Genetske promjene uvjetovane onečišćenjem

Sa pojačanim onečišćenjem okoliša koji uzrokuje čovjek, razni organizmi se moraju nositi na razne načine. Samo onečišćenje može imati direktan ili indirektan utjecaj. Kao direktan utjecaj navode se razne mutacije i oštećenja DNA molekule i kromosoma, a kao indirektan utjecaj genetski drift i genetska adaptacija. Genetska adaptacija obuhvaća brze genetske promjene koje odgovaraju na prirodne promjene i koje će omogućiti bolju vijabilnost nekog organizma, odnosno populacije. Međutim genetske adaptacije se ne mogu stalno odvijati, jer postoji spora selekcija koji eliminira jedinke podložne mutacijama. Komparativne analize nam omogućuju da se rezultati dobiveni na jednim genima kandidatima primjene i na druge organizme uključujući i vrste koje nisu modelni organizmi.With substantial and increasing enviromental pollution which is caused by man, different organisms have to cope with it in various ways. Contamination itself may have direct or indirect influence. Direct effects are set of various mutations and lesions which implicate DNA molecules and chromosomes, and indirect effects are genetic drift and genetic adaptation. Genetic adaptation includes rapid genetic changes that are response to environmental changes, and that will provide better viability for some organism or population. However, genetic adaptation can not be conducted to infinity because there is a slow selection, that eliminates the individuals subjected to mutations. Comparative analysis make it possible to apply results, which are obtained in a single application of candidate loci, on other organisms, including species that are not model organisms

Genetske promjene uvjetovane onečišćenjem

Sa pojačanim onečišćenjem okoliša koji uzrokuje čovjek, razni organizmi se moraju nositi na razne načine. Samo onečišćenje može imati direktan ili indirektan utjecaj. Kao direktan utjecaj navode se razne mutacije i oštećenja DNA molekule i kromosoma, a kao indirektan utjecaj genetski drift i genetska adaptacija. Genetska adaptacija obuhvaća brze genetske promjene koje odgovaraju na prirodne promjene i koje će omogućiti bolju vijabilnost nekog organizma, odnosno populacije. Međutim genetske adaptacije se ne mogu stalno odvijati, jer postoji spora selekcija koji eliminira jedinke podložne mutacijama. Komparativne analize nam omogućuju da se rezultati dobiveni na jednim genima kandidatima primjene i na druge organizme uključujući i vrste koje nisu modelni organizmi.With substantial and increasing enviromental pollution which is caused by man, different organisms have to cope with it in various ways. Contamination itself may have direct or indirect influence. Direct effects are set of various mutations and lesions which implicate DNA molecules and chromosomes, and indirect effects are genetic drift and genetic adaptation. Genetic adaptation includes rapid genetic changes that are response to environmental changes, and that will provide better viability for some organism or population. However, genetic adaptation can not be conducted to infinity because there is a slow selection, that eliminates the individuals subjected to mutations. Comparative analysis make it possible to apply results, which are obtained in a single application of candidate loci, on other organisms, including species that are not model organisms

The “Big Bang” in obese fat: Events initiatingobesity-induced adipose tissue inflammation

Obesity is associated with the accumulation of pro-inflammatory cells in visceral adiposetissue (VAT), which is an important underlying cause of insulin resistance and progres-sion to diabetes mellitus type 2 (DM2). Although the role of pro-inflammatory cytokinesin disease development is established, the initiating events leading to immune cell acti-vation remain elusive. Lean adipose tissue is predominantly populated with regulatorycells, such as eosinophils and type 2 innate lymphocytes. These cells maintain tissuehomeostasis through the excretion of type 2 cytokines, such as IL-4, IL-5, and IL-13,which keep adipose tissue macrophages (ATMs) in an anti-inflammatory, M2-like state.Diet-induced obesity is associated with the loss of tissue homeostasis and developmentof type 1 inflammatory responses in VAT, characterized by IFN-γ. A key event is a shiftof ATMs toward an M1 phenotype. Recent studies show that obesity-induced adipocytehypertrophy results in upregulated surface expression of stress markers. Adipose stressis detected by local sentinels, such as NK cells and CD8+T cells, which produce IFN-γ,driving M1 ATM polarization. A rapid accumulation of pro-inflammatory cells in VATfollows, leading to inflammation. In this review, we provide an overview of events lead-ing to adipose tissue inflammation, with a special focus on adipose homeostasis and theobesity-induced loss of homeostasis which marks the initiation of VAT inflammation

Polymorphism in HER2/neu gene in sporadic colorectal carcinoma tumorigenesis

U Hrvatskoj je karcinom debelog crijeva na trećem mjestu po učestalosti, dok je na drugom mjestu kao uzrok smrti od raka. Većina karcinoma debelog crijeva posljedica je stupnjevitog procesa tijekom kojeg iz dobroćudnog adenoma kao posljedica naslijeđenih ili stečenih mutacija nastaje zloćudni tumor. Postojeći prognostički parametri još uvijek samo djelomično daju informacije o toku i ishodu ove bolesti, tako da postoji potreba za pronalaskom novih dijagnostičkih i prognostičkih molekularnih biljega. Jedan od tih biljega mogao bi biti i HER-2. Receptor HER-2 je tirozin kinaza, kodirana genom HER-2/neu, koja ima glavnu ulogu u aktivaciji signalnog puta važnog u proliferaciji stanica. Molekularnom analizom polimorfizama gena HER-2/neu ustanovljeno je da određeni polimorfizmi utječu na pojačanu autofosforilaciju i tirozin kinaznu aktivnost što može utjecati na povećanu sklonost obolijevanju ili lošiju prognozu bolesti. Cilj ovog diplomskog rada bio je istražiti povezanost polimorfizma c.1963A>G (rs1136201, I655V) u genu HER-2/neu sa sklonošću obolijevanju i preživljenjem oboljelih od sporadičnog karcinoma debelog crijeva. Rezultati istraživanja pokazali su da postoji povezanost između polimorfizma I655V i sklonosti obolijevanju.In Croatia, colorectal cancer is the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths. Colorectal cancer is a result of multistep process in which malignant colorectal carcinoma develops from benign adenoma, as a result of somatic or inherited mutations. Existing prognostic markers give only partial information about course and outcome of this disease, so there is a constant need for development and discovery of novel disease-related diagnostic and prognostic molecular markers. One of these new markers could be also HER-2. HER-2 is a cell membrane receptor tyrosine kinase, encoded by HER-2/neu gene, and is normally involved in the signal transduction pathways leading to cell growth and proliferation. Previous studies suggested that certain polymorphisms of the HER-2 gene (e.g. I655V) might result in increased autophosphorylation and tyrosine kinase activation. It is possible that these polymorphisms are associated with the increased susceptibility to colon cancer and poor prognosis. The aim of this study was to investigate the potential correlation of polymorphism c.1963A>G (rs1136201, I655V) in HER-2/neu gene with susceptibility to disease and survival of patients suffering from sporadic colorectal cancer. Results showed that I655V polymorphism is related to increased risk for sporadic colon cancer development

Interactions between adipose tissue and the immune system in health and malnutrition

Adipose tissue provides the body with a storage depot of nutrients that is drained during times of starvation and replenished when food sources are abundant. As such, it is the primary sensor for nutrient availability in the milieu of an organism, which it communicates to the body through the excretion of hormones. Adipose tissue regulates a multitude of body functions associated with metabolism, such as gluconeogenesis, feeding and nutrient uptake. The immune system forms a vital layer of protection against micro-organisms that try to gain access to the nutrients contained in the body. Because infections need to be resolved as quickly as possible, speed is favored over energy-efficiency in an immune response. Especially when immune cells are activated, they switch to fast, but energy-inefficient anaerobic respiration to fulfill their energetic needs. Despite the necessity for an effective immune system, it is not given free rein in its energy expenditure. Signals derived from adipose tissue limit immune cell numbers and activity under conditions of nutrient shortage, whereas they allow proper immune cell activity when food sources are sufficiently available. When excessive fat accumulation occurs, such as in diet-induced obesity, adipose tissue becomes the site of pathological immune cell activation, causing chronic low-grade systemic inflammation. Obesity is therefore associated with a number of disorders in which the immune system plays a central role, such as atherosclerosis and non-alcoholic steatohepatitis. In this review, we will discuss the way in which adipose tissue regulates activity of the immune system under healthy and pathological condition

NK cells link obesity-induced adipose stress to inflammation and insulin resistance

An important cause of obesity-induced insulin resistance is chronic systemic inflammation originating in visceral adipose tissue (VAT). VAT inflammation is associated with the accumulation of proinflammatory macrophages in adipose tissue, but the immunological signals that trigger their accumulation remain unknown. We found that a phenotypically distinct population of tissue-resident natural killer (NK) cells represented a crucial link between obesity-induced adipose stress and VAT inflammation. Obesity drove the upregulation of ligands of the NK cell-activating receptor NCR1 on adipocytes; this stimulated NK cell proliferation and interferon-gamma (IFN-gamma) production, which in turn triggered the differentiation of proinflammatory macrophages and promoted insulin resistance. Deficiency of NK cells, NCR1 or IFN-gamma prevented the accumulation of proinflammatory macrophages in VAT and greatly ameliorated insulin sensitivity. Thus NK cells are key regulators of macrophage polarization and insulin resistance in response to obesity-induced adipocyte stress