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In the sterically hindered title compound, C26H17ClN2O6S, the carbazole ring has a maximum deviation from planarity of 0.067 (4) Å for the C atom connected to the aldehyde group. The carbazole moiety forms a dihedral angle of 72.8 (1)° with the nitro-substituted benzene ring. The O atom of the meth-oxy group deviates by 0.186 (1) Å from the adjacent carbazole moiety. The phenyl-sulfonyl group forms intra-molecular C-H⋯O bonds between sulfone O atoms and the carbazole moiety, resulting in two S(6) rings. In the crystal, the nitrated benzene rings are linked via C-H⋯O inter-actions forming infinite C(7) chains along [100]. The crystal packing is also characterized by C-H⋯π inter-actions, which result in inversion dimers.

In the title compound, C26H18Cl2N2O5S, the carbazole ring system is essentially planar with a maximum deviation of 0.0498 (16) Å for the N atom. The carbazole ring system is almost orthogonal to the phenyl-sulfonyl and di-chloro-substituted nitro-phenyl rings, making dihedral angles of 84.23 (7) and 85.46 (12)°, respectively. The mol-ecular structure features intra-molecular C-H⋯O inter-actions, which generate two S(6) ring motifs. In the crystal, mol-ecules are linked by C-Cl⋯O halogen bonds [3.016 (3) Å, 166.63 (5)°], which generate infinite C(8) chains running parallel to [010].

In the title compound C24H17BrN2O5S, the phenyl ring makes dihedral angles of 85.4 (2) and 8.8 (2)° with the indole ring system and the nitro-benzene ring, respectively, while the indole ring system and nitrobenzene ring make a dihedral angle of 80.1 (2)°. In the crystal, weak C-H⋯O inter-actions link the mol-ecules, forming a two-dimensional network parallel to the bc plane.

In the title compound, C25H20N2O5S, the phenyl ring makes dihedral angles of 89.88 (8) and 13.98 (8)°, respectively, with the indole ring system and the nitro-benzene ring. The dihedral angle between the indole ring system and the nitro-benzene ring is 88.48 (11)°. The mol-ecular structure is stabilized by a weak intra-molecular C-H⋯O inter-action. In the crystal, π-π inter-actions, with centroid-centroid distances of 3.6741 (18) and 3.8873 (17) Å, link the mol-ecules into layers parallel to the ab plane.

Apoptotic proteins play key roles in understanding the mechanism of programmed cell death. Knowledge about the subcellular localization of apoptotic protein is constructive in understanding the mechanism of programmed cell death, determining the functional characterization of the protein, screening candidates in drug design, and selecting protein for relevant studies. It is also proclaimed that the information required for determining the subcellular localization of protein resides in their corresponding amino acid sequence. In this work, a new biological feature, class pattern frequency of physiochemical descriptor, was effectively used in accordance with the amino acid composition, protein similarity measure, CTD (composition, translation, and distribution) of physiochemical descriptors, and sequence similarity to predict the subcellular localization of apoptosis protein. AdaBoost with the weak learner as Random-Forest was designed for the five modules and prediction is made based on the weighted voting system. Bench mark dataset of 317 apoptosis proteins were subjected to prediction by our system and the accuracy was found to be 100.0 and 92.4 %, and 90.1 % for self-consistency test, jack-knife test, and tenfold cross validation test respectively, which is 0.9 % higher than that of other existing methods. Beside this, the independent data (N151 and ZW98) set prediction resulted in the accuracy of 90.7 and 87.7 %, respectively. These results show that the protein feature represented by a combined feature vector along with AdaBoost algorithm holds well in effective prediction of subcellular localization of apoptosis proteins. The user friendly web interface "APSLAP" has been constructed, which is freely available at http://apslap.bicpu.edu.in and it is anticipated that this tool will play a significant role in determining the specific role of apoptosis proteins with reliability.

In the title compound, C18H16BrNO3S, the dihedral angle between the phenyl ring and the indole ring system is 89.91 (11)°. The mol-ecular structure features weak C-H⋯O and C-H⋯Br hydrogen bonds. In the crystal, mol-ecules are linked by weak C-H⋯O hydrogen bonds, forming chains along the a-axis direction. The chains are further linked by C-H⋯π inter-actions, forming a layer parallel to the ab plane.

In the title compound, C18H16ClNO2S, the indole ring system forms a dihedral angle of 75.07 (8)° with the phenyl ring. The mol-ecular structure is stabilized by a weak intra-molecular C-H⋯O hydrogen bond. In the crystal, mol-ecules are linked by weak C-H⋯O hydrogen bonds, forming a chain along [10-1]. C-H⋯π inter-actions are also observed, leading to a three-dimensional network.

In the title compound, C25H19FN2O5S, the substituted phenyl ring makes a dihedral angle of 12.26 (9)° with the indole ring system. The nitro group is twisted at an angle of 26.92 (8)° out of the plane of the ring to which it is attached. The mol-ecular structure is stabilized by weak C-H⋯O hydrogen bonds. In the crystal, weak C-H⋯O, C-H⋯F and π-π [centroid-centroid distance = 3.6645 (11) Å] inter-actions link the mol-ecules, forming a three-dimensional network.

In the title compound, C25H19ClN2O5S, the phenyl ring forms dihedral angles of 79.62 (12) and 80.02 (13)° with the indole ring system and the benzene ring, respectively. The nitro group is twisted at an angle of 22.39 (11)° with respect to the attached benzene ring. In the crystal, mol-ecules assemble into double layers in the ab plane via C-H⋯O inter-actions.

In the title compound, C24H18N2O5S, the S atom has a distorted tetra-hedral configuration, with bond angles varying from 105.11 (7) to 119.98 (8)°. As a result of the electron-withdrawing character of the phenyl-sulfonyl group, the N-Csp (2) bond lengths [1.414 (2) and 1.413 (2) Å] are slightly longer than the reported value of 1.355 (14) Å for N atoms with a planar configuration. The indole moiety is essentially planar, with a maximum deviation of 0.0177 (14) Å for the N atom. The phenyl ring of the sulfonyl substituent makes a dihedral angle of 85.70 (7)° with the mean plane of the indole moiety. The mol-ecular structure features intra-molecular C-H⋯O hydrogen bonds, which generate S(6) and S(12) ring motifs. In the crystal, adjacent mol-ecules are linked via C-H⋯O hydrogen bonds, forming infinite C(7) chains running along the a-axis direction. The crystal packing also features C-H⋯π inter-actions, which form a three-dimensional structure.

A novel one pot synthesis of calothrixin B and its analogs is achieved involving an FeCl3-mediated domino reaction of enamines in dry DMF at reflux. Alternatively, the enamines upon interaction with CuBr2 in DMF at reflux led to the formation of 1-phenylsulfony-2-(2'-nitroaryl)-4-hydroxycarbazole-3-carbaldehydes in excellent yields.

Chloroplasts are organelles found in plant system and other photosynthetic eukaryotes. Since a large number of essential pathways take place in this organelle, proteins in the chloroplast are considered vital. Therefore, knowledge about the subchloroplast localization of the chloroplast proteins will provide precise information in understanding its interaction within the chloroplast. To address this, an AdaBoost-based prediction system to predict the subchloroplast localization of chloroplast proteins (SCLAP) was developed. It integrates three different sequence-based features for prediction, beside the addition of similarity-based module for significant improvement in prediction performance. SCLAP achieved an overall accuracy of 89.3% in jackknife cross-validation test against the benchmark dataset, which was considered highest among existing tools and equals the SubIdent, and 85.9% accuracy in new error-free dataset. Evaluation of SCLAP with the independent dataset, five-fold cross-validation, and their corresponding receiver operator characteristic curve analysis demonstrated the SCLAP's efficient performance. SCLAP is the webserver implementation of our algorithm written in PERL. The server can be used to predict the subchloroplast localization of chloroplast proteins ( http://sclap.bicpu.edu.in/predict.php ).

Plants in nature may face a wide range of favorable or unfavorable biotic and abiotic factors during their life cycle. Any of these factors may cause stress in plants; therefore, they have to be more adaptable to stressful environments and must acquire greater response to different stresses. The objective of this study is to retrieve and arrange data from the literature in a standardized electronic format for the development of information resources on potential stress responsive genes in Arabidopsis thaliana. This provides a powerful mean for manipulation, comparison, search, and retrieval of records describing the nature of various stress responsive genes in Arabidopsis thaliana. The database is based exclusively on published stress tolerance genes associated with plants.

In the title compound, C(17)H(15)NO(4)S, the six-membered ring of the indole unit makes a dihedral angle of 72.40 (5)° with the phenyl ring. The mol-ecular structure features a short C-H⋯O contact.

In the title compound, C(16)H(13)NO(3)S, the sulfonyl-bound phenyl ring forms a dihedral angle of 84.17 (6)° with the indole ring system. An intra-molecular C-H⋯O hydrogen bond generates an S(6) ring motif. The crystal structure exhibits weak inter-molecular C-H⋯O hydrogen bonds and π-π inter-actions between the five- and six-membered rings of the indole group [centroid-centroid distance = 3.6871 (9) Å].

Vibrio abundance generally displays seasonal patterns. In temperate coastal areas, temperature and salinity influence Vibrio growth, whereas in tropical areas this pattern is not obvious. The present study assessed the dynamics of Vibrio in the Arabian Sea, 1-2 km off Mangalore on the south-west coast of India, during temporally separated periods. The two sampling periods were signified by oligotrophic conditions, and stable temperatures and salinity. Vibrio abundance was estimated by culture-independent techniques in relation to phytoplankton community composition and environmental variables. The results showed that the Vibrio density during December 2007 was 10- to 100-fold higher compared with the February-March 2008 period. High Vibrio abundance in December coincided with a diatom-dominated phytoplankton assemblage. A partial least squares (PLS) regression model indicated that diatom biomass was the primary predictor variable. Low nutrient levels suggested high water column turnover rate, which bacteria compensated for by using organic molecules leaking from phytoplankton. The abundance of potential Vibrio predators was low during both sampling periods; therefore it is suggested that resource supply from primary producers is more important than top-down control by predators., (© 2011 Society for Applied Microbiology and Blackwell Publishing Ltd.)

In the title compound, C(22)H(18)N(2)O(4)S, the dihedral angle between the phenyl-sulfonyl ring and the methyl-phenyl ring is 67.78 (7)°. In the crystal, mol-ecules are linked by weak inter-molecular C-H⋯O inter-actions into a zigzag chain along the [101] direction.

In the title compound, C(15)H(12)INO(2)S, the sulfonyl-bound phenyl ring forms a dihedral angle 82.84 (9)° with the indole ring system. The mol-ecular structure is stabilized by a weak intra-molecular C-H⋯O hydrogen bond. The crystal structure exhibits weak inter-molecular C-H⋯π inter-actions and π-π inter-actions between the indole groups [centroid-centroid distance between the five-membered and six-membered rings of the indole group = 3.7617 (18) Å].

In the title compound, C(26)H(23)NO(4)S, the phenyl, tolyl and ester groups make dihedral angles of 82.28 (5), 77.67 (6) and 8.52 (6)°, respectively, with the indole ring system. The S atom of the sulfonyl group is displaced by 0.1968 (4) Å from the indole mean plane. The mol-ecular structure is stabilized by weak intra-molecular C-H⋯O inter-actions. The crystal structure structure features short intramolecular C-H⋯O contacts and π-π stacking inter-actions between the phenyl and tolyl groups [centroid-centroid distance = 3.9448 (11) Å].

Oral methotrexate is the benchmark against which other disease-modifying anti rheumatic drugs are measured. The use of parenteral methotrexate for those failing to tolerate or respond to oral therapy is accepted, but indications for its use and its place in the therapeutic ladder have not been fully investigated. We assessed the use of parenteral methotrexate (MTX) in our rheumatoid arthritis (RA) population and compared the characteristics of these patients to a matched group of those on oral therapy. We compared response rates to each approach using DAS 28 scores, ESR and visual analogue scales. Inferences on costs of parenteral therapy were made and predictors of response defined. We found that 10% of our total RA patient population were on parenteral methotrexate, having failed to tolerate or respond to oral therapy. Seventy-five percent of these met the criteria for the use of anti-tumour necrosis factor (TNF) agents. Overall response rates were equivalent to those obtained by responders to oral MTX. Patients on parenteral therapy were younger and were more likely to have extreme values of body mass index (BMI) than those on oral therapy. The approach was economically viable, although many patients unnecessarily attended hospital to receive their injections. We advocate consideration of parenteral MTX in all RA patients unresponsive to oral therapy prior to treatment with anti-TNF therapy. Response to parenteral therapy can be predicted by low BMI (below 22 kg/m(2)), possibly as a result of malabsorption, or by high BMI (over 30) as a result of gastrointestinal intolerance. A mechanism to deliver this option through self-administration in the community should be encouraged.

This article documents the addition of 512 microsatellite marker loci and nine pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Alcippe morrisonia morrisonia, Bashania fangiana, Bashania fargesii, Chaetodon vagabundus, Colletes floralis, Coluber constrictor flaviventris, Coptotermes gestroi, Crotophaga major, Cyprinella lutrensis, Danaus plexippus, Fagus grandifolia, Falco tinnunculus, Fletcherimyia fletcheri, Hydrilla verticillata, Laterallus jamaicensis coturniculus, Leavenworthia alabamica, Marmosops incanus, Miichthys miiuy, Nasua nasua, Noturus exilis, Odontesthes bonariensis, Quadrula fragosa, Pinctada maxima, Pseudaletia separata, Pseudoperonospora cubensis, Podocarpus elatus, Portunus trituberculatus, Rhagoletis cerasi, Rhinella schneideri, Sarracenia alata, Skeletonema marinoi, Sminthurus viridis, Syngnathus abaster, Uroteuthis (Photololigo) chinensis, Verticillium dahliae, Wasmannia auropunctata, and Zygochlamys patagonica. These loci were cross-tested on the following species: Chaetodon baronessa, Falco columbarius, Falco eleonorae, Falco naumanni, Falco peregrinus, Falco subbuteo, Didelphis aurita, Gracilinanus microtarsus, Marmosops paulensis, Monodelphis Americana, Odontesthes hatcheri, Podocarpus grayi, Podocarpus lawrencei, Podocarpus smithii, Portunus pelagicus, Syngnathus acus, Syngnathus typhle,Uroteuthis (Photololigo) edulis, Uroteuthis (Photololigo) duvauceli and Verticillium albo-atrum. This article also documents the addition of nine sequencing primer pairs and sixteen allele specific primers or probes for Oncorhynchus mykiss and Oncorhynchus tshawytscha; these primers and assays were cross-tested in both species., (© 2009 Blackwell Publishing Ltd.)

Introduction: An increased prevalence of musculoskeletal disease is recognised in diabetes and is a common source of disability. It is known to predominantly affect the upper limbs especially the hand and shoulder. The relationship with other complications of diabetes and glycaemic control is uncertain. We designed this study to clarify these relationships, and to assess differences between types 1 and 2 diabetes., Methods: We identified a group of 96 people with established diabetes and examined them for the presence of locomotor disease focussing on the upper limbs. We recorded the mean HbA1c and the presence of diabetic complications, together with the health assessment questionnaire (HAQ) score. We explored correlations between locomotor disease and these variables using logistic regression. We compared data between type 1 and type 2 diabetics and contrasted the amalgamated data with that of a matched control population of medical out patients using Students t tests., Results: Locomotor disease was present in 75% of diabetics with the upper limb the commonest site for abnormalities. This prevalence was significantly higher than that seen in the controls (53%) [p=0.02]. Shoulder capsulitis (25%), carpal tunnel syndrome (20%), tenosynovitis (29%), limited joint mobility (28%) and Dupuytrens contracture (13%) were the most frequent findings and were much commoner than in controls. Capsulitis usually coexisted with other upper limb abnormalities and best predicted the presence of retinopathy and/or neuropathy. The mean HbA1c was significantly higher in patients with combined shoulder and hand problems (9.1%) than in those with no upper limb problems (8.0%) [p=0.018]. The pattern of results was similar in type 1 and type 2 diabetes, although the prevalence of abnormalities and mean HAQ were significantly greater in type 2 patients, which may be in part a function of their greater mean age., Conclusion: Upper limb locomotor abnormalities are very common in diabetes and are associated with worse glycaemic control and more diabetic complications. Assessment of upper limb locomotor disease in diabetes should include an estimate of glycaemic control and a search for other complications.

The search for diverse plant growth-promoting (PGP) diazotrophic bacteria is gaining momentum as efforts are made to exploit them as biofertilizers for various economically important crops. In the present study, 17 diazotrophic strains belonging to eight different genera isolated from rice paddy fields were screened for multiple PGP traits and evaluated for their inoculation effects on canola and rice plants. All of the strains tested positive for 1- aminocyclopropane-1-carboxylate (ACC) deaminase activity and production of indole 3-acetic acid (IAA) and ammonia (NH3). Additionally, four of the strains were able to solubilize phosphorus (P), five tested positive for zinc (Zn) solubilization and sulfur (S) oxidation, and eight strains produced siderophores. Based on the presence of multiple PGP traits, 10 strains were selected for inoculation studies. Treatment with Herbaspirillum sp. RFNB26 resulted in maximum root length (54.3%), seedling vigor, and dry biomass in canola, whereas Paenibacillus sp. RFNB4 exhibited the lowest activity under gnotobiotic conditions. However, under pot culture conditions, Paenibacillus sp. RFNB4 significantly increased plant height and dry biomass production by 42.3% and 29.5%, respectively. Canola plants and rhizosphere soils inoculated with Bacillus sp. RFNB6 exhibited significantly higher nitrogenase activity. In greenhouse experiments, Serratia sp. RFNB18 increased rice plant height by 35.1%, Xanthomonas sp. RFNB24 enhanced biomass production by 84.6%, and rice rhizosphere soils inoculated with Herbaspirillum sp. RFNB26 exhibited the highest nitrogenase activity. Our findings indicate that most of the selected strains possess multiple PGP properties that significantly improve the growth parameters of the two plants when tested under controlled conditions.

This review article describes our present understanding of interstitial lung disease (ILD) complicating rheumatoid arthritis (RA). It discusses its high prevalence and clinical relevance, our recent improvement in understanding both its pathology and physiology, and our expectations of ongoing research into the immunology and genetics of the disease. An important section relates to the effects of drugs routinely used in the treatment of the articular manifestations of RA on the lung, especially in the presence of ILD. The major focus of the article is on therapeutic intervention, and here we discuss traditional and often unsuccessful approaches to treatment, leading on to discuss newly introduced therapeutic options such as anticoagulation and oral N-acetylcysteine. In the later sections, we focus our attention on several promising new therapeutic agents, including mycophenolate and new monoclonal antibody therapies, reviewing the limited literature available to support the use of these agents, concluding with a number of other aspects of treatment that are worthy of consideration.

A wide range of web based prediction and annotation tools are frequently used for determining protein function from sequence. However, parallel processing of sequences for annotation through web tools is not possible due to several constraints in functional programming for multiple queries. Here, we propose the development of APAF as an automated protein annotation filter to overcome some of these difficulties through an integrated approach.

A facile, one-pot synthesis of thio and selenourea derivatives from amines using tetrathiomolybdate 1 and tetraselenotungstate 2 as sulfur and selenium transfer reagents, respectively, is reported. The compounds were tested for their activity as urease inhibitors and some of the compounds showed potent activity in the nanomolar range towards jack bean urease.

In recent years, virtual learning is growing rapidly. Universities, colleges, and secondary schools are now delivering training and education over the internet. Beside this, resources available over the WWW are huge and understanding the various techniques employed in the field of Bioinformatics is increasingly complex for students during implementation. Here, we discuss its importance in developing and delivering an educational system in Bioinformatics based on e-learning environment.

Thiosulfate oxidation and mixotrophic growth with succinate or methanol plus thiosulfate was examined in nutrient-limited mixotrophic condition for Methylobacterium oryzae CBMB20, which was recently characterized and reported as a novel species isolated from rice. Methylobacterium oryzae was able to utilize thiosulfate in the presence of sulfate. Thiosulfate oxidation increased the protein yield by 25% in mixotrophic medium containing 18.5 mmol.L-1 of sodium succinate and 20 mmol.L-1 of sodium thiosulfate on day 5. The respirometric study revealed that thiosulfate was the most preferable reduced inorganic sulfur source, followed by sulfur and sulfite. Thiosulfate was predominantly oxidized to sulfate and intermediate products of thiosulfate oxidation, such as tetrathionate, trithionate, polythionate, and sulfur, were not detected in spent medium. It indicated that bacterium use the non-S4 intermediate sulfur oxidation pathway for thiosulfate oxidation. Thiosulfate oxidation enzymes, such as rhodanese and sulfite oxidase activities appeared to be constitutively expressed, but activity increased during growth on thiosulfate. No thiosulfate oxidase (tetrathionate synthase) activity was detected.

Aim: To examine the zinc (Zn) solubilization potential and nematicidal properties of Gluconacetobacter diazotrophicus., Methods and Results: Atomic Absorption Spectrophotometer, Differential Pulse Polarography and Gas Chromatography Coupled Mass Spectrometry were used to estimate the total Zn and Zn(2+) ions and identify the organic acids present in the culture supernatants. The effect of culture filtrate of Zn-amended G. diazotrophicus PAl5 on Meloidogyne incognita in tomato was examined under gnotobiotic conditions. Gluconacetobacter diazotrophicus PAl5 effectively solubilized the Zn compounds tested and 5-ketogluconic acid was identified as the major organic acid aiding the solubilization of zinc oxide. The presence of Zn compounds in the culture filtrates of G. diazotrophicus enhanced the mortality and reduced the root penetration of M. incognita under in vitro conditions., Conclusions: 5-ketogluconic acid produced by G. diazotrophicus mediated the solubilization process and the available Zn(2+) ions enhanced the nematicidal activity of G. diazotrophicus against M. incognita., Significance and Impact of the Study: Zn solubilization and enhanced nematicidal activity of Zn-amended G. diazotrophicus provides the possibility of exploiting it as a plant growth promoting bacteria.

Gluconacetobacter diazotrophicus an endophytic diazotroph also encountered as rhizosphere bacterium is reported to possess different plant growth promoting characteristics. In this study, we assessed the zinc solubilizing potential of G. diazotrophicus under in vitro conditions with different Zn compounds using glucose or sucrose as carbon sources. G. diazotrophicus showed variations in their solubilization potential with the strains used and the Zn compounds tested. G. diazotrophicus PAl5 efficiently solubilized the Zn compounds tested and ZnO was effectively solubilized than ZnCO(3) or Zn(3)(PO(4))(2). The soluble Zn concentration was determined in the culture supernatant through Atomic Absorption Spectrophotometer. Gas chromatography coupled Mass Spectrometry analysis revealed 5-ketogluconic acid, a derivative of gluconic acid as the major organic acid produced by G. diazotrophicus PAl5 cultured with glucose as carbon source. This organic anion may be an important agent that helped in the solubilization of insoluble Zn compounds.

Objective: There is little information on the natural history of patients with rheumatoid arthritis (RA) and associated interstitial lung disease (ILD). Cryptogenic fibrosing alveolitis (CFA) is known to have a poor longterm prognosis, and we compared the 2 conditions through a longitudinal prospective study., Methods: We previously compared baseline clinical, physiological, and radiological characteristics in 18 RA-ILD patients with 18 case controls with CFA. Clinical, physiological, and radiological assessment was repeated in all survivors at 5 years, and data on treatment and mortality were collected., Results: The median age in each group was 77 years and 10 patients in each group were male. More patients with RA-ILD survived to 5 years (8 RA-ILD vs 2 CFA; p = 0.03), and median survival was significantly longer for patients with RA-ILD (60 mo) compared to CFA (27 mo; p

Routine ophthalmoscopic screening for retinopathy of prematurity (ROP) from the age of 2 weeks is necessary to detect and treat fulminate ROP.

Endophytic bacteria were isolated from the tissues of surface sterilized roots, stems, and leaves of fifty different crop plants. Phenotypic, biochemical tests and species-specific PCR assay permitted identification of four isolates of Gluconacetobacter diazotrophicus from root tissues of carrot (Daucus carota L.), raddish (Raphanus sativus L.), beetroot (Beta vulgaris L.) and coffee (Coffea arabica L.). Further the plant growth promoting traits such as nitrogenase activity, production of phytohormone indole acetic acid (IAA), phosphorus and zinc solubilization were assessed. Significant nitrogenase activity was recorded among the isolates and all the isolates produced IAA in the presence of tryptophan. Though all the four isolates efficiently solubilized phosphorus, the zinc solubilizing ability differed among the isolates.

Unlabelled: Metachromatic leukodystrophy is a lysosomal lipid storage disorder. It is caused by mutations in the gene for arylsulphatase A, an enzyme involved in the degradation of the sphingolipid 3'-O-sulphogalactosylceramide (sulphatide). This membrane lipid can be found in various cell types, but in particularly high concentrations in the myelin of the nervous system. Patients suffer from progressive, finally lethal, demyelination due to accumulation of sulphatide. In the nervous system, lipid storage not only affects oligodendrocytes but also neurons and, in addition, leads to astrogliosis and activation of microglia. At the cellular level, lysosomal sulphatide storage also affects the lipid composition of myelin itself and has consequences for the amount and localization of particular myelin membrane-associated proteins. Here we review data, largely based on an arylsulphatase A knock-out mouse model of metachromatic leukodystrophy., Conclusion: The knock-out mouse model of metachromatic leukodystrophy has provided insights into the histopathological and cellular consequences of sulphatide storage.

Rheumatoid arthritis (RA) is a common cause of disability in the western population, with an annual incidence of 0.05% and a prevalence of 1%. Although a small percentage of patients go into natural remission, the untreated disease progresses to cause disability, morbidity and early mortality. Unravelling of the cytokine network in the pathogenesis of RA has led to the development of drugs that target these cytokines and prevent joint damage. Three biological anticytokine agents, etanercept, infliximab and anakinra, are now available for use in RA. More experience will quantify their safety and benefits. The potency of the older disease-modifying antirheumatic drugs (DMARDs), such as methotrexate and sulfasalazine, is also being realised, especially when used early in the disease process and in combination. Leflunomide is a new DMARD with efficacy similar to methotrexate and sulfasalazine. Symptomatic treatment of RA with nonsteroidal anti-inflammatory drugs has also undergone a revolution with the availability of a new class of COX-2-specific inhibitors. These drugs control inflammation and provide pain relief with less GI toxicity. Management of comorbid conditions associated with RA and its treatment (i.e., osteoporosis, cardiovascular and lung disease) has also become a priority for the rheumatologist. It is hoped that more aggressive use of conventional DMARDs and biological agents will result in less disability and a higher proportion of patients achieving remission.

BACKGROUND: Patients with rheumatoid arthritis (RA) frequently develop dyspepsia which may be due to peptic ulceration. There have been conflicting published data on the possible interactive roles of nonsteroidal anti-inflammatory drugs (NSAIDs) and colonisation of the gastric antrum with Helicobacter pylori in the development of peptic ulceration. METHODS: We have prospectively assessed the prevalence of peptic ulcers in dyspeptic RA patients and investigated the factors responsible. We endoscoped 100 RA patients comparing the endoscopic findings to those in 100 age- and sex-matched dyspeptic control subjects. Data on NSAID consumption and Helicobacter colonisation were collected for each patient. RESULTS: Endoscopic evidence of peptic ulceration was found in 29 RA patients and in 16 of the control subjects (P=0.03). Multiple ulcers (>2) were found in significantly more RA patients than in controls (10 vs. 2). NSAIDs were being used by 60 RA patients and 22 controls (P<0.001). Helicobacter was found in 41 RA patients and in 33 controls (P=NS). The consumption of NSAIDs conferred a relative risk (RR) of ulceration of 8.67 (1.19-62.87), while the presence of Helicobacter gave a RR for ulcers of 3.71 (0.37-37.35) in RA patients. The RR for the combination of NSAID consumption and Helicobacter colonisation was 14.44 (2.05-101). The corresponding RRs for the dyspeptic controls were 2.13, 1.57 and 1.42 (all P=NS). CONCLUSIONS: Rheumatoid patients have more major and more multiple pathology than age-, sex- and symptom-matched controls. This is due mainly to their increased consumption of NSAIDs. The prevalence of Helicobacter was no greater in RA patients than in controls, but Helicobacter infection increased the risk of NSAID-induced ulceration.

Community-based watershed management (CBWM) has gained prominence in developing world towards integrated resource management for livelihood enhancement of the poor, due to failure of large-scale river valley projects. This paradigm shift has enabled to narrow the divide between the state and community, and marks a beginning for the State towards a "learning organisation" that is adaptive to the changing social and environmental condition. The paper examines the role of State in institutionalising CBWM in three Indian states. It calls for the State to create an enabling institutional environment for coordination among institutions to emerge by devolving adequate responsibilities. This would offer opportunities for institutions to negotiate their concerns and build credibility for a long lasting institutional solution towards integrating resource management.