Very low prevalence of bovine tuberculosis in cattle in Sylhet district of Bangladesh.

Bovine tuberculosis (bTB), a chronic zoonotic disease in cattle, has a substantial socio-economic and public health impact. This study was conducted to estimate the prevalence and geographical distribution of bTB in the Sylhet district of Bangladesh. A cross-sectional study was conducted at all 12 upazilas of Sylhet district, which included 512 randomly selected cattle from 48 farms. Selected animals were tested with the Caudal Fold Tuberculin (CFT) test to identify bTB-positive cattle. Out of 512 cattle, only one animal was identified as a reactor, providing an estimated prevalence of 0.19% (95% Confidence Interval; 0-0.58%). The only positive reactor was found in Zakiganj upazila. As the prevalence of bTB in cattle in Sylhet appears to be low, it indicates that most of the upazilas of Sylhet district are free of the bTB infection. This prevalence is lower than the reported prevalence in other parts of Bangladesh. Thus, attempts should be made to maintain the current situation of bTB infection in cattle of Sylhet district.

Carboxylate-functionalized foldamer inhibitors of HIV-1 integrase and Topoisomerase 1: artificial analogues of DNA mimic proteins.

Inspired by DNA mimic proteins, we have introduced aromatic foldamers bearing phosphonate groups as synthetic mimics of the charge surface of B-DNA and competitive inhibitors of some therapeutically relevant DNA-binding enzymes: the human DNA Topoisomerase 1 (Top1) and the human HIV-1 integrase (HIV-1 IN). We now report on variants of these anionic foldamers bearing carboxylates instead of phosphonates. Several new monomers have been synthesized with protecting groups suitable for solid phase synthesis (SPS). Six hexadecaamides have been prepared using SPS. Proof of their resemblance to B-DNA was brought by the first crystal structure of one of these DNA-mimic foldamers in its polyanionic form. While some of the foldamers were found to be as active as, or even more active than, the original phosphonate oligomers, others had no activity at all or could even stimulate enzyme activity in vitro. Some foldamers were found to have differential inhibitory effects on the two enzymes. These results demonstrate a strong dependence of inhibitory activity on foldamer structure and charge distribution. They open broad avenues for the development of new classes of derivatives that could inhibit the interaction of specific proteins with their DNA target thereby influencing the cellular pathways in which they are involved.

Crystal structure of d(CCGGGGTACCCCGG)2 at 1.4†Šresolution.

The X-ray crystal structure of the DNA tetradecamer sequence d(CCGGGGTACCCCGG)2 is reported at 1.4 Šresolution in the tetragonal space group P41212. The sequence was designed to fold as a four-way junction. However, it forms an A-type double helix in the presence of barium chloride. The metal ion could not be identified in the electron-density map. The crystallographic asymmetric unit consists of one A-type double helix with 12 base pairs per turn, in contrast to 11 base pairs per turn for canonical A-DNA. A large number of solvent molecules have been identified in both the grooves of the duplex and around the backbone phosphate groups.

The novel double-folded structure of d(GCATGCATGC): a possible model for triplet-repeat sequences.

The structure of the decadeoxyribonucleotide d(GCATGCATGC) is presented at a resolution of 1.8 Å. The decamer adopts a novel double-folded structure in which the direction of progression of the backbone changes at the two thymine residues. Intra-strand stacking interactions (including an interaction between the endocylic O atom of a ribose moiety and the adjacent purine base), hydrogen bonds and cobalt-ion interactions stabilize the double-folded structure of the single strand. Two such double-folded strands come together in the crystal to form a dimer. Inter-strand Watson-Crick hydrogen bonds form four base pairs. This portion of the decamer structure is similar to that observed in other previously reported oligonucleotide structures and has been dubbed a `bi-loop'. Both the double-folded single-strand structure, as well as the dimeric bi-loop structure, serve as starting points to construct models for triplet-repeat DNA sequences, which have been implicated in many human diseases.

What parents should know while their child is on MDT: insights from a qualitative study in eastern India.

In order to provide high quality leprosy services to children affected by leprosy, it is necessary to actively engage parents. A qualitative study was undertaken as part of routine monitoring of field activities in West Bengal, India. A non-probability sample of 20 parents whose child was currently undergoing treatment was interviewed to explore the experiences of parents with regard to the diagnosis of leprosy and the treatment of their child. The most common initial symptom was a white patch and the median duration between recognition of the symptom and care-seeking was 6 months. The most commonly reported side-effect was a black discolouration which had led to non-adherence as well as resulting in school absenteeism. None of the parents had any knowledge of reactions. Although current strategies have enabled early case detection, there are challenges related to ensuring treatment completion. Emphasis should be laid on interpersonal communication to empower parents, enabling them to appreciate the side-effects and recognise the complications early and be actively engaged as a treatment partner while their child is on MDT.

Structure of d(CCCCGGTACCGGGG)2 at 1.65†Šresolution.

The crystal structure of the tetradecanucleotide d(CCCCGGTACCGGGG)2 has previously been reported as an A-type double helix at a resolution of 2.5 Šin space group P41. Here, the structure of this sequence was determined at a significantly higher resolution of 1.65 Šin space group P41212. The differences in crystal packing between the former and latter are described. The crystallographic asymmetric unit consists of one tetradecanucleotide duplex that spans more than one full turn of the A-helix. This structure allowed the unambiguous identification of solvent interactions.

Structure of d(CCGGGACCGG)4 as a four-way junction at 1.6†Šresolution: new insights into solvent interactions.

The crystal structure of the decamer sequence d(CCGGGACCGG)(4) has previously been reported at 2.16 Šresolution as a four-way junction. Here, the structure of this sequence is reported at the significantly higher resolution of 1.6 Å, which is the highest resolution reported for a four-way junction. This allowed the unambiguous identification of an extensive hydration network with distinct patterns and solvent-mediated interactions that shed new light on the role of water in the formation and stabilization of junction structures.

Structure of the tetradecanucleotide d(CCCCGGTACCGGGG)2 as an A-DNA duplex.

The crystal structure of the tetradecanucleotide sequence d(CCCCGGTACCGGGG)(2) has been determined at 2.5 Å resolution in the tetragonal space group P4(1). This sequence was designed with the expectation of a four-way junction. However, the sequence crystallized as an A-DNA duplex and represents more than one full turn of the A-helix. The crystallographic asymmetric unit consists of one tetradecanucleotide duplex. The structural parameters of the A-type DNA duplex structure and the crystal-packing arrangement are described. One Mn(2+) ion was identified with direct coordination to the N7 position of G(13) and a water molecule at the major-groove side of the C(2)·G(13) base pair.