Synthesis of phosphodiester-containing bacterial cell wall components : teichoic acids, capsular polysaccharides and phosphatidyl glycerol analogues

This thesis describes the synthesis of various teichoic acid (TA)-fragments, capsular polysaccharide (CPS)-mimics and a toolbox of glycerol phosphate probes. Most of these molecules feature one or more phosphodiester functions, the introduction of which has been accomplished with phosphoramidite chemistry. The versatility of glycerol- and carbohydrate building blocks provided with a 2-cyanoethyl-protected phosphoramidite is illustrated by their application both in solution and in automated solid phase syntheses of TA and CPS oligomers as well as probes. The CPS-mimics are based on a polysaccharide present in the capsule of the gram negative bacterium Neisseria meningitidis, the pathogen that is the major cause of bacterial meningitis. The TA-fragments described in this thesis correspond to lipoteichoic acids (LTA) and wall teichoic acids (WTA) from Enterococcus faecalis and Enterococcus faecium, two commensal Gram-positive bacteria inhabiting the gastrointestinal tract. In both these bacterial families multi-drug-resistant strains have evolved and they are responsible for the majority of hospital-acquired infections. Enterococcal LTA generally consists of sn-glycerol-1-phosphate repeating units that can be decorated with carbohydrate- or D-alanyl appendages on the 2-OH of the glycerol moieties. The biosynthetic machinery of WTA is more complicated and can result in completely different structures

A comparison of some laboratory techniques for the estimation of the digestibility of the organic matter in forage samples.

The 194 samples of forage were of 6 groups; grass or other forage dried, fresh or ensiled. Workers from 5 institutes analysed some of the samples by their usual methods, 10 methods altogether. Digestibility estimated with sheep was regressed on the other results and correlation coefficients and residual standard deviations were calculated; those were closer for groups of forages than for all forages together. The least accurate predictor of digestibility in vivo was crude fibre content, which is much used in the Netherlands. The best method for each fodder group was the method of Tilley and Terry (NAR 34, 156) as modified by Koelen, Kemmink and Dijkstra (De bepaling van de voederwaarde van ruwvoeders met behulp van de in vitroverteerbaarheid. Internal Report, Institute for Animal Feeding and Nutrition Research 'Hoorn' (1969), No. 27, available in English). It took least work but required sheep rumen fluid. For all groups together, the cell-wall constituents method of Gaillard and Nijkamp (NAR 38, 8034) was better for 54 samples but the residual standard deviation was higher than within groups; it required more labour, but not rumen fluid. (Abstract retrieved from CAB Abstracts by CABI’s permission

Relationship between infarct tissue characteristics and left ventricular remodeling in patients with versus without early revascularization for acute myocardial infarction as assessed with contrast-enhanced cardiovascular magnetic resonance imaging

Left ventricular (LV) remodeling following myocardial infarction (MI) is the result of complex interactions between various factors, including presence or absence of early revascularization. The impact of early revascularization on the relationship between infarct tissue characteristics and LV remodeling is incompletely known. Therefore, we investigated in patients with versus without successful early revascularization for acute MI potential relations between infarct tissue characteristics and LV remodeling with contrast-enhanced (CE) cardiovascular magnetic resonance (CMR). Patients with versus without successful early revascularization underwent CE-CMR for tissue characterization and assessment of LV remodeling including end-diastolic and end-systolic volumes, LV ejection fraction, and wall motion score index (WMSI). CE-CMR images were analyzed for infarct tissue characteristics including core-, peri- and total-infarct size, transmural extent, and regional scar scores. In early revascularized patients (n = 46), a larger area of infarct tissue correlated significantly with larger LV dimensions and a more reduced LV function (r = 0.39-0.68; all P ≤ 0.01). Multivariate analyses identified peri-infarct size as the best predictor of LV remodeling parameters (R2 = 0.44-0.62). In patients without successful early revascularization (n = 47), there was no correlation between infarct area and remodeling parameters; only peri-infarct size versus WMSI (r = 0.33; P = 0.03) and transmural extent versus LVEF (r = -0.27; P = 0.07) tended to be related. A correlation between infarct tissue characteristics and LV remodeling was found only in patients with early successful revascularization. Peri-infarct size was found to be the best determinant of LV remodeling. Our findings stress the importance of taking into account infarct tissue characteristics and success of revascularization when LV remodeling is studie

Моральна свідомість та релігійна віра в перспективі філософії Іммануїла Канта

У статті розкриваються головні ідеї та логічна структура філософії релігії Іммануїла Канта у її зв’язку з практичною філософією. Обґрунтовано тезу про те, що розуміння Кантом головних релігійних ідей – особистого безсмертя та Бога − було дуже неортодоксальним і наближає його філософію до індійської релігійно-філософської традиції.В статье раскрываются главные идеи и логическая структура философии религии Иммануила Канта в связи с его практической философией. Обосновывается тезис о том, что понимание Кантом главных религиозных идей – личного бессмертия и Бога − было очень неортодоксальным и сближает его философию с индийской религиозно-философской традицией.The article explains main ideas and logical structure of Immanuel Kant’s philosophy of religion in its connection with practical philosophy. It argues that Kant’s views of main religious ideas – personal immortality and God − were very unorthodox and congenial with Indian religious-philosophical tradition

Infarct tissue characterization in implantable cardioverter-defibrillator recipients for primary versus secondary prevention following myocardial infarction: a study with contrast-enhancement cardiovascular magnetic resonance imaging

Knowledge about potential differences in infarct tissue characteristics between patients with prior life-threatening ventricular arrhythmia versus patients receiving prophylactic implantable cardioverter-defibrillator (ICD) might help to improve the current risk stratification in myocardial infarction (MI) patients who are considered for ICD implantation. In a consecutive series of (ICD) recipients for primary and secondary prevention following MI, we used contrast-enhanced (CE) cardiovascular magnetic resonance (CMR) imaging to evaluate differences in infarct tissue characteristics. Cine-CMR measurements included left ventricular end-diastolic and end-systolic volumes (EDV, ESV), left ventricular ejection fraction (LVEF), wall motion score index (WMSI), and mass. CE-CMR images were analyzed for core, peri, and total infarct size, infarct localization (according to coronary artery territory), and transmural extent. In this study, 95 ICD recipients were included. In the primary prevention group (n = 66), LVEF was lower (23 ± 9 % vs. 31 ± 14 %; P < 0.01), ESV and WMSI were higher (223 ± 75 ml vs. 184 ± 97 ml, P = 0.04, and 1.89 ± 0.52 vs. 1.47 ± 0.68; P < 0.01), and anterior infarct localization was more frequent (P = 0.02) than in the secondary prevention group (n = 29). There were no differences in infarct tissue characteristics between patients treated for primary versus secondary prevention (P > 0.6 for all). During 21 ± 9 months of follow-up, 3 (5 %) patients in the primary prevention group and 9 (31 %) in the secondary prevention group experienced appropriate ICD therapy for treatment of ventricular arrhythmia (P < 0.01). There was no difference in infarct tissue characteristics between recipients of ICD for primary versus secondary prevention, while the secondary prevention group showed a higher frequency of applied ICD therapy for ventricular arrhythmia.\u

The influence of the polyene filipin on the extrinsic pathway of blood coagulation

The inhibition by filipin in the extrinsic blood clotting system takes place at two sites: (1) at the interaction of factor VII, tissue thromboplastin and Ca++, and (2) at the prothrombinase level. Both formation and enzymatic activity of the prothrombinase are inhibited.The cholesterol content of the lipid that is used to form the prothrombinase complex determines the degree of inhibition by filipin. The inhibition increases the higher the sterol content. The adsorption of factors Xa and V onto lipid surface is enhanced by filipin. This increased adsorption does not lead to an increase in prothrombinase production

Regional Differences in Presence of Shiga toxin-producing Escherichia coli Virulence-Associated Genes in the Environment in the North West and East Anglian regions of England

Shiga toxin-producing Escherichia coli is carried in the intestine of ruminant animals, and outbreaks have occurred after contact with ruminant animals or their environment. The presence of STEC virulence genes in the environment was investigated along recreational walking paths in the North West and East Anglia regions of England. In all, 720 boot sock samples from walkers’ shoes were collected between April 2013 and July 2014. Multiplex PCR was used to detect E. coli based on the amplification of the uidA gene and investigate STEC-associated virulence genes eaeA, stx1 and stx2. The eaeA virulence gene was detected in 45·5% of the samples, where stx1 and/or stx2 was detected in 12·4% of samples. There was a difference between the two regions sampled, with the North West exhibiting a higher proportion of positive boot socks for stx compared to East Anglia. In univariate analysis, ground conditions, river flow and temperature were associated with positive boot socks. The detection of stx genes in the soil samples suggests that STEC is present in the English countryside and individuals may be at risk for infection after outdoor activities even if there is no direct contact with animals. Significance and Impact of the Study: Several outbreaks within the UK have highlighted the danger of contracting Shiga toxin-producing Escherichia coli from contact with areas recently vacated by livestock. This is more likely to occur for STEC infections compared to other zoonotic bacteria given the low infectious dose required. While studies have determined the prevalence of STEC within farms and petting zoos, determining the risk to individuals enjoying recreational outdoor activities that occur near where livestock may be present is less researched. This study describes the prevalence with which stx genes, indicative of STEC bacteria, were found in the environment in the English countryside

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In het voormalige doorvoerkamp Westerbork graven archeologen sindsdeze week naar sporen van het dagelijks leven. ‘De vraag dient zich aanvan wie Westerbork eigenlijk is.’ Door Ana van Es en Maarten Keulemans