36 research outputs found
Parameterization and classification of the protein universe via geometric techniques
No full textWe present a scheme for the classification of 3487 non-redundant protein structures into 1207 non-hierarchical clusters by using recurring structural patterns of three to six amino acids as keys of classification. This results in several signature patterns, which seem to decide membership of a protein in a functional category. The patterns provide clues to the key residues involved in functional sites as well as in protein–protein interaction. The discovered patterns include a “glutamate double bridge ” of superoxide dismutase, the functional interface of the serine protease and inhibitor, interface of homo/hetero dimers, and functional sites of several enzyme families. We use geometric invariants to decide superimposability of structural patterns. This allows the parameterization of patterns and dis-covery of recurring patterns via clustering. The geometric invariant-based approach eliminates the computationally explosive step of pair-wise com-parison of structures. The results provide a vast resource for the biologists for experimental validation of the proposed functional sites, and for the design of synthetic enzymes, inhibitors and drugs
Frequencies of hepatitis B and C infections among haemodialysis and peritoneal dialysis patients in Asia-Pacific countries: analysis of registry data
No full textBackground: The impact of dialysis modality on the rates and types of infectious complications has not been well studied. The aim of the present investigation was to evaluate the rates of hepatitis C virus (HCV) and hepatitis B virus (HBV) infections in peritoneal dialysis (PD) and haemodialysis (HD) patients in the Asia-Pacific region. Methods: The study included the most recent period-prevalent data recorded in the national or regional dialysis registries of the 10 Asia-Pacific countries/areas (Australia, New Zealand, Japan, China, Taiwan, Korea, Thailand, Hong Kong, Malaysia and India), where such data were available. Longitudinal data were also available for all incident Australian and New Zealand patients commencing dialysis between 1 April 1995 and 31 December 2005. Rates of HCV and HBV infections were compared by chi-square, Poisson regression and Kaplan–Meier survival analyses, as appropriate. Results: Data were obtained on 201 590 patients (HD 173 788; PD 27 802). HCV seroprevalences ranged between 0.7% and 18.1% across different countries and were generally higher in HD versus PD populations (7.9% ± 5.5% versus 3.0% ± 2.0%, P = 0.01). Seroconversion rates on dialysis were also significantly higher in HD patients (incidence rate ratio PD versus HD 0.33, 95% CI 0.13–0.75). HCV infection was highly predictive of mortality in Japan (relative risk 1.37, 95% CI 1.15–1.62, P = 0.003) and in Australia and New Zealand (adjusted hazards ratio 1.29, 95% CI 1.05–1.58). HBV infection data were limited, but less clearly influenced by dialysis modality. Conclusions: Dialysis modality selection significantly influences the risk of HCV infection experienced by end-stage renal failure patients in the Asia-Pacific region. No such association could be identified for HBV infection.David W. Johnson, Hannah Dent, Qiang Yao, Anders Tranaeus, Chiu-Chin Huang, Dae-Suk Han, Vivekanand Jha, Tao Wang, Yoshindo Kawaguchi and Jiaqi Qian
The impact of CKD identification in large countries: The burden of illness
No full textChronic kidney disease (CKD) is becoming a major public health issue worldwide and an important contributor to the overall non-communicable disease burden. It is associated with major serious consequences including increased risk of mortality, end-stage renal disease, accelerated cardiovascular disease (CVD), mineral and bone disease, adverse metabolic and nutritional consequences, infections, reduced cognitive function and increased risk of acute kidney injury. Mortality from CVD is estimated to be at least 8-to 10-fold higher in CKD subjects compared to non-CKD subjects. Estimates from different parts of the world, especially large countries, reveal an increasing incidence and prevalence of CKD. This is partly attributed to the global increasing prevalence of diabetes, hypertension, obesity and CVD. The global economic impact of CKD is tremendous. This calls for the need of a global effort to raise awareness of CKD, to incorporate prevention of CKD progression program in the public health agenda and to implement programs for early screening and detection of CKD, especially in high-risk population so to allow early institution of treatment to prevent further CKD progression. Hopefully, by doing so, we may reduce CKD burden globally over time and, most importantly, improve the health outcomes of patients with CKD. © 2012 The Author.link_to_OA_fulltex
Accurate Demarcation of Protein Domain Linkers Based on Structural Analysis of Linker Probable Region
Get PDFIn multi-domainproteins, the domainsare connected by a flexible unstructured region called as protein domain linker. The accurate demarcation of these linkers holds a key to understanding of their biochemical and evolutionary attributes. This knowledge helps in designing a suitable linker for engineering stable multi-domain chimeric proteins. Here we propose a novel method for the demarcation of the linker based on a three-dimensional protein structure and a domain definition. The proposed method is based on biological knowledge about structural flexibility of the linkers. We performed structural analysis on a linker probable region (LPR) around domain boundary points of known SCOP domains. The LPR was described using a set of overlapping peptide fragments of fixed size. Each peptide fragment was then described by geometricinvariants (GIs) and subjected to clustering process where the fragments corresponding to actual linker comeupasoutliers.We then discover the actual linkers by finding the longest continuous stretch ofoutlier fragments from LPRs. This method was evaluated on a benchmark dataset of 51 continuous multi-domain proteins, where it achieves F1 score of 0.745 (0.83precision and 0.66recall). When the method was applied on 725 continuous multi-domain proteins, it was able to identify novel linkers that were not reported previously. This method can be used in combination with supervised /sequence based linker prediction methods for accurate linker demarcation.
A founder mutation in the GMPPB gene [c.1000G > A (p.Asp334Asn)] causes a mild form of limb-girdle muscular dystrophy/congenital myasthenic syndrome (LGMD/CMS) in South Indian patients
No full text\ua9 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.Twelve patients from seven unrelated South Indian families with a limb-girdle muscular dystrophy-congenital myasthenic syndrome (LGMD/CMS) phenotype and recessive inheritance underwent deep clinical phenotyping, electrophysiological evaluation, muscle histopathology, and next-generation sequencing/Sanger sequencing–based identification of the genetic defect. Homozygosity mapping was performed using high-throughput genome-wide genotyping for mapping the mutation and to evaluate the founder effect. The age of disease onset among patients ranged from childhood to 40 years of age. The key clinical manifestations observed were progressive fatigable limb-girdle weakness, muscle hypertrophy/atrophy, and preferential weakness in a dystrophic pattern. The ages at last follow-up ranged from 30 to 64 years; nine were independently ambulant, two required assistance, and one was wheelchair-bound. Lower limb muscle MRI showed varying degrees of fat replacement in the glutei, hamstrings, anterior leg muscles, and medial gastrocnemius. All patients showed significant decrement on repetitive nerve stimulation (RNS). Muscle biopsy in 7 patients revealed varying degrees of dystrophic and neurogenic changes. Treatment with pyridostigmine and/or salbutamol resulted in variable improvement in 10 patients. Genetic analysis showed an identical homozygous GMPPB mutation c.1000G > A (p.Asp334Asn) in all affected patients. A region of homozygosity (6Mbp) was observed flanking the c.1000G > A change in carrier chromosomes. This study identifies c.1000G > A in GMPPB as a common founder mutation in an ethnic community of South Indian descent with milder yet variable degree of clinical presentation of GMPPB-associated LGMD-CMS
Department of Error: Mapping geographical inequalities in childhood diarrhoeal morbidity and mortality in low-income and middle-income countries, 2000–17: analysis for the Global Burden of Disease Study 2017 (The Lancet (2020) 395(10239) (1779–1801), (S0140673620301148), (10.1016/S0140-6736(20)30114-8))
Get PDFReiner RC Jr, Hay SI. Mapping geographical inequalities in childhood diarrhoeal morbidity and mortality in low-income and middle-income countries, 2000–17: analysis for the Global Burden of Disease Study 2017. Lancet 2020; 395: 1779–801—In this Article, the author byline has been amended to Local Burden of Disease Diarrhoea Collaborators. This correction has been made to the online version as of June 4, 2020, and the printed version is correct
Chronic kidney disease: Global dimension and perspectives
No full textSummary Chronic kidney disease is defined as a reduced glomerular filtration rate, increased urinary albumin excretion, or both, and is an increasing public health issue. Prevalence is estimated to be 8-16% worldwide. Complications include increased all-cause and cardiovascular mortality, kidney-disease progression, acute kidney injury, cognitive decline, anaemia, mineral and bone disorders, and fractures. Worldwide, diabetes mellitus is the most common cause of chronic kidney disease, but in some regions other causes, such as herbal and environmental toxins, are more common. The poorest populations are at the highest risk. Screening and intervention can prevent chronic kidney disease, and where management strategies have been implemented the incidence of end-stage kidney disease has been reduced. Awareness of the disorder, however, remains low in many communities and among many physicians. Strategies to reduce burden and costs related to chronic kidney disease need to be included in national programmes for non-communicable diseases. © 2013 Elsevier Ltd.link_to_subscribed_fulltex
Author Correction: Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017
No full textReport of the asian forum of chronic kidney disease initiative (AFCKDI) 2007. "current status and perspective of CKD in asia": Diversity and specificity among asian countries
No full textClinical and Experimental Nephrology133249-25
Characterising acute and chronic care needs: insights from the Global Burden of Disease Study 2019
No full textChronic care manages long-term, progressive conditions, while acute care addresses short-term conditions. Chronic conditions increasingly strain health systems, which are often unprepared for these demands. This study examines the burden of conditions requiring acute versus chronic care, including sequelae. Conditions and sequelae from the Global Burden of Diseases Study 2019 were classified into acute or chronic care categories. Data were analysed by age, sex, and socio-demographic index, presenting total numbers and contributions to burden metrics such as Disability-Adjusted Life Years (DALYs), Years Lived with Disability (YLD), and Years of Life Lost (YLL). Approximately 68% of DALYs were attributed to chronic care, while 27% were due to acute care. Chronic care needs increased with age, representing 86% of YLDs and 71% of YLLs, and accounting for 93% of YLDs from sequelae. These findings highlight that chronic care needs far exceed acute care needs globally, necessitating health systems to adapt accordingly.
© 2025. The Author(s)
