Characterization of binding of human fibrinogen to the surface of germ-tubes and mycelium of candida albicans

The binding of human fibrinogen to germ-tubes and mycelium of Candida albicans, forms usually found in infected tissues, was studied in vitro by an immunofluorescence assay. Binding was quantified by using 125I-labelled fibrinogen. The degree of binding differed according to the morphological form of the fungus. Binding relative to that of the yeast form was greater for mycelium (12-fold) than for germ-tube (7.7-fold). Pretreatment of yeasts with fragments D and E (terminal degradation products of fibrinogen) before fibrinogen binding showed that fragment D possessed a higher affinity for C. albicans than fragment E. Binding of fibrinogen was diminished when C. albicans was pretreated with 2-mercaptoethanol alone or in combination with pronase, or pretreated with alpha-mannosidase or trypsin. Binding was not decreased by pretreatment with pronase alone or chitinase. Inhibition experiments using C. albicans dialysed culture filtrate, C. albicans mannan, chitin, sugars or amino sugars were done by preabsorbing the fibrinogen with each of the above mentioned compounds. C. albicans dialysed culture filtrate inhibited the binding more strongly than C. albicans mannan. However, fibrinogen binding to C. albicans was not significantly reduced by mannose, several other sugars or chitin. These studies demonstrate the existence of a fibrinogen-binding factor (FBF) strongly associated with the surface of germ-tube and filamentous forms of C. albicans, and indicate a possible role for FBF in the pathogenicity of C. albicans.     

Picturing beach erosion and deposition trends using PSInSAR: an example from the non-barred southern west coast of India

Coastal dynamics can rapidly alter beach morphology. In some places, such as the non-barred southern west coast of India, studying changes to beach morphology is a relatively arduous task. Persistent Scatterer Interferometric Synthetic Aperture Radar (PSInSAR), a remote sensing technique that utilizes stacks of radar images for accurate long-term monitoring of ground features, allows for detailed observations of coastal morphodynamics. Twenty-two single look complex (SLC) synthetic aperture radar (SAR) Sentinel-1A images, acquired from 4 March 2016 to 3 June 2017, are used to monitor geomorphological processes such as coastal erosion and deposition. Ground deformation measurements from PSInSAR processing shows the coast stretching?~?70 km between Thaickal and Munambam is highly dynamic, characterized by phases of erosion and deposition. The highest negative displacement of ? 24.9 mm at Thaickal versus the?+?7.6 mm at Chellanam in the north show the co-existing milieus of erosion and deposition. PSInSAR results concur with corresponding Google Earth images. In addition, beach sediment texture and scanning electron microscope grain micro-texture in the beach segment further corroborate temporal phases of erosion and deposition. Two locations are identified as typical erosional sites, while one location typified deposition. Erosion and deposition or rebuilding of beaches, usually correspond respectively with the onset and offset of SW monsoon wave climate in the Arabian Sea. When zones of deposition are mainly located in the proximity of river and/or lake inlets, stretches characterized by erosion are distal to inlets. Linear regression analyses of displacement–time series plots were used to identify general erosion or depositional regimes along beach segments. Results from this study illustrate how PSInSAR is a capable and reliable processing tool for monitoring temporal phases of coastal morpho-dynamics.

     

8-Modified-2'-deoxyadenosine analogues induce delayed polymerization arrest during HIV-1 reverse transcription

The occurrence of resistant viruses to any of the anti-HIV-1 compounds used in the current therapies against AIDS underlies the urge for the development of new drug targets and/or new drugs acting through novel mechanisms. While all anti-HIV-1 nucleoside analogues in clinical use and in clinical trials rely on ribose modifications for activity, we designed nucleosides with a natural deoxyribose moiety and modifications of position 8 of the adenine base. Such modifications might induce a steric clash with helix αH in the thumb domain of the p66 subunit of HIV-1 RT at a distance from the catalytic site, causing delayed chain termination. Eleven new 2'-deoxyadenosine analogues modified on position 8 of the purine base were synthesized and tested in vitro and in cell-based assays. In this paper we demonstrate for the first time that chemical modifications on position 8 of 2'-deoxyadenosine induce delayed chain termination in vitro, and also inhibit DNA synthesis when incorporated in a DNA template strand. Furthermore, one of them had moderate anti-HIV-1 activity in cell-culture. Our results constitute a proof of concept indicating that modification on the base moiety of nucleosides can induce delayed polymerization arrest and inhibit HIV-1 replication.     

Long-Term GABA Administration Induces Alpha Cell-Mediated Beta-like Cell Neogenesis

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Functional MRI of the Olfactory System in Conscious Dogs

We depend upon the olfactory abilities of dogs for critical tasks such as detecting bombs, landmines, other hazardous chemicals and illicit substances. Hence, a mechanistic understanding of the olfactory system in dogs is of great scientific interest. Previous studies explored this aspect at the cellular and behavior levels; however, the cognitive-level neural substrates linking them have never been explored. This is critical given the fact that behavior is driven by filtered sensory representations in higher order cognitive areas rather than the raw odor maps of the olfactory bulb. Since sedated dogs cannot sniff, we investigated this using functional magnetic resonance imaging of conscious dogs. We addressed the technical challenges of head motion using a two pronged strategy of behavioral training to keep dogs'' head as still as possible and a single camera optical head motion tracking system to account for residual jerky movements. We built a custom computer-controlled odorant delivery system which was synchronized with image acquisition, allowing the investigation of brain regions activated by odors. The olfactory bulb and piriform lobes were commonly activated in both awake and anesthetized dogs, while the frontal cortex was activated mainly in conscious dogs. Comparison of responses to low and high odor intensity showed differences in either the strength or spatial extent of activation in the olfactory bulb, piriform lobes, cerebellum, and frontal cortex. Our results demonstrate the viability of the proposed method for functional imaging of the olfactory system in conscious dogs. This could potentially open up a new field of research in detector dog technology.     

Selective protections on 2-allyloxycarbonylamino-1,6-anhydro-2-deoxy-beta-D-glucopyranose.

Regioselective monoacetylation of 2-allyloxycarbonylamino-1,6-anhydro-2-deoxy-beta-D-glucopyranose (1) gave a mixture of 3-O-acetyl and 4-O-acetyl derivatives, the structures of which were established by two-dimensional, phase-sensitive NOESY and confirmed by chemical proofs. The benzylation of 1, on the other hand, led to 2-allyloxycarbonylamino-1,6-anhydro-3,4-di- (5) or 2-allyloxycarbonylamino-1,6-anhydro-2-N-benzyl-3,4-di-O-benzyl-2-d eoxy-beta-D- glucopyranose (10). The regioselective cleavage of 5 with titanium tetrachloride gave the expected 3-O-benzyl derivative, the structure of which was ascertained by chemical proofs; the same reaction performed on 10 led to the opening of the anhydro ring to afford 3-benzyl-[3,4-di-O-benzyl-1,2-dideoxy-alpha-D-glucopyrano]-[2,1-d] -2- oxazolidone.