DNA hydroxymethylation and improved growth of Nile tilapia (Oreochromis niloticus) during domestication

Doctoral thesis (PhD) - Nord University, 2020The worldwide demand for fish consumption is highly dependent on aquaculture production because commercial fishing reached its maximum exploitation since the 90’s. However, continued expansion of the aquaculture industry in a sustainable manner is dependent on several factors, including domestication of new species and establishment of selective breeding programmes. Domestication of new fish species is a rather complex and long process but the deployment of new molecular tools could improve and accelerate it through the holistic characterization of fish genomes. This thesis is based on the hypothesis that epigenetic mechanisms underlie genome-wide adaptation under captivity, since genetic mutations and allele shifts alone cannot explain the rapid transcriptomic changes of fish undergoing domestication. In a series of experiments, we investigated the role of DNA hydroxymethylation during the early stages of fish domestication, and its potential involvement in regulating somatic growth. At first, we discovered that the DNA hydroxymethylome in fast muscle changes rapidly within a single generation of domestication. As a result of our 5-hydroxymethylcytosine (5hmC) profiling at single nucleotide resolution, we were able to identify that 5hmCs are largely enriched within gene bodies, which supports the notion that they are functionally relevant epigenetic modifications. The annotation of differentially hydroxymethylated genes between wild and first-generation of fish under captivity revealed that the changes occurred primarily within genes involved in immunity, growth and neuronal activity. By comparing gene expression profiles in muscle between wild and first generation of Nile tilapia in captivity, we showed that immune-related genes were upregulated in the wild fish, while genes involved in metabolism and muscle-specific functions were downregulated. These findings revealed that the first generation of fish undergoing domestication is strongly influenced by the environmental conditions under captivity, namely the lack of pathogens and the optimal conditions of water temperature, oxygen, pH and diet. Thus, we provided for the first time a link between environmentally-mediated DNA hydroxymethylation and gene regulation in fish undergoing domestication. To further explore the connection between DNA hydroxymethylation and somatic growth, we compared the liver hydroxymethylomes of slow- and fast-growing full siblings and examined the 5hmC abundance in three major tissues that compose the somatotropic axis. Interestingly, we identified several differentially hydroxymethylated genes between slowand fast-growers. These genes were involved in signaling pathways related to cell growth, survival and proliferation such as the PI3K-Akt, the Ras- and Rho- protein signal transduction pathways. By comparing the DNA hydroxymethylomes among the muscle, liver and pituitary, we identified several differentially hydroxymethylated growth factors, receptors and enhancers with major implications in growth, metabolism and skeletal muscle development. Taken together, this thesis provides for the first time a direct link between DNA hydroxymethylation and fish domestication and associates epigenetic marks at single nucleotide resolution to somatic growth using cutting-edge molecular tools. When validated, these epigenetic markers can potentially improve current breeding strategies in aquaculture by providing a holistic approach for broodstock selection.publishedVersio

The Right to Health under International Law

Outline: * The International Legal Framework Surrounding the Right to Health * Key Aspects of the Right to Health * Obligations on States towards the Right to Health *Embargos and the Right to Health – Access to Medicine

Combined Approaches in Sialolithiasis of Major Salivary Glands

Combined (endoscopic-transcutaneous) techniques are an effective treatment for large and/or impacted stones of the major salivary glands. This approach results in high rates of symptom improvement and gland preservation. The complication rates are relatively low, further supporting the use of these techniques as an additional tool between the classic sialendoscopy and the external classic procedures of gland removal. In this chapter, we describe the combined approach for the parotid gland and the submandibular gland and finally, the retrograde sialendoscopy through the surgical field of an open approach

Lower Urinary Tract Symptoms (LUTS) and Sexual Function and Dysfunction

In recent years, the coexistence of sexual dysfunction (SD) and lower urinary tract symptoms (LUTS) has become a popular topic for researchers. Numerous clinical epidemiologic studies have been planned for this reason and have evaluated the relationship between these seemingly irrelevant urological conditions. The connection between SD and LUTS has already been acknowledged, and common pathophysiological pathways have been recognized. In this chapter was attempted to evaluate the impact on patient’s quality of life (QoL), common pathophysiological pathways and therapy aspects of this condition. SD and LUTS are common problems among the general population and affect a great percentage of urological patients. It is a subject that affects the community in social, financial, and psychological terms. In this case, research for new treatment options has been triggered as phosphodiesterase type 5 inhibitors established their role as the widely approved combination therapy

The Effect of Locally Delivered Doxycycline in the Treatment of Chronic Periodontitis. A Clinical and Microbiological Cohort Study

Objectives: To evaluate the efficacy of locally delivered doxycycline as an adjunct to non-surgical treatment with the use of an ultrasonic device compared to scaling and root planing using hand instruments, by means of clinical and microbiological criteria.Material and Methods: Thirty three patients with chronic periodontitis participated in this cohort study and were divided into two groups. Patients in control group received scaling and root planing using hand instruments, whereas patients in control group received ultrasonic debridement and 8.8% doxycycline gel was applied after initial therapy and at 3 months at preselected sites. Clinical recordings concerning probing pocket depth, clinical attachment level, plaque index and gingival bleeding index were performed at baseline, 3 and 6 months after baseline. Subgingival samples were analysed using the “checkerboard” DNA-DNA hybridisation technique for Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola.Results: Both treatments resulted in significant improvement in all clinical recordings. Six months after the treatment a statistically significant decrease was observed for Porphyromonas gingivalis in both of groups and Treponema denticola in the control group (P < 0.05). No inter-group differences were observed (P < 0.05).Conclusions: Both treatment modalities provided comparable clinical and microbiological results in the treatment of chronic periodontitis

Genome-wide hydroxymethylation profiles in liver of female Nile tilapia with distinct growth performance

The mechanisms underlying the fast genome evolution that occurs during animal domestication are poorly understood. Here, we present a genome-wide epigenetic dataset that quantifies DNA hydroxymethylation at single nucleotide resolution among full-sib Nile tilapia (Oreochromis niloticus) with distinct growth performance. In total, we obtained 355 million, 75 bp reads from 5 large- and 5 small-sized fish on an Illumina NextSeq500 platform. We identified several growth-related genes to be differentially hydroxymethylated, especially within gene bodies and promoters. Previously, we proposed that DNA hydroxymethylation greatly affects the earliest responses to adaptation and potentially drives genome evolution through its targeted enrichment and elevated nucleotide transversion rates. This dataset can be analysed in various contexts (e.g., epigenetics, evolution and growth) and compared to other epigenomic datasets in the future, namely DNA methylation and histone modifications. With forthcoming advancements in genome research, this hydroxymethylation dataset will also contribute to better understand the epigenetic regulation of key genomic features, such as cis-regulatory and transposable elements.publishedVersio

Nasal mucosal melanoma presenting as central type vertigo: a case report

Nasal mucosal melanoma presents usually with epistaxis, nasal obstruction and facial pain. However melanoma tends to give distant metastases at an early stage, having rare clinical presentations

TARGETING MYOGENESIS MODULATION VIA CRISPR/CAS9-MEDIATION IN FARMED NILE TILAPIA

Abstract from a conference report; Report on the 6th Genomics in Aquaculture (GIA) Symposium Held in Granada, Spain, 4–6 May 2022.acceptedVersio

Socioekonomski uzroci i alohtone vrste slatkovodnih rakova u Evropi

Strane vrste slatkovodnih rakova (NICS) prelaze po brojnosti autohtone u mnogim evropskim zemljama, predstavljajući pretnju biodiverzitetu zbog širenja "kuge" rakova, agresivne invazije i antagonističkog delovanja. Iako je biološka osnova ovog stanja dobro proučena, moguća uloga socijalnih, ekonomskih i demografskih činilaca za ovu situaciju je praktično ignorisana. U pokušaju da se ispitaju takvi odnosi, mi predlažemo da je gustina ljudske populacije i ekonomski rast meren kao rast domaćeg proizvoda (GDP) per capita pozitivno povezan sa povećanim brojem NICS-a u Evropskoj Uniji. Ovo je očigledno u zemljama sa većim ukupnim ekološkim tragom. U gornjem kontekstu hitno su potrebne akcije da se povrate/uravnoteže postojeće i projektovane ekološke promene prouzrokovane prisustvom NICS-a