In yellow-necked mouse, Apodemus flavicollis, B chromosomes are present in almost all populations in a wide range of frequencies that are often stable from year to year, but contribution of Bs to genetic and phenetic structure and their maintenance in the absence of accumulation mechanism, are poorly explored in general. Therefore, we intend to analyse population structure across ecologically different habitats and those situated at the altitude edges of species distribution. Genetic profile of populations will be obtained using molecular markers while phenetic structure will be attained from skull shape analyses, as well as from life-history traits.

Adaptive variation will be investigated by measuring variation at highly polymorphic molecular markers. In the context of genetic structure and presence of Bs, prevalence and intensity of macro parasites dominant for this species, as well as virus's presence, will be monitored. We suppose that obtained data, together with data from analysis of Bs transmission from cages, will allow understanding the contribution of B chromosome polymorphism to genetic diversity and adaptability of species across different environments. Further understanding of mechanism of Bs maintenance in populations is also expected.

In modern biology there are two alternative experimental approaches for the study of different phenomena, which impact the evolution of living being – laboratory evolution and investigations in the wild.

LABORATORY EVOLUTION

Laboratory evolution allows the study of populations across multiple generations under strictly defined and reproducible conditions, but without the direct choice of reproducing individuals by the experimenter, in contrast to natural populations, where environmental conditions can be an efficient evolutionary factor that produces adaptations.

By employing "laboratory natural selection" as a tool to investigate determinants of life-history evolution, four types of laboratory populations of the seed beetle, Acanthoscelides obtectus, have been established (each type was replicated four times and observed over 200 generations): populations selected at high (K) and low (r) larval densities (density-dependent selection), and populations in which selection was imposed on either early (E) or late (L) reproduction (age-specific selection). Using these populations, the future investigations will focus on the following topics: 1. The evolutionary outcomes of density-dependent and age–specific selection, 2. The quantitative-genetic basis of the life-history traits that respond to these two selection types, 3. The evolution of ageing and late life, 4. The evolution of pre-zygotic and post-zygotic reproductive isolation between populations within each selection regime.

The aim of our research is to examine the effects of selected plant extracts, phytoestrogens (genistein, daidzein), steroid (estradiol, progesterone, testosterone, dexamethasone) and peptide hormones (somatostatin, calcitonin, ghrelin) on neuroendocrine and mineral homeostases in rats. Herbal and nature alternatives to hormone replacement therapy are intensively advertised for maintenance of hormone balance, prevention of cardiovascular problems, atherosclerosis and osteoporosis in both sexes. Assessments of effects of these substances on: (i) hypothalamo-pituitary -adrenal, -somatotropic, -thyroid and -gonadal axes; (ii) neuroendocrine C-cells, bones, parathyroid glands and kidneys; and (iii) cellular mechanics are important for evaluation of their health risks / benefits and potential use in treatment of cancer, cardiovascular and other diseases. The examinations are carried out in rats of different age (adult, middle and old age) and sex, with special emphasis on models of andropause and menopause. In vitro studies of cellular mechanics are performed using erythrocytes or prostate cancer cells. Glucocorticoids are used in human pregnancies at risk of preterm delivery because they reduce neonatal mortality and morbidity. However, this treatment enhances maturational processes and provokes permanent changes in physiological systems. Thus, short-term beneficial effects of prenatal glucocorticoids are, at the same time, the ones that increase the long-term risks of dysregulation of the metabolic function and endocrine axes, including stress response, growth and reproduction. Effects of prenatal glucocorticoid overexposure are examined in rats from their fetal period of life till adulthood.

The Balkan Peninsula, where Serbia is situated, is a dendroflora diversity centre (IUCN), home to forests comprised of relict, endemic, economically important (or potentially important) and endangered forest species, unique in time and space. Serbia's gorges, canyon valleys and mountain massifs represent particularly rich reservoirs and treasure troves of the genofund. It is these refugia that have enabled the preservation and reproduction of the rich and varied flora, particularly tertiary relicts and endemorelicts, and represent veritable museums in vivo of special scientific importance. The diversity of small local populations is also of particular importance, as is the diversity of those on the edges of forest belts, the most sensitive parts of the ecosystem. The project presumes that the autochthonous forest flora and vegetation of our part of the Balkan Peninsula contain populations whose presence, specific genetic structure, chemical composition, morphophysiological and reproductive characteristics reveal the history of the vegetation and contribute to a better understanding of the plants' adaptive potential to survive in adverse environmental conditions.

Modulation of immune response and cell death represents a key strategy in the therapy of cancer and inflammatory disorders such as multiple sclerosis, and diabetes. However, targeting inflammation for therapeutic reasons is very complex, due to numerous underlying damaging pathways. The main goal is therefore to gain insight into control molecular mechanisms of these disorders and, thus, contribute to the design of therapeutics for prevention and treatment of the diseases. It is proposed to investigate the role and mode of action of biologically active microenvironment molecules (cytokines, ROS, NOS, hormones) and genetic factors in regulation of proliferation, differentiation, function, and cell death of immune and target tissue cells, in both physiological and pathological conditions. To establish basic control mechanisms of inflammation, immune response to (auto)antigens and resistance to anti-tumor immune response, the role of relevant intercellular mediators and intracellular signaling pathways, our research will be performed by in vivo and in vitro approaches using animal models of human diseases in inbred and/or genetically modified murine strains, and primary or transformed cell populations of various origins. In addition, cytotoxic, cytoprotective and immunomodulatory potential of various pharmacological agents or natural plant and animal products will be investigated, as well as intra- and intercellular mechanisms underlying the observed biological effects.

This project comprises a group of research tasks centered around the common use of in vitro culture techniques. They include:

Morphogenesis in vitro: Research on shoot regeneration and multiplication, rhyzogenesis, somatic embriogenesis and androgenesis are done on Allium schoenoprassum, Frittilaria meleagris, Iris reichenbachii, Arabidopsis thaliana, Pinus peuce, Pinus heldreichii and wheat, birds-foot trefoil and cabbage subspecies. Protocols designed for specific organogenesis pathways are elaborated and confirmed with cytological and histological studies. Effect of GA3 are studied in regeneration of spinach and bird-foot trefoil. Interaction of GA3 with other hormones is studied by use of light and scanning electron microscopy an in situ hybridization. Following the expression of genes for GA20 oxidase, KNOX/STM and LAS orthologues. Senescence and apoptosis are studied on tobacco leaves.

In anthropogenically degraded habitats, plants are often limited by multiple stress factors that act simultaneously, threatening the functioning of plants and exhausting their adaptive potential.

Our research is based on studying plants' physiological, biochemical and morphological responses to the effects of multiple stressors. These determine their adaptive capacity to survive and/or develop tolerance to stress in such habitats. Research will be undertaken at two types of such habitats: ash deposits at the 'Nikola Tesla-A' thermal power plant in Obrenovac (initially biologically empty areas with high pollutant levels) and urban zones in Belgrade (highly polluted degraded areas). In aiming to establish plants' ecophysiological adaptive strategies for surviving in multiple stress conditions in degraded habitats, research will focus on defining the ecological factors that limit plant survival and functioning in degraded habitats, establishing the synergetic, antagonistic or additive effects of multiple stressors, identifying structural and functional plant damage, and defining plants' adaptive response to the effects of multiple stress and their adaptive potential to survive in such conditions. Identification of the adaptive strategies of plants that colonise, survive and function at thermal power plant ash deposits and in urban zones subject to chronic pollution can be a guide for creating activities aimed at the ecological restoration of disturbed ecosystems.

Diabetes mellitus is a complex metabolic disorder that can be presented in two major forms, as type 1 diabetes (T1D) and the much more common type 2 diabetes (T2D). While their etiologies are different, both diabetes types are characterized by hyperglycemia resulting either from insufficient insulin levels in T1D, or an insensitivity of target cells to insulin in T2D. In T1D, the death of insulin-producing pancreatic β-cells in an autoimmune response is a comparatively rapid event, whereas in T2D loss of β-cell mass occurs over years as interactions of extrinsic stressors and intrinsic factors continually impair β-cell functioning. The decline in the total mass of functional β-cells required to provide insulin for maintaining glucose homeostasis underlies diabetes development. Insight into the molecular control mechanisms in β-cells and the pathology of diabetes has laid the foundation for the paradigm for diabetes treatment based on the application of strategies that support functional β-cells by suppressing cytotoxic cell signaling and preventing the activation of cell death pathways. Our research is focused on β-cells as the principal element in diabetes development, and on hepatocytes and cardiomyocytes as the targets of diabetic complications. Our experimental systems include the in vivo model of streptozotocin (STZ)-induced diabetes in the rat, and in vitro models employing different cell lines maintained in culture.

Our current research focuses on the neurobiology of sleep and sleep-related breathing in the animal models "in vivo" of healthy aging and neuropathology of the most common neurodegenerative diseases of elderly (Alzheimer's Disease (AD), Parkinson's Disease (PD), different types of dementia), aimed to give a new insight into understanding of normal and abnormal sleep, the mechanisms of sleep related behavioural disorders, particularly sleep apnea syndrome, and to identify the neural networks responsible for modifying the regulation of sleep and breathing pattern in different sleep/wake states.

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