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BackgroundRecent climatic history has strongly impacted plant populations, but little is known about its effect on microbes. Alders, which host few and specific symbionts, have high genetic diversity in glacial refugia. Here, we tested the prediction that communities of root symbionts survived in refugia with their host populations. We expected to detect endemic symbionts and a higher species richness in refugia as compared to recolonized areas.MethodsWe sampled ectomycorrhizal (EM) root tips and the nitrogen-fixing actinomycete Frankia communities in eight sites colonized by Alnus glutinosa subsp. barbata close to the Caucasus in Georgia. Three sites were located in the Colchis, one major Eurasian climatic refugia for Arcto-Tertiary flora and alders, and five sites were located in the recolonized zone. Endemic symbionts and plant ITS variants were detected by comparing sequences to published data from Europe and another Tertiary refugium, the Hyrcanian forest. Species richness and community structure were compared between sites from refugia and recolonized areas for each symbionts.ResultsFor both symbionts, most MOTUs present in Georgia had been found previously elsewhere in Europe. Three endemic Frankia strains were detected in the Colchis vs two in the recolonized zone, and the five endemic EM fungi were detected only in the recolonized zone. Frankia species richness was higher in the Colchis while the contrary was observed for EM fungi. Moreover, the genetic diversity of one alder specialist Alnicola xanthophylla was particularly high in the recolonized zone. The EM communities occurring in the Colchis and the Hyrcanian forests shared closely related endemic species.DiscussionThe Colchis did not have the highest alpha diversity and more endemic species, suggesting that our hypothesis based on alder biogeography may not apply to alder’s symbionts. Our study in the Caucasus brings new clues to understand symbioses biogeography and their survival in Tertiary and ice-age refugia, and reveals that isolated host populations could be of interest for symbiont diversity conservation.

Nobiletin is an O-methylated flavonoid found in citrus peels that have anticancer, antiviral, neuroprotective, anti-inflammatory activities and depending on the cell types exhibits both pro-or anti-apoptotic properties. We have found that nobiletin decreases oxygen consumption by bovine brain isolated mitochondria in the presence of glutamate and malate and increases in the presence of succinate. In parallel, nobiletin increases NADH oxidation, a-ketoglutarate dehydrogenase activities and through matrix substrate-level phosphorylation elevates the a-ketoglutarate-dependent production of ATP. In addition, nobiletin reduces the production of peroxides in the presence of complex I substrates and slightly enhances succinate-driven H 2 O 2 formation. Besides, nobiletin induces transient elevation of membrane potential followed by mild depolarization. Affinity purified nobiletin binding proteins revealed one major anti-NDUFV1 positive protein with 52kD and NADH: ubiquinone oxidoreductase activity. This fraction can produce peroxide that is inhibited by nobiletin. We propose that nobiletin may act as a mild "uncoupler", which through activation of a-ketoglutarate dehydrogenase (a-KGDH)-complex and acceleration of matrix substratelevel phosphorylation maintains membrane potential at an abnormal level. This switch in mitochondrial metabolism could elevate succinate-driven oxygen consumption that may underlay in both pro-and anti-apoptotic effects of nobiletin.

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Nobiletin restores reduced mitochondrial metabolism in hypothyroid rat hippocampus through acceleration of matrix substrate-level phosphorylation that may be important for the prevention of hypometabolic complications in neurological disorders.

Francesco M (2020) Is multidisciplinary learning valuable to build a breast cancer specialist career? The perspective of the first 2 cohorts of the ESO-ULM Certificate of Competence in Breast Cancer (CCB)

e13529 Background: The availability of comprehensive cancer care in different regions is the main problem in developing countries. In fact, the cancer centers are centralized and patients fail to receive the proper medical care in regions. The situation is critical for patients living in the zones of conflict. In Georgia we have cancer centers only in two cities Tbilisi and Kutaisi. The aim of the study was to investigate the rate of gastric cancer diagnoses in different regions of Georgia, that could be a model for developing countries. Methods: The spread of gastric cancer in Georgia was investigated retrospectively by analyzing the cases reported in different regions based on 5 years national cancer registry data from 2015 to 2021. The data included the number of cases, age, sex, and stage of gastric cancer. Data from all regions of Georgia were analyzed including occupied regions as Abkhazia and Tskhinvali. Other regions were – Tbilisi, Adjara, Guria, Imereti, Kakheti, Mstkheta, Racha, Samtskhe, Kvemo Kartli, Shida Kartli. Results: A total of 1825 patients with gastric cancer were evaluated during the period of 2015-2021 years. The highest number of diagnosed cases were reported in Tbilisi, with 258 cases in males and 200 cases in females, followed by Imereti (Kutaisi) with 125 cases in males and 80 cases in females and Adjara 132 cases in males and 56 cases in females. The other regions had lower numbers of diagnosed cases, with the lowest being Tskhinvali with only three cases in males and six cases in females. In Abkhazia were 44 cases in males and 19 cases in females. In terms of stage distribution there was no difference between the regions, the majority of patients were stage IV accounting 42 % of all cases, 28% was stage III, 10 % was stage II, 5% was stage I and 15% was of unknown stage. Age ranges were different according to the sex and regions – in Tbilisi 35-83 in males and 26-94 in females, in Adjara 29-88 in males and 28-84 in females, in Abkhazia 35-83 in males and 41-83 in females, in Guria 37-91 in males and 39-83 in females, in Imereti 37-88 in males and 34-84 in females, in Kakheti 34-85 in males and 37-89 in females, in Mtskheta 34-91 in males and 50-84 in females, in Racha 31-72 in males and 30-81 in females, in Samegrelo 33-96 in males and 21-90 in females, in Samtskhe 43-94 in males and 38-81 in females, in Kvemo Kartli 26-85 in males and 38-90 in females, in Shida Kartli 39-85 in males and 38-90 in females, in Tskhinvali 66-84 in males and 33-76 in females. Conclusions: The study found that availability of comprehensive care for gastric cancer including diagnosing is limited in the regions of Georgia, with the lowest rates in occupied regions. To improve the cancer care in developing countries such as Georgia international and national strategies are needed.

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