Qualitative and quantitative Cdk control of the budding yeast cell cycle

Timely and ordered progression through the cell cycle is crucial for error-free proliferation of cells. In eukaryotes, cell division cycle is controlled by the master regulator cyclin-cyclin dependent kinase (Cdk) complexes. However, it is still unclear how cyclin-Cdk complexes ensure the order in the cell cycle so that DNA replication in S phase always precedes chromosome segregation in mitosis. Two models have been put forward to explain cell cycle ordering by cyclin-Cdk complexes. The qualitative model suggests that distinct substrate specificities of the different cyclins at successive cell cycle stages order substrate phosphorylation. In contrast, the quantitative model for Cdk control of the cell cycle suggests that the overall gradual increase in Cdk activity from G1 to mitosis orders cell cycle progression. In line with the quantitative model, a single cyclin-Cdk complex is sufficient to order the fission yeast cell cycle. However, the relative contributions of qualitative and quantitative Cdk control in other organisms is incompletely understood. In this project, I investigate cyclin specificity and redundancy in the budding yeast S. cerevisiae, which encodes three G1 (Cln1-3), two S (Clb5 and Clb6) and four G2/M (Clb1-4) cyclins that are orthologous to those found in many metazoans, including humans. With an aim to identify the minimal set of cyclins required to drive the ordered cell cycle progression in budding yeast, I have removed seven of the nine cyclins, establishing a strain harbouring one G1 cyclin, Cln2, and a mitotic cyclin, Clb2, that is expressed from an S phase cyclin CLB5 promoter in addition to its own promoter. In this strain, expressing a third copy of Clb2 under control of CLN2 promoter is sufficient to order DNA replication and chromosome segregation in the absence of Cln2. However, these cells cannot polarise or form buds. My findings indicate that the budding yeast G1 cyclin Cln2 has evolved to carry unique crucial functions to couple cell cycle progression to morphogenetic events.Open Acces

The protective effect of an aqueous extract from Smilax excelsa l. against carbon tetrachloride-induced liver injury in rats

Background: Because reactive oxygen species (ros) contribute to the pathogenesis of various acute and chronic liver diseases, dietary antioxidants and drugs from herbal origins have been proved to be beneficial as therapeutic agents in reversing hepatotoxicity and oxidative stress. The objective of this study was to investigate the protective effect of an aqueous extract from smilax excelsa l. Shoots and leaves against acute ccl4-induced liver injury as well as the changes in antioxidative defense system in female wistar albino rats.Materials and Methods: S. Excelsa extract was administered orally in doses of 100, 200 and 400 mg/kg body weight, once daily for 9 days. Acute hepatic toxicity was induced by intraperitoneal injection of ccl4 (1 ml/kg) on the 10th day. 24 h after ccl4 intoxication, biochemical and histopathological analyses were undertaken on sera and liver tissues.Results: Ccl4 challenge caused significant increases in the activities of liver enzymes as well as the levels of bilirubin, malondialdehyde and nitric oxide, while total serum protein levels and antioxidant defense system parameters were reduced significantly compared to the normal group. Administration of s. Excelsa extract at a dose of 400 mg/kg resulted in a suppression of ccl4-induced lipid peroxidation and altered oxidative stress parameters to nearly normal values in comparison to ccl4-treated rats. Nevertheless the extract did not reduce the extent of ccl4-induced mild liver injury, as seen by the histopathology of liver damage.Conclusion: The results of this study suggest that s. Excelsa could protect the liver tissues against ccl4-induced oxidative stress probably by increasing antioxidative defense activities.Keywords: Antioxidant enzymes, carbon tetrachloride, liver injury, smilax excelsa, hepatoprotective activit

THE PROTECTIVE EFFECT OF AN AQUEOUS EXTRACT FROM SMILAX EXCELSA L. AGAINST CARBON TETRACHLORIDE-INDUCED LIVER INJURY IN RATS

Background: Because reactive oxygen species (ros) contribute to the pathogenesis of various acute and chronic liver diseases, dietary antioxidants and drugs from herbal origins have been proved to be beneficial as therapeutic agents in reversing hepatotoxicity and oxidative stress. The objective of this study was to investigate the protective effect of an aqueous extract from smilax excelsa l. Shoots and leaves against acute ccl4-induced liver injury as well as the changes in antioxidative defense system in female wistar albino rats. Materials and Methods: S. Excelsa extract was administered orally in doses of 100, 200 and 400 mg/kg body weight, once daily for 9 days. Acute hepatic toxicity was induced by intraperitoneal injection of ccl4 (1 ml/kg) on the 10th day. 24 h after ccl4 intoxication, biochemical and histopathological analyses were undertaken on sera and liver tissues. Results: Ccl4 challenge caused significant increases in the activities of liver enzymes as well as the levels of bilirubin, malondialdehyde and nitric oxide, while total serum protein levels and antioxidant defense system parameters were reduced significantly compared to the normal group. Administration of s. Excelsa extract at a dose of 400 mg/kg resulted in a suppression of ccl4-induced lipid peroxidation and altered oxidative stress parameters to nearly normal values in comparison to ccl4-treated rats. Nevertheless the extract did not reduce the extent of ccl4-induced mild liver injury, as seen by the histopathology of liver damage. Conclusion: The results of this study suggest that s. Excelsa could protect the liver tissues against ccl4-induced oxidative stress probably by increasing antioxidative defense activities

Post COVID-19 irritable bowel syndrome

Objectives: The long-term consequences of COVID-19 infection on the gastrointestinal tract remain unclear. Here, we aimed to evaluate the prevalence of gastrointestinal symptoms and post-COVID-19 disorders of gut-brain interaction after hospitalisation for SARS-CoV-2 infection. Design: GI-COVID-19 is a prospective, multicentre, controlled study. Patients with and without COVID-19 diagnosis were evaluated on hospital admission and after 1, 6 and 12 months post hospitalisation. Gastrointestinal symptoms, anxiety and depression were assessed using validated questionnaires. Results: The study included 2183 hospitalised patients. The primary analysis included a total of 883 patients (614 patients with COVID-19 and 269 controls) due to the exclusion of patients with pre-existing gastrointestinal symptoms and/or surgery. At enrolment, gastrointestinal symptoms were more frequent among patients with COVID-19 than in the control group (59.3% vs 39.7%, p<0.001). At the 12-month follow-up, constipation and hard stools were significantly more prevalent in controls than in patients with COVID-19 (16% vs 9.6%, p=0.019 and 17.7% vs 10.9%, p=0.011, respectively). Compared with controls, patients with COVID-19 reported higher rates of irritable bowel syndrome (IBS) according to Rome IV criteria: 0.5% versus 3.2%, p=0.045. Factors significantly associated with IBS diagnosis included history of allergies, chronic intake of proton pump inhibitors and presence of dyspnoea. At the 6-month follow-up, the rate of patients with COVID-19 fulfilling the criteria for depression was higher than among controls. Conclusion: Compared with controls, hospitalised patients with COVID-19 had fewer problems of constipation and hard stools at 12 months after acute infection. Patients with COVID-19 had significantly higher rates of IBS than controls. Trial registration number: NCT04691895