SmgGDS-607 Regulation of RhoA GTPase Prenylation Is Nucleotide-Dependent.

Protein prenylation involves the attachment of a hydrophobic isoprenoid moiety to the C-terminus of proteins. Several small GTPases, including members of the Ras and Rho subfamilies, require prenylation for their normal and pathological functions. Recent work has suggested that SmgGDS proteins regulate the prenylation of small GTPases in vivo. Using RhoA as a representative small GTPase, we directly test this hypothesis using biochemical assays and present a mechanism describing the mode of prenylation regulation. SmgGDS-607 completely inhibits RhoA prenylation catalyzed by protein geranylgeranyltransferase I (GGTase-I) in an in vitro radiolabel incorporation assay. SmgGDS-607 inhibits prenylation by binding to and blocking access to the C-terminal tail of the small GTPase (substrate sequestration mechanism) rather than via inhibition of the prenyltransferase activity. The reactivity of GGTase-I with RhoA is unaffected by addition of nucleotides. In contrast, the affinity of SmgGDS-607 for RhoA varies with the nucleotide bound to RhoA; SmgGDS-607 has a higher affinity for RhoA-GDP compared to RhoA-GTP. Consequently, the prenylation blocking function of SmgGDS-607 is regulated by the bound nucleotide. This work provides mechanistic insight into a novel pathway for the regulation of small GTPase protein prenylation by SmgGDS-607 and demonstrates that peptides are a good mimic for full-length proteins when measuring GGTase-I activity.

The effect of vaccine on COVID-19 spread by function-on-scalar regression model: a case study of Africa.

Aim: This paper aimed to study the effect of the vaccine on the reproduction rate of coronavirus in Africa from January 2021 to November 2021. Subject and methods: Functional data analysis (FDA), a relatively new area in statistics, can describe, analyze, and predict data collected over time, space, or other continuum measures in many countries every day and is increasingly common across scientific domains. For our data, the first step of functional data is smoothing. We used the B-spline method to smooth our data. Then, we apply the function-on-scalar and Bayes function-on-scalar models to fit our data. Results: Our results indicate a statistically significant relationship between the vaccine and the rate of virus reproduction and spread. When the vaccination rate falls, the reproduction rate also decreases. Furthermore, we found that the effect of latitude and the region on the reproduction rate depends on the region. We discovered that in Middle Africa, from the beginning of the year until the end of the summer, the impact is negative, implying that the virus spread due to a decrease in the vaccination rates. Conclusion: The study found that vaccination rates significantly impact the virus's reproduction rate.

Insecticide resistance to organophosphates in Culex pipiens complex from Lebanon.

BACKGROUND: Analysis of Culex pipiens mosquitoes collected from a single site in Lebanon in 2005, revealed an alarming frequency of ace-1 alleles conferring resistance to organophosphate insecticides. Following this, in 2006 the majority of municipalities switched to pyrethroids after a long history of organophosphate usage in the country; however, since then no studies have assessed the impact of changing insecticide class on the frequency of resistant ace-1 alleles in C. pipiens. METHODS: C. pipiens mosquitoes were captured indoors from 25 villages across the country and subjected to established methods for the analysis of gene amplification at the Ester locus and target site mutations in ace-1 gene that confer resistance to organophosphates. RESULTS: We conducted the first large-scale screen for resistance to organosphosphates in C. pipiens mosquitoes collected from Lebanon. The frequency of carboxylesterase (Ester) and ace-1 alleles conferring resistance to organophosphates were assessed among C. pipiens mosquitoes collected from 25 different villages across the country between December 2008 and December 2009. Established enzymatic assay and PCR-based molecular tests, both diagnostic of the major target site mutations in ace-1 revealed the absence of the F290V mutation among sampled mosquitoes and significant reduction in the frequency of G119S mutation compared to that previously reported for mosquitoes collected from Beirut in 2005. We also identified a new duplicated ace-1 allele, named ace-1D13, exhibiting a resistant phenotype by associating a susceptible and a resistant copy of ace-1 in a mosquito line sampled from Beirut in 2005. Fisher's exact test on ace-1 frequencies in the new sample sites, showed that some populations exhibited a significant excess of heterozygotes, suggesting that the duplicated allele is still present. Starch gel electrophoresis indicated that resistance at the Ester locus was mainly attributed to the Ester2 allele, which exhibits a broad geographical distribution. CONCLUSIONS: Our analysis suggests that the frequency of resistant ace-1 alleles in mosquito populations can be downshifted, and in certain cases (F290V mutation) even eliminated, by switching to a different class of insecticides, possibly because of the fitness cost associated with these alleles.