The chemistry and biology of trypanosomal trans-sialidases: virulence factors in Chagas disease and sleeping sickness

trans-Sialidases constitute a special group of the sialidase family. They occur in some trypanosome species and, in a unique reversible reaction, transfer sialic acids from one glycosidic linkage with galactose (donor) to another galactose (acceptor), to form (α2-3)-sialyl linkages. Trypanosomes cause such devastating human diseases as Chagas disease in South America (Trypanosoma cruzi) or sleeping sickness in Africa (Trypanosoma brucei). The trans-sialidases strongly contribute to the pathogenicity of the trypanosomes by scavenging sialic acids from the host or blood meal to coat the parasite surface; this aids their survival strategy in the insect's intestine, and in the blood circulation or cells of the host, and serves to compromise the immune system of the human or animal host. American and African trypanosomes express trans-sialidases at different stages of their vector/host development. They are transmitted to humans by insect vectors (tsetse fly or other insect "bug" species). trans-Sialidase activity with varying linkage specificity has also been found in a few bacteria species and in human serum. trans-Sialidases are of increasing practical importance for the chemo-enzymatic synthesis of sialylated glycans. The search for appropriate inhibitors of trans-sialidases and vaccination strategies is intensifying, as less toxic medicaments for the treatment of these widespread and often chronic tropical diseases are required.     

Unifying Energetic Disorder from Charge Transport and Band Bending in Organic Semiconductors

Characterizing the density of states (DOS) width accurately is critical in understanding the charge‐transport properties of organic semiconducting materials as broader DOS distributions lead to an inferior transport. From a morphological standpoint, the relative densities of ordered and disordered regions are known to affect charge‐transport properties in films; however, a comparison between molecular structures showing quantifiable ordered and disordered regions at an atomic level and its impact on DOS widths and charge‐transport properties has yet to be made. In this work, for the first time, the DOS distribution widths of two model conjugated polymer systems are characterized using three different techniques. A quantitative correlation between energetic disorder from band‐bending measurements and charge transport is established, providing direct experimental evidence that charge‐carrier mobility in disordered materials is compromised due to the relaxation of carriers into the tail states of the DOS. Distinction and quantification of ordered and disordered regions of thin films at an atomic level is achieved using solid‐state NMR spectroscopy. An ability to compare solid‐state film morphologies of organic semiconducting polymers to energetic disorder, and in turn charge transport, can provide useful guidelines for applications of organic conjugated polymers in pertinent devices.     

Photochemische Reaktionen von Pyrazolidon-(3)-betainen. V. Photooxydation heteroaromatischer N-Ylide

Photochemical Reactions of 3-Pyrazolidone Betains. V. Photooxidation of Heteroaromatic N-Ylids The dye-sensitized photooxidation of the heteroaromatic N-ylids 3a and 3b yields 1-isoquinolone 8 together with ethyl mesoxalate 13 and bis(benzoyl-isoquinol-1-on-2-yl-methyl)ether 10 , respectively. These are decomposition products of fivemembered ring peroxides, formed by reaction of singlet oxygen with the N-ylids. One mole of the ylids 3c, 4 and 5 gives complete conversion with 0.5 moles of singlet oxygen, yielding the corresponding heteroaromatic and mesoxalic acid derivatives, respectively. The products and the oxygen consumption are discussed to be due to reaction of one molecule of the ylid with one molecule of alkylhydroperoxide 18 , formed as a primary product. N-Ylids 3c, 4 and 5 react in the same manner with hydrogen hydroperoxide or perbenzoic acid to the corresponding heteroaromatic and mesoxalic acid derivatives. For the reaction between 3c and substituted perbenzoic acids the HAMMETT correlation gives ϱ = +0.94.     

Intimin from enteropathogenic Escherichia coli restores murine virulence to a Citrobacter rodentium eaeA mutant: induction of an immunoglobulin A response to intimin and EspB

The formation of attaching and effacing (A/E) lesions is central to the pathogenesis of enteropathogenic Escherichia coli (EPEC)-mediated disease in humans and Citrobacter rodentium (formerly C. freundii biotype 4280)-mediated transmissible colonic hyperplasia in mice. Closely related outer membrane proteins, known as intimins, are required for formation of the A/E lesion by both EPEC (Int(EPEC)) and C. rodentium (Int(CR)). A secreted protein, EspB (formally EaeB), is also necessary for A/E-lesion formation. Here we report that expression of a cloned Int(EPEC), encoded by plasmid pCVD438, restores murine virulence to an intimin-deficient mutant of C. rodentium DBS255. Replacement of Cys937 with Ala abolished the ability of the cloned EPEC intimin to complement the deletion mutation in DBS255. Ultrastructural examination of tissues from wild-type C. rodentium and DBS255(pCVD438)-infected mice revealed multiple A/E lesion on infected cells and loss of contact between enterocytes and basement membrane. Histological investigation showed that although both wild-type C. rodentium and DBS255(pCVD438) colonized the descending colon and induced colonic hyperplasia in orally infected 21-day-old mice, the latter strain adhered to epithelial cells located deeper within crypts. Nonetheless, infection with the wild-type strain was consistently more virulent, as indicated by a higher mortality rate. All the surviving mice, challenged with either wild-type C. rodentium or DBS255(pCVD438), developed a mucosal immunoglobulin A response to intimin and EspB. These results show that C. rodentium infection provides a relevant, simple, and economic model to investigate the role of EPEC proteins in the formation of A/E lesions in vivo and in intestinal disease.     

Seasonal variations of elemental carbon in urban aerosols as measured by two common thermal-optical carbon methods

Two commonly employed laboratory-based elemental carbon (EC) and organic carbon (OC) thermal/optical methods for the analysis of ambient particulate matter were used to analyze 709 twenty-four hour integrated PM_2.5 samples along with 76 field blanks from the St. Louis-Midwest Supersite in East St. Louis, Illinois. The two laboratory ECOC methods were the Aerosol Characterization Experiment—Asia (ACE-Asia) method based on National Institute of Occupational Safety and Health (NIOSH 5040) method and the Interagency Monitoring of Protected Visual Environments (IMPROVE) protocol. As in previous intercomparisons between these two methods, there was excellent agreement for total carbon (i.e. sum of EC and OC), but significant differences were observed in the split between the measured EC and OC. The 709 daily PM_2.5 samples spanned a time series of two years that allowed an assessment of seasonal relationships between the EC reported by the two methods. Seasonal average ACE-Asia and IMPROVE EC concentration values were highest in the fall and lowest in the spring. Differences between the seasonal average IMPROVE and ACE-Asia EC concentration values were about 40% greater in summer compared to winter. While IMPROVE EC values were always larger than ACE-Asia EC, the EC difference between these methods exhibited a strong seasonal variation with largest differences occurring in the spring and especially summer with the smallest differences in the fall and winter. Seasonal average EC differences (IMPROVE − ACE-Asia) were anti-correlated with molecular markers for biomass burning and mobile source emissions that had wintertime maximum concentrations. The EC difference between methods did have a moderate positive correlation with indicators of secondary organic aerosol and sulfate suggesting that oxidized organic aerosol associated with atmospheric processing or other secondary components of ambient aerosol could be associated with the seasonal differences between these EC measurements.     

Generation of reactive oxygen species and activity of platelet-activating factor acetylhydrolase in human monocyte-derived macrophages

Monocytes were prepared from healthy human volunteers and were allowed to differentiate into macrophages by adhesion to plastic surface and cultured over 7 days in presence of either 10% fetal calf serum (FCS), human control serum or serum from hyperlipaemic patients. Hyperlipaemic serum stimulated the differentiation (measured as an increase in cellular protein and DNA content) to a higher extent when compared to control serum and FCS. With all sera a marked increase of the cellular activity of the enzyme platelet-activating factor acetylhydrolase (PAF-AH) and a tremendous decrease in the capacity of cells to generate reactive oxygen species (ROS) was observed. After seven days of culture the increase in PAH-AH activity was about 19-fold with hyperlipaemic serum, 11-fold with control serum and 6-fold with FCS. During the same period of time ROS generation measured as zymosan-induced chemiluminescence decreased by about 98% and no significant differences between the three types of serum were found. The results indicate that the activity of PAF-AH and the capacity of ROS generation which are both assumed to play an important role in the oxidation of low-density lipoproteins (LDL) and thus in the development of atherosclerosis, change in opposite direction during the differentiation of blood monocytes into macrophages, and that hyperlipaemic serum stimulates PAF-AH activity but not ROS generation.     

Coupled heat conductors

This paper deals with the heat flow between two temperature levels through any number of long (or one - dimensional) heat conductors connected in parallel. The heat conductors may have different temperature dependent thermal conductivities and may be coupled by arbitrary heat leaks to each other.The independence of the total heat flow of the thermal coupling between these conductors is pointed out. Further, a simple method is presented for computing the common temperature distribution in the longitudinal direction of such heat conductors which are perfectly coupled to each other. For other kinds of couplings via finite heat leaks between the conductors the approximate temperature distributions are calculated. All computations are straightforward and are demonstrated by examples.