Održivo upravljanje okolišem u marinskim područjima: primjer Crnog mora

The EU Marine Strategy Directive (2008/56/EC) proposes four marine regions as a political geographic framework for implementation of the Community\u27s environmental policy. This study critically analyzes the state-based approach, which the Directive uses to outline the regions\u27 boundaries. It suggests that environmental sustainability of marine odies strongly depends on the geographic congruence between their watersheds and the borders of the respective environmental management system, i.e., marine regions have to be environmentally managed within their watersheds. The proposed watershed-based approach also takes into consideration all elements – water, land, and air – of marine regions, which is a conditio sine qua non for their integrated and sustainable management. In the case of the Black Sea region in particular, the borders of a watershed-based environmental management system include a much wider set of stakeholder countries and enable a higher level of environmental cooperation among them.Direktiva marinske strategije Europske unije (2008/56/EC) predlaže četiri marinska područja kao političko geografski okvir za primjenu politike o zaštiti okoliša u Europskoj uniji. Ovaj rad kritički analizira pristup koji se temelji na državnim granicama, a kojim se Direktiva koristi za određivanje granica regija. Autor također smatra da održivost okoliša u marinskim područjima uvelike ovisi o geografskom podudaranju između pojedinih sljevova i granicama njihovih sustava upravljanja okolišem, tj. okolišem u marinskim područjima treba upravljati unutar njihovih sljevova. Predloženi pristup koji se temelji na granicama sljevova također u obzir uzima sve elemente marinskih sustava (voda, zemlja i zrak), koji su conditio sine qua non za integralno i održivo upravljanje. Crno more je dobar primjer u kojem sustav upravljanja okolišem koji je određen granicama slijeva uključuje puno veći broj zemalja dionika te omogućuje višu razinu suradnje među zemljama vezano uz upravljanje okolišem

c-Abl mediated tyrosine phosphorylation of Aha1 activates its co-chaperone function in cancer cells

The ability of Heat Shock Protein 90 (Hsp90) to hydrolyze ATP is essential for its chaperone function. The co-chaperone Aha1 stimulates Hsp90 ATPase activity, tailoring the chaperone function to specific "client" proteins. The intracellular signaling mechanisms directly regulating Aha1 association with Hsp90 remain unknown. Here, we show that c-Abl kinase phosphorylates Y223 in human Aha1 (hAha1), promoting its interaction with Hsp90. This, consequently, results in an increased Hsp90 ATPase activity, enhances Hsp90 interaction with kinase clients, and compromises the chaperoning of non-kinase clients such as glucocorticoid receptor and CFTR. Suggesting a regulatory paradigm, we also find that Y223 phosphorylation leads to ubiquitination and degradation of hAha1 in the proteasome. Finally, pharmacologic inhibition of c-Abl prevents hAha1 interaction with Hsp90, thereby hypersensitizing cancer cells to Hsp90 inhibitors both in vitro and ex vivo

RESEARCH OF THE BIOTOPE DIVERSITY FOR THE PURPOSES OF ECONOMIC VALUATION OF ECOSYSTEM SERVICES IN CHEPELARE MUNICIPALITY (THE RHODOPES REGION OF BULGARIA)

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Functional Amyloid Formation within Mammalian Tissue

Amyloid is a generally insoluble, fibrous cross-β sheet protein aggregate. The process of amyloidogenesis is associated with a variety of neurodegenerative diseases including Alzheimer, Parkinson, and Huntington disease. We report the discovery of an unprecedented functional mammalian amyloid structure generated by the protein Pmel17. This discovery demonstrates that amyloid is a fundamental nonpathological protein fold utilized by organisms from bacteria to humans. We have found that Pmel17 amyloid templates and accelerates the covalent polymerization of reactive small molecules into melanin—a critically important biopolymer that protects against a broad range of cytotoxic insults including UV and oxidative damage. Pmel17 amyloid also appears to play a role in mitigating the toxicity associated with melanin formation by sequestering and minimizing diffusion of highly reactive, toxic melanin precursors out of the melanosome. Intracellular Pmel17 amyloidogenesis is carefully orchestrated by the secretory pathway, utilizing membrane sequestration and proteolytic steps to protect the cell from amyloid and amyloidogenic intermediates that can be toxic. While functional and pathological amyloid share similar structural features, critical differences in packaging and kinetics of assembly enable the usage of Pmel17 amyloid for normal function. The discovery of native Pmel17 amyloid in mammals provides key insight into the molecular basis of both melanin formation and amyloid pathology, and demonstrates that native amyloid (amyloidin) may be an ancient, evolutionarily conserved protein quaternary structure underpinning diverse pathways contributing to normal cell and tissue physiology

Chemical and Biological Folding Contribute to Temperature-Sensitive ΔF508 CFTR Trafficking

Proteostasis (Balch et al. (2008) Science 319: 916) refers to the biology that maintains the proteome in health and disease. Proteostasis is challenged by the most common mutation in cystic fibrosis, ΔF508, a chloride channel (the cystic fibrosis transmembrane conductance regulator (CFTR)) that exhibits a temperature-sensitive phenotype for coupling to the coatomer complex II (COPII) transport machine for exit from the endoplasmic reticulum (ER). Whether rescue of export of ΔF508-CFTR at reduced temperature simply reflects energetic stabilization of the chemical fold defined by its primary sequence, or requires a unique proteostasis environment is unknown. We now show that reduced temperature (30°C) export of ΔF508 does not occur in some cell types despite efficient export of wild-type CFTR. We find ΔF508 export requires a local biological folding environment that is sensitive to heat/stress inducible factors found in some cell types suggesting that the energetic stabilization by reduced temperature is necessary, but not sufficient for export of ΔF508. Thus, the cell may require a proteostasis environment that is in part distinct from the wild-type pathway to restore ΔF508 coupling to COPII. These results are discussed in the context of the energetics of the protein fold and the potential application of small molecules to achieve a proteostasis environment favoring export of a functional form of ΔF508

Using small molecules to facilitate exchange of bicarbonate and chloride anions across liposomal membranes

Bicarbonate is involved in a wide range of biological processes, which include respiration, regulation of intracellular pH and fertilization. In this study we use a combination of NMR spectroscopy and ion-selective electrode techniques to show that the natural product prodigiosin, a tripyrrolic molecule produced by microorganisms such as Streptomyces and Serratia, facilitates chloride/bicarbonate exchange (antiport) across liposomal membranes. Higher concentrations of simple synthetic molecules based on a 4,6-dihydroxyisophthalamide core are also shown to facilitate this antiport process. Although it is well known that proteins regulate Cl-/HCO3- exchange in cells, these results suggest that small molecules may also be able to regulate the concentration of these anions in biological systems

Towards integrated mapping and assessment of ecosystems and their services in Bulgaria: The Central Balkan case study

The aim of the EU Biodiversity Strategy to 2020 isto maintain and enhance ecosystem services (ES) in Europe and requires all Member States to map and assess the state of ecosystems and their services in the respective national territories. The EU-funded project ESMERALDA analyses ES mapping and assessment methods and approaches in their biophysical, social and economical perspectives, as well as their application in different case studies. The project also aims at the development of an integrated and consistent assessment framework. In Bulgaria, methodological guides for evaluation and mapping of the services provided by the nine main types of ecosystems have been prepared together with the respective proposals for their implementation in the national assessment. The Bulgarian research team analyses and tests various aspects of ecosystem services mapping and assessment, such as alternative economic assessments, multi-criteria analyses and biophysical assessment approaches, mapping challenges and local population surveys. In this paper paper, we review the ES activities in Bulgaria and present selected mapping and assessment methods tested in the Central Balkan case study area. It provides relevant examples for the implementation of integrated mapping and assessment of ecosystem services at local and regional level, where different mapping approaches and techniques are embedded within diverse policy contexts. The main goal of the study is to investigate how the assessment results can support the integration of the ecological functions of the Central Balkan National Park with the economic opportunities that it creates for the local and regional communities. A tiered approach has been used to organise the mapping and assessment exercises in the study area, in order to meet the needs for integrated ecosystem assessment and overcome the limitations of data availability. At tier 1, the study performs identification and initial ES mapping of the whole area. At tier 2, it applies economic valuation for the Municipality of Karlovo by using statistical data and the contingent valuation method. At tier 3, the investigation applies modelling methods to assess carbon storage and flood regulation on a larger scale. The results are presented in the form of maps at all levels, which use a uniform 0 to 5 assessment scale. The integrated approach presented here ensures a clear communication of the end results to the respective decision-makers

Semen-Derived Amyloid Fibrils Drastically Enhance HIV Infection

SummarySexual intercourse is the major route of HIV transmission. To identify endogenous factors that affect the efficiency of sexual viral transmission, we screened a complex peptide/protein library derived from human semen. We show that naturally occurring fragments of the abundant semen marker prostatic acidic phosphatase (PAP) form amyloid fibrils. These fibrils, termed Semen-derived Enhancer of Virus Infection (SEVI), capture HIV virions and promote their attachment to target cells, thereby enhancing the infectious virus titer by several orders of magnitude. Physiological concentrations of SEVI amplified HIV infection of T cells, macrophages, ex vivo human tonsillar tissues, and transgenic rats in vivo, as well as trans-HIV infection of T cells by dendritic or epithelial cells. Amyloidogenic PAP fragments are abundant in seminal fluid and boost semen-mediated enhancement of HIV infection. Thus, they may play an important role in sexual transmission of HIV and could represent new targets for its prevention

Anion-transport mechanism of a triazole-bearing derivative of prodigiosine: a candidate for cystic fibrosis therapy

Cystic fibrosis (CF) is a genetic lethal disease, originated from the defective function of the CFTR protein, a chloride and bicarbonate permeable transmembrane channel. CF mutations affect CFTR protein through a variety of molecular mechanisms which result in different functional defects. Current therapeutic approaches are targeted to specific groups of patients that share a common functional defect. We seek to develop an innovative therapeutic approach for the treatment of CF using anionophores, small molecules that facilitate the transmembrane transport of anions. We have characterized the anion transport mechanism of a synthetic molecule based on the structure of prodigiosine, a red pigment produced by bacteria. Anionophore-driven chloride efflux from large unilamellar vesicles is consistent with activity of an uniporter carrier that facilitates the transport of anions through lipid membranes down the electrochemical gradient. There are no evidences of transport coupling with protons. The selectivity sequence of the prodigiosin inspired EH160 ionophore is formate > acetate > nitrate > chloride > bicarbonate. Sulfate, phosphate, aspartate, isothionate, and gluconate are not significantly transported by these anionophores. Protonation at acidic pH is important for the transport capacity of the anionophore. This prodigiosin derived ionophore induces anion transport in living cells. Its low toxicity and capacity to transport chloride and bicarbonate, when applied at low concentration, constitute a promising starting point for the development of drug candidates for CF therapy.European Union’s Horizon 2020 research and innovation programme under grant agreement No 667079 and Consejería de Educación de la Junta de Castilla y León (Project BU092U16)

Structurally simple lipid bilayer transport agents for chloride and bicarbonate

A new series of structurally simple compounds containing thiourea groups have been shown by a combination of ion-selective electrode and 13C NMR techniques to be potent chloride-bicarbonate exchange agents that function at low concentration in POPC and POPC/cholesterol membranes.<br/