[MxyR of Mycobacterium tuberculosis Responds to Xylan; an Unusual Ligand for a MarR Family Transcriptional Regulator].

Among the repertoire of MarR family transcriptional regulators in Mycobacterium tuberculosis, gene rv3095 (mxyR) encodes Mycobacterial Xylan Regulator, MxyR. Gene mxyR is divergently oriented from a hydrolase (rv3094c), oxidoreductase (rv3093c) and an ABC transporter (rv3092c) and convergently oriented with xylanase (rv3096). Xylanase is commonly used by plant pathogenic microbes where they degrade xylan, the major component of hemicellulose. We have purified the transcriptional regulatory protein encoded by rv3095 and its molecular interactions were studied in detail using electrophoretic mobility shift assay. MxyR interacts with its upstream intergenic region mxyO with high specificity and at a dissociation constant of 5.01 ± 0.017 nM. Notably, this binding is attenuated by specific carbohydrate ligands such as xylan, L-Arabinose and D-Galactose with an IC50 values of 22.7 ± 1.02 ng/µL, 360.8 ± 24.25 ng/µL and 2320.0 ± 96.97 µg/µL, respectively. Consequently, it is evident that this association changes the conformation of the DNA binding helix α4 making the transcriptional regulator incompatible with binding to its cognate DNA, allowing xylanase and other genes to be transcribed. This study establishes the natural ligands of MxyR of M. tuberculosis providing insight on metabolic regulation of the carbohydrate, xylan.

Respirable dust measured downwind during rock dust application.

The Pittsburgh Mining Research Division of the U.S. National Institute for Occupational Safety and Health (NIOSH) conducted underground evaluations in an attempt to quantify respirable rock dust generation when using untreated rock dust and rock dust treated with an anticaking additive. Using personal dust monitors, these evaluations measured respirable rock dust levels arising from a flinger-type application of rock dust on rib and roof surfaces. Rock dust with a majority of the respirable component removed was also applied in NIOSH's Bruceton Experimental Mine using a bantam duster. The respirable dust measurements obtained downwind from both of these tests are presented and discussed. This testing did not measure miners' exposure to respirable coal mine dust under acceptable mining practices, but indicates the need for effective continuous administrative controls to be exercised when rock dusting to minimize the measured amount of rock dust in the sampling device.

Histological Alterations in the Body Wall of the Tropical Earthworm Eudrilus eugeniae Exposed to Hexavalent Chromium.

The tropical earthworm Eudrilus eugeniae was chronically exposed to hexavalent chromium (Cr) in its substrate over a concentration range from 0.24 to 893 mg kg(-1). Histological alterations in the body wall epithelium included cell fusion, reduction in thickness of the epithelial layer, a marked increase in pyknotic nuclei and epithelial sloughing. Similar changes were noted in the circular and longitudinal muscles with damage being indicated by the prominent inter-muscular cell spaces and disintegration. Many of these noted alterations intensified with increasing levels of exposure. It is significant that some of the changes recorded here were evident even at the lowest concentration of 0.24 mg kg(-1), an environmentally relevant concentration. Hence, the observed trends could be taken as an early warning to the imminent threats of heavy metal pollution to epigeic earthworm species.

Ecological ramifications of marine debris in mangrove ecosystems: Estimation of substrate coverage and physical effects of marine debris on mangrove ecosystem in Negombo Lagoon, Sri Lanka.

The adverse environmental impacts on mangrove ecosystems due to anthropogenic marine debris contamination have attracted public attention not only in Sri Lanka but worldwide. Therefore, quantification of marine debris in sensitive ecosystems like mangroves is critical to assess the impacts on ecosystem vitality and services. We conducted this study to assess the abundance and density of marine debris in Negombo lagoon, Western Province, Sri Lanka. We selected two sites (n = 2) using the purposive sampling technique. Marine debris cover and concentration were calculated to explore the extent of pollution from marine debris. The findings revealed that 9.83 ± 1.05 % of the substrate of the mangrove ecosystem is covered by debris. Nine types of marine debris were recorded, and a higher abundance belonged to single-use plastic items. A significantly higher debris cover was found in Kadolkele (18.80 ± 1.74 %, n = 120) than in Molekadolwetiya (0.85 ± 0.03 %, n = 120) (One-way ANOVA, p < 0.05). The study indicated that the mangroves in lagoon are highly polluted with marine debris and act as "litter catchers." Correlation coefficient analysis was used to find the impact of debris cover on physical damage to roots, seedlings, and undergrowth vegetation. Correlation analysis revealed that physical damage to seedlings and branches/barks have a positive correlation with debris cover. To conserve these valuable coastal habitats in Negombo lagoon, it is recommended to take remedial measures to reduce arriving debris loads and to remove the debris present in mangroves.

Enhanced sentiment extraction architecture for social media content analysis using capsule networks.

Recent research has produced efficient algorithms based on deep learning for text-based analytics. Such architectures could be readily applied to text-based social media content analysis. The deep learning techniques, which require comparatively fewer resources for language modeling, can be effectively used to process social media content data that change regularly. Convolutional Neural networks and recurrent neural networks based approaches have reported prominent performance in this domain, yet their limitations make them sub-optimal. Capsule networks sufficiently warrant their applicability in language modelling tasks as a promising technique beyond their initial usage of image classification. This study proposes an approach based on capsule networks for social media content analysis, especially for Twitter. We empirically show that our approach is optimal even without the use of any linguistic resources. The proposed architectures produced an accuracy of 86.87% for the Twitter Sentiment Gold dataset and an accuracy of 82.04% for the CrowdFlower US Airline dataset, indicating state-of-the-art performance. Hence, the research findings indicate noteworthy accuracy enhancement for text processing within social media content analysis.

Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes.

Antigen-specific immunotherapy is an immunomodulatory strategy for autoimmune diseases, such as type 1 diabetes, in which patients are treated with autoantigens to promote immune tolerance, stop autoimmune ß-cell destruction and prevent permanent dependence on exogenous insulin. In this study, human proinsulin peptide C19-A3 (known for its positive safety profile) was conjugated to ultrasmall gold nanoparticles (GNPs), an attractive drug delivery platform due to the potential anti-inflammatory properties of gold. We hypothesised that microneedle intradermal delivery of C19-A3 GNP may improve peptide pharmacokinetics and induce tolerogenic immunomodulation and proceeded to evaluate its safety and feasibility in a first-in-human trial. Allowing for the limitation of the small number of participants, intradermal administration of C19-A3 GNP appears safe and well tolerated in participants with type 1 diabetes. The associated prolonged skin retention of C19-A3 GNP after intradermal administration offers a number of possibilities to enhance its tolerogenic potential, which should be explored in future studies.

The imaging features of MACROLANE™ in breast augmentation.

Macrolane™ is an injectable, biocompatible, soft-tissue filler that has been available in the UK since 2008 and is promoted for use in breast augmentation. There are few data available on the long-term effects of this relatively new product and concerns have been raised about the implications for breast imaging, in particular breast screening. In this context we present a spectrum of imaging appearances and complications encountered to date.

Incidence of metastasis to level V lymph nodes in clinically positive necks among Sri Lankan patients with oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) remains the most common cancer among males in Sri Lanka. Metastasis to neck is a crucial prognostic factor. A modified radical/radical neck dissection including levels I -V, was performed in patients with OSCC who had a clinically positive neck (cN+). Currently, evidence suggests that sparing level V in a cN+ may be justified due to less chance of metastasis in early stages of the disease. To the best of our knowledge, the incidence of metastasis to level V in patients with cN+s has not been previously investigated in a Sri Lankan context. We aimed to determine level V lymph node metastasis and related clinicopathological indicators in cN+s in patients with OSCC. A multicentre retrospective study investigated postoperative biopsy reports of 187 patients for five years. OSCC patients with cN+s who underwent neck dissections of levels I-V were included. Only 6.4% of patients had histopathologically positive level V lymph nodes. A total of 127 lymph nodes were harvested from level V of those who showed level V positivity and out of them 68 were positive with a third of cases showing extranodal extension (ENE). The buccal mucosa (n=4) and lateral aspect of the anterior two thirds of the tongue (n=4) were the common primary sites for level V metastasis. In patients who showed positivity in levels III and IV, a considerably higher probability of level V nodes being positive was seen, which was statistically significant (p = 0.0001). We have concluded that the routine performance of a modified radical/radical neck dissection for cN+s should be stopped, as the incidence of Level V positivity is significantly low. Assessing the cN+ for N stage, status of levels III and IV, pattern of invasion, differentiation, and the site may be used instead as predictors for level V positivity.

Social inequality in perceived oral health among Sri Lankan adolescents.

OBJECTIVES: to assess socio-economic inequalities in two perceived oral health outcomes namely perceived oral health status and perceived oral impacts among adolescents in Sri Lanka. DESIGN: A cross-sectional study where the data where collected by means of structured questionnaires to the children and their parents. PARTICIPANTS: A total 1,225 15-year-old adolescents attending state, private and international schools in the Colombo district of Sri Lanka. RESULTS: Inverse social gradients in perceived oral health status and perceived oral impacts were observed in relation to six socioeconomic indicators in the bivariate analyses. Adolescents from lower social positions had significantly reported more oral impacts and had rated their oral health as poor. But it was mainly the indicators of family material affluence that emerged as significant predictors of perceived oral health outcomes in the logistic regression analyses. CONCLUSION: The study demonstrates the existence of significant social gradients in perceived oral health outcomes among adolescents from a developing country. Further studies to assess causes of social gradients in perceived oral health outcomes are recommended.

Synthesis of cellulose microcrystals (CMC)/nylon 6,10 composite by incorporating CMC isolated from Pandanus ceylanicus.

The paper presents a novel candidate plant: Pandanus ceylanicus (PC) for cellulose extraction. The plant showed an average of 91.5 ±â€¯0.2 % of cellulose yield which is the highest yield for Pandanus species reported. Cellulose was extracted from the leaves of the plant by carrying out alkali and bleaching treatments, and cellulose microcrystals (CMC) were isolated from extracted cellulose fibers with sulphuric acid treatment. Chemical composition of PC leaves was investigated at different stages of treatment by using TAPPI standard methods. The extracted globular shaped CMC crystals had an average diameter less than a micro meter. Results revealed that PC leaves are an efficient source of micro-cellulose which result in a high yield than most lignocellulosic biomasses. The CMCs were successfully incorporated with nylon 6,10 by in-situ interfacial polymerization of sebacoyl chloride and hexamethylenediamine in the presence of CMC. The CMC/nylon 6,10 composite showed improved water absorption with low water retention time.

Development of a psychometric scale to assess satisfaction with dental care among Sri Lankans.

OBJECTIVE: To develop and validate a psychometric scale to assess dental satisfaction among Sri Lankans. DESIGN: A population based cross sectional study, where the data were collected by a postal questionnaire. A 22-item scale was developed to measure dental satisfaction. PARTICIPANTS: 1,000 Sri Lankans aged 18-75 years, selected by cluster sampling with probability proportionate to size technique, using National Voters' register. OUTCOME MEASURES: Reliability of the scale was assessed by internal consistency using Cronbach's alpha and corrected item-total correlations. Construct validity was determined by factor analysis and acceptability was assessed by percentage of item-specific non-response. RESULTS: The overall response rate was 30.9%. Among respondents, analysis was limited to dental care users within two years (n=117). Item-specific non-response was low, ranging from 3.4% to 9.4%. Four (negatively worded) items were removed from the scale due to poor internal consistency (corrected item-total correlations <0.2). After removal, corrected item-total correlations of remaining 18 items were improved, ranging from 0.23 to 0.76. Factor analysis revealed a four factor solution, interpreted as: "outcome of care/clinic context" (8-items), 'factors related to treatment process" (7-items), "convenience" (2-items) and "cost of care" (single item). Identified factors explained 64.56% of the variance of the scale. The Cronbach's alpha values for the first three dimensions were 0.90, 0.87 and 0.60 respectively and for the overall construct it was 0.91. CONCLUSIONS: The present scale appeared to be a valid and reliable instrument for measuring dental satisfaction among Sri Lankans, but merits further refinements to explore detailed aspects of it.

Clinical Validation of Eye Vergence as an Objective Marker for Diagnosis of ADHD in Children.

OBJECTIVE: ADHD youth show poor oculomotor control. Recent research shows that attention-related eye vergence is weak in ADHD children. METHOD: To validate vergence as a marker to classify ADHD, we assessed the modulation in the angle of vergence of children ( n = 43) previously diagnosed with ADHD while performing an attention task and compared the results with age-matched clinical controls ( n = 19) and healthy peers ( n = 30). RESULTS: We observed strong vergence responses in healthy participants and weak vergence in the clinical controls. ADHD children showed no significant vergence responses. Machine-learning models classified ADHD patients ( n = 21) from healthy controls ( n = 21) with an accuracy of 96.3% (false positive [FP]: 5.12%; false negative [FN]: 0%; area under the curve [AUC]: 0.99) and ADHD children ( n = 11) from clinical controls ( n = 14) with an accuracy of 85.7% (FP: 4.5%; FN: 19.2%, AUC: 0.90). CONCLUSION: In combination with an attention task, vergence responses can be used as an objective marker to detect ADHD in children.

Social gradient in dental caries among adolescents in Sri Lanka.

The aim of the present study was to assess the social inequality in dental caries among adolescents in Sri Lanka. A total of 1,225 15-year-olds were selected using a stratified cluster sampling technique from schools in the Colombo district. The data were collected by means of an oral examination and questionnaires to both children and their parents. There were statistically significant inverse gradients between caries prevalence, caries experience (DMFS) and all five socio-economic indicators considered. Maternal education and family affluence emerged as significant predictors of dental caries. The magnitude of social inequality in dental caries was assessed using the slope index of inequality (SII) and the concentration index based on the concentration curve. SII for all socio-economic indicators were negative and, except in relation to father's occupation, they were statistically significant. With the socio-economic groups ordered from the lowest to the highest, a negative SII indicates that caries experience decreased with improving socio-economic status. The concentration index for DMFS was negative (-0.111) and statistically significant, indicating disproportionate concentration of dental caries among the poor children. In conclusion, this study has shown the existence of a social gradient with respect to dental caries among adolescents in Sri Lanka and it also illustrates the use of SII and concentration index as tools to determine the magnitude of social inequality in dental caries.

Inflammatory Bacteriome and Oral Squamous Cell Carcinoma.

Results from microbiome studies on oral cancer have been inconsistent, probably because they focused on compositional analysis, which does not account for functional redundancy among oral bacteria. Based on functional prediction, a recent study revealed enrichment of inflammatory bacterial attributes in oral squamous cell carcinoma (OSCC). Given the high relevance of this finding to carcinogenesis, we aimed here to corroborate them in a case-control study involving 25 OSCC cases and 27 fibroepithelial polyp (FEP) controls from Sri Lanka. DNA extracted from fresh biopsies was sequenced for the V1 to V3 region with Illumina's 2 × 300-bp chemistry. High-quality nonchimeric merged reads were classified to the species level with a prioritized BLASTN-based algorithm. Downstream compositional analysis was performed with QIIME (Quantitative Insights into Microbial Ecology) and linear discriminant analysis effect size, while PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) was utilized for bacteriome functional prediction. The OSCC tissues tended to have lower species richness and diversity. Genera Capnocytophaga, Pseudomonas, and Atopobium were overrepresented in OSCC, while Lautropia, Staphylococcus, and Propionibacterium were the most abundant in FEP. At the species level, Campylobacter concisus, Prevotella salivae, Prevotella loeschii, and Fusobacterium oral taxon 204 were enriched in OSCC, while Streptococcus mitis, Streptococcus oral taxon 070, Lautropia mirabilis, and Rothia dentocariosa among others were more abundant in FEP. Functionally, proinflammatory bacterial attributes, including lipopolysaccharide biosynthesis and peptidases, were enriched in the OSCC tissues. Thus, while the results in terms of species composition significantly differed from the original study, they were consistent at the functional level, substantiating evidence for the inflammatory nature of the bacteriome associated with OSCC.

Inositol signaling and plant growth.

Living organisms have evolved to contain a wide variety of receptors and signaling pathways that are essential for their survival in a changing environment. Of these, the phosphoinositide pathway is one of the best conserved. The ability of the phosphoinositides to permeate both hydrophobic and hydrophilic environments, and their diverse functions within cells have contributed to their persistence in nature. In eukaryotes, phosphoinositides are essential metabolites as well as labile messengers that regulate cellular physiology while traveling within and between cells. The stereospecificity of the six hydroxyls on the inositol ring provides the basis for the functional diversity of the phosphorylated isomers that, in turn, generate a selective means of intracellular and intercellular communication for coordinating cell growth. Although such complexity presents a difficult challenge for bench scientists, it is ideal for the regulation of cellular functions in living organisms.

Histidine switch controlling pH-dependent protein folding and DNA binding in a transcription factor at the core of synthetic network devices.

Therapeutic strategies have been reported that depend on synthetic network devices in which a urate-sensing transcriptional regulator detects pathological levels of urate and triggers production or release of urate oxidase. The transcription factor involved, HucR, is a member of the multiple antibiotic resistance (MarR) protein family. We show that protonation of stacked histidine residues at the pivot point of long helices that form the scaffold of the dimer interface leads to reversible formation of a molten globule state and significantly attenuated DNA binding at physiological temperatures. We also show that binding of urate to symmetrical sites in each protein lobe is communicated via the dimer interface. This is the first demonstration of regulation of a MarR family transcription factor by pH-dependent interconversion between a molten globule and a compact folded state. Our data further suggest that HucR may be utilized in synthetic devices that depend on detection of pH changes.

Factors associated with perceived oral health status in older individuals.

AIM: To assess factors associated with perception of oral health in older individuals. DESIGN: A cross sectional study. SETTING: A densely populated urban area in Sri Lanka. PARTICIPANTS: 585 older adults aged 60 years and above of which 475 were living at home and 110 in institutions. The present analysis is limited to 235 subjects who were subjected to a clinical oral examination. METHOD: The data were collected by means of an interviewer-administered questionnaire and a clinical oral examination. RESULTS: Overall, 48% of the dentate and 42% of the edentate perceived their oral health as poor. The final model of the hierarchical logistic regression analysis for the dentate revealed that presence of retained roots, mobile teeth, >20 missing teeth and perceived need for dental care were significantly associated with poor perceived oral health status. For the edentate, perceived need for dental care, loss of taste sensation and difficulty in eating were significantly associated with poor perceived oral health status. CONCLUSIONS: Factors associated with perceived oral health status differed between the dentate and the edentate. Clinical oral health indicators emerged as significant predictors of perceived oral health status in the dentate although the explanatory power of these indicators on perception of oral health was low.