The indirect estimation of mutation rates in man

The need for generating reliable estimates of mutation rate in man has been emphasized by a number of geneticists. The present study estimates the rate of mutation at cistron level using data on electromorphs in a number of human populations. The number and frequency of private electromorphs, both rare and polymorphic, have been enumerated in relatively isolated populations from Australia, Papua New Guinea, India and. sub- Saharan Africa. It. is noticed that the recovery of these electrophoretic variants is directly related to the number of genes sampled, the size of the polypeptide subunit electrophoresed and the molecular constraints arising from the assembly of multimeric proteins. Mutation rates in 38 individual populations have been generated in the present study by five different methods. The average estimates of mutation rate obtained by the methods of Kimura and Ohta (1969) and Rothman and Adams (1978) are 5.99x10 ^ and 6.39x10 ^/locus per generation respectively. The estimates by the rare allele methods of Nei (1977) and Chakraborty (1981) and by a new method, suggested in the present study, utilizing singletons, are comparatively smaller, being 4.62x10 2.55x10 ^ and 2.86x10 locus per generation respectively. The estimates of mutation rate generated here show regional/ethnic differences. The significance of these differences, however, cannot be properly evaluated since large standard errors are known to be associated with the estimates of the number of alleles segregating and the population size, two of the parameters indispensible to the indirect approaches. The suggestion of Nei et al. (1976b) regarding the variability in mutation rates of various protein loci has been tested using the data on rare alleles in 12 different human populations. The results indicate the existence of significant correlation between subunit molecular weights and the number and frequency of rare alleles. The present results have indicated the existence of variability in the estimates of mutation rate more or less at the same level as that generated from indirect estimates of "classical" traits. The need for deciding the order of magnitude of mutation rate in man is alive as ever

A PILOT STUDY FOR EVALUATION OF ROLE OF B-MODE ULTRASOUND AND STRAIN ELASTOGRAPHY IN DIFFERENTIATING BENIGN AND MALIGNANT BREAST MASSES

Background: Early detection of malignant lesions is critical key stone for the successful management of breast cancer. Conventional B-mode ultrasound although could not replace the histopathology which is still gold standard, plays an important role in the diagnostic pathways by using the Breast Imaging Reporting and Data System (BIRADS) lexicon (standardized by American College of Radiology [ACR]). Although characterization of solid breast masses by sonography has improved greatly since the early 1990s, specificity remains low and a large number of biopsies result in benign diagnosis. Strain elastography and strain ratio (SR) are recent techniques which may help in increasing the specificity of ultrasound. Methods: The present study was a pilot study aimed to establish a correlation between B-mode ultrasound and strain elastography in differentiating benign and malignant breast masses and to compare the results of B- mode ultrasound and Strain Elastography with fine-needle aspiration cytology/ biopsy findings. It was a prospective study conducted in the Department of Radio-diagnosis of Rajindra Hospital, Patiala. A total of 40 patients who presented with the complaint of palpable breast lump were evaluated with B-Mode Ultrasonography (USG) and Strain elastography (using elastography score [ES] and SR). Results: The study group (40 patients with breast lumps) comprised 38 (95%) female patients and 2 (5%) male patients. Among the group 29 were benign and 11 were malignant. Fibroadenoma followed by fibrocystic disease was the most common benign pathologies and invasive ductal carcinoma followed by Ductal Carcinoma in situ was the most common malignant pathologies. Sensitivity, specificity, and diagnostic accuracy of B-Mode USG in diagnosing palpable breast lump are 72.7%, 86.2%, and 82.5%, respectively, while that of strain elastography in diagnosing palpable breast lump are 81.8%, 93.10%, and 90.0%, respectively. Using strain ratio (SR) only the sensitivity, specificity, and diagnostic accuracy was found to be 93.1%, 100%, and 95% better than B-Mode USG and shear elastography alone separately and combined. The mean SR for a benign mass is 2.00±0.97 and for a malignant mass is 5.40±1.55. Conclusion: Ultrasound elastography (using ES) has a higher sensitivity, specificity and diagnostic accuracy in differentiating benign and malignant breast masses then B mode USG (using BIRADS). Using SR alone has shown better sensitivity, specificity, and diagnostic accuracy but its standalone or in combination diagnostic application has to be followed up with further studies

Australia\u27s health 2006 : the tenth biennial report of the Australian Institute of Health and Welfare

The report shows that Australians generally have good health and are privileged to have a range of health care services available to them. There are stark exceptions to this that can be confronting&mdash;even if well-known already&mdash;notably the generally much poorer health status of Indigenous Australians.Health care service provider and funding arrangements are both increasingly complex and increasingly costly to both individuals and taxpayers. A continuing challenge is how to balance both the complementary and competitive perspectives of government and non-government agencies, professional groups, and small businesses. Overall, national expenditure on health was 9.7% of GDP in 2003&ndash;04; and average health expenditure per person has grown by an average 3.8% each year between 1997&ndash;98 to 2002&ndash;03. Expenditure on aids and appliances, health research and pharmaceuticals contributed more to this growth than other areas.While the ageing of the population is having a significant impact on the number and type of health care services delivered, high quality services for children continue to be a priority. Australia&rsquo;s health 2006 has a special chapter focusing on children and their health. The chapter highlights the fact that while our children are generally very healthy, there are concerns that their ongoing health could be affected by more and more of them becoming overweight or obese. Levels of diabetes are now rising among our children and it is a continuing concern that asthma and mental health problems affect so many of them.<br /

In silico targeting enterotoxin from Staphylococcus aureus with selected flavonoids: Hope for the discovery of natural anti-mastitis agents

Staphylococcus aureus is a facultative anaerobe and catalase-positive bacterium responsible for various skin infections and life-threatening problems, including bacteremia and pneumonia. This bacterium produces a bunch of superantigens in the blood called enterotoxin. This toxin is responsible for food poisoning and toxic shock syndrome. Moreover, Bovine mastitis is also associated with S. aureus. Further, S. aureus related to drug resistance makes the infection more dreadful. Now a day, various natural compounds such as phytochemicals are gaining importance as they are effective against many diseases, including S. aureus infections. The present study used molecular docking of three ligands, i.e., Kaempferol, Apigenin, and Quercetin, with enterotoxin A from S. aureus. The docking study revealed that the binding energy of ligands with receptors was -6.6 to -6.9 Kcal/mol. Kaempferol had the highest binding affinity of -6.9 Kcal/mol, suggesting it has a potential against S. aureus. Therefore, in the current research, we have tried to identify occurring compounds that might be used to develop an effective anti-S.aureus agent. The findings are encouraging and will aid researchers in creating new mastitis-fighting medications based on natural phytochemicals

In silico targeting of osmoporin protein of Salmonella to identify anti-Salmonellosis phyto-compounds

Salmonella enterica serotype typhi is a gram-negative, rod-shaped bacterium, and has flagella with the human body as its only reservoir. Typhoid fever was found to cause 21.7 million illnesses and 216,000 fatalities worldwide in 2000, and the International Vaccine Institute estimated 11.9 million cases and 129,000 deaths in low- and middle-income countries in 2010. More than 10 million patients were infected with S. typhi each year and the mortality rate is associated with more than 0.1 million patients. Moreover, it is also associated with drug resistance globally which makes the disease more dreadful. Other than antibiotics, various flavonoids showed medicinal effects against many diseases including S. typhi infection. Flavonoids are a type of plant bioactive metabolite that have potential medicinal efficacy. The goal of this study was to see if certain flavonoids (ellagic acid, eriodictyol, and naringenin) could interact with the outer membrane of osmoporin (PDB ID: 3uu2) receptor in Salmonella and helps in inhibiting its growth. To look for probable ligand-receptor binding relationships, we used Pyrxmolecular docking software. The molecular docking results were analyzed using the Biovia discovery studio visualizer. The current study discovered that selected plant-based compounds interacted with an outer membrane of the osmoporin receptor, resulting in minimization of energy in the range of-6.6 to -7.8 Kcal/mol

Australia\u27s health 2004 : the ninth biennial report of the Australian Institute of Health and Welfare

Australia\u27s Health 2004 is the ninth biennial health report of the Australian Institute of Health and Welfare. It is the nation\u27s authoritative source of information on patterns of health and illness, determinants of health, the supply and use of health services, and health services expenditure. The report also includes a special chapter on the health of older Australians. Australia\u27s Health 2004 is an essential reference and information resource for all Australians with an interest in health

In Silico Targeting of influenza virus haemagglutinin receptor protein using Diosmetin, Tangeritin, and Anthocyanidins as potential drugs

Influenza viruses cause acute respiratory illnesses in birds, humans, and other mammals, and are a major public health concern around the world. Pandemic flu could be caused by an unforeseen human adaptation of an influenza subtype or strain rather than currently circulating influenza viruses. The need for plant metabolites-based new anti-influenza drugs appears to be urgent. Blocking Haemeagglutinin (HA) protein is one of the most appealing drug targets to halt the growth of the virus. The influenza virus can acquire resistance to currently existing therapies, therefore necessitating the development of new medications. The plant's bioactive metabolites, flavanoids are having potential medicinal efficacy. The current study aimed to identify certain flavonoids (Diosmetin, Tangeritin, and Anthocyanidins) that might interact with the HA protein of the influenza virus and help in inhibiting its growth. We used PyRx v0.8 for virtual screening and docking studies. The highest binding affinity docked structures were analyzed using PyMOL and Discovery Studio Visualizer. The present study revealed that these naturally occurring compounds interacted with HA protein, resulting in the minimization of energy in the range of -5.2 to -7.0 kcal/mol. Diosmetin showed the best binding affinity of -7.0Kcal/mol. The molecular binding studies revealed that Diosmetin, Tangeritin, and Anthocyanidins are potential compounds to test against HA protein and can be used to develop effective anti-influenza agents

First report on National Health Priority Areas 1996

Focuses on the health of Australians by documenting progress towards goals and targets for the five priority areas of cardiovascular health, cancer control, injury prevention and control, mental health, and diabetes mellitus

Cloning and expression of cultural filtrate proteins from novel and native strains of Mycobacterium avium subspecies paratuberculosis and their application in ELISA based sero-diagnosis of Johne's disease

Johne's disease (JD), caused by Mycobacterium avium subspecies paratuberculosis (MAP), is endemic in livestock leading to low per animal productivity. MAP as survives pasteurization, poses a public health problem because of high exposure to animals and humans. There is an urgent need for newer diagnostic tests with high specificity and sensitivity as the current ones suffer from lower sensitivity and specificity. In present study, six Mycobacterium avium subspecies paratuberculosis (MAP)-specific culture filtrate proteins (CFPs) were produced and evaluated for sero-diagnosis of MAP infection in goat and cattle herds in India. Genes encoding for six MAP-CFPs were amplified and cloned into easy cloning vector pJET1.2/pTZ57R followed by sub-cloning into expression vector pET28a (+)/pET22b (+) containing C-terminal Histidine. Recombinant CFPs (r-CFPs) expressions were optimized in Escherichia coli (Rosetta cells) and purified using Ni-NTA affinity chromatography. In SDS-PAGE, MAP CFPs viz., 1693c, 2168c, ModD, 85C, Pep AN and Pep AC showed 22, 24, 55, 38, 20 and 25 kDa molecular masses, respectively. Identity of these r-CFPs was further confirmed by immuno-blotting. We developed six different ELISAs using the six individual r-CFPs and one additional ELISA i.e. cocktail ELISA (c-ELISA) was prepared using cocktail of all 6 r-CFPs. The performance of all seven ELISAs were further evaluated against whole cell protoplasmic based indigenous ELISA (i-ELISA). c-ELISA showed almost similar sensitivity as shown by i-ELISA. However, individual r-CFP based ELISA could not reach up to the sensitivity of cocktail of six r-CFPs. None of the r-CFP showed any false positive (as compare to i-ELISA) thereby specificity was 100%. Results of ELISA tests based on cocktail of r-CFPs, ModD and 85C were quite similar to i-ELISA from goat sera whereas in cattle serum c-ELISA was comparable with i-ELISA. Our study showed a comparable specificity of c-ELISA for the diagnosis of JD and it may have applicability in region where disease is endemic. Future validation of c-ELISA against gold standard or confirmatory tests would give a better insight on its diagnostic potential over i-ELISA

Cloning and expression of cultural filtrate proteins from novel and native strains of Mycobacterium avium subspecies paratuberculosis and their application in ELISA based sero-diagnosis of Johne's disease

219-229Johne's disease (JD), caused by Mycobacterium avium subspecies paratuberculosis (MAP), is endemic in livestock leading to low per animal productivity. MAP as survives pasteurization, poses a public health problem because of high exposure to animals and humans. There is an urgent need for newer diagnostic tests with high specificity and sensitivity as the current ones suffer from lower sensitivity and specificity. In present study, six Mycobacterium avium subspecies paratuberculosis (MAP)-specific culture filtrate proteins (CFPs) were produced and evaluated for sero-diagnosis of MAP infection in goat and cattle herds in India. Genes encoding for six MAP-CFPs were amplified and cloned into easy cloning vector pJET1.2/pTZ57R followed by sub-cloning into expression vector pET28a (+)/pET22b (+) containing C-terminal Histidine. Recombinant CFPs (r-CFPs) expressions were optimized in Escherichia coli (Rosetta cells) and purified using Ni-NTA affinity chromatography. In SDS-PAGE, MAP CFPs viz., 1693c, 2168c, ModD, 85C, Pep AN and Pep AC showed 22, 24, 55, 38, 20 and 25 kDa molecular masses, respectively. Identity of these r-CFPs was further confirmed by immuno-blotting. We developed six different ELISAs using the six individual r-CFPs and one additional ELISA i.e. cocktail ELISA (c-ELISA) was prepared using cocktail of all 6 r-CFPs. The performance of all seven ELISAs were further evaluated against whole cell protoplasmic based indigenous ELISA (i-ELISA). c-ELISA showed almost similar sensitivity as shown by i-ELISA. However, individual r-CFP based ELISA could not reach up to the sensitivity of cocktail of six r-CFPs. None of the r-CFP showed any false positive (as compare to i-ELISA) thereby specificity was 100%. Results of ELISA tests based on cocktail of r-CFPs, ModD and 85C were quite similar to i-ELISA from goat sera whereas in cattle serum c-ELISA was comparable with i-ELISA. Our study showed a comparable specificity of c-ELISA for the diagnosis of JD and it may have applicability in region where disease is endemic. Future validation of c-ELISA against gold standard or confirmatory tests would give a better insight on its diagnostic potential over i-ELISA