Biološke i ekološke karakteristike crnke umbra krameri kao osnov za in-situ i ex-situ zaštitu

The analysis of ecological characteristics and morphological-genetic differentiation of populations of the European mudminnow (Umbra krameri Walbaum, 1792) from the localities Lugomir and Bakreni Batar in Serbia and the locality Gromiželj in Bosnia and Herzegovina provides a basis for future activities related to in situ and ex situ conservation of one of the most endangered species in the region. Physical and chemical habitat parameters, aquatic plant and fish species composition, as well as invertebrate assemblages from mud and submerged vegetation at all investigated localities are consistent with the literature data which indicates that European mudminnow lives in typical habitats within its range. Population structure was analysed with regard to measured body lengths and weights, sex ratio and the age of the sampled individuals. The results show that the mean lengths and weights of the most frequent age classes (1+ and 2+) are rather uniform at all investigated localities. Younger (0+) and older (3+ and 4+) individuals were recorded in Gromiželj; males outnumber females in samples from Lugomir and Bakreni Batar, while females outnumber males in samples from Gromiželj. Individuals from Gromiželj show the highest absolute and relative growth. The growth of this species varies and depends on several factors, such as physical and chemical environmental parameters, food availability, population density, presence of predators, etc. Qualitative and quantitative composition of European mudminnow diet was determined on the basis of its gastrointestinal contents. The obtained results indicate that the European mudminnow is a zoophagous species and an opportunistic predator. The morphological variability (body size and shape) was analyzed using the methods of geometric morphometrics, while the genetic diversity of the analyzed populations was determined by applying the molecular-genetic methods (microsatellites and mitochondrial DNA). These analyses indicate high level of compatibility between the morphological variability and the genetic diversity. Namely, the Danube River population from Lugomir differs from the Sava River populations from Bakreni Batar and Gromiželj, the latter two having a significantly higher level of similarities and relatedness. All obtained results are extremely important for implementing the adequate measures of active protection, conservation, and improvement of recent populations, most notably repopulation, reintroduction, and aquaculture of the European mudminnow in ex situ conditions and at controlled natural spawning sites within their habitats.Na osnovu analize ekoloških karakteristika i morfološko-genetičke diferencijacije populacija crnke (Umbra krameri Walbaum, 1792) sa lokaliteta Lugomir i Bakreni Batar u Srbiji kao i sa lokaliteta Gromiželj u Bosni i Hercegovini, dat je osnov za buduće aktivnosti na in-situ i ex-situ zaštiti jedne od najugroženijih vrsta riba na ovim prostorima. Analiza fizičko-hemijskih parametara vode i kvalitativnog sastava zajednice biljaka, riba, akvatičnih beskičmenjaka iz mulja i submerzne vegetacije pokazala je da su na svim istraživanim lokalitetima rezultati u skladu sa literaturnim podacima koji ukazuju na to da crnka naseljava tipična staništa u okviru svog areala. U odnosu na dužinu i težinu, pol i uzrast uzorkovanih jedinki, analizirana je struktura populacija, koja je pokazala da su na svim istraživanim lokalitetima srednje vrednosti dužinskih i težinskih parametara kod najfrekventnijih uzrasnih klasa (1+ i 2+) prilično ujednačene, da su na Gromiželju evidentirane i mlađe (0+) i starije (3+ i 4+) jedinke, kao i da mužjaci dominiraju u uzorcima iz Lugomira i Bakrenog Batara, a ženke u uzorku iz Gromiželja. Analizom dužinskog i težinskog rasta, najveći apsolutni i relativni priraštaj ustanovljen je kod jedinki sa lokaliteta Gromiželj, a konstatovano je i da rast crnke varira i zavisi od više faktora, kao što su fizičko-hemijski parametri sredine, dostupnost hrane, gustina populacija, prisutni predatori itd. Na osnovu želudačno-crevnog sadržaja utvrđen je kvalitativno-kvantitativni sastav ishrane crnke, koji ukazuje na to da crnka predstavlja zoofagnu vrstu i oportunističkog predatora. Metodama geometrijske morfometrije analizirana je varijabilnost spoljašnje morfologije, odnosno varijabilnost veličine i oblika tela istraživanih populacija, a upotrebom molekularno-genetičkih metoda (mikrosateliti i mitohondrijalna DNK), utvrđena je i genetička raznovrsnost analiziranih populacija. Uz visok stepen podudarnosti dobijenih rezultata korišćenjem navedenih metoda, utvrđeno je jasno razdvajanje dunavske populacije sa lokaliteta Lugomir u odnosu na savske populacije sa lokaliteta Bakreni Batar i Gromiželj, koje pokazuju znatno veći stepen međusobne sličnosti i srodnosti. Svi dobijeni rezultati ovih istraživanja od izuzetne su važnosti za preduzimanje odgovarajućih mera aktivne zaštite, očuvanja i unapređenja stanja recentnih populacija, od kojih su najznačajniji repopulacija, reintrodukcija i akvakultura crnke u ex situ uslovima i u kontrolisanim prirodnim plodištima na samim staništima

Antagonism of EGFR and HER3 Enhances the Response to Inhibitors of the PI3K-Akt Pathway in Triple-Negative Breast Cancer

Both abundant epidermal growth factor receptor (EGFR or ErbB1) and high activity of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway are common and therapeutically targeted in triple-negative breast cancer (TNBC). However, activation of another EGFR family member [human epidermal growth factor receptor 3 (HER3) (or ErbB3)] may limit the antitumor effects of these drugs. We found that TNBC cell lines cultured with the EGFR or HER3 ligand EGF or heregulin, respectively, and treated with either an Akt inhibitor (GDC- 0068) or a PI3K inhibitor (GDC-0941) had increased abundance and phosphorylation of HER3. The phosphorylation of HER3 and EGFR in response to these treatments was reduced by the addition of a dual EGFR and HER3 inhibitor (MEHD7945A). MEHD7945A also decreased the phosphorylation (and activation) of EGFR and HER3 and the phosphorylation of downstream targets that occurred in response to the combination of EGFR ligands and PI3K-Akt pathway inhibitors. In culture, inhibition of the PI3K-Akt pathway combined with either MEHD7945A or knockdown of HER3 decreased cell proliferation compared with inhibition of the PI3K-Akt pathway alone. Combining either GDC-0068 orGDC-0941 with MEHD7945A inhibited the growth of xenografts derived from TNBC cell lines or from TNBC patient tumors, and this combination treatment was also more effective thancombining eitherGDC-0068 orGDC-0941 with cetuximab, anEGFR-targeted antibody.After therapy with EGFR-targeted antibodies, some patients had residual tumors with increased HER3 abundance and EGFR/HER3 dimerization (an activating interaction). Thus, we propose that concomitant blockade of EGFR, HER3, and the PI3K-Akt pathway in TNBC should be investigated in the clinical setting