Functional analysis of the microtubule-end vbinding protein CLASP2

Microtubules play an important role in many essential cell functions, such as maintenance of cell shape, intracellular transport, positioning of cell organelles and formation of the mitotic spindle during cell division. Microtubules perform many of their cellular tasks by changing their organization and stability in response to the needs of the cell. These processes are highly regulated, mainly by heterologous protein interactions between microtubules and specific regulatory proteins. Microtubule associated proteins (MAPs) play an essential role in controlling the dynamic instability of microtubules, thus controlling the state of their assembly and organization in cells. Particularly interesting is the group of MAPs that bind specifically to the plus ends of microtubules, where they can influence microtubule behavior and microtubule connections with other cellular structures. The best examples of such proteins are cytoplasmic linker proteins (CLIPs), as well as CLIPassociated proteins, or CLASPs. The aim of this thesis was to investigate role of CLASPs on microtubule behavior, in particular the involvement and in vivo function of CLASP 2

Short- and long-term effects of hemodialysis on platelet and monocyte activity markers of atherosclerosis in patients with end-stage renal disease

Background: In hemodialysis (HD) patients cardiovascular events represent the predominant cause of mortality. Since platelet and monocyte activity markers play an important role in cardiovascular mortality, this study assessed the influence of HD on these markers. Methods: Forty one HD patients (25 male, 16 female) were included. Blood samples were obtained before and after a single HD session at baseline and again after an elapsed period of 114 ± 21 days (91–175 days) on maintenance hemodialysis. Surface expression of CD40L and CD62P on platelets, tissue factor binding on monocytes and platelet-monocyte aggregates were measured by flow cytometry. Plasma levels of monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFa) and soluble CD40L were analyzed by enzyme linked immunosorbent assay. Results: Tissue factor on monocytes was significantly increased after a single HD session at baseline (p = 0.041), whereas platelet-monocyte aggregates, the expression of CD40L and CD62P on platelets did not change significantly. After a mean of 114 ± 21 days of HD therapy, tissue factor on monocytes (p < 0.0001), platelet-monocytes aggregates (p < 0.0001), plasma levels of MCP-1 (p = 0.012) and TNFa (p = 0.046) were significantly decreased compared to baseline values. In contrast, platelet surface expression of CD40L and CD62P as well as plasma levels of sCD40L and IL-6 were not attenuated significantly. There was no significant correlation detected between the markers examined and the cumulative time on hemodialysis. Conclusions: Platelet and monocyte activity markers assessed in this study do not appear to be significantly increased by HD therapy. Therefore, these markers probably cannot be accountable for increased cardiovascular mortality in chronic HD patients

Traganje za izvornim stenama nafti depresije Drmno, južni deo Panonskog basena, Srbija

In a search for source rocks of the crude oils of the Drmno depression (Southern part of the Pannonian Basin, Serbia), based on bulk and specific organic geochemical parameters, six out of eight Sirakovo, Bubusinac and Bradarac sedimentary core samples were found to possess typical source rock characteristics. By comparing the results observed for these sedimentary samples with the corresponding propel-ties of the crude oils from the Sirakovo and Bradarac oil-gas fields, a positive organic geochemical oil-source rock correlation was experienced for the first time within this basin. This finding may be considered as an important step towards the ultimate organic geochemical/geological interpretation of the Drmno depression.Ispitivani su sedimenti iz bušotina koje pripadaju lokacijama Sirakovo Bubušinac i Bradarac (depresija Drmno). Primenjene su organsko-geohemijske metode (određivanje sadržaja organskog ugljenika, bitumena i ugljovodonika, kao i određivanje raspodele i obilnosti bioloških markera tipa n-alkana izoprenoidnih alifatičnih alkana, triterpana i sterana) sa ciljem da se proceni njihova naftna potencijalnost. Za šest uzoraka utvrđen je visok stepen maturisanosti organske supstance, pripadnost "oil generation" fazi (Rr = 0,70 – 0,80 %), tercijarna starost i pretežno terestrijalno poreklo. Poređenjem sa sirovim naftama iz već otkrivenih naftnih ležišta bliskog lokaliteta (Sirakovo i Bradarac) utvrđena je značajna sličnost i prema maturisanosti i prema poreklu, na osnovu čega je između ispitivanih uzoraka sedimenata i nafti, prvi put kada je u pitanju depresija Drmno, definisana pozitivna korelacija nafta-izvorna stena

Aktivnost Pt3Ru2/C nanokatalizatora u oksidaciji CO

The electrocatalytic activity of Pt3Ru2/C nanocatalyst toward the electro-oxidation of bulk CO was examined in acid and alkaline solution at ambient temperature using the thin-film, rotating disk electrode (RDE) method. The catalyst was characterized by XRD analysis. The XRD pattern revealed that the Pt3Ru2/C catalyst consisted of two structures, i.e., Pt-Ru-fcc and Ruhcp (a solid solution of Ru in Pt and a small amount of Ru or a solid solution of Pt in Ru). Electrocatalytic activities were measured by applying potentiodynamic and steady state techniques. The oxidation of CO on the Pt3Ru2/C catalyst was influenced by pH and anions from the supporting electrolytes. The Pt3Ru2/C was more active in alkaline than in acid solution, as well as in perchloric than in sulfuric acid. Comparison of CO oxidation on Pt3Ru2/C and Pt/C revealed that the Pt3Ru2/C was more active than Pt/C in acid solution, while both catalysts had a similar activity in alkaline solution.Elektrohemijska oksidacija CO ispitivana je na nanokatalizatoru Pt3Ru2 dispergovanom na aktivnom uglju kao nosaču u kiseloj i alkalnoj sredini na sobnoj temperaturi korišćenjem metode rotirajuće disk elektrode (RDE). Katalizator je okarakterisan difrakcijom X-zraka (XRD) i dobijeni rezultati su pokazali da se legura Pt3Ru2 sastoji od dve faze: čvrstog rastvora Ru u Pt i od malih količina čistog Ru ili čvrstog rastvora Pt u Ru. Elektrokatalitička aktivnost ovog katalizatora za oksidaciju CO je ispitivana cik- ličnom voltametrijom i pokazan je efekat pH i efekat anjona iz nosećeg elektrolita. Pt3Ru2/C katalizator je aktivniji u alkalnoj nego u kiseloj sredini, ukazujući na činjenicu da u alkaliji Pt može da adsorbuje OH čestice na isto tako niskim potencijalima kao i Ru i na taj način ubrzava reakciju oksidacije CO u poređenju sa kiselinom. Pokazano je da adsorpcija bisulfatnih anjona iz nosećeg elektrolita pomera početni potencijal reakcije ka pozitivnijim vrednostima i smanjuje brzinu oksidacije CO. Poređenjem aktivnosti Pt/C i Pt3Ru2/C katalizatora u oksidaciji CO u kiseloj i alkalnij sredini pokazano je da je ta razlika znatno manja u alkalnoj nego u kiseloj sredini

Expression in Yeast Links Field Polymorphisms in PfATP6 to in Vitro Artemisinin Resistance and Identifies New Inhibitor Classes

Background. The mechanism of action of artemisinins against malaria is unclear, despite their widespread use in combination therapies and the emergence of resistance. Results. Here, we report expression of PfATP6 (a SERCA pump) in yeast and demonstrate its inhibition by artemisinins. Mutations in PfATP6 identified in field isolates (such as S769N) and in laboratory clones (such as L263E) decrease susceptibility to artemisinins, whereas they increase susceptibility to unrelated inhibitors such as cyclopiazonic acid. As predicted from the yeast model, Plasmodium falciparum with the L263E mutation is also more susceptible to cyclopiazonic acid. An inability to knockout parasite SERCA pumps provides genetic evidence that they are essential in asexual stages of development. Thaperoxides are a new class of potent antimalarial designed to act by inhibiting PfATP6. Results in yeast confirm this inhibition. Conclusions. The identification of inhibitors effective against mutated PfATP6 suggests ways in which artemisinin resistance may be overcom

Alcohol abuse and alcohol depen

Abstract Alcoholism results from an interplay between genetic and environmental factors, and is linked to brain defects and associated cognitive, emotional, and behavioral impairments. A confluence of findings from neuroimaging, physiological, neuropathological, and neuropsychological studies of alcoholics indicate that the frontal lobes, limbic system, and cerebellum are particularly vulnerable to damage and dysfunction. An integrative approach employing a variety of neuroscientific technologies is essential for recognizing the interconnectivity of the different functional systems affected by alcoholism. In that way, relevant experimental techniques can be applied to assist in determining the degree to which abstinence and treatment contribute to the reversal of atrophy and dysfunction. Keywords Alcoholism . Frontal lobes . Limbic system . Cerebellum . Right hemisphere Alcoholic beverages contain ethanol, a psychoactive drug with relaxant and euphoric effects, consumed by people throughout the world. In general, the effects of alcohol intoxication follow a biphasic time course as the initial feelings of relaxation and exuberance give way to hangover, exhaustion, and depression, or vomiting and loss of consciousness in cases of higher doses (Nagoshi and Wilson 1989). Criteria for classifying someone as an alcoholic vary Risky drinking patterns for men are defined as consuming more than 14 drinks per week, or more than four drinks in a single day at least once a month; for women, the limits are more than seven drinks per week and three drinks per da

Evaluation of saturated and aromatic hydrocarbons oil-oil maturity correlation parameters (SE Pannonian Basin, Serbia)

Twenty three crude oils from the Serbian part of the Pannonian Basin (14 from the Vojvodina Province and 9 from the Drmno Depression) were investigated, aimed at an evaluation of oil-oil maturity correlation parameters based on the distribution and abundance of saturated biomarkers and alkylarene constituents. Factor and cluster analyses were used for this purpose. Factor analyses using varimax rotation were first run separately, i.e., of maturity parameters based on the abundance of (a) n-alkanes and isoprenoids, (b) steranes and triterpanes, (c) alkylnaphthalenes, and (d) alkylphenanthrenes. These analyses yielded 9 important "maturity factors". Eight of them, showing higher than 30 % of variance, were further involved in another factor analysis, as well as in cluster analysis using the Ward method. In this way, all maturity parameters based on saturated biomarkers and alkylarenes were evaluated and ranged, considering the fact that the observed factors represented their linear combinations. The results showed that in the correlation of crude oils from the Serbian part of the Pannonian Basin, the most important were maturity parameters based on isomerization reactions involving one methyl group in thermodynamically less stable alpha-methylnaphthalenes, ethylnaphthalenes, dimethylnaphthalenes and methylphenanthrenes, and their change into more stable isomers with the methyl group in the beta-position in the aromatic ring. Processes constituting high loadings factor 2 and factor 3 parameters were also defined. Hierarchy between the "factors" and parameters were controlled, and approved, by cluster analysis using the Ward method. Finally, the investigated crude oils were correlated by factor and cluster analyses, using all the important "maturity factors". Differences in maturity were observed between the Vojvodina and Drmno Depression crude oils, as well as between oils originating from South Banat, North Banat and the Velebit oil field (Vojvodina locality)

Phenanthrene and Methylphenanthrene Isomers in Maturity Assessment of Biodegraded Crude Oils (Sakhalin, Russia)

This paper is aimed at defining two new advantageous maturation parameters based on distribution and abundance of phenanthrene (P) and methylphenanthrene (MP) isomers in the tricyclic fraction of aromatic hydrocarbons: MPI 3+1/PAI 1 and [2(2-MP+3-MP)+P]/1-MP. The applicability of newly proposed parameters was checked by correlation analysis. Depth of the reservoir rock, diasterane maturation parameter, as well as several typical aromatic fraction maturation parameters were used for this purpose. The examined oils (fourteen samples from nine oil fields of Sakhalin Island, Russia), were of Miocene age and from reservoir rocks of relatively wide range of depths (73-2841 m). All samples represented biodegraded, or mixtures of biodegraded and nonbiodegraded oils [1]

Cross-Sectional Area of the Rotator Cuff Muscles in MRI - Is there Evidence for a Biomechanical Balanced Shoulder?

OBJECTIVE To provide in-vivo evidence for the common biomechanical concept of transverse and craniocaudal force couples in the shoulder that are yielded by both the rotator cuff muscles (RCM) and the deltoid and to quantitatively evaluate and correlate the cross-sectional areas (CSA) of the corresponding RCM as a surrogate marker for muscle strength using MRI. MATERIALS AND METHODS Fifty patients (mean age, 36 years; age range, 18-57 years; 41 male, 9 female) without rotator cuff tears were included in this retrospective study. Data were assessed by two readers. The CSA (mm2) of all rotator cuff muscles was measured on parasagittal T1-weighted FSE sequence at two different positions (at the established "y-position" and at a more medial slice in the presumably maximal CSA for each muscle, i.e., the "set position"). The CSA of the deltoid was measured on axial intermediate-weighted FSE sequences at three positions. CSA measurements were obtained using 1.5 Tesla MR-arthrographic shoulder. Pearson's correlation for the corresponding CSA of the force couple as well as was the intraclass correlation coefficient for the inter- and intra-reader agreement was calculated. RESULTS The mean CSA was 770 mm2 (±167) and 841 mm2 (±191) for the supraspinatus (in the y- and set-positions, respectively) and 984 mm2 (±241) and 1568 mm2 (±338) for the infraspinatus. The mean CSA was 446 mm2 (±129) and 438 mm2 (±128) for the teres minor (in the y- and set-positions, respectively) and 1953 mm2 (±553) and 2343 mm2 (±587) for the subscapularis. The three measurements of the deltoid revealed a CSA of 3063 mm2 (±839) for the upper edge, 3829 mm2 (±836) for the lower edge and 4069 mm2 (±937) for the middle of the glenoid. At the set position Pearson's correlation of the transverse force couple (subscapularis/infraspinatus) showed a moderate positive correlation of r = 0.583 (p<0.0001) and a strong correlation when the CSA of the teres minor was added to the infraspinatus CSA (r = 0.665, p = 0.0008) and a strong positive correlation of the craniocaudal force couple (supraspinatus/deltoid) that ranged from r = 0.565-0.698 (p<0.0001). Inter-reader agreement (ranged from 0.841 to 0.997, p = 0.0007) and intra-reader agreement were excellent (ranged from 0.863 to 0.999, p = 0.0006). CONCLUSION The significant correlation of the CSA of the RCM that form the transverse (subscapularis/infraspinatus-teres minor) and craniocaudal (supraspinatus/deltoid) force couple measured by MR-arthrography supports the biomechanical concept of a dynamically balanced shoulder in patients with an intact rotator cuff