DNA double strand break position leads to distinct gene expression changes and regulates VSG switching pathway choice

Antigenic variation is an immune evasion strategy used by Trypanosoma brucei that results in the periodic exchange of the surface protein coat. This process is facilitated by the movement of variant surface glycoprotein genes in or out of a specialized locus known as bloodstream form expression site by homologous recombination, facilitated by blocks of repetitive sequence known as the 70-bp repeats, that provide homology for gene conversion events. DNA double strand breaks are potent drivers of antigenic variation, however where these breaks must fall to elicit a switch is not well understood. To understand how the position of a break influences antigenic variation we established a series of cell lines to study the effect of an I-SceI meganuclease break in the active expression site. We found that a DNA break within repetitive regions is not productive for VSG switching, and show that the break position leads to a distinct gene expression profile and DNA repair response which dictates how antigenic variation proceeds in African trypanosomes.

Amelioration of Diabetic Nephropathy by Targeting Autophagy via Rapamycin or Fasting: Relation to Cell Apoptosis/Survival

Autophagy has been demonstrated to have a beneficial effect on diabetic nephropathy (DN). Rapamycin, an inhibitor of mTOR, was shown to stimulate β-cell autophagy. However, its effects on preventing or ameliorating DN is unclear, and its effects are worth studying. As fasting is now an attractive protective strategy, we aim to compare its effect to rapamycin effects on pancreatic and renal cells. Twenty-eight adult male Wistar Albino rats were randomly divided into four groups, using streptozotocin (STZ) to induce diabetes mellitus (DM). Autophagy was induced by two ways; rapamycin or fasting. The extent of autophagy and apoptosis were investigated by measuring the level of LC3B and p53 proteins, respectively, in pancreatic and kidney tissues using Western blotting (WB) technique and imaging the renal cells under transmission electron microscope. The efflux transporter P-glycoprotein was quantified by WB as well. Rapamycin-induced autophagy occurred concurrently with apoptosis. On the other hand, fasting supported P-glycoprotein recovery and renal cell survival together with disabling β-cells apoptosis. In conclusion, this study provides a potential link between rapamycin or fasting for the cross-regulation of apoptosis and autophagy in the setting of cell stress as DN. Unlike rapamycin, fasting enhanced the active expression of ABCB1 efflux protein, providing insights on the potential ameliorative effects of fasting in DN that require further elucidation.

Polycomb Requires Chaperonin Containing TCP-1 Subunit 7 for Maintaining Gene Silencing in Drosophila

In metazoans, heritable states of cell type-specific gene expression patterns linked with specialization of various cell types constitute transcriptional cellular memory. Evolutionarily conserved Polycomb group (PcG) and trithorax group (trxG) proteins contribute to the transcriptional cellular memory by maintaining heritable patterns of repressed and active expression states, respectively. Although chromatin structure and modifications appear to play a fundamental role in maintenance of repression by PcG, the precise targeting mechanism and the specificity factors that bind PcG complexes to defined regions in chromosomes remain elusive. Here, we report a serendipitous discovery that uncovers an interplay between Polycomb (Pc) and chaperonin containing T-complex protein 1 (TCP-1) subunit 7 (CCT7) of TCP-1 ring complex (TRiC) chaperonin in Drosophila. CCT7 interacts with Pc at chromatin to maintain repressed states of homeotic and non-homeotic targets of PcG, which supports a strong genetic interaction observed between Pc and CCT7 mutants. Depletion of CCT7 results in dissociation of Pc from chromatin and redistribution of an abundant amount of Pc in cytoplasm. We propose that CCT7 is an important modulator of Pc, which helps Pc recruitment at chromatin, and compromising CCT7 can directly influence an evolutionary conserved epigenetic network that supervises the appropriate cellular identities during development and homeostasis of an organism.

Metallothionein-2A protect Cardiomyocytes from Ischemia/Reperfusion through inhibiting p38

The resumption of coronary artery blood supply is often accompanied by myocardial ischemia/reperfusion (I/R) injury after the occurrence of myocardial infarction, shock, cardiac surgery and other events. Metallothionein-2A (MT2A) has the functions of scavenging free radicals, anti-oxidative stress, anti-apoptosis, anti-autophagy, promoting vascular growth. The activation of p38 MAPK pathway can induce cardiomyocyte apoptosis in H9c2 cardiomyocytes during I/R, thereby aggravating the myocardial I/R injury. However, it is not clear that the effect of MT2A on p38 in cardiomyocytes under I/R. A simulated I/R model was used. Our objective was to investigate the protective effect of MT2A on I/R-caused mortality in H9c2 cardiomyocytes through its influence on p38, as well as the relationships among these processes. The results indicate that both endogenously overexpressed MT2A and exogenously added MT2A can inhibit the active expression of p38 during I/R. Based on these results, I/R induces apoptosis and p-p38 in cardiomyocytes. MT2A can inhibit the active expression of p38. MT2A protects cardiomyocytes from I/R injury, and that p38 is one of the molecules of MT2A against I/R injury in cardiomyocytes.

DNA double strand break position leads to distinct gene expression changes and regulates VSG switching pathway choice.

Antigenic variation is an immune evasion strategy used by Trypanosoma brucei that results in the periodic exchange of the surface protein coat. Underlying this process is the movement of variant surface glycoprotein genes in or out of a specialized locus known as bloodstream form expression site by homologous recombination, facilitated by blocks of repetitive sequence known as the 70-bp repeats, that provide homology for gene conversion events. DNA double strand breaks are potent drivers of antigenic variation, however where these breaks must fall to elicit a switch is not well understood. To understand how the position of a break influences antigenic variation we established a series of cell lines to study the effect of an I-SceI meganuclease break in the active expression site. We found that a DNA break within repetitive regions is not productive for VSG switching, and show that the break position leads to a distinct gene expression profile and DNA repair response which dictates how antigenic variation proceeds in African trypanosomes.

Overexpression of a methyl-CpG-binding protein gene OsMBD707 leads to larger tiller angles and reduced photoperiod sensitivity in rice

Background Methyl-CpG-binding domain (MBD) proteins play important roles in epigenetic gene regulation, and have diverse molecular, cellular, and biological functions in plants. MBD proteins have been functionally characterized in various plant species, including Arabidopsis, wheat, maize, and tomato. In rice, 17 sequences were bioinformatically predicted as putative MBD proteins. However, very little is known regarding the function of MBD proteins in rice. Results We explored the expression patterns of the rice OsMBD family genes and identified 13 OsMBDs with active expression in various rice tissues. We further characterized the function of a rice class I MBD protein OsMBD707, and demonstrated that OsMBD707 is constitutively expressed and localized in the nucleus. Transgenic rice overexpressing OsMBD707 displayed larger tiller angles and reduced photoperiod sensitivity—delayed flowering under short day (SD) and early flowering under long day (LD). RNA-seq analysis revealed that overexpression of OsMBD707 led to reduced photoperiod sensitivity in rice and to expression changes in flowering regulator genes in the Ehd1-Hd3a/RFT1 pathway. Conclusion The results of this study suggested that OsMBD707 plays important roles in rice growth and development, and should lead to further studies on the functions of OsMBD proteins in growth, development, or other molecular, cellular, and biological processes in rice.

Smell dysfunction in patients with COVID-19

Coronavirus disease 2019 (COVID-19) is the cause of a global pandemic and the object of numerous studies worldwide. COVID-19 has many clinical manifestations, but smell dysfunction has become its unique “visiting card”. The purpose of this review is to analyze scientific data on anosmia in COVID-19 based on the results of primary research using PubMed, Google Scholar, and eLIBRARY databases. Olfactory dysfunction is a very common symptom in COVID-19: up to 85% of patients report these subjective sensations, but objective olfactory testing shows a higher prevalence — up to 98%. Up to 27% of patients may experience a sudden onset of anosmia as the first symptom. Therefore, anosmia can be crucial in timely identification of individuals infected with SARS-CoV 2. A feature of olfactory disorders in COVID-19 is the preservation of normal transnasal air flow conditions, when edema, hyperemia of the nasal mucosa and rhinorrhea characteristic of other respiratory viral infections are expressed slightly or aren`t expressed at all. Many studies show that the olfactory epithelium of the nasal cavity is an area of enhanced binding, replication, and accumulation of SARS-CoV2, which is due to the active expression of two host receptors (APF2 and TMPS2 proteases) by numerous non-neuronal olfactory epithelium cells. It is supposed that supporting cells of the olfactory epithelium are primarily affected, and olfactory receptor neurons and olfactory bulb neurons are affected secondarily. However, the final clinical and pathophysiological significance of olfactory symptoms remains to be determined

Texts rendering into a foreign language. Distant learning experience

This article examines the effectiveness of pedagogical techniques and means of stimulating educational motivation during the classes “Rendering and annotating text in a foreign language” in distant learning in higher education. Experimental training was conducted to test the effectiveness of the authors’ electronic text rendering tutorial for students learning Italian as a second language. The experiment was carried out among the 2-nd and 3-rd year students of the Linguistics department in the Institute of Foreign Languages of the RUDN University in the 2019-2020 and 2020-2021 academic years. Currently e-learning has successfully integrated into the system of traditional education and is no longer seen as an alternative. The authors of this article focused on a combination of resources and tools from the Microsoft Teams platform and elaborated tutorial on rendering to motivate learners with distant learning. The article describes pedagogical practices for enhancing the motivation of students. We are talking about texts for rendering all major genres, functional styles, various topics, taking into account the level of students’ preparedness. With the aim of involving students in rendering activities and active expression of their own opinion, the researchers used an “ interpretive abstract “and included the paragraph “ OPPINIONE “ as its component. Experimental verification, its results and conclusions showed that combined rendering training based on e- tutorial developed by the authors and Microsoft Teams platform activates students’ motivation and contributes to their involvement in the process. The experiment showed another strong point of distant learning: it made a great contribution to the development of students’ independence, self-discipline and responsibility. 220.

Characterization of genome-wide association study data reveals spatiotemporal heterogeneity of mental disorders

Background Psychiatric disorders such as schizophrenia (SCZ), bipolar disorder (BIP), major depressive disorder (MDD), attention deficit-hyperactivity disorder (ADHD), and autism spectrum disorder (ASD) are often related to brain development. Both shared and unique biological and neurodevelopmental processes have been reported to be involved in these disorders. Methods In this work, we developed an integrative analysis framework to seek for the sensitive spatiotemporal point during brain development underlying each disorder. Specifically, we first identified spatiotemporal gene co-expression modules for four brain regions three developmental stages (prenatal, birth to 11 years old, and older than 13 years), totaling 12 spatiotemporal sites. By integrating GWAS summary statistics and the spatiotemporal co-expression modules, we characterized the risk genes and their co-expression partners for five disorders. Results We found that SCZ and BIP, ASD and ADHD tend to cluster with each other and keep a distance from other psychiatric disorders. At the gene level, we identified several genes that were shared among the most significant modules, such as CTNNB1 and LNX1, and a hub gene, ATF2, in multiple modules. Moreover, we pinpointed two spatiotemporal points in the prenatal stage with active expression activities and highlighted one postnatal point for BIP. Further functional analysis of the disorder-related module highlighted the apoptotic signaling pathway for ASD and the immune-related and cell-cell adhesion function for SCZ, respectively. Conclusion Our study demonstrated the dynamic changes of disorder-related genes at the network level, shedding light on the spatiotemporal regulation during brain development.

Overexpression of a methyl-CpG-binding Protein Gene OsMBD707, Leads to Larger Tiller Angles and Reduced Photoperiod Sensitivity in Rice

Background: Methyl-CpG-binding domain (MBD) proteins play important roles in epigenetic gene regulation, and have diverse molecular, cellular, and biological functions in plants. MBD proteins have been functionally characterized in various plant species, including Arabidopsis, wheat, maize, and tomato. In rice, 17 sequences were bioinformatically predicted as putative MBD proteins. However, very little is known regarding the function of MBD proteins in rice.Results: We explored the expression patterns of the rice OsMBD family genes and identified 13 OsMBDs with active expression in various rice tissues. We further characterized the function of a rice class I MBD protein OsMBD707, and demonstrated that OsMBD707 is constitutively expressed and localized in the nucleus. Transgenic rice overexpressing OsMBD707 displayed larger tiller angles and reduced photoperiod sensitivity—delayed flowering under short day (SD) and early flowering under long day (LD). RNA-seq analysis revealed that overexpression of OsMBD707 led to reduced photoperiod sensitivity in rice through regulating expression of key flowering regulator genes in the Ehd1-Hd3a/RFT1 pathway.Conclusion: The results of this study demonstrated that OsMBD707 plays important roles in rice growth and development, and should lead to further studies on the functions of OsMBD proteins in growth, development, or other molecular, cellular, and biological processes in rice.