The Gene Ontology knowledgebase in 2023.

The Gene Ontology (GO) knowledgebase (http://geneontology.org) is a comprehensive resource concerning the functions of genes and gene products (proteins and noncoding RNAs). GO annotations cover genes from organisms across the tree of life as well as viruses, though most gene function knowledge currently derives from experiments carried out in a relatively small number of model organisms. Here, we provide an updated overview of the GO knowledgebase, as well as the efforts of the broad, international consortium of scientists that develops, maintains, and updates the GO knowledgebase. The GO knowledgebase consists of three components: (1) the GO-a computational knowledge structure describing the functional characteristics of genes; (2) GO annotations-evidence-supported statements asserting that a specific gene product has a particular functional characteristic; and (3) GO Causal Activity Models (GO-CAMs)-mechanistic models of molecular "pathways" (GO biological processes) created by linking multiple GO annotations using defined relations. Each of these components is continually expanded, revised, and updated in response to newly published discoveries and receives extensive QA checks, reviews, and user feedback. For each of these components, we provide a description of the current contents, recent developments to keep the knowledgebase up to date with new discoveries, and guidance on how users can best make use of the data that we provide. We conclude with future directions for the project.

Effects of chronic exposure to lead, cadmium, and manganese mixtures on oxidative stress in rat liver and heart.

The aim of this study was to assess the effects of chronic combined exposure to low, environmental doses of Cd, Pb, and Mn on oxidative stress in the liver and heart of rats and on their liver function parameters. Male Wistar rats were divided randomly into eight groups. For nine months controls were receiving drinking water alone, whereas the exposed groups were receiving drinking water with Pb (0.2 mg L(-1)), Cd (1 mg L(-1)), and Mn (2 mg L(-1)) alone or in combinations. Malondialdehyde (MDA) significantly increased in both heart and liver of the animals after combined exposure to metals. Heart MDA correlated with blood Cd, Pb, and Mn and liver MDA with blood Cd. Aspartate aminotransferase (AST) activity and bilirubin concentration also increased significantly in the animal group exposed to all three metals and correlated positively with blood Cd, Pb, and Mn. Our study has confirmed the synergistic effect of the Cd, Mn, and Pb combination on the increase in heart MDA. A similar synergy was observed for Pb+Mn in the increase of serum alanine aminotransferase (ALT) activity as an indicator of liver function.

[The correlations between aging of the human body, oxidative stress and reduced efficiency of repair systems]. / Starzenie sie organizmu a stres oksydacyjny oraz zmniejszona sprawnosc systemów naprawczych.

The article presents an current knowledge overview about the importance of oxidative stress and reduced efficiency of repair processes during the aging process of the human body. Oxidative damage to cellular macromolecules (proteins, lipids, nucleic acids), are formed under the influence of reactive oxygen species (ROS). They are the part of important mechanism which is responsible for the process of aging and the development of many diseases. The most important effects result from DNA damage, due to the mutations formation, which can lead to the development of tumors. However, a well-functioning repair systems (i.a. homologous recombination) remove the damage and prevent harmful changes in the cells. Lipid peroxidation products also cause oxidative modification of nucleic acids (and proteins). Proteins and fats also have repair systems, but much simpler than those responsible for the repair of nucleic acids. Unfortunately, with increasing age, they are more weakened, which contributes to increase numbers of cell damage, and consequently development of diseases specific to old age: cancer, neurodegenerative diseases or atherosclerosis.

[Subclinical hypothyroidism influences ventricular repolarization measured by QTc interval]. / Subkliniczna niedoczynnosc tarczycy ma wplyw na repolaryzacje komór serca, mierzona skorygowanym odstepem QT (QTc).

UNLABELLED: Thyroid disorders exert a major effect on cardiac function and on ECG. Few studies examined the effect of thyroid hormones on ventricular repolarization, measured by corrected QT interval (QTc). Prolonged QTc is associated with increased risk of arrythmias and cardiac mortality. The aim of this study was to examine the influence of subclinical hypothyroidism on ventricular repolarization measured by corrected QTc in standard 12-lead electrocardiogram. The examined group consisted of 32 patients with hypothyroidism, the controls were 39 healthy individuals. The mean corrected QTc was 0.434, SD +/- 0.0296 seconds and 0.414, SD +/- 0.0208 in the examined groups and in controls, respectively (p < 0.01). QTc did not correlate with free thyroxine concentrations (p = 0.4064). In the group with subclinical hypothyroidism we did not observe a significant difference in heart rate (74.3 vs. 73.7, SD +/- 13.58, NS). CONCLUSION: Corrected QT intervals were significantly prolonged in patients with subclinical hypothyroidism.

[Prolonged ventricular repolarization measured by QTc interval in hyperthyroidism]. / Wydluzenie repolaryzacji komór mierzonej za pomoca odstepu QTc w przebiegu nadczynnosci tarczycy.

UNLABELLED: Thyroid dysfunction exerts an effect on cardiac function and on an electrocardiographic curve. Few studies analyzed the influence of thyroid hormones on heart repolarization. Heart repolarization is assessed in every-day-practice with corrected QT interval in ECG. Prolonged QTc is associated with increased risk for heart rythm disturbances and mortality. The aim of this study was to assess the effect of hyperthyroidism on heart repolarization, measured with QT corrected by Bazett's formula. MATERIAL AND METHODS: The study group included 68 hyperthyroid patients (30 males, 38 females, mean age 39+/-10 yrs) and the controls were 39 in age and sex matched healthy subjects. TSH and free thyroxine were assessed. The QTc was measured in a standard 12 lead ECG. RESULTS: In the study group the heart rhythm was faster when compared to controls (91.8 vs.73.7, SD+/-16.11, p<0.0001). The mean corrected QT (QTc) was 0.430, SD+/-0.0273 sec., in controls respectively: 0.414, SD+/-0.0208 sec., p<0.01. QTc did not correlate with free thyroxine concentrations (p=0.2785). CONCLUSIONS: Corrected QT intervals were significantly prolonged in hyperthyroid patients, although they did not reach high values.