs), conserved chaperones).. Under normal conditions, the mRNA and protein levels of the main hsp genes are low but they increase rapidly upon heat shock (HS). This is achieved due to the presence of an RNA Polymerase II pausing complex located +30-50 bp from TSS. This complex maintains a partially synthesized RNA strand of said length, poised to resume synthesis, and undergoes subsequent transcriptional inactivation to restore transcript levels after environmental stabilization.MethodsThe Gal4/UAS system was used to modify dAxud1 expression in a tissue specific manner. A DAxud1-GFP fusion was expressed in salivary glands to perform polytene chromosome immunofluorescence and chromatin immunoprecipitation. DAxud1 genome occupancy data was achieved expressing Dam-DAxud1 in imaginal wing discs using Gal4/UAS (TaDa-seq).ResultsUsing TaDa-seq, we demonstrate that DAxud1 protein is present mainly near the TSS of significant occupied genes, most frequently in the first intron. This results also revealed DAxud1 is present in hsp genes, mainly in promoter zone. Following these results, we found that, under dAxud knockdown, larvae and adults flies have a diminished thermotolerance, despite showing an increase in hsp transcripts in larval tissues. We performed polytene chromosome immunofluorescence for DAxud1-GFP, revealing extensive, but dynamic localization on chromatin in hsp70 loci. This was confirmed with chromatin immunoprecipitation. We also found that DAxud1 overexpression leads to an enrichment of RNA Polymerase II at the 5’ end of the hsp70 gene, with a decrease in its transcripts. Importantly, we show interaction of DAxud1 with NELF-B, a component of the transcriptional pausing complex, and knockdown of both genes individually has similar effects on hsp70 transcription.ConclusionDAxud1 protein is a component of chromatin, that relocates under stress conditions such as heat shock, playing a role in maintaining RNA Polymerase II stalled at the 5’ of hsp70, possibly through a pausing mechanism based on its interaction with NELF-B.

Genome-wide phenotypic RNAi screen in the Drosophila wing: Phenotypic description of functional classes

The Drosophila genome contains approximately 14.000 protein coding genes encoding all the necessary information to sustain cellular physiology, tissue organization, organism development and behavior. In this manuscript we describe in some detail the phenotypes in the adult fly wing generated after knockdown of approximately 80% of Drosophila genes. We combined this phenotypic description with a comprehensive molecular classification of the Drosophila proteins into classes that summarize the main expected or known biochemical/functional aspect of each protein. This information, combined with mRNA expression levels and in situ expression patterns, provides a simplified atlas of the Drosophila genome, from housekeeping proteins to the components of the signaling pathways directing wing development, that might help to further understand the contribution of each gene group to wing formation.

Genetic and Phenotypic Characteristics of Congenital Hypothyroidism in a Chinese Cohort

BackgroundThe molecular etiology and the genotype–phenotype correlation of congenital hypothyroidism (CH) remain unclear.MethodsWe performed genetic analysis in 42 newborns with CH using whole-exome sequencing. Patients were divided into a single-gene group and a multi-gene group according to the number of affected genes, or divided into a monoallelic group, a biallelic group, and an oligogenic group according to the pattern of the detected variants. The clinical characteristics were compared between groups.ResultsThyroid dysgenesis (TD) was observed in 10 patients and goiter in 5 patients, whereas 27 patients had normal-sized gland-in-situ (GIS). We identified 58 variants in five genes in 29 patients. The genes with the most frequent variants were DUOX2 (70.7%), followed by TSHR (12.1%), DUOXA2 (10.3%), and TPO (5.2%). Variants in the genes causing dyshormonogenesis (DH) were more common than those in the genes causing TD (87.9% versus 12.1%). Among the patients with detected variants, 26 (89.7%) were harboring a single gene variant (single-gene group), which include 22 patients harboring biallelic variants (biallelic group) and four patients harboring monoallelic variants (monoallelic group). Three (10.3%) patients harbored variants in two or three genes (multi-gene group or oligogenic group). Compared with the single-gene group, the levothyroxine (L-T4) dose at 1 year of age was higher in the multi-gene group (p = 0.018). A controllable reduction in the L-T4 dose was observed in 25% of patients in the monoallelic group and 59.1% of patients in the biallelic group; however, no patients with such reduction in the L-T4 dose were observed in the oligogenic group.ConclusionsPatients with normal-sized GIS accounted for the majority of our cohort. Genetic defects in the genes causing DH were more common than those in the genes causing TD, with biallelic variants in DUOX2 being dominant. DH might be the leading pathophysiology of CH in Chinese individuals.

Predictive Value of Gross Extranodal Extension for Differentiated Thyroid Carcinoma Persistence/Recurrence

Objective We systematically investigated the predictive value of gross extranodal extension (gENE) for differentiated thyroid carcinoma persistence/recurrence. Study Design Retrospective study. Setting A tertiary care hospital. Methods This study was divided into 2 groups according to gENE status: the gENE group and non-gENE group. We compared the disease persistence/recurrence rates of these 2 groups in the entire cohort and by individual risk group (intermediate/high risk), analyzed whether gENE was an independent risk factor for disease persistence/recurrence, and explored the impact of gENE-specific features on disease persistence/recurrence. Results There were 989 patients who satisfied the inclusion criteria: 57 patients in the gENE group and 932 in the non-gENE group. The disease persistence/recurrence rate of the gENE group was higher than that of the non-gENE group in the entire cohort and by individual risk group ( P < .05 for each). Unexpectedly, the outcomes of the gENE group with intermediate risk were similar to those of the non-gENE group with high risk ( P = .72). For the entire cohort, gENE was an independent predictor for disease persistence/recurrence (odds ratio, 2.89; 95% CI, 1.39-6.00; P = .005). Specific features of gENE ( P > .05 for each) were not related to disease persistence/recurrence. Conclusion Patients with gENE and intermediate risk might be regraded as high risk. Specific features of gENE have no impact on disease persistence/recurrence.

The Choice of Candidates in Survival Markers Based on Coordinated Gene Expression in Renal Cancer

We aimed to identify and investigate genes that are essential for the development of clear cell renal cell carcinoma (ccRCC) and sought to shed light on the mechanisms of its progression and create prognostic markers for the disease. We used real-time PCR to study the expression of 20 genes that were preliminarily selected based on their differential expression in ccRCC, in 68 paired tumor/normal samples. Upon ccRCC progression, seven genes that showed an initial increase in expression showed decreased expression. The genes whose expression levels did not significantly change during progression were associated mainly with metabolic and inflammatory processes. The first group included CA9, NDUFA4L2, EGLN3, BHLHE41, VWF, IGFBP3, and ANGPTL4, whose expression levels were coordinately decreased during tumor progression. This expression coordination and gene function is related to the needs of tumor development at different stages. Specifically, the high correlation coefficient of EGLN3 and NDUFA4L2 expression may indicate the importance of the coordinated regulation of glycolysis and mitochondrial metabolism. A panel of CA9, EGLN3, BHLHE41, and VWF enabled the prediction of survival for more than 3.5 years in patients with ccRCC, with a probability close to 90%. Therefore, a coordinated change in the expression of a gene group during ccRCC progression was detected, and a new panel of markers for individual survival prognosis was identified.

Providing an optimized model to detect driver genes from heterogeneous cancer samples using restriction in subspace learning

Extracting the drivers from genes with mutation, and segregation of driver and passenger genes are known as the most controversial issues in cancer studies. According to the heterogeneity of cancer, it is not possible to identify indicators under a group of associated drivers, in order to identify a group of patients with diseases related to these subgroups. Therefore, the precise identification of the related driver genes using artificial intelligence techniques is still considered as a challenge for researchers. In this research, a new method has been developed using the subspace learning method, unsupervised learning, and with more constraints. Accordingly, it has been attempted to extract the driver genes with more precision and accurate results. The obtained results show that the proposed method is more to predict the driver genes and subgroups of driver genes which have the highest degree of overlap due to p-value with known driver genes in valid databases. Driver genes are the benchmark of MsigDB which have more overlap compared to them as selected driver genes. In this article, in addition to including the driver genes defined in previous work, introduce newer driver genes. The minister will define newer groups of driver genes compared to other methods the p-value of the proposed method was 9.21e-7 better than previous methods for 200 genes. Due to the overlap and newer driver genes and driver gene group and subgroups. The results show that the p value of the proposed method is about 2.7 times less than the driver sub method due to overlap, indicating that the proposed method can identify driver genes in cancerous tumors with greater accuracy and reliability.

Genetic Component and Vr-Wr Graphical Analysis in Blackgram [Vigna mungo (L.) Hepper]

Background: To develop a new high yielding variety, it is important to generate utilitarian recombinants and devise an appropriate strategy for selection and advancement of those recombinants. Method: Keeping this in mind, genetic components of yield and its related traits were determined in nine genotypes of blackgram through half diallel analysis using Hayman’s numerical and graphical approach. Conclusion: The estimates of genetic components deduced the role of non-additive gene action in the inheritance of all traits. The Vr-Wr graphical analysis revealed that assumptions laid by Hayman for diallel analysis were seldom fulfilled. Epistatic effect was predominant in all traits except days to 75 per cent maturity. Unidirectional dominance was observed in days to 75 per cent maturity, pods per plants and seed yield per plant and crude protein content. One major gene group was found controlling all traits except days to 75 per cent maturity and branches per plant. These findings can be used by breeders to devise appropriate selection methodology for yield improvement in blackgram.

Synthesis And Properties Of New Ionophors Based On Oil And Fat Industry Waste

Using characteristic ion of the fraudulent resins is considered In article in sorption process gold of the extraction. They Are Presented: scheme of the technological process of the syntheses efficient ionit incorporated phosphorus gossypol resins; the mode to technologies of the reception ionit introduction phosphoric group gossypol of the resin; the technical features ionit phosphorus containing gossypol of the resin on base gossypol resins butter to fatty industry TSh 86-38: 2006. It Is Installed that received ионит possible aplying ion for extraction of the non-ferrous metals, as follows for extraction ion honeys from concentrated solution hydra metallurgical production and is determined that, ion exchange runs only then, when ion gene group dissociation. It Is Revealled that received ионит the phosphoric group gossypol of the resin for extraction and sorptions ion non-ferrous metals corresponds to the confirmed specificationses, in accordance with which is planned to issue in the manner of grain, applicable as sorbent for extraction ion non-ferrous metals from concentrated solution. It Is Determined that received by syntheses phosphoric group gossypol of the resin efficient ионит, after washer with water and after hydrolysis saves its spherical form and in this form possible send on stock-room.