Book Review

Acute cholesterol depletion is generally associated with decreased or abolished T cell signalling but it can also cause T cell activation. This anomaly has been addressed in Jurkat T cells using progressive cholesterol depletion with methyl-beta-cyclodextrin (MBCD). At depletion levels higher than 50% there is substantial cell death, which explains reports of signalling inhibition. At 10–20% depletion levels, tyrosine phosphorylation is increased, ERK is activated and there is a small increase in cytoplasmic Ca2+. Peripheral actin polymerisation is also triggered by limited cholesterol depletion. Strikingly, the lipid raft marker GM1 aggregates upon cholesterol depletion and these aggregated domains concentrate the signalling proteins Lck and LAT, whereas the opposite is true for the non lipid raft marker the transferrin receptor. Using PP2, an inhibitor of Src family kinase activation, it is demonstrated that the lipid raft aggregation occurs independently of and thus upstream of the signalling response. Upon cholesterol depletion there is an increase in overall plasma membrane order, indicative of more ordered domains forming at the expense of disordered domains. That cholesterol depletion and not unspecific effects of MBCD was behind the reported results was confirmed by performing all experiments with MBCD–cholesterol, when no net cholesterol extraction took place. We conclude that non-lethal cholesterol depletion causes the aggregation of lipid rafts which then induces T cell signalling

Effect of Salt Valency and Concentration on Shear and Extensional Rheology of Aqueous Polyelectrolyte Solutions For Enhanced Oil Recovery

The injection of polymer solutions into an oil basin can lead to enhanced oil recovery (EOR) by increasing the microscopic sweep of the reservoir, improving the water-oil motility ratio, and thus leading to greater yield from oil fields. In this contribution, we characterize both shear and extensional rheological response of aqueous solutions of partially hydrolyzed polyacrylamide (HPAM), the most commonly used polymer for EOR, for velocity gradients in both the flow direction (extensional) and perpendicular to flow (shear) arise in EOR applications. As HPAM is a charged polymer, to better emulate the environment in oil basins, the rheological response was investigated in presence of salt, sodium chloride, and calcium chloride, with concentrations 3.7 × 10−4 − 1.5 M, as a function of polymer molecular weight (2–10 million g/mol) and concentration (0.005–0.3 wt%). The extensional relaxation times and extensional viscosity are measured using dripping-onto-substrate (DoS) rheometry protocols, and a commercial shear rheometer was utilized for characterizing the shear rheology response. The polyelectrolyte solutions formed by HPAM exhibit shear thinning in steady shear, but show strain hardening in response to extensional flow. Even though an increase in monovalent salt concentration leads to a decrease in both shear viscosity and extensional relaxation times, an increase in divalent salt concentration leads to an increase in extensional viscosity and relaxation time, implying that ion coordination can play a role in the presence of multivalent ions

Alkylamino and aralkylamino derivatives of avarone and its mimetic as selective agents against non-small cell lung cancer cells, their antibacterial and antifungal potential

In this paper, the synthesis of fourteen alkylamino and arylamino derivatives of sesquiterpene quinone avarone and its model compound tert-butylquinone is described. Branched, cyclic, allylic and benzylic alkylamino/arylamino groups were introduced into the quinone moiety. For all the obtained derivatives, their biological activity and redox properties were studied. The cytotoxic activity of the synthesized derivatives towards multidrug resistant (MDR) human non-small cell lung carcinoma NCI-H460/R cells, their sensitive counterpart NCI-H460 and human normal keratinocytes (HaCaT) was investigated. The antimicrobial activity towards Gram-positive and Gram-negative bacteria, and fungal cultures was determined. Some of the synthesized derivatives showed selectivity for cancer cells, including MDR cells. Regarding their cell death induction potential, the most promising compounds were allylamino derivatives, preferentially triggering apoptosis, with high selectivity for cancer cells, including MDR cells. Several compounds showed promising antimicrobial activity, comparable to those of commercial antibiotic and antimycotic agents

Comparative toxicity evaluation of targeted anticancer therapeutics in embryonic zebrafish and sea urchin models

Cancer drug resistance and poor selectivity towards cancer cells demand the constant search for new therapeutics. PI3K-Akt-mTOR and RAS-MAPK-ERK signaling pathways are key mechanisms involved in cell survival, proliferation, differentiation, and metabolism and their deregulation in cancer can promote development of therapy resistance. We investigated the effects of targeted inhibitors (wortmannin, GSK690693, AZD2014 and tipifarnib) towards these two pathways on early zebrafish and sea urchin development to assess their toxicity in normal, fast proliferating cells. PI3K inhibitor wortmannin and RAS inhibitor tipifarnib displayed highest toxicity while GSK690693, a pan-Akt kinase inhibitor, exhibited a less significant impact on embryo survival and development. Moreover, inhibition of the upstream part of the PI3K-Akt-mTOR pathway (wortmannin/GSK690693 co-treatment) produced a synergistic effect and impacted zebrafish embryo survival and development at much lower concentrations. Dual mTORC1/mTORC2 inhibitor AZD2014 showed no considerable effects on embryonic cells of zebrafish in concentrations substantially toxic in cancer cells. AZD2014 also caused the least prominent effects on sea urchin embryo development compared to other inhibitors. Significant toxicity of AZD2014 in human cancer cells, its capacity to sensitize resistant cancers, lower antiproliferative activity against human normal cell lines and fast proliferating embryonic cells could make this agent a promising candidate for anticancer therapy

Procena uticaja navodnjavanja višegodišnjih zasada na stabilnost strukturnih mikroagregata i rizik od stvaranja pokorice

The soil structure is very dynamic measure, especially in the topsoil horizon, given that changes can occur under the influence of climatic factors, cultivated plants, amelioration measures and tillage. In the area of the Danube region, in September 2015, it was conducted the study on the effect of the perennial plants irrigation on the structural microaggregates stability and the risk of the soil crusting on three selected locations in agricultural soil samples taken from the surface layer (0-30 cm). In the analysed soil samples in disturbed state it was determined the ratio between the total content of particles of less than 0.002 mm (clay) in soil samples prepared with sodium pyrophosphate and the content of such particles in soil suspension prepared with water. The degree of the stability of microaggregates was expressed according to Vageler, in relation to their estimated stability index. The risk of the soil crust formation was determined according to a Van der Watt & Claassen pattern. The obtained results showed that the soil samples have stable to very stable degree of the structural microaggregates stability and that an irrigation did not significantly affect the analysed parameter. In the analysed samples the risk of the soil crusting is high to borderline.Struktura zemljišta je veoma dinamična veličina, naročito u orničnom horizontu, koji je i ispitivan, obzirom da do promena može doći pod uticajem klimatskih činilaca, gajenih biljaka, primenjenih meliorativnih mera i obrade. Na području Podunavske oblasti, tokom septembra 2015. godine, sprovedena su ispitivanja uticaja navodnjavanja višegodišnjih zasada na stabilnost strukturnih mikroagregata i rizik od stvaranja pokorice na tri odabrane lokacije u uzorcima poljoprivrednog zemljišta iz površinskog sloja (0-30 cm). U ispitivanim uzorcima zemljišta u poremećenom stanju, određen je stepen stabilnosti mikroagregata, izražen prema Vageler-u, na osnovu određenog odnosa između ukupnog sadržaja čestica manjih od 0,002 mm (gline) u uzorku zemljišta pripremljenog sa natrijum pirofosfatom i sadržaja tih čestica u suspenziji zemljišta pripremljenog sa vodom. Određen je i rizik od stvaranja pokorice, po obrascu Van der Watt & Claassena. Dobijeni rezultati pokazuju da ispitivani uzorci zemljišta imaju stabilan do vrlo stabilan stepen stabilnosti strukturnih mikroagregata i da navodnjavanje nije u znatnoj meri uticalo na ispitivani parametar. U ispitivanim uzorcima rizik od stvaranja pokorice je visok do graničan

Predictors of poor neonatal outcomes in fetuses diagnosed with congenital urinary tract anomalies

Objectives: Urinary tract anomalies account for approximately one-quarter of all antenatally detected anomalies. The aim of this study was to identify factors associated with severe adverse neonatal outcomes of a prenatally diagnosed urinary tract anomaly.Material and methods: A retrospective-prospective study included 101 pregnant women with prenatally diagnosed fetal urinary tract anomalies presented to the Council for Fetal Anomalies. Prenatal diagnoses were compared with autopsy findings in cases of terminated pregnancy or with clinical and operative findings of the infants.Results: The mortality rate in the group of patients with fetal obstructive uropathy (60 patients) was 10% and in the group of patients with fetal multicystic dysplastic kidney (38 patients) 15.7%. Surgery was performed on 53.4% of the children, whereas more than half of the operations involved resolving associated urinary tract anomalies. Postoperative renal function deterioration occurred in 19% of the children.Conclusions: The prognosis of renal function in obstructive uropathies is excellent if oligoamnios does not develop prenatally and in case of timely provided surgical care is provided postnatally. The finding of the bilateral multicystic dysplastic kidney is associated with poor prognosis. The prognosis in fetal unilateral multicystic dysplastic kidney depends primarily on the condition of the contralateral kidney and the existence of associated anomalies

GABA-Producing Natural Dairy Isolate From Artisanal Zlatar Cheese Attenuates Gut Inflammation and Strengthens Gut Epithelial Barrier in vitro

Probiotic bacteria are recognized for their health-promoting properties, including maintenance of gut epithelial integrity and host immune system homeostasis. Taking into account the beneficial health-promoting effects of GABA, the presence of the gadB gene, encoding glutamate decarboxylase that converts L-glutamate to GABA, was analyzed in Lactic Acid Bacteria (LAB) natural isolates from Zlatar cheese. The results revealed that 52% of tested Lactobacillus spp. and 8% of Lactococcus spp. isolates harbor the gadB gene. Qualitative and quantitative analysis of GABA production performed by thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC) revealed the highest GABA production by Lactobacillus brevis BGZLS10-17. Since high GABA-producing LAB natural isolates are the most valuable source of naturally produced GABA, the probiotic properties of BGZLS10-17 were characterized. This study demonstrated high adhesion of BGZLS10-17 strain to Caco-2 cells and the ability to decrease the adhesion of Escherichia coli ATCC25922 and Salmonella enterica C29039. Treatment of differentiated Caco-2 cells monolayer with BGZLS10-17 supernatant containing GABA alleviated inflammation (production of IL-8) caused by IL-1β and significantly stimulated the expression of tight junction proteins (zonulin, occludin, and claudin 4), as well as the expression of TGF-β cytokine leading to the conclusion that immunosuppression and strengthening the tight junctions can have significant role in the maintenance of intestinal epithelial barrier integrity. Taken together the results obtained in this study support the idea that using of GABA producing BGZLS10-17 probiotic strain could be a good strategy to modulate immunological response in various inflammatory diseases, and at the same time, it could be a good candidate for adjunct starter culture for production of GABA-enriched dairy foods and beverages offering new perspectives in designing the novel functional foods