Active compensation for changes in TDH3 expression mediated by direct regulators of TDH3 in Saccharomyces cerevisiae.

Genetic networks are surprisingly robust to perturbations caused by new mutations. This robustness is conferred in part by compensation for loss of a gene's activity by genes with overlapping functions, such as paralogs. Compensation occurs passively when the normal activity of one paralog can compensate for the loss of the other, or actively when a change in one paralog's expression, localization, or activity is required to compensate for loss of the other. The mechanisms of active compensation remain poorly understood in most cases. Here we investigate active compensation for the loss or reduction in expression of the Saccharomyces cerevisiae gene TDH3 by its paralog TDH2. TDH2 is upregulated in a dose-dependent manner in response to reductions in TDH3 by a mechanism requiring the shared transcriptional regulators Gcr1p and Rap1p. TDH1, a second and more distantly related paralog of TDH3, has diverged in its regulation and is upregulated by another mechanism. Other glycolytic genes regulated by Rap1p and Gcr1p show changes in expression similar to TDH2, suggesting that the active compensation by TDH3 paralogs is part of a broader homeostatic response mediated by shared transcriptional regulators.

Directed evolution unlocks oxygen reactivity for a nicotine-degrading flavoenzyme.

The flavoenzyme nicotine oxidoreductase (NicA2) is a promising injectable treatment to aid in the cessation of smoking, a behavior responsible for one in ten deaths worldwide. NicA2 acts by degrading nicotine in the bloodstream before it reaches the brain. Clinical use of NicA2 is limited by its poor catalytic activity in the absence of its natural electron acceptor CycN. Without CycN, NicA2 is instead oxidized slowly by dioxygen (O2), necessitating unfeasibly large doses in a therapeutic setting. Here, we report a genetic selection strategy that directly links CycN-independent activity of NicA2 to growth of Pseudomonas putida S16. This selection enabled us to evolve NicA2 variants with substantial improvement in their rate of oxidation by O2. The encoded mutations cluster around a putative O2 tunnel, increasing flexibility and accessibility to O2 in this region. These mutations further confer desirable clinical properties. A variant form of NicA2 is tenfold more effective than the wild type at degrading nicotine in the bloodstream of rats.

The Cynosure of CtBP: Evolution of a Bilaterian Transcriptional Corepressor.

Evolution of sequence-specific transcription factors clearly drives lineage-specific innovations, but less is known about how changes in the central transcriptional machinery may contribute to evolutionary transformations. In particular, transcriptional regulators are rich in intrinsically disordered regions that appear to be magnets for evolutionary innovation. The C-terminal Binding Protein (CtBP) is a transcriptional corepressor derived from an ancestral lineage of alpha hydroxyacid dehydrogenases; it is found in mammals and invertebrates, and features a core NAD-binding domain as well as an unstructured C-terminus (CTD) of unknown function. CtBP can act on promoters and enhancers to repress transcription through chromatin-linked mechanisms. Our comparative phylogenetic study shows that CtBP is a bilaterian innovation whose CTD of about 100 residues is present in almost all orthologs. CtBP CTDs contain conserved blocks of residues and retain a predicted disordered property, despite having variations in the primary sequence. Interestingly, the structure of the C-terminus has undergone radical transformation independently in certain lineages including flatworms and nematodes. Also contributing to CTD diversity is the production of myriad alternative RNA splicing products, including the production of "short" tailless forms of CtBP in Drosophila. Additional diversity stems from multiple gene duplications in vertebrates, where up to five CtBP orthologs have been observed. Vertebrate lineages show fewer major modifications in the unstructured CTD, possibly because gene regulatory constraints of the vertebrate body plan place specific constraints on this domain. Our study highlights the rich regulatory potential of this previously unstudied domain of a central transcriptional regulator.

Fitness effects but no temperature-mediated balancing selection at the polymorphic Adh gene of Drosophila melanogaster.

Polymorphism in the alcohol dehydrogenase (ADH) protein of Drosophila melanogaster, like genetic variation in many other enzymes, has long been hypothesized to be maintained by a selective trade-off between thermostability and enzyme activity. Two major Adh variants, named Fast and Slow, are distributed along latitudinal clines on several continents. The balancing selection trade-off hypothesis posits that Fast is favored at high latitudes because it metabolizes alcohol faster, whereas Slow is favored at low latitudes because it is more stable at high temperatures. Here we use biochemical and physiological assays of precisely engineered genetic variants to directly test this hypothesis. As predicted, the Fast protein has higher catalytic activity than Slow, and both the Fast protein and regulatory variants linked to it confer greater ethanol tolerance on transgenic animals. But we found no evidence of a temperature-mediated trade-off: The Fast protein is not less stable or active at high temperatures, and Fast alleles increase ethanol tolerance and survivorship at all temperatures tested. Further, analysis of a population genomic dataset reveals no signature of balancing selection in the Adh gene. These results provide strong evidence against balancing selection driven by a stability/activity trade-off in Adh, and they justify caution about this hypothesis for other enzymes except those for which it has been directly tested. Our findings tentatively suggest that environment-specific selection for the Fast allele, coupled with demographic history, may have produced the observed pattern of Adh variation.

An Incompatibility between a mitochondrial tRNA and its nuclear-encoded tRNA synthetase compromises development and fitness in Drosophila.

Mitochondrial transcription, translation, and respiration require interactions between genes encoded in two distinct genomes, generating the potential for mutations in nuclear and mitochondrial genomes to interact epistatically and cause incompatibilities that decrease fitness. Mitochondrial-nuclear epistasis for fitness has been documented within and between populations and species of diverse taxa, but rarely has the genetic or mechanistic basis of these mitochondrial-nuclear interactions been elucidated, limiting our understanding of which genes harbor variants causing mitochondrial-nuclear disruption and of the pathways and processes that are impacted by mitochondrial-nuclear coevolution. Here we identify an amino acid polymorphism in the Drosophila melanogaster nuclear-encoded mitochondrial tyrosyl-tRNA synthetase that interacts epistatically with a polymorphism in the D. simulans mitochondrial-encoded tRNA(Tyr) to significantly delay development, compromise bristle formation, and decrease fecundity. The incompatible genotype specifically decreases the activities of oxidative phosphorylation complexes I, III, and IV that contain mitochondrial-encoded subunits. Combined with the identity of the interacting alleles, this pattern indicates that mitochondrial protein translation is affected by this interaction. Our findings suggest that interactions between mitochondrial tRNAs and their nuclear-encoded tRNA synthetases may be targets of compensatory molecular evolution. Human mitochondrial diseases are often genetically complex and variable in penetrance, and the mitochondrial-nuclear interaction we document provides a plausible mechanism to explain this complexity.

Thermally activated surface oxygen defects at the perimeter of Au/TiO2: a DFT+U study.

Density functional theory calculations were performed to examine the formation of oxygen atom vacancies on three model surfaces namely, clean anatase TiO2(001) and, Au3 and Au10 clusters supported on anatase TiO2(001). On the Au/TiO2 systems, three different types of lattice oxygen atoms can be identified: the Ti-O-Au bridge, the Ti-O-Ti bridge in the perimeter of the Au cluster and the Ti-O-Ti bridge away from the Au cluster, the oxygen atoms on the clean surface. The variation in ΔG° with temperature for surface O vacancy formation was calculated for these three situations using total-energy, vibrational structure and optimized geometries of the material surfaces and the O2 molecule. The calculations reveal that the O defect formation on the clean anatase TiO2(001) surface seems very difficult due to the large positive value of ΔG° (290 kJ mol(-1)) from 0 to 650 K. However, the presence of the Au cluster on the TiO2 surface changes the surface chemistry of the TiO2 significantly. We observed that the trend in ΔG° variation for the vacancy formation from the Ti-O-Au bridge is the same as on Au3/TiO2 and Au10/TiO2 systems, almost constant with large positive values of ΔG° around 250 and 350 kJ mol(-1), respectively. The ΔG° for the perimeter defect formation (Ti-O-Ti bridge in the perimeter of the Au cluster) is smaller for Aun/TiO2 systems than the clean TiO2 surface, however, the vacancy formation is possible only for the Au10/TiO2 system (close to 506 K). Finally, extended calculations for other oxygen atoms on the Au10/TiO2 model reveal that the trend in ΔG° variation is similar for all the interface or perimeter O atoms around the Au cluster with marginal differences in the numerical value of ΔG°. Since, the surface O atoms are activated only in the presence of a particular sized Au, we propose that a Au catalyzed Mars-van Krevelen mechanism could be a possible reaction mechanism for CO oxidation on Au/TiO2 catalysts at slightly elevated temperatures.

Removal of Ni(II) from aqueous solution by using micellar enhanced ultrafiltration.

To explore the potential of micellar enhanced ultrafiltration (MEUF) process for the treatment of industrial effluent, herein, we report the surfactant-based separation of a metal ion [Ni(II)] from the aqueous solution using two different anionic surfactants viz. dioctyl sodium sulfosuccinate (DSS) and sodium dodecyl sulfate (SDS). By following a systematic investigation, we utilized two membranes with different pore sizes viz. 10,000 MWCO (molecular weight cutoff) and 30,000 MWCO and determined the rejection coefficient and permeate flux of the Ni(II) from aqueous at 1.5 bar trans-membrane pressure. The experimental results showed higher percentage of Ni(II) retention upon using the micellar solution of SDS compared with the solution containing DSS surfactant. In addition, the retention of Ni(II) ions incorporated in the micelles of surfactants was also found to be higher upon using 10,000 MWCO membrane compared with 30,000 MWCO membrane. Hence, we suggest that the combination of SDS surfactant and 10,000 MWCO membrane is a potent solution for the removal of metal ions from aqueous solutions via MEUF process.

A shape memory hydrogel induced by the interactions between metal ions and phosphate.

A novel ferric-phosphate induced shape memory (SM) hydrogel is prepared by the one-step copolymerization of isopropenyl phosphonic acid (IPPA) and acrylamide (AM) in the presence of a crosslinker polyethylene glycol diacrylate (PEGDA). Different from the traditional SM hydrogels, our SM hydrogel can be processed into various shapes as needed and recovers to its original form in 'multiconditions' such as in the presence of a reducing agent or in the presence of a competitive complexing agent. This unique feature is attributed to the fact that the oxidized ferric ions show a high complexation ability with phosphate groups of IPPA, which acts as a physical crosslinker to form the secondary networks within the hydrogels to induce the shape memory effect. The memory behavior was totally reversible, owing to Fe3+ that can be reduced to Fe2+ and extracted by the complexing agent. Particularly, the SM hydrogels exhibit controllable and good mechanical characteristics by introduction of the ferric ions, i.e., the elastic modulus can increase from 2 kPa to 70 kPa dramatically. Learning from biological systems, phosphate-metal ion based hydrogels could become an attractive candidate for various biomedical and environmental applications.

Thermodynamic and spectroscopic investigation of interactions between reactive red 223 and reactive orange 122 anionic dyes and cetyltrimethyl ammonium bromide (CTAB) cationic surfactant in aqueous solution.

The present study describes the conductometric and spectroscopic study of the interaction of reactive anionic dyes, namely, reactive red 223 and reactive orange 122 with the cationic surfactant cetyltrimethyl ammonium bromide (CTAB). In a systematic investigation, the electrical conductivity data was used to calculate various thermodynamic parameters such as free energy (ΔG), enthalpy (ΔH), and the entropy (ΔS) of solubilization. The trend of change in these thermodynamic quantities indicates toward the entropy driven solubilization process. Moreover, the results from spectroscopic data reveal high degree of solubilization, with strong interactions observed in the cases of both dyes and the CTAB. The spontaneous nature of solubilization and binding was evident from the observed negative values of free energies (ΔG p and ΔG b).

Plasticity and environment-specific relationships between gene expression and fitness in Saccharomyces cerevisiae.

Phenotypic evolution is shaped by interactions between organisms and their environments. The environment influences how an organism's genotype determines its phenotype and how this phenotype affects its fitness. To better understand this dual role of the environment in the production and selection of phenotypic variation, we empirically determined and compared the genotype-phenotype-fitness relationship for mutant strains of the budding yeast Saccharomyces cerevisiae in four environments. Specifically, we measured how mutations in the promoter of the metabolic gene TDH3 modified its expression level and affected its growth on media with four different carbon sources. In each environment, we observed a clear relationship between TDH3 expression level and fitness, but this relationship differed among environments. Genetic variants with similar effects on TDH3 expression in different environments often had different effects on fitness and vice versa. Such environment-specific relationships between phenotype and fitness can shape the evolution of phenotypic plasticity. The set of mutants we examined also allowed us to compare the effects of mutations disrupting binding sites for key transcriptional regulators and the TATA box, which is part of the core promoter sequence. Mutations disrupting the binding sites for the transcription factors had more variable effects on expression among environments than mutations disrupting the TATA box, yet mutations with the most environmentally variable effects on fitness were located in the TATA box. This observation suggests that mutations affecting different molecular mechanisms are likely to contribute unequally to regulatory sequence evolution in changing environments.

Divergence of Grainy head affects chromatin accessibility, gene expression, and embryonic viability in Drosophila melanogaster.

Pioneer factors are critical for gene regulation and development because they bind chromatin and make DNA more accessible for binding by other transcription factors. The pioneer factor Grainy head (Grh) is present across metazoans and has been shown to retain a role in epithelium development in fruit flies, nematodes, and mice despite extensive divergence in both amino acid sequence and length. Here, we investigate the evolution of Grh function by comparing the effects of the fly (Drosophila melanogaster) and worm (Caenorhabditis elegans) Grh orthologs on chromatin accessibility, gene expression, embryonic development, and viability in transgenic D. melanogaster. We found that the Caenorhabditis elegans ortholog rescued cuticle development but not full embryonic viability in Drosophila melanogaster grh null mutants. At the molecular level, the C. elegans ortholog only partially rescued chromatin accessibility and gene expression. Divergence in the disordered N-terminus of the Grh protein contributes to these differences in embryonic viability and molecular phenotypes. These data show how pioneer factors can diverge in sequence and function at the molecular level while retaining conserved developmental functions at the organismal level.

Breakthroughs in Alzheimer's Research: A Path to a More Promising Future?

Background: Alzheimer's disease (AD) is a widespread neurodegenerative disorder with a significant global impact, affecting approximately 50 million individuals, and projections estimate that up to 152 million people will be affected by 2050. AD is characterized by beta-amyloid plaques and tau tangles in the brain, leading to cognitive decline. Summary: Recent research on AD has made significant strides, including the development of an "amyloid clock" biomarker that tracks AD progression through positron emission tomography (PET) scans. Surf4 and other genes have been discovered to play a role in regulating beta-amyloid toxicity, while inhibiting the enzyme hexokinase-2 has shown positive results in preclinical studies. New brain mapping techniques have identified early brain-based causes of cognitive changes in AD, and biomarkers such as neuronal pentraxin protein Nptx2 and astrocytic 7-subunit of the nicotinic acetylcholine receptors (7nAChRs) show potential for early detection. Other approaches, such as replenishing the enzyme Tip60, selectively degrading the modified protein p-p38 with PRZ-18002, and targeting the protein voltage-dependent anion channel-1 (VDAC1), have shown promise in enhancing cognitive function and preventing pathophysiological alterations linked to AD. Baseline blood samples and other biomarkers such as urine formic acid, p-tau 198, microRNAs, and glial fibrillary acidic protein (GFAP) have also been discovered for early detection and intervention of AD. Additionally, recent FDA approvals for medications such as aducanumab and lecanemab provide options for reducing AD symptoms and improving function, while clinical trials for dementia vaccines show promise for the nasal and beta-amyloid 40 vaccines as well as vaccinations targeting tau. Key Messages: These advancements in AD research, including biomarker discovery and the development of disease-modifying treatments, are crucial steps towards improving the lives of those affected by AD and finding a cure for this debilitating disease.

Comparing the efficacy of corticosteroids among patients with community-acquired pneumonia in the ICU versus non-ICU settings: A systematic review and meta-analysis.

BACKGROUND: Despite the potential of corticosteroids in treating community-acquired pneumonia (CAP), conflicting evidence exists regarding their effect on mortality. To address this gap and provide new insights, we conducted a pre-specified subgroup meta-analysis of corticosteroid use in CAP patients, focusing on the ICU versus non-ICU subsets. METHODS: We searched PubMed, Cochrane Central Register of Controlled Trials and SCOPUS from inception to May 2023 for randomized controlled trials (RCTs). The primary outcomes of interest were mortality, need for mechanical ventilation, need for ICU admission, and treatment failure. Secondary outcomes analysed were the need for hospital readmission, length of hospital stay, length of ICU stay, gastrointestinal (GI) bleeding, secondary infections, and hyperglycaemic events. The results were analysed through the random-effects model. A p-value < 0.05 was considered significant. RESULTS: Eighteen randomized controlled trials (n = 4472) analyzing patients withCAP were included. Our results suggest that corticosteroids significantly reduced the incidence of mortality (RR: 0.66; 95 % CI: 0.54, 0.81; P = <0.0001) and need for mechanical ventilation (RR: 0.57; 95 % CI: 0.44, 0.73; P = <0.00001). It was also observed that corticosteroids significantly decrease the lengths of ICU (MD: -1.67; 95 % CI: -2.97, -0.37; P = 0.01) and hospital stay (MD: -1.94; 95 % CI: -2.89, -0.98; P = 0.0001), while increasing the number of hyperglycemic events (RR: 1.68; 95 % CI: 1.32, 2.12; P = <0.0001) and hospital readmissions (RR: 1.19; 95 % CI: 1.04, 1.37; P = 0.01). CONCLUSIONS: The results of this meta-analysis demonstrate that corticosteroids yield improved outcomes in CAP patients with regard to reduced mortality and the need for mechanical ventilation. It highlights the need for further large-scale RCTs with the proposed, specific stratifications.

Focus on current and emerging treatment options for glioma: A comprehensive review.

This comprehensive review delves into the current updates and challenges associated with the management of low-grade gliomas (LGG), the predominant primary tumors in the central nervous system. With a general incidence rate of 5.81 per 100000, gliomas pose a significant global concern, necessitating advancements in treatment techniques to reduce mortality and morbidity. This review places a particular focus on immunotherapies, discussing promising agents such as Zotiraciclib and Lerapolturev. Zotiraciclib, a CDK9 inhibitor, has demonstrated efficacy in glioblastoma treatment in preclinical and clinical studies, showing its potential as a therapeutic breakthrough. Lerapolturev, a viral immunotherapy, induces inflammation in glioblastoma and displays positive outcomes in both adult and pediatric patients. Exploration of immunotherapy extends to Pembrolizumab, Nivolumab, and Entrectinib, revealing the challenges and variabilities in patient responses. Despite promising preclinical data, the monoclonal antibody Depatuxizumab has proven ineffective in glioblastoma treatment, emphasizing the critical need to understand resistance mechanisms. The review also covers the success of radiation therapy in pediatric LGG, with evolving techniques, such as proton therapy, showing potential improvements in patient quality of life. Surgical treatment is discussed in the context of achieving a balance between preserving the patient's quality of life and attaining gross total resection, with the extent of surgical resection significantly influencing the survival outcomes. In addition to advancements in cancer vaccine development, this review highlights the evolving landscape of LGG treatment, emphasizing a shift toward personalized and targeted therapies. Ongoing research is essential for refining strategies and enhancing outcomes in the management of LGG.

Association between depression and stroke risk in adults: a systematic review and meta-analysis.

Introduction: Stroke is a significant global health concern, and numerous studies have established a link between depression and an increased risk of stroke. While many investigations explore this link, some overlook its long-term effects. Depression may elevate stroke risk through physiological pathways involving nervous system changes and inflammation. This systematic review and meta-analysis aimed to assess the association between depression and stroke. Methodology: We conducted a comprehensive search of electronic databases (PubMed, Embase, Scopus, and PsycINFO) from inception to 9 April 2023, following the Preferred Reporting Items for Systemic Review and Meta-analysis (PRISMA) and Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. We included all articles assessing the association between different stroke types and depression, excluding post-stroke depression. Two investigators independently extracted data and assessed quality using the Newcastle-Ottawa Scale and Cochrane Risk of Bias tool, utilizing a random-effects model for data synthesis. The primary outcome was the association of depression with stroke, with a secondary focus on the association of antidepressants with stroke. Results: The initial search yielded 10,091 articles, and 44 studies were included in the meta-analysis. The pooled analysis revealed a significant association between depression and stroke risk, with an overall hazard ratio of 1.41 (95% CI 1.32, 1.50; p < 0.00001), indicating a moderately positive effect size. Subgroup analyses showed consistent associations with ischemic stroke (HR = 1.30, 95% CI 1.13, 1.50; p = 0.007), fatal stroke (HR = 1.39, 95% CI 1.24, 1.55; p < 0.000001), and hemorrhagic stroke (HR = 1.33, 95% CI 1.01, 1.76; p = 0.04). The use of antidepressants was associated with an elevated risk of stroke (HR = 1.28, 95% CI 1.05, 1.55; p = 0.01). Conclusion and relevance: This meta-analysis indicates that depression moderately raises the risk of stroke. Given the severe consequences of stroke in individuals with depression, early detection and intervention should be prioritized to prevent it. Systematic review registration: Prospero (CRD42023472136).

Preoperative anxiety management in pediatric patients: a systemic review and meta-analysis of randomized controlled trials on the efficacy of distraction techniques.

Background: This study addresses the pervasive issue of heightened preoperative anxiety in healthcare, particularly among pediatric patients. Recognizing the various sources of anxiety, we explored both pharmacological and nonpharmacological interventions. Focusing on distraction techniques, including active and passive forms, our meta-analysis aimed to provide comprehensive insights into their impact on preoperative anxiety in pediatric patients. Methods: Following the PRISMA and Cochrane guidelines, this meta-analysis and systematic review assessed the efficacy of pharmaceutical and distraction interventions in reducing pain and anxiety in pediatric surgery. This study was registered on PROSPERO (CRD42023449979). Results: This meta-analysis, comprising 45 studies, investigated pharmaceutical interventions and distraction tactics in pediatric surgery. Risk of bias assessment revealed undisclosed risks in performance and detection bias. Distraction interventions significantly reduced preoperative anxiety compared to control groups, with notable heterogeneity. Comparison with Midazolam favored distraction techniques. Subgroup analysis highlighted varied efficacies among distraction methods, with a notable reduction in anxiety levels. Sensitivity analysis indicated stable results. However, publication bias was observed, suggesting a potential reporting bias. Conclusion: Our study confirms distraction techniques as safe and effective for reducing pediatric preoperative anxiety, offering a valuable alternative to pharmacological interventions. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=449979, PROSPERO [CRD42023449979].

Current and Emerging Treatments for Urothelial Carcinoma: A Focus on Enfortumab Vedotin.

Urothelial carcinoma is a common malignancy that affects the urinary system, with bladder cancer being the most prevalent form. Although the management of early-stage disease has seen significant improvements, the treatment of locally advanced and metastatic urothelial carcinoma remains challenging. Over the past decade, there has been an explosion in the number of therapies available for the treatment of advanced disease, with immune checkpoint inhibitors and antibody-drug conjugates leading the way. Enfortumab vedotin is an antibody-drug conjugate that targets Nectin-4, a protein that is overexpressed in urothelial carcinoma cells. In clinical trials, it has shown promising outcomes for the treatment of advanced urothelial carcinoma that has progressed after chemotherapy or immunotherapy. The US Food and Drug Administration has granted expedited approval for enfortumab vedotin in the treatment of advanced urothelial carcinoma. This review provides an overview of the current and emerging treatments for urothelial carcinoma, with a particular focus on enfortumab vedotin. We discuss the mechanisms of action, clinical efficacy, safety, and ongoing research of enfortumab vedotin, along with the current landscape of other approved therapies and promising agents in development. The aim of this review is to provide a comprehensive and up-to-date summary of the available treatment options for urothelial carcinoma, including their limitations and future prospects.

DAXI (DaxibotulinumtoxinA) - An Innovative Approach for Frown Lines.

Glabellar frown lines, also known as worry lines, are a common sign of aging. The current treatment option for glabellar lines is subjective and ranges from economical anti-wrinkle creams and skin resurfacing techniques such as microdermabrasion and fillers to highly expensive facelifts. Botox® has been the mainstream treatment for decades, but the suggested time between treatments for most toxins is 12-16 weeks, and evidence shows that patients being treated for glabellar lines want longer-lasting results. Recently, on September 16th, the US Food and Drug Administration (FDA) approved the development of daxibotulinumtoxinA (DAXI) for injection based on clinical trials (SAKURA 1, 2, and 3). These encouraging findings followed by FDA approval mean that the need for repeated treatments to sustain the desired outcome has decreased. DAXI could be a reliable and secure choice for reducing the appearance of wrinkles on the face caused by muscle activity, and its long duration has the potential to enhance the treatment of both therapeutic and cosmetic disorders.

Seasonal Variation and Geographical Distribution of COVID-19 across Nigeria (March 2020-July 2021).

Globally, the novel corona virus infection has continued to witness a growing number of cases since December 2019 when the outbreak was discovered and noted in China. Despite this has not been well studied for the case of COVID-19, human contact, public moveableness and environmental variables could have an impact onairborne'spropagation and virus continuance, such as influenza virus. This study aimed to determine the seasonal variation and geographical distribution of COVID-19 across Nigeria. An internet based archival research design was employed for this study on the seasonal variation and geographical distribution of COVID-19 across Nigeria. This involved the use of goggle mobility data and world map on Corona Virus Infection (COVID-19). The search strategy for getting information for this research was done electronically. The keywords in the case search using the goggle mobility software was "COVID-19 Update", "COVID-19 Update in Nigeria", 'COVID-19 Winter Report', "COVID-19 Case Fatality March 2020-July 2021", "COVID-19 Case Fatality in Nigeria". The data gotten from the goggle motor updates were entered into Statistical Package for the Social Sciences (SPSS) which was used in the analysis of the study. Results from the study, reported that official COVID-19 cases number was significantly higher in the Dry season (October 2020-April 2021) with 59.0% (127,213) compared to 41.0% (85,176) in the wet/rainy season (May-September) it revealed that the dry and rainy seasons had a COVID-19 prevalence of 0.063 and 0.041 respectively. Further results from the study showed that the prevalence of COVID-19 was 0.07% in the North-Central, 0.04% in both the North-East and North-West, 0.03% in the South-West, 0.09% in the South-South, and the highest prevalence of 0.16% in the South-East. Considering the case Fatality rate of COVID-19 during the Dry and Wet Seasons. The study revealed that North-Central had a death toll of 196 (10.4%) out of 9457 confirmed COVID-19 cases hence a fatality of 2.07. Fatality rate of 1.49% in South western Nigeria, South-South Nigeria, 1.49%, South-East accounted to a fatality rate of 1.25%. Nigeria based on the finding of this study records increased fatality in Dry season over wet seasons. The study concluded that prevalence of COVID-19 varies in seasons in Nigeria Hence; further Data and Meteorological analysis on weather variations towards the SARS-CoV-2 Virus spread should be evaluated by future researchers. It is imperative to ensure strict and controlled application of social measures, such as social distancing, mandatory wearing of non-medical masks to prevent droplets from entering the respiratory tract, screening of affected patients along with quarantine is essential to defeat and improve infection control.

Mechanisms of regulatory evolution in yeast.

Studies of regulatory variation in yeast - at the level of new mutations, polymorphisms within a species, and divergence between species - have provided great insight into the molecular and evolutionary processes responsible for the evolution of gene expression in eukaryotes. The increasing ease with which yeast genomes can be manipulated and expression quantified in a high-throughput manner has recently accelerated mechanistic studies of cis- and trans-regulatory variation at multiple evolutionary timescales. These studies have, for example, identified differences in the properties of cis- and trans-acting mutations that affect their evolutionary fate, experimentally characterized the molecular mechanisms through which cis- and trans-regulatory variants act, and illustrated how regulatory networks can diverge between species with or without changes in gene expression.