The Target of Rapamycin Signalling Pathway in Ageing and Lifespan Regulation

Ageing is a complex trait controlled by genes and the environment. The highly conserved mechanistic target of rapamycin signalling pathway (mTOR) is a major regulator of lifespan in all eukaryotes and is thought to be mediating some of the effects of dietary restriction. mTOR is a rheostat of energy sensing diverse inputs such as amino acids, oxygen, hormones, and stress and regulates lifespan by tuning cellular functions such as gene expression, ribosome biogenesis, proteostasis, and mitochondrial metabolism. Deregulation of the mTOR signalling pathway is implicated in multiple age-related diseases such as cancer, neurodegeneration, and auto-immunity. In this review, we briefly summarise some of the workings of mTOR in lifespan and ageing through the processes of transcription, translation, autophagy, and metabolism. A good understanding of the pathway’s outputs and connectivity is paramount towards our ability for genetic and pharmacological interventions for healthy ageing and amelioration of age-related disease

The content of heavy metals in the leaves of Hypericum perforatum L. on serpentinite soils in Serbia

St John's wort is one of the best known and used medicinal plants. The demands for St John's wort in Serbia is still supplied by the collection of native plants. Therefore it was necessary to examine the concentration of heavy metals in the soil and in plant material on serpentinites and to assess the potential safe harvesting and further utilisation of this plant species. The research was performed on three serpentinite sites in Serbia: Zlatibor, Divčibare and Goč. The main soil types were determined and the contents of 7 chemical elements were analyzed in the soil and in the plant material. It was determined that the soils of all three localities had increased concentrations of nickel, chromium and manganese. The St John's wort plant material (leaves) showed the increased concentrations of iron, nickel and chromium. It was concluded that St John's wort was a tolerant species regarding the heavy metal content, and it was recommended to avoid its harvesting on the investigated localities

Taxonomic and ecological investigation of Vaccinium L. genus in Serbia

Врсте рода Vaccinium су листопадни или зимзелени жбунови или полужбунови које се сврставају у фамилију Ericaceae. Широко су распрострањене у планинским регионима централне Европе, као и у бореалним и суб-арктичким регионима северне Европе, посебно у приземном спрату четинарских шума. На подручје Србије у брдским и планинским регионима налазе се три врсте овог рода: V. myrtillus, V. uliginosum и V. vitis-idaea. Ове врсте су дугоживеће, њихова репродуктивна стратегија обухвата и вегетативно и генеративно размножавање, њихове цветове опрашују инсекти или су самооплодне, а семена разносе птице. Резултати добијени морфо-анатомским истраживањима одабраних карактера листова проучаваних врста статистички су обрађени коришћењем програма “Statistica” (StatSoft, Inc., Tulsa, OK, USA). На основу анализираник морфо-анатомских карактера листова, утврђена је јасна диференцијација између проучаваних врста, док се диференцијација између популација у оквиру исте врсте не уочава. Варијабилност проучаваних морфо – анатомских карактеристика листова доведена је у везу са одређеним еколошким факторима. Кластер анализом морфо- анатомских карактеристика листова указала је на могућност постојање генетичке варијабилности између популација, што је потврђено молекуларно – генетичким истраживањима. За потребе молекуларно-генетичких истраживања, ДНК је изолована из младих листова проучаваних врста. За проучавање генетичког диверзитета и варијабилности коришћени су RAPD маркери. Обрада података вршена је употребом неколико софтвера: POPGENE, PAST, NTSYSpc, Arlequin и STRUCTURE 2.2...The species of the Vaccinium genus include deciduous or evergreen shrubs which belong to the family Ericaceae. They are widespread in the mountainous regions of central Europe and in the boreal and sub-arctic regions of northern Europe, particularly on the ground floor of coniferous forests. In the hilly and mountainous regions on the territory of Serbia, three species of this genus are described: V. myrtillus, V. uliginosum and V. vitis-idaea. These species are longlived, their reproductive strategy includes vegetative and generative reproduction, their flowers are pollinated by insects, they can also be selfpollinated, and their seeds are dispersed by birds. The results obtained by morpho-anatomical investigation of leaves were statistically analyzed using the program “Statistica” (StatSoft, Inc., Tulsa, OK, USA). Based on the analysis of the morpho-anatomical character of leaves, a clear differentiation between the investigated species was noticed, while the differentiation between the populations within the same species was not observed. The variability of the studied morpho - anatomical leaf characteristics were correlated with certain environmental factors. The cluster analysis of morpho-anatomical leaf characteristics indicated the possibility of the existence of genetic variation among the populations, which was confirmed by molecular - genetic research. For the purposes of molecular genetic studies, DNA was extracted from young leaves of the studied species. For the study of genetic diversity and variability RAPD markers were used. Data analysis was performed using several kinds of software: POPGENE, PAST, NTSYSpc, Arlequin and STRUCTURE 2.2..

Seed quantity and quality in fruit heads of Aster lanceolatus Willd.: Implications for invasion success

Aster lanceolatus Willd. is a herbaceous perennial that is considered invasive in many European countries. In Serbia, this plant inhabits wet habitats and forms widespread monospecific stands. The objective of this research is to determine whether generative reproduction has an important role in the expansion of this species to new areas. In 13 different localities, fruit heads were collected from lateral and terminal parts of infructescence. Seed quantity and germination parameters were determined for seeds in the fruit heads. The results showed that the position of the fruit heads did not have a major impact on germination parameters. However, germination parameters differed among the localities. The findings of this study suggest that A. lanceolatus produces a great amount of viable seeds that germinate in an amount sufficient to ensure a successful spread of this invasive species to new areas. [Projekat Ministarstva nauke Republike Srbije, br. 43007: Studying climate change and its influence on the environment: impacts, adaptation and mitigation

Utjecaj početnog eksplantata i regulatora rasta na kulturu kalusnoga tkiva europske tise (Taxus baccata L. Washingtonii)

The effects of explant source, medium composition and growth regulators were examined in order to optimize the induction and selection of fast growing callus lines of European yew (Taxus baccata L. Washingtonii). Callus cultures were induced from isolated mature zygotic embryos or from segments of juvenile branches. Following two months of growth on induction medium (MS + 3.0 mg/L NAA, 0.5 mg/L kinetin, 100 mg/L arginine, 2.5 % sucrose and 0.8 % agar), callus proliferation was induced in 86.4 % of embryo explants and 100 % of branch-cutting explants. The growth potential of established callus lines was found to vary in response to genetic potential and culture medium composition. The growth rate of stem-derived callus obtained on induction medium was superior to that obtained using all other tested media modifications (duplication time 9.6 days). However, the growth of embryo-derived callus lines was enhanced by increasing the iron content from 27.8 to 55.6 mg/L FeSO4 ∙7H2O in the maintaining MS medium (duplication time for line E2 was 8.5 days). In two out of three embryo-derived lines, tissue growth was further improved by transferring onto modified B5 medium (duplication time for lines E2 end E5 was 4 and 5.7 days, respectively). HPLC analysis confirmed the presence of the anticancer agent cephalomannine in calli grown on B5 medium and a taxane-like substance in calli grown on MS medium.Ispitan je utjecaj eksplantata i sastav hranidbene podloge na rast kalusnih linija europske tise. Kalusne kulture potaknute su na eksplantatima čitavih zrelih zigotnih embrija i odsječaka jednogodišnjih grančica odrasle biljke. Nakon dva mjeseca uzgoja na indukcijskoj podlozi (MS s dodatkom 3,0 mg/L NAA, 0,5 mg/L kinetina, 100 mg/L arginina, 25 g/L saharoze i 8 g/L agara) proliferacija kalusa postignuta je na 86,4 % embrijskih eksplantata i na 100 % eksplantata grančice. Rast ustaljenih kalusnih linija ovisio je o genetskom potencijalu i sastavu hranidbene podloge. Najbolji prirast svježe mase kalusa dobivenog iz tkiva grančice ostvaren je na indukcijskoj podlozi (vrijeme udvostručenja mase kalusa bilo je 9,6 dana). Kalus induciran iz embrija rastao je brže na podlozi MS s povećanim udjelom željeza (55,6 mg/L umjesto 27,8 mg/L FeSO4 ∙ 7H20) pa je masa tkiva linije E2 udvostručena za 8,5 dana. Prirast mase tkiva u dvije od tri embrijske kalusne linije poboljšan je supkultiviranjem na modificiranu podlogu B5 (tkivna masa linija E2 i E5 udvostručena je nakon 4, odnosno 5,7 dana). Analizom HPLC u kalusnim kulturama uzgajanim na podlozi B5 dokazana je prisutnost antikancerogene tvari cefalomanina, a u kalusnom tkivu raslom na podlozi MS prisutnost neodređene tvari slične taksanu

Biotope mapping of the Kumodraž stream watershed

Increasing negative changes in the biosphere, many of them irreversible, impose the need for the recording of the state of abiotic and biotic environmental factors in order that, with adequate measures, left over significant areas protect, degradation process slows down and lost area compensation accordance with possibilities. Therefore, for ecological planning in many developed countries, method of mapping and assessment of biotopes was introduced, firstly in rural areas and later in urban zones as well. Due to characteristic position in the transition direction from the city frindge to towards its core, area of the Kumodraž watershed area offered good basis for the application and examination of urban biotope mapping procedures. Different ways of land use, preservation of the relatively large area of open urban areas between two types of build structures and part of the free course of the Kumodraž stream offer good base for the assumption that habitats worth being preserved can be expected. The paper present results of the investigations carried out in 2006, which were compared with previous investigations as well as with the state in 2009. Prominent heterogeneity of and use, spreading of illegal settlements, but also existence of structures, which can be significant for encasement of the system of green and open spaces indicate on inadequate development of this area and also need for further investigations, which would lead to adequately planning solutions. By the mapping of the whole stream waters head and collection of attributes which characterize biotopes in details information bases for the further work on the assessment of the town biotope was obtained, as well as for argumentation for the directing the development towards protection of the remaining green areas of the city fringe

Reconstruction of the thumb defect following subungual melanoma resection using Foucher’s flap

No abstract availabl

Molecular Mechanisms of Lithium Action: Switching the Light on Multiple Targets for Dementia Using Animal Models

Lithium has long been used for the treatment of psychiatric disorders, due to its robust beneficial effect as a mood stabilizing drug. Lithium’s effectiveness for improving neurological function is therefore well-described, stimulating the investigation of its potential use in several neurodegenerative conditions including Alzheimer’s (AD), Parkinson’s (PD) and Huntington’s (HD) diseases. A narrow therapeutic window for these effects, however, has led to concerted efforts to understand the molecular mechanisms of lithium action in the brain, in order to develop more selective treatments that harness its neuroprotective potential whilst limiting contraindications. Animal models have proven pivotal in these studies, with lithium displaying advantageous effects on behavior across species, including worms (C. elegans), zebrafish (Danio rerio), fruit flies (Drosophila melanogaster) and rodents. Due to their susceptibility to genetic manipulation, functional genomic analyses in these model organisms have provided evidence for the main molecular determinants of lithium action, including inhibition of inositol monophosphatase (IMPA) and glycogen synthase kinase-3 (GSK-3). Accumulating pre-clinical evidence has indeed provided a basis for research into the therapeutic use of lithium for the treatment of dementia, an area of medical priority due to its increasing global impact and lack of disease-modifying drugs. Although lithium has been extensively described to prevent AD-associated amyloid and tau pathologies, this review article will focus on generic mechanisms by which lithium preserves neuronal function and improves memory in animal models of dementia. Of these, evidence from worms, flies and mice points to GSK-3 as the most robust mediator of lithium’s neuro-protective effect, but it’s interaction with downstream pathways, including Wnt/β-catenin, CREB/brain-derived neurotrophic factor (BDNF), nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and toll-like receptor 4 (TLR4)/nuclear factor-κB (NFκB), have identified multiple targets for development of drugs which harness lithium’s neurogenic, cytoprotective, synaptic maintenance, anti-oxidant, anti-inflammatory and protein homeostasis properties, in addition to more potent and selective GSK-3 inhibitors. Lithium, therefore, has advantages as a multi-functional therapy to combat the complex molecular pathology of dementia. Animal studies will be vital, however, for comparative analyses to determine which of these defense mechanisms are most required to slow-down cognitive decline in dementia, and whether combination therapies can synergize systems to exploit lithium’s neuro-protective power while avoiding deleterious toxicity