Cholinergic deficiency in the cholinergic system as a pathogenetic link in the formation of various syndromes in COVID-19.

According to recent data, several mechanisms of viral invasion of the central nervous system (CNS) have been proposed, one of which is both direct penetration of the virus through afferent nerve fibers and damage to the endothelium of cerebral vessels. It has been proven that the SARS-CoV-2 virus affects pathologically not only the human cardiorespiratory system but is also associated with a wide range of neurological diseases, cerebrovascular accidents, and neuromuscular pathologies. However, the observed post-COVID symptom complex in patients, manifested in the form of headache, "fog in the head," high temperature, muscle weakness, lowering blood pressure, does it make us think about the pathophysiological mechanisms that contribute to the development of this clinical picture? One possible explanation is a disruption in the signaling of the acetylcholine system (AChS) in the body. Viral invasions, and in particular COVID-19, can negatively affect the work of the AChS, disrupting its coordination activities. Therefore, the main goal of this literature review is to analyze the information and substantiate the possible mechanisms for the occurrence of post-COVID syndrome in people who have had COVID-19 from the standpoint of AChS dysfunctions.

Participation of nitrogen oxide and its metabolites in the genesis of hyperimmune inflammation in COVID-19.

Despite the success in the tactics of treating COVID-19, there are many unexplored issues related to the development and progression of the process in the lungs, brain, and other organs, as well as the role of individual elements, in particular, nitric oxide (NO), and in the pathogenesis of organ damage. Based on the analyzed literature data, we considered a possible pathophysiological mechanism of action of NO and its derivatives in COVID-19. It can be noted that hyperimmune systemic inflammation and "cytokine storm" are enhanced by the production of NO, products of its oxidation ("nitrosative stress"). It is noted in the work that as a result of the oxidation of NO, a large amount of the toxic compound peroxynitrite is formed, which is a powerful proinflammatory agent. Its presence significantly damages the endothelium of the vascular walls and also oxidizes lipids, hemoglobin, myoglobin, and cytochrome, binds SH-groups of proteins, and damages DNA in the target cells. This is confirmed by the picture of the vessels of the lungs on computed tomography and the data of biochemical studies. In case of peroxynitrite overproduction, inhibition of the synthesis of NO and its metabolic products seems to be justified. Another aspect considered in this work is the mechanism of damage by the virus to the central and peripheral nervous system, which remains poorly understood but may be important in understanding the consequences, as well as predicting brain functions in persons who have undergone COVID-19. According to the analyzed literature, it can be concluded that brain damage is possible due to the direct effect of the virus on the peripheral nerves and central structures, and indirectly through the effect on the endothelium of cerebral vessels. Disturbances in the central nervous regulation of immune responses may be associated with the insufficient function of the acetylcholine anti-inflammatory system. It is proposed to further study several approaches to influence various links of NO exchange, which are of interest for theoretical and practical medicine.

Should we transfer poor quality embryos?

BACKGROUND: To evaluate if it is safe and effective to transfer poor quality embryos. METHODS: It was a retrospective analysis using individual patient data with positive controls. All patients undergoing embryo transfers of poor quality embryos on day 3 or on day 5 as part of fresh In Vitro Fertilization (IVF) cycles performed between 2012 and 2016. This study assessed a total of 738 poor quality embryos from 488 IVF programs. 261 embryo transfers were performed on day 3 (402 embryos were transferred) and 227 on day 5 (336 embryos were transferred). Control group consisted of 9893 fair and good quality embryos from 5994 IVF programs. Outcome rates were compared with two-tailed Fisher exact test using fisher.test function in R software. 95% confidence intervals for proportions were calculated using the Clopper-Pearson method with binom.test function in R. The groups of patients with poor vs. good and fair quality embryos were compared by age, body mass index(BMI), number of oocytes, female and male main diagnosis, cycle type, controlled ovarian stimulation (COS) protocol, the starting day of gonadotropin administration, the starting dose of gonadotropins, the total dose of gonadotropins, the total number of days of gonadotropins administration, the starting day of gonadotropin-releasing hormone (GnRH) agonist administration, the total number of ampoules of GnRH-agonist used, day of the trigger of ovulation administration and the type of the trigger of ovulation using the Student's t-test for interval variables and with the chi-square test for nominal variables. RESULTS: No significant differences in the implantation rate, clinical pregnancy rate, miscarriage rate, live births, and the number of children born were found between the groups of poor quality embryos transferred on day 3 and day 5. Though the implantation rate was lower for the group of poor quality embryos, than for the control (13.9% vs 37.2%), statistically significant differences between the proportion of implanted embryos which resulted in clinical pregnancies and live births in both groups were not observed (72% vs 78.2 and 55.8% vs 62.0% respectively). CONCLUSION: Transfer of poor quality embryos at either day 3 or day 5 have a low potential for implantation, though those embryos which successfully implanted have the same potential for live birth as the embryos of fair and good quality. This study supports that it is safe to transfer poor quality embryos when they are the only option for fresh embryo transfer (ET).

Genomic exaptation enables Lasius niger adaptation to urban environments.

BACKGROUND: The world is rapidly urbanizing, and only a subset of species are able to succeed in stressful city environments. Efficient genome-enabled stress response appears to be a likely prerequisite for urban adaptation. Despite the important role ants play in the ecosytem, only the genomes of ~13 have been sequenced so far. Here, we present the draft genome assembly of the black garden ant Lasius niger - the most successful urban inhabitant of all ants - and we compare it with the genomes of other ant species, including the closely related Camponotus floridanus. RESULTS: Sequences from 272 M Illumina reads were assembled into 41,406 contigs with total length of 245 MB, and N50 of 16,382 bp, similar to other ant genome assemblies enabling comparative genomic analysis. Remarkably, the predicted proteome of L. niger is significantly enriched relative to other ant genomes in terms of abundance of domains involved in nucleic acid binding, DNA repair, and nucleotidyl transferase activity, reflecting transposable element proliferation and a likely genomic response. With respect to environmental stress, we note a proliferation of various detoxification genes, including glutatione-S-transferases and those in the cytochrome P450 families. Notably, the CYP9 family is highly expanded with 19 complete and 21 nearly complete members - over twice as many compared to other ants. This family exhibits the signatures of strong directional selection, with eleven positively selected positions in ligand-binding pockets of enzymes. Gene family contraction was detected for several components of the olfactory system, accompanied by instances of both directional selection and relaxation. CONCLUSIONS: Our results suggest that the success of L. niger in urbanized areas may be the result of fortuitous coincidence of several factors, including the expansion of the CYP9 cytochrome family due to coevolution with parasitic fungi, the diversification of DNA repair systems as an answer to proliferation of retroelements, and the reduction of olfactory system and behavioral preadaptations from non-territorial subdominant life strategies found in natural environments. Diversification of cytochromes and DNA repair systems along with reduced odorant communication are the basis of L. niger pollutant resistance and polyphagy, while non-territorial and mobilization strategies allows more efficient exploitation of large but patchy food sources.

Evolutionary genomics of Culex pipiens: global and local adaptations associated with climate, life-history traits and anthropogenic factors.

We present the first genome-wide study of recent evolution in Culex pipiens species complex focusing on the genomic extent, functional targets and likely causes of global and local adaptations. We resequenced pooled samples of six populations of C. pipiens and two populations of the outgroup Culex torrentium. We used principal component analysis to systematically study differential natural selection across populations and developed a phylogenetic scanning method to analyse admixture without haplotype data. We found evidence for the prominent role of geographical distribution in shaping population structure and specifying patterns of genomic selection. Multiple adaptive events, involving genes implicated with autogeny, diapause and insecticide resistance were limited to specific populations. We estimate that about 5-20% of the genes (including several histone genes) and almost half of the annotated pathways were undergoing selective sweeps in each population. The high occurrence of sweeps in non-genic regions and in chromatin remodelling genes indicated the adaptive importance of gene expression changes. We hypothesize that global adaptive processes in the C. pipiens complex are potentially associated with South to North range expansion, requiring adjustments in chromatin conformation. Strong local signature of adaptation and emergence of hybrid bridge vectors necessitate genomic assessment of populations before specifying control agents.