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D Sen

Publications and source records attributed to D Sen.

At least 55 records · Page 3Linked to original sources

The DNA structures at the ends of eukaryotic chromosomes.

The sequence organisation of the telomeric regions is extremely similar for all eukaryotes examined to date. Subtelomeric areas may contain large sequence arrays of middle repetitive, complex elements that sometimes have similarities to retrotransposons. In between and within these complex sequences are short, satellite-like repeats. These areas contain very few genes and are thought to be organised into a heterochromatin-like domain. The terminal regions almost invariably consist of short, direct repeats. These repeats usually contain clusters of 2-4 G residues and the strand that contains these clusters (the G strand) always forms the extreme 3'-end of the chromosome. Thus, most telomeric repeats are clearly related to each other which in turn suggests a common evolutionary origin. A number of different structures can be formed by single-stranded telomeric G strand repeats and, as has been suggested recently, by the G strand. Since the main mechanism for the maintenance of telomeric repeats predicts the occurrence of single-stranded extensions of the G strand, the propensity of G-rich DNA to fold into alternative DNA structures may have implications for telomere biology.

Animals↗

Evidence for the metal-cofactor independence of an RNA phosphodiester-cleaving DNA enzyme.

BACKGROUND: RNA and DNA are polymers that lack the diversity of chemical functionalities that make proteins so suited to biological catalysis. All naturally occurring ribozymes (RNA catalysts) that catalyze the formation, transfer and hydrolysis of phosphodiesters require metal-ion cofactors for their catalytic activity. We wished to investigate whether, and to what extent, DNA molecules could catalyze the cleavage (by either hydrolysis or transesterification) of a ribonucleotide phosphodiester in the absence of divalent or higher-valent metal ions or, indeed, any other cofactors. RESULTS: We performed in vitro selection and amplification experiments on a library of random-sequence DNA that incorporated a single ribonucleotide, a suitable site for cleavage. Following 12 cycles of selection and amplification, a 'first generation' of DNA enzymes (DNAzymes) cleaved their internal ribonucleotide phosphodiesters at rates approximately 10(7)-fold faster than the spontaneous rate of cleavage of the dinucleotide ApA in the absence of divalent cations. Re-selection from a partially randomized DNA pool yielded 'second generation' DNAzymes that self-cleaved at rates of approximately 0.01 min-1 (a 10(8)-fold rate enhancement over the cleavage rate of ApA). The properties of these selected catalysts were different in key respects from those of metal-utilizing ribozymes and DNAzymes. The catalyzed cleavage took place in the presence of different chelators and ribonuclease inhibitors. Trace-metal analysis of the reaction buffer (containing very high purity reagents) by inductively coupled plasma-optical emission spectrophotometry indicated that divalent or higher-valent metal ions do not mediate catalysis by the DNAzymes. CONCLUSIONS: Our results indicate that, although ribozymes are sometimes regarded generically to be metalloenzymes, the nucleic acid components of ribozymes may play a substantial role in the overall catalysis. Given that metal cofactors increase the rate of catalysis by ribozymes only approximately 10(2)-10(3)-fold above that of the DNAzyme described in this paper, it is conceivable that substrate positioning, transition-state stabilization or general acid/base catalysis by the nucleic acid components of ribozymes and DNAzymes may contribute significantly to their overall catalytic performance.

Base Sequence↗

General practices and health and safety at work.

There is a lack of knowledge and understanding of health and safety legislation in general practice surgeries. As a result, compliance with such laws is also seriously lacking. However, both knowledge and compliance can be significantly improved through information, guidance and contact with the Health and Safety Executive (HSE).

Family Practice↗

Recognition of anionic porphyrins by DNA aptamers.

DNA sequences were isolated by in vitro selection for binding to N-methylmesoporphyrin IX (NMM), a molecule that behaves as a stable transition-state analogue for porphyrin chelatases. Clones approximately 280 and approximately 120 nucleotides long were obtained, which bound to NMM with sub-micromolar affinity but bound mesoporphyrin IX (MPIX), as well as various metalloderivatives of MPIX, with lower affinity. Footprinting experiments with dimethyl sulfate, DNase I, and bound hemin molecules activated by superoxide identified a series of short guanine-rich motifs to be the binding sites for the various porphyrins. One clone, PS2, examined in depth, gave a methylation footprint with bound NMM but not with bound MPIX nor with a number of metalloporphyrins. The binding domain PS2, synthesized as a short oligonucleotide, itself showed high-affinity binding to NMM. The binding sequences from different clones were loosely homologous, and the footprinting data were consistent with their folding to form one or more guanine quartets in the presence of NMM. Ultraviolet--visible absorption and circular dichroism spectroscopy of the DNA--NMM complexes indicates, however, that the interaction is not primarily intercalative in nature. The preferential binding of NMM by these aptamers raises the possibility of their being able to catalyze the chelation of metal ions by the porphyrin MPIX.

Base Sequence↗

Synapsable DNA.

We describe a simple innovation that allows DNA double helices to stably bind one another at specific sites, with regulatable affinity, under physiological conditions. This type of DNA synapsis requires neither an unraveling of the participating duplexes not heteroduplex formation, and is achieved by the intermolecular dimerization of short blocks of guanine-guanine mismatch base-pairs introduced within standard Watson-Crick duplexes. We propose that in vivo such "sticky" guanine domains, formed transiently in cruciforms, could initiate illegitimate recombination events. In practical terms, this type of synapsis, achievable in vitro by simply mixing the participating duplexes, could provide a novel and general technology for the self-assembly of arrays of important DNA sequences, and serve as a tool for investigating certain protein-DNA interactions in vivo.

Base Sequence↗

Enterotoxigenic Escherichia coli associated diarrhoea among infants aged less than six months in Calcutta, India.

The role of enterotoxigenic Escherichia coli (ETEC) as etiologic agents of diarrhoea in infants aged less than six months was assessed in a hospital based study in Calcutta, India. Of the 218 cases examined, ETEC strains were isolated from 26 (11.9%) cases. Among these, in 17 cases ETEC was the sole infecting pathogen (p = 0.0085). Of the 26 isolates (each isolate representing a case), 24 were distributed among seven different O:K:H serotypes and two different colonization factor antigens (CFAs) I and II. Two of the remaining isolation were untypable, non-haemagglutinating, and were non-hydrophobic as measured by the salt aggregation test (SAT). Of the 26 ETEC strains detected, 15 (57.7%) produced heat-labile toxin (LT) only, 8 (30.8%) liberated heat-stable toxin (ST) only, and the remaining 3 (11.5%) produced both LT and ST. No ETEC strain was isolated from the 102 age-matched controls included in this study. All the ETEC isolates were multiple drug resistant. The study showed that the diarrhoea due to ETEC was of brief duration, mostly within the range of 3 to 7 days.

Anti-Bacterial Agents↗

The significance of enteroaggregative Escherichia coli in the etiology of hospitalized diarrhoea in Calcutta, India and the demonstration of a new honey-combed pattern of aggregative adherence.

Previous studies have identified enteroadherent Escherichia coli that exhibit localized adherence, diffuse adherence and atypical diffuse adherence as diarrhoeagenic agents associated with infantile diarrhoea in Calcutta, India. In this study, a DNA probe specific for enteroaggregative adherence was used to determine the etiological significance of enteroaggregative E. coli in the causation of diarrhoea. From a total of 330 strains of E. coli recovered from 159 cases of acute secretory diarrhoea and 174 cases of invasive diarrhoea, 20 strains hybridized with the probe, whereas of the 25 E. coli strains recovered from 25 healthy controls only 1 strain hybridized with the probe. Of the 21 probe positive strains, 19 adhered to HeLa cells in the typical stacked-brick pattern while 2 strains recovered from 2 cases of secretory diarrhoea adhered to the glass surface in a hitherto undescribed formation which we have termed, based on the appearance, as the honey-comb pattern. The enteroaggregative E. coli strains identified in this study did not produce any conventional enterotoxins and were significantly associated with patients with secretory diarrhoea (10.7%) than with invasive diarrhoea (1.7%). The results of this study indicate that enteroaggregative E. coli play a causal role in acute secretory diarrhoea in this part of the world which lends credence to the involvement of a potent toxin in the pathogenesis of EAggEC mediated infections.

Bacterial Adhesion↗

Manic depressive disorder and lithium over the decades: the very educational case of Mrs. L.

BACKGROUND: Manic depressive disorder is a recurrent illness with a variable clinical course. Before the advent of modern pharmacotherapy, ECT was a common treatment; more recently, lithium has become the long-term treatment of choice, but it is a treatment that is not without complications. METHOD: The psychiatric and medical history of an 80-year-old patient was reviewed and analyzed based on clinical interview and medical records. The findings were integrated with literature review to illustrate a number of important clinical points about manic depressive disorder and its treatment. RESULTS: (1) ECT is an effective treatment for mania, (2) a sustained remission may occur spontaneously, (3) a mania-depression-euthymia episode sequence predicts favorable response to lithium, (4) lithium discontinuation is not without risk, (5) lithium continuation is not without risk (thyroid, kidneys, eyes). CONCLUSION: The case of Mrs. L illustrates the longitudinal course of manic depressive disorder and how it can be influenced by treatment and withdrawal of treatment. It also illustrates the potential of lithium for causing adverse effects on several organ systems.

Aged↗