Pex7p translocates in and out of peroxisomes in Saccharomyces cerevisiae

Pex7p is the soluble receptor responsible for importing into peroxisomes newly synthesized proteins bearing a type 2 peroxisomal targeting sequence. We observe that appending GFP to Pex7p's COOH terminus shifts Pex7p's intracellular distribution from predominantly cytosolic to predominantly peroxisomal in Saccharomyces cerevisiae. Cleavage of the link between Pex7p and GFP within peroxisomes liberates GFP, which remains inside the organelle, and Pex7p, which exits to the cytosol. The reexported Pex7p is functional, resulting in import of thiolase into peroxisomes and improved growth of the yeast on oleic acid. These results support the “extended shuttle” model of peroxisome import receptor function and open the way to future studies of receptor export

Molecular analysis of the LDLR gene in coronary artery disease patients from the Indian population

BACKGROUND: Cardiovascular disease is a leading cause of mortality in Indian population. Mutations in LDLR, APOB and PCSK9 genes may lead to Familial Hypercholesterolemia, an autosomal dominant disorder which in turn leads to cardiovascular diseases. The primary objective of this study is to analyze these genes in CAD patients of Indian population. METHODS: A total of 30 patients were selected out of 300 CAD patients based on UK-Simon Broome criteria from South India. The gDNA was isolated by organic extraction method and the exons and exon-intron boundaries of LDLR gene, APOB (exon 26) and PCSK9 (exon 7) were screened by PCR-high resolution melt analysis. The amplicons showing shift in melting pattern were sequenced to find out the variation. RESULTS: This study reports three novel variations, an intronic deletion c.694+8_694+18del in intron 4, a synonymous variation c.966 C>T [p. (N322=)] in exon 7 and a deletion insertion c.1399_1340delinsTA [p. (T467Y)] in exon 10, two recurrent variations c.862G>A [p. (E288K)] in exon 6 and a splice site variation c.1845+2T>C in exon-intron junction of exon 12 in LDLR gene and PCSK9 gene had c.1180+17C>T change in intron 7. However there are no pathogenic variations in APOB and PCSK9 genes in Indian population. In silico analysis predicted all the variations as pathogenic except the synonymous variation. CONCLUSION: This report adds five new variations to the spectrum of LDLR variations in Indian population. This study also suggests that UK Simon Broom criteria can be followed to categorize FH patients in Indian population

Cdc37 has distinct roles in protein kinase quality control that protect nascent chains from degradation and promote posttranslational maturation

Cdc37 is a molecular chaperone that functions with Hsp90 to promote protein kinase folding. Analysis of 65 Saccharomyces cerevisiae protein kinases (∼50% of the kinome) in a cdc37 mutant strain showed that 51 had decreased abundance compared with levels in the wild-type strain. Several lipid kinases also accumulated in reduced amounts in the cdc37 mutant strain. Results from our pulse-labeling studies showed that Cdc37 protects nascent kinase chains from rapid degradation shortly after synthesis. This degradation phenotype was suppressed when cdc37 mutant cells were grown at reduced temperatures, although this did not lead to a full restoration of kinase activity. We propose that Cdc37 functions at distinct steps in kinase biogenesis that involves protecting nascent chains from rapid degradation followed by its folding function in association with Hsp90. Our studies demonstrate that Cdc37 has a general role in kinome biogenesis

Role of Alanine Racemase Mutations in Mycobacterium tuberculosis d-Cycloserine Resistance.

A screening of more than 1,500 drug-resistant strains of Mycobacterium tuberculosis revealed evolutionary patterns characteristic of positive selection for three alanine racemase (Alr) mutations. We investigated these mutations using molecular modeling, in vitro MIC testing, as well as direct measurements of enzymatic activity, which demonstrated that these mutations likely confer resistance to d-cycloserine

Prevalence of rheumatoid arthritis in low– and middle–income countries: A systematic review and analysis

Background: Rheumatoid arthritis (RA) is an autoimmune disorder that affects the small joints of the body. It is one of the leading causes of chronic morbidity in high–income countries, but little is known about the burden of this disease in low– and middle–income countries (LMIC). Methods: The aim of this study was to estimate the prevalence of RA in six of the World Health Organization's (WHO) regions that harbour LMIC by identifying all relevant studies in those regions. To accomplish this aim various bibliographic databases were searched: PubMed, EMBASE, Global Health, LILACS and the Chinese databases CNKI and WanFang. Studies were selected based on pre–defined inclusion criteria, including a definition of RA based on the 1987 revision of the American College of Rheumatology (ACR) definition. Results: Meta–estimates of regional RA prevalence rates for countries of low or middle income were 0.40% (95% CI: 0.23–0.57%) for Southeast Asian, 0.37% (95% CI: 0.23–0.51%) for Eastern Mediterranean, 0.62% (95% CI: 0.47–0.77%) for European, 1.25% (95% CI: 0.64–1.86%) for American and 0.42% (95% CI: 0.30–0.53%) for Western Pacific regions. A formal meta–analysis could not be performed for the sub–Saharan African region due to limited data. Male prevalence of RA in LMIC was 0.16% (95% CI: 0.11–0.20%) while the prevalence in women reached 0.75% (95% CI: 0.60–0.90%). This difference between males and females was statistically significant (P < 0.0001). The prevalence of RA did not differ significantly between urban and rural settings (P = 0.353). These prevalence estimates represent 2.60 (95% CI: 1.85–3.34%) million male sufferers and 12.21 (95% CI: 9.78–14.67%) million female sufferers in LMIC in the year 2000, and 3.16 (95% CI: 2.25–4.05%) million affected males and 14.87 (95% CI: 11.91–17.86%) million affected females in LMIC in the year 2010. Conclusion: Given that majority of the world’s population resides in LMIC, the number of affected people is substantial, with a projection to increase in the coming years. Therefore, policy makers and health–care providers need to plan to address a significant disease burden both socially and economically

CURATION AND MANAGEMENT OF CULTURAL HERITAGE THROUGH LIBRARIES

Libraries, museums and archives hold valuable collections in a variety of media, presenting a vast body of knowledge rooted in the history of human civilisation. These form the repository of the wisdom of great works by thinkers of past and the present. The holdings of these institutions are priceless heritage of the mankind as they preserve documents, ideas, and the oral and written records. To value the cultural heritage and to care for it as a treasure bequeathed to us by our ancestors is the major responsibility of libraries. The past records constitute a natural resource and are indispensable to the present generation as well as to the generations to come. Libraries preserve the documentary heritage resources for which they are primarily responsible. Any loss of such materials is simply irreplaceable. Therefore, preserving this intellectual, cultural heritage becomes not only the academic commitment but also the moral responsibility of the librarians/information scientists, who are in charge of these repositories. The high quality of the papers and the discussion represent the thinking and experience of experts in their particular fields. The contributed papers also relate to the methodology used in libraries in Asia to provide access to manuscripts and cultural heritage. The volume discusses best practices in Knowledge preservation and how to collaborate and preserve the culture. The book also deals with manuscript and archives issues in the digital era. The approach of this book is concise, comprehensively, covering all major aspects of preservation and conservation through libraries. The readership of the book is not just limited to library and information science professionals, but also for those involved in conservation, preservation, restoration or other related disciplines. The book will be useful for librarians, archivists and conservators. We thank the Sunan Kalijaga University, Special Libraries Association- Asian Chapter for their trust and their constant support, all the contributors for their submissions, the members of the Local and International Committee for their reviewing effort for making this publication possible

Bronchiectasis in India:results from the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) and Respiratory Research Network of India Registry

BACKGROUND: Bronchiectasis is a common but neglected chronic lung disease. Most epidemiological data are limited to cohorts from Europe and the USA, with few data from low-income and middle-income countries. We therefore aimed to describe the characteristics, severity of disease, microbiology, and treatment of patients with bronchiectasis in India. METHODS: The Indian bronchiectasis registry is a multicentre, prospective, observational cohort study. Adult patients ( 6518 years) with CT-confirmed bronchiectasis were enrolled from 31 centres across India. Patients with bronchiectasis due to cystic fibrosis or traction bronchiectasis associated with another respiratory disorder were excluded. Data were collected at baseline (recruitment) with follow-up visits taking place once per year. Comprehensive clinical data were collected through the European Multicentre Bronchiectasis Audit and Research Collaboration registry platform. Underlying aetiology of bronchiectasis, as well as treatment and risk factors for bronchiectasis were analysed in the Indian bronchiectasis registry. Comparisons of demographics were made with published European and US registries, and quality of care was benchmarked against the 2017 European Respiratory Society guidelines. FINDINGS: From June 1, 2015, to Sept 1, 2017, 2195 patients were enrolled. Marked differences were observed between India, Europe, and the USA. Patients in India were younger (median age 56 years [IQR 41-66] vs the European and US registries; p&lt;0\ub70001]) and more likely to be men (1249 [56\ub79%] of 2195). Previous tuberculosis (780 [35\ub75%] of 2195) was the most frequent underlying cause of bronchiectasis and Pseudomonas aeruginosa was the most common organism in sputum culture (301 [13\ub77%]) in India. Risk factors for exacerbations included being of the male sex (adjusted incidence rate ratio 1\ub717, 95% CI 1\ub703-1\ub732; p=0\ub7015), P aeruginosa infection (1\ub729, 1\ub710-1\ub750; p=0\ub7001), a history of pulmonary tuberculosis (1\ub720, 1\ub707-1\ub734; p=0\ub7002), modified Medical Research Council Dyspnoea score (1\ub732, 1\ub725-1\ub739; p&lt;0\ub70001), daily sputum production (1\ub716, 1\ub703-1\ub730; p=0\ub7013), and radiological severity of disease (1\ub703, 1\ub701-1\ub704; p&lt;0\ub70001). Low adherence to guideline-recommended care was observed; only 388 patients were tested for allergic bronchopulmonary aspergillosis and 82 patients had been tested for immunoglobulins. INTERPRETATION: Patients with bronchiectasis in India have more severe disease and have distinct characteristics from those reported in other countries. This study provides a benchmark to improve quality of care for patients with bronchiectasis in India. FUNDING: EU/European Federation of Pharmaceutical Industries and Associations Innovative Medicines Initiative inhaled Antibiotics in Bronchiectasis and Cystic Fibrosis Consortium, European Respiratory Society, and the British Lung Foundation

Synthesis, isomerisation and biological properties of mononuclear ruthenium complexes containing the bis[4(4 '-methyl-2,2 '-bipyridyl)]-1,7-heptane ligand

A series of mononuclear ruthenium(II) complexes containing the tetradentate ligand bis[4(4’-methyl-2,2’- bipyridyl)]-1,7-heptane have been synthesised and their biological properties examined. In the synthesis of the [Ru(phen’)(bb7)]2+ complexes (where phen’ = 1,10-phenanthroline and its 5-nitro-, 4,7-dimethyland 3,4,7,8-tetramethyl- derivatives), both the symmetric cis-α and non-symmetric cis-β isomers were formed. However, upon standing for a number of days (or more quickly under harsh conditions) the cis-β isomer converted to the more thermodynamically stable cis-α isomer. The minimum inhibitory concentrations (MIC) and the minimum bactericidal concentrations (MBC) of the ruthenium(II) complexes were determined against six strains of bacteria: Gram-positive Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA); and the Gram-negative Escherichia coli (E. coli) strains MG1655, APEC, UPEC and Pseudomonas aeruginosa (P. aeruginosa). The results showed that the [Ru(5-NO2phen)- (bb7)]2+ complex had little or no activity against any of the bacterial strains. By contrast, for the other cisα-[Ru(phen’)(bb7)]2+ complexes, the antimicrobial activity increased with the degree of methylation. In particular, the cis-α-[Ru(Me4phen)(bb7)]2+ complex showed excellent and uniform MIC activity against all bacteria. By contrast, the MBC values for the cis-α-[Ru(Me4phen)(bb7)]2+ complex varied considerably across the bacteria and even within S. aureus and E. coli strains. In order to gain an understanding of the relative antimicrobial activities, the DNA-binding affinity, cellular accumulation and water–octanol partition coefficients (log P) of the ruthenium complexes were determined. Interestingly, all the [Ru(phen’)- (bb7)]2+ complexes exhibited stronger DNA binding affinity (Ka ≈ 1 × 107 M−1 ) than the well-known DNAintercalating complex [Ru(phen)2(dppz)]2+ (where dppz = dipyrido[3,2-a:2’,3’-c]phenazine)