Sarah Qureshi | COMSATS - Academia.edu (original) (raw)
Papers by Sarah Qureshi
ResearcHER: The Power and Potential of Research Careers for Women
Journal of Cardiac Failure
Teledermatology (TD) is an emerging modality for providing remote dermatologic care with high dia... more Teledermatology (TD) is an emerging modality for providing remote dermatologic care with high diagnostic and management concordance compared to face-to-face clinic dermatology. TD training among dermatology residency programs in the United States has not been characterized. We disseminated a survey to all dermatology residents at ACGME accredited programs in the United States to explore the prevalence and distribution of TD training and trainee perceptions of TD. One hundred out of a potential 1170 responses (RR 8.5%) were collected from residents in every geographic location from all years in training: 67/100 of residents reported that TD was practiced at their institutions, although at these sites only 21/100 residents participated in clinical sessions. Residents with TD exposure were more likely to feel comfortable managing a TD consult after residency (p<0.001), but were not more likely to incorporate teledermatology into their future plans. Results of this study provide insi...
To report the prevalence of dental diseases among the 12-year-old students in a Peri-urban area o... more To report the prevalence of dental diseases among the 12-year-old students in a Peri-urban area of Karachi, Pakistan. This crossectional study was carried out on a sample comprising of 83 subjects, 67 males and 21 females using the WHO prescribed form and diagnostic criteria. It was found that the dental fluorosis was 32%, which is comparably higher than a similar study, conducted in the USA. The oral hygiene of the subjects was poor whereas most ofthe subjects were caries free. This study highlights the importance of public health awareness of oral diseases, as this will reduce the burden of curative dental services in a country like Pakistan with financial limitations.
Dermatology Online Journal, 2016
The Harvard community has made this article openly available. Please share how this access benefi... more The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Qureshi, Sarah, and Arash Mostaghimi. "Exposure to teledermatology and resident preparedness for future practice: results of a national survey." Dermatology online journal 22, no. 7 (2016). Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:33785895 Terms of Use This article was downloaded from Harvard University's DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-ofuse#LAA eScholarship provides open access, scholarly publishing services to the University of California and delivers a dynamic research platform to scholars worldwide.
International Journal of Infectious Diseases, 2020
Objectives: Coronavirus Disease 2019 (COVID-19) is a new respiratory and systemic disease which n... more Objectives: Coronavirus Disease 2019 (COVID-19) is a new respiratory and systemic disease which needs quick identification of potential critical patients. This meta-analysis aimed to explore the relationship between lymphocyte count and the severity of COVID-19. Methods: A comprehensive systematic literature search was carried out to find studies published from December 2019 to 22 March 2020 from five databases. The language of literatures included English and Chinese. Mean difference (MD) of lymphocyte count in COVID-19 patients with or without severe disease and odds ratio (OR) of lymphopenia for severe form of COVID-19 was evaluated with this meta-analysis. Results: Overall 13 case-series with a total of 2282 cases were included in the study. The pooled analysis showed that lymphocyte count was significantly lower in severe COVID-19 patients (MD-0.31 Â10 9 /L; 95%CI:-0.42 to-0.19 Â 10 9 /L). The presence of lymphopenia was associated with nearly threefold increased risk of severe COVID-19 (Random effects model, OR = 2.99, 95% CI: 1.31-6.82). Conclusions: Lymphopenia is a prominent part of severe COVID-19 and a lymphocyte count of less than 1.5 Â 10 9 /L may be useful in predicting the severity clinical outcomes.
Pakistan Journal of Medical Sciences, 2019
Objectives: This study was aimed to compare the body mass index (BMI) and waist-to-hip ratio (WHR... more Objectives: This study was aimed to compare the body mass index (BMI) and waist-to-hip ratio (WHR) in their ability to predict type 2 diabetes risk in a large prospective cohort of men and women in Pakistan. Methods: This was a case-control study conducted at Diabetic and medical OPD of GTTH. Anthropometric measures including BMI and WHR were analyzed. Student’s t-test, Chi-squared test along with Cramer’s V value, was applied to evaluate association between variables. Receiver operating curve (ROC) was used to assess anthropometric measures. Results: The study included 804 diabetics and 396 non-diabetics between 30–60 years of age. Comparing the BMI parameters it was found that 717 (89·2%) in diabetic group were overweight or obese (p-value < 0·001). On comparing the WHR, 97·9% diabetics had increased WHR (p-value <0·001). Both BMI & WHR were further compared using ROC curve which found out that WHR had an area under ROC of 0·720 & BMI has 0·680, suggesting that WHR is more b...
Pakistan Journal of Public Health, 2018
Background: The incidence and prevalence of prostate cancer is increasing in Pakistan in recent y... more Background: The incidence and prevalence of prostate cancer is increasing in Pakistan in recent years. Prostate cancer is the second most common cancer among men in the whole world. Methods: A descriptive cross-sectional study was done using a questionnaire having questions related to symptoms and treatment options of Prostate cancer. A total of 352 healthy males aged 18 years and above were included in the study. Questionnaire was handed over to 102 healthy male attendants of patients presenting to outpatient department, Mayo hospital Lahore. A soft copy was also formatted using google forms and emailed to around 250 men of different age groups studying or working at various public and private sector nonmedical colleges and universities of Lahore. Descriptive statistics including mean, percentages and standard deviation was used to conclude results. Results: Out of 352 participants, more than half (55.7%) of the participants had heard of the prostate cancer while the others did not...
Journal of Cell Science & Therapy, 2016
Purpose: The declining physician-scientist number is alarming. Therefore, this study is designed ... more Purpose: The declining physician-scientist number is alarming. Therefore, this study is designed to establish early exposure to undergraduate research interest in science careers and generates physician-scientist workforces. Materials and methods: In this paper, we report the experience and student's perceptions of an innovative summer research program and examine how it could influence students' interest in research careers.
Lasers in Medical Science, 2016
Aminolevulinic acid (ALA) photodynamic therapy (PDT) is an emerging modality in the treatment of ... more Aminolevulinic acid (ALA) photodynamic therapy (PDT) is an emerging modality in the treatment of acne. While ablative fractional lasers have been used to enhance drug delivery into the epidermis, recent evidence suggests that non-ablative fractional photothermolysis may also improve uptake of ALA. We explored the use of non-ablative 1550 nm laser as a safe alternative in the delivery of ALA prior to red-light PDT for refractory inflammatory and cystic acne. Subjects referred for treatment of acne refractory to several topical and oral regimens, including isotretinoin, were pre-treated with nonablative fractional photothermolysis (NAFP). This was followed by 20 % ALA application with an incubation time of 1-3 h and then exposure to 50-100 J/cm 2 red light. Follow-up was at 1, 3, and 6 months. In all three cases, patients demonstrated marked reduction in inflammatory lesions. Two subjects had remission of acne after a single combination treatment. Non-ablative fractional laser applied immediately prior to PDT may be used in the treatment of acne with minimal side effects and fewer sessions needed than PDT alone. This may be due to enhanced delivery of ALA from pre-treating the skin with non-ablative fractional photothermolysis.
Cureus, 2016
Irritable bowel syndrome (IBS) has been identified as one of the more highly prevalent and costly... more Irritable bowel syndrome (IBS) has been identified as one of the more highly prevalent and costly gastrointestinal disorders. Despite its uncertain etiology, risk factors, such as stress and academic load, are well correlated with the prevalence of the disease. Being in one of the most stressful and challenging environments, medical students are predisposed to have high rates of IBS. The socioeconomic burden of the disease on its sufferers is devastating as their quality of life is reduced, mandating additional health care precautions. The aim of this article, therefore, is to review the current literature about IBS among medical students, its prevalence, associated risk factors, and diagnostic criteria. Additionally, different solutions and management options are recommended to control the disease.
Nutrition, 2017
The aim of the present study was to investigate the effect of a common variant of the fat mass an... more The aim of the present study was to investigate the effect of a common variant of the fat mass and obesity associated (FTO) gene, rs3751812 in obese Pakistani individuals, compare this effect with nonobese controls of the same ethnicity, and then correlate it with serum lipid profile and anthropometric parameters. We genotyped 475 samples using TaqMan allelic discrimination assay. Serum total cholesterol, triacylglycerols, and high- (HDL-C) and low-density lipoprotein cholesterol (LDL-C) concentrations were measured. Statistical analysis was done by SPSS version 22 and the results were analyzed for any significant associations. Results demonstrated that the variant is significantly associated with obesity in Pakistan. The study found, for the first time, that the variant has a significant effect on lowering HDL-C and increasing LDL-C. Among anthropometric measures, the variant showed significant association with body mass index and weight. The study concludes that the FTO variant is consistently associated with obesity in the Pakistani population and its association with anthropometric and lipid parameters show that it may mediate its role by altering fat deposition and disturbing serum lipid profile. However, future studies with larger sample size are needed to validate the results of the present study.
Journal of Infectious Diseases, 2015
Background. An ecological correlation between invasive cervical cancer incidence and burden of so... more Background. An ecological correlation between invasive cervical cancer incidence and burden of soil-transmitted helminths (STH) is hypothesized to explain the excess in detectable human papillomavirus (HPV) infection in Latin America, via a global T-helper type 2 (Th2)-biased mucosal immune response secondary to STH infection. Methods. The association between current STH infection and HPV prevalence was compared in regions of Peru where STH is or is not endemic. Adjusted prevalence ratios (PRs) with robust variance were estimated as an effect measure of STH infection on HPV prevalence in each study site. Soluble immune marker profiles in STH-infected and STH-uninfected women were compared using Spearman rank correlation with the Sidak correction. Results. Among women in the helminth-endemic region of the Peruvian Amazon, those with STH infection women had a 60% higher prevalence of HPV, compared with those without STH infection (PR, 1.6; 95% confidence interval, 1.0-2.7). Non-STH parasitic/protozoal infections in the non-STH-endemic population of Peru were not associated with HPV prevalence. In Iquitos, A Th2 immune profile was observed in cervical fluid from helminth-infected women but not helminth-uninfected women. Conclusions. A proportion of the increased HPV prevalence at older ages observed in Latin America may be due to a population-level difference in the efficiency of immunological control of HPV across the lifespan due to endemic STH infection.
PLoS genetics, 2015
Translation initiation factor eIF4E mediates mRNA selection for protein synthesis via the mRNA 5&... more Translation initiation factor eIF4E mediates mRNA selection for protein synthesis via the mRNA 5'cap. A family of binding proteins, termed the 4E-BPs, interact with eIF4E to hinder ribosome recruitment. Mechanisms underlying mRNA specificity for 4E-BP control remain poorly understood. Saccharomyces cerevisiae 4E-BPs, Caf20p and Eap1p, each regulate an overlapping set of mRNAs. We undertook global approaches to identify protein and RNA partners of both 4E-BPs by immunoprecipitation of tagged proteins combined with mass spectrometry or next-generation sequencing. Unexpectedly, mass spectrometry indicated that the 4E-BPs associate with many ribosomal proteins. 80S ribosome and polysome association was independently confirmed and was not dependent upon interaction with eIF4E, as mutated forms of both Caf20p and Eap1p with disrupted eIF4E-binding motifs retain ribosome interaction. Whole-cell proteomics revealed Caf20p mutations cause both up and down-regulation of proteins and that ...
SAE Technical Paper Series, 2004
Indian journal of pathology & microbiology
Maryland journal of international law and trade, 1995
2. See discussion infra part III.B (regarding Chinese and Vietnamese policies). 3. See Lawrence G... more 2. See discussion infra part III.B (regarding Chinese and Vietnamese policies). 3. See Lawrence Gostin, Introduction to INTERNATIONAL LAW AND AIDS INTERNATIONAL RESPONSE, CURRENT ISSUES, AND FUTURE DIRECTIONS Xi, xv (Lawrence Gostin & Lane Porter eds., American Bar Association, 1992). [Hereinafter INTERNATIONAL LAW AND AIDS]. 4. See discussion infra part III.A. 5. See discussion infra part III.A.1 (regarding Costa Rica, South Africa and Thailand). 6. See discussion infra part III.A.2 (regarding Korea, Bulgaria, Czechoslovakia, and Sweden). 7. See discussion infra part III.A.3 (regarding France and the United Kingdom). .8. See, e.g., discussion infra part V. 9. See discussion infra part VII. 10. See discussion infra part IV. 11. See discussion infra part V.A. 12. See discussion infra part VI.C. 13. See discussion infra part VII.E. 14. Id. 15. World AIDS Day, 14 WORLD HEALTH FORUM 205 (1993). 16. Id. 1995] 32. Id. 33. See discussion infra part III.A. 34. See discussion infra part III.A.1. 35. See discussion infra part III.A.2. 36. See discussion infra part III.A.3.
Genome Biology, 2015
Background: The selection and regulation of individual mRNAs for translation initiation from a co... more Background: The selection and regulation of individual mRNAs for translation initiation from a competing pool of mRNA are poorly understood processes. The closed loop complex, comprising eIF4E, eIF4G and PABP, and its regulation by 4E-BPs are perceived to be key players. Using RIP-seq, we aimed to evaluate the role in gene regulation of the closed loop complex and 4E-BP regulation across the entire yeast transcriptome. Results: We find that there are distinct populations of mRNAs with coherent properties: one mRNA pool contains many ribosomal protein mRNAs and is enriched specifically with all of the closed loop translation initiation components. This class likely represents mRNAs that rely heavily on the closed loop complex for protein synthesis. Other heavily translated mRNAs are apparently under-represented with most closed loop components except Pab1p. Combined with data showing a close correlation between Pab1p interaction and levels of translation, these data suggest that Pab1p is important for the translation of these mRNAs in a closed loop independent manner. We also identify a translational regulatory mechanism for the 4E-BPs; these appear to self-regulate by inhibiting translation initiation of their own mRNAs. Conclusions: Overall, we show that mRNA selection for translation initiation is not as uniformly regimented as previously anticipated. Components of the closed loop complex are highly relevant for many mRNAs, but some heavily translated mRNAs interact poorly with this machinery. Therefore, alternative, possibly Pab1p-dependent mechanisms likely exist to load ribosomes effectively onto mRNAs. Finally, these studies identify and characterize a complex self-regulatory circuit for the yeast 4E-BPs.
Molecular and Cellular Biology, 2004
Childhood ataxia with central nervous system hypomyelination (CACH), or vanishing white matter le... more Childhood ataxia with central nervous system hypomyelination (CACH), or vanishing white matter leukoencephalopathy (VWM), is a fatal brain disorder caused by mutations in eukaryotic initiation factor 2B (eIF2B). eIF2B is essential for protein synthesis and regulates translation in response to cellular stresses. We performed mutagenesis to introduce changes equivalent to 12 human CACH/VWM mutations in three subunits of the equivalent factor from yeast (Saccharomyces cerevisiae) and analyzed effects on cell growth, translation, and gene expression in response to stresses. None of the mutations is lethal or temperature sensitive, but almost all confer some defect in eIF2B function significant enough to alter growth or gene expression under normal or stress conditions. Biochemical analyses indicate that mutations analyzed in eIF2B␣ and-reduce the steady-state level of the affected subunit, while the most severe mutant tested, eIF2B V341D (human eIF2B V316D), forms complexes with reduced stability and lower eIF2B activity. eIF2B␦ is excluded from eIF2B V341D complexes. eIF2B v341D function can be rescued by overexpression of eIF2B␦ alone. Our findings imply CACH/VWM mutations do not specifically impair responses to eIF2 phosphorylation, but instead cause protein structure defects that impair eIF2B activity. Altered protein folding is characteristic of other diseases, including cystic fibrosis and neurodegenerative disorders such as Huntington, Alzheimer's, and prion diseases.
Translation Initiation: Cell Biology, High-Throughput Methods, and Chemical-Based Approaches, 2007
The eukaryotic initiation factor 2B (eIF2B) is a five-subunit guanine nucleotide exchange factor,... more The eukaryotic initiation factor 2B (eIF2B) is a five-subunit guanine nucleotide exchange factor, that functions during translation initiation to catalyze the otherwise slow exchange of GDP for GTP on its substrate eIF2. Assays to measure substrate interaction and guanine nucleotide release ability of eIF2B require the complex to be purified free of interacting proteins. We have also found that a subcomplex of two subunits, gamma and epsilon or the largest one, epsilon alone, promotes this activity. Within eIF2Bepsilon, the catalytic center requires the C-terminal 200 residues only. Here, we describe our protocols for purifying the Saccharomyces cerevisiae eIF2B complexes and the catalytic subunit using FLAG-tagged proteins overexpressed in yeast cells. Using commercially available FLAG-affinity resin and high salt buffer, we are able to purify active eIF2B virtually free of contaminants.
ResearcHER: The Power and Potential of Research Careers for Women
Journal of Cardiac Failure
Teledermatology (TD) is an emerging modality for providing remote dermatologic care with high dia... more Teledermatology (TD) is an emerging modality for providing remote dermatologic care with high diagnostic and management concordance compared to face-to-face clinic dermatology. TD training among dermatology residency programs in the United States has not been characterized. We disseminated a survey to all dermatology residents at ACGME accredited programs in the United States to explore the prevalence and distribution of TD training and trainee perceptions of TD. One hundred out of a potential 1170 responses (RR 8.5%) were collected from residents in every geographic location from all years in training: 67/100 of residents reported that TD was practiced at their institutions, although at these sites only 21/100 residents participated in clinical sessions. Residents with TD exposure were more likely to feel comfortable managing a TD consult after residency (p<0.001), but were not more likely to incorporate teledermatology into their future plans. Results of this study provide insi...
To report the prevalence of dental diseases among the 12-year-old students in a Peri-urban area o... more To report the prevalence of dental diseases among the 12-year-old students in a Peri-urban area of Karachi, Pakistan. This crossectional study was carried out on a sample comprising of 83 subjects, 67 males and 21 females using the WHO prescribed form and diagnostic criteria. It was found that the dental fluorosis was 32%, which is comparably higher than a similar study, conducted in the USA. The oral hygiene of the subjects was poor whereas most ofthe subjects were caries free. This study highlights the importance of public health awareness of oral diseases, as this will reduce the burden of curative dental services in a country like Pakistan with financial limitations.
Dermatology Online Journal, 2016
The Harvard community has made this article openly available. Please share how this access benefi... more The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Qureshi, Sarah, and Arash Mostaghimi. "Exposure to teledermatology and resident preparedness for future practice: results of a national survey." Dermatology online journal 22, no. 7 (2016). Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:33785895 Terms of Use This article was downloaded from Harvard University's DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-ofuse#LAA eScholarship provides open access, scholarly publishing services to the University of California and delivers a dynamic research platform to scholars worldwide.
International Journal of Infectious Diseases, 2020
Objectives: Coronavirus Disease 2019 (COVID-19) is a new respiratory and systemic disease which n... more Objectives: Coronavirus Disease 2019 (COVID-19) is a new respiratory and systemic disease which needs quick identification of potential critical patients. This meta-analysis aimed to explore the relationship between lymphocyte count and the severity of COVID-19. Methods: A comprehensive systematic literature search was carried out to find studies published from December 2019 to 22 March 2020 from five databases. The language of literatures included English and Chinese. Mean difference (MD) of lymphocyte count in COVID-19 patients with or without severe disease and odds ratio (OR) of lymphopenia for severe form of COVID-19 was evaluated with this meta-analysis. Results: Overall 13 case-series with a total of 2282 cases were included in the study. The pooled analysis showed that lymphocyte count was significantly lower in severe COVID-19 patients (MD-0.31 Â10 9 /L; 95%CI:-0.42 to-0.19 Â 10 9 /L). The presence of lymphopenia was associated with nearly threefold increased risk of severe COVID-19 (Random effects model, OR = 2.99, 95% CI: 1.31-6.82). Conclusions: Lymphopenia is a prominent part of severe COVID-19 and a lymphocyte count of less than 1.5 Â 10 9 /L may be useful in predicting the severity clinical outcomes.
Pakistan Journal of Medical Sciences, 2019
Objectives: This study was aimed to compare the body mass index (BMI) and waist-to-hip ratio (WHR... more Objectives: This study was aimed to compare the body mass index (BMI) and waist-to-hip ratio (WHR) in their ability to predict type 2 diabetes risk in a large prospective cohort of men and women in Pakistan. Methods: This was a case-control study conducted at Diabetic and medical OPD of GTTH. Anthropometric measures including BMI and WHR were analyzed. Student’s t-test, Chi-squared test along with Cramer’s V value, was applied to evaluate association between variables. Receiver operating curve (ROC) was used to assess anthropometric measures. Results: The study included 804 diabetics and 396 non-diabetics between 30–60 years of age. Comparing the BMI parameters it was found that 717 (89·2%) in diabetic group were overweight or obese (p-value < 0·001). On comparing the WHR, 97·9% diabetics had increased WHR (p-value <0·001). Both BMI & WHR were further compared using ROC curve which found out that WHR had an area under ROC of 0·720 & BMI has 0·680, suggesting that WHR is more b...
Pakistan Journal of Public Health, 2018
Background: The incidence and prevalence of prostate cancer is increasing in Pakistan in recent y... more Background: The incidence and prevalence of prostate cancer is increasing in Pakistan in recent years. Prostate cancer is the second most common cancer among men in the whole world. Methods: A descriptive cross-sectional study was done using a questionnaire having questions related to symptoms and treatment options of Prostate cancer. A total of 352 healthy males aged 18 years and above were included in the study. Questionnaire was handed over to 102 healthy male attendants of patients presenting to outpatient department, Mayo hospital Lahore. A soft copy was also formatted using google forms and emailed to around 250 men of different age groups studying or working at various public and private sector nonmedical colleges and universities of Lahore. Descriptive statistics including mean, percentages and standard deviation was used to conclude results. Results: Out of 352 participants, more than half (55.7%) of the participants had heard of the prostate cancer while the others did not...
Journal of Cell Science & Therapy, 2016
Purpose: The declining physician-scientist number is alarming. Therefore, this study is designed ... more Purpose: The declining physician-scientist number is alarming. Therefore, this study is designed to establish early exposure to undergraduate research interest in science careers and generates physician-scientist workforces. Materials and methods: In this paper, we report the experience and student's perceptions of an innovative summer research program and examine how it could influence students' interest in research careers.
Lasers in Medical Science, 2016
Aminolevulinic acid (ALA) photodynamic therapy (PDT) is an emerging modality in the treatment of ... more Aminolevulinic acid (ALA) photodynamic therapy (PDT) is an emerging modality in the treatment of acne. While ablative fractional lasers have been used to enhance drug delivery into the epidermis, recent evidence suggests that non-ablative fractional photothermolysis may also improve uptake of ALA. We explored the use of non-ablative 1550 nm laser as a safe alternative in the delivery of ALA prior to red-light PDT for refractory inflammatory and cystic acne. Subjects referred for treatment of acne refractory to several topical and oral regimens, including isotretinoin, were pre-treated with nonablative fractional photothermolysis (NAFP). This was followed by 20 % ALA application with an incubation time of 1-3 h and then exposure to 50-100 J/cm 2 red light. Follow-up was at 1, 3, and 6 months. In all three cases, patients demonstrated marked reduction in inflammatory lesions. Two subjects had remission of acne after a single combination treatment. Non-ablative fractional laser applied immediately prior to PDT may be used in the treatment of acne with minimal side effects and fewer sessions needed than PDT alone. This may be due to enhanced delivery of ALA from pre-treating the skin with non-ablative fractional photothermolysis.
Cureus, 2016
Irritable bowel syndrome (IBS) has been identified as one of the more highly prevalent and costly... more Irritable bowel syndrome (IBS) has been identified as one of the more highly prevalent and costly gastrointestinal disorders. Despite its uncertain etiology, risk factors, such as stress and academic load, are well correlated with the prevalence of the disease. Being in one of the most stressful and challenging environments, medical students are predisposed to have high rates of IBS. The socioeconomic burden of the disease on its sufferers is devastating as their quality of life is reduced, mandating additional health care precautions. The aim of this article, therefore, is to review the current literature about IBS among medical students, its prevalence, associated risk factors, and diagnostic criteria. Additionally, different solutions and management options are recommended to control the disease.
Nutrition, 2017
The aim of the present study was to investigate the effect of a common variant of the fat mass an... more The aim of the present study was to investigate the effect of a common variant of the fat mass and obesity associated (FTO) gene, rs3751812 in obese Pakistani individuals, compare this effect with nonobese controls of the same ethnicity, and then correlate it with serum lipid profile and anthropometric parameters. We genotyped 475 samples using TaqMan allelic discrimination assay. Serum total cholesterol, triacylglycerols, and high- (HDL-C) and low-density lipoprotein cholesterol (LDL-C) concentrations were measured. Statistical analysis was done by SPSS version 22 and the results were analyzed for any significant associations. Results demonstrated that the variant is significantly associated with obesity in Pakistan. The study found, for the first time, that the variant has a significant effect on lowering HDL-C and increasing LDL-C. Among anthropometric measures, the variant showed significant association with body mass index and weight. The study concludes that the FTO variant is consistently associated with obesity in the Pakistani population and its association with anthropometric and lipid parameters show that it may mediate its role by altering fat deposition and disturbing serum lipid profile. However, future studies with larger sample size are needed to validate the results of the present study.
Journal of Infectious Diseases, 2015
Background. An ecological correlation between invasive cervical cancer incidence and burden of so... more Background. An ecological correlation between invasive cervical cancer incidence and burden of soil-transmitted helminths (STH) is hypothesized to explain the excess in detectable human papillomavirus (HPV) infection in Latin America, via a global T-helper type 2 (Th2)-biased mucosal immune response secondary to STH infection. Methods. The association between current STH infection and HPV prevalence was compared in regions of Peru where STH is or is not endemic. Adjusted prevalence ratios (PRs) with robust variance were estimated as an effect measure of STH infection on HPV prevalence in each study site. Soluble immune marker profiles in STH-infected and STH-uninfected women were compared using Spearman rank correlation with the Sidak correction. Results. Among women in the helminth-endemic region of the Peruvian Amazon, those with STH infection women had a 60% higher prevalence of HPV, compared with those without STH infection (PR, 1.6; 95% confidence interval, 1.0-2.7). Non-STH parasitic/protozoal infections in the non-STH-endemic population of Peru were not associated with HPV prevalence. In Iquitos, A Th2 immune profile was observed in cervical fluid from helminth-infected women but not helminth-uninfected women. Conclusions. A proportion of the increased HPV prevalence at older ages observed in Latin America may be due to a population-level difference in the efficiency of immunological control of HPV across the lifespan due to endemic STH infection.
PLoS genetics, 2015
Translation initiation factor eIF4E mediates mRNA selection for protein synthesis via the mRNA 5&... more Translation initiation factor eIF4E mediates mRNA selection for protein synthesis via the mRNA 5'cap. A family of binding proteins, termed the 4E-BPs, interact with eIF4E to hinder ribosome recruitment. Mechanisms underlying mRNA specificity for 4E-BP control remain poorly understood. Saccharomyces cerevisiae 4E-BPs, Caf20p and Eap1p, each regulate an overlapping set of mRNAs. We undertook global approaches to identify protein and RNA partners of both 4E-BPs by immunoprecipitation of tagged proteins combined with mass spectrometry or next-generation sequencing. Unexpectedly, mass spectrometry indicated that the 4E-BPs associate with many ribosomal proteins. 80S ribosome and polysome association was independently confirmed and was not dependent upon interaction with eIF4E, as mutated forms of both Caf20p and Eap1p with disrupted eIF4E-binding motifs retain ribosome interaction. Whole-cell proteomics revealed Caf20p mutations cause both up and down-regulation of proteins and that ...
SAE Technical Paper Series, 2004
Indian journal of pathology & microbiology
Maryland journal of international law and trade, 1995
2. See discussion infra part III.B (regarding Chinese and Vietnamese policies). 3. See Lawrence G... more 2. See discussion infra part III.B (regarding Chinese and Vietnamese policies). 3. See Lawrence Gostin, Introduction to INTERNATIONAL LAW AND AIDS INTERNATIONAL RESPONSE, CURRENT ISSUES, AND FUTURE DIRECTIONS Xi, xv (Lawrence Gostin & Lane Porter eds., American Bar Association, 1992). [Hereinafter INTERNATIONAL LAW AND AIDS]. 4. See discussion infra part III.A. 5. See discussion infra part III.A.1 (regarding Costa Rica, South Africa and Thailand). 6. See discussion infra part III.A.2 (regarding Korea, Bulgaria, Czechoslovakia, and Sweden). 7. See discussion infra part III.A.3 (regarding France and the United Kingdom). .8. See, e.g., discussion infra part V. 9. See discussion infra part VII. 10. See discussion infra part IV. 11. See discussion infra part V.A. 12. See discussion infra part VI.C. 13. See discussion infra part VII.E. 14. Id. 15. World AIDS Day, 14 WORLD HEALTH FORUM 205 (1993). 16. Id. 1995] 32. Id. 33. See discussion infra part III.A. 34. See discussion infra part III.A.1. 35. See discussion infra part III.A.2. 36. See discussion infra part III.A.3.
Genome Biology, 2015
Background: The selection and regulation of individual mRNAs for translation initiation from a co... more Background: The selection and regulation of individual mRNAs for translation initiation from a competing pool of mRNA are poorly understood processes. The closed loop complex, comprising eIF4E, eIF4G and PABP, and its regulation by 4E-BPs are perceived to be key players. Using RIP-seq, we aimed to evaluate the role in gene regulation of the closed loop complex and 4E-BP regulation across the entire yeast transcriptome. Results: We find that there are distinct populations of mRNAs with coherent properties: one mRNA pool contains many ribosomal protein mRNAs and is enriched specifically with all of the closed loop translation initiation components. This class likely represents mRNAs that rely heavily on the closed loop complex for protein synthesis. Other heavily translated mRNAs are apparently under-represented with most closed loop components except Pab1p. Combined with data showing a close correlation between Pab1p interaction and levels of translation, these data suggest that Pab1p is important for the translation of these mRNAs in a closed loop independent manner. We also identify a translational regulatory mechanism for the 4E-BPs; these appear to self-regulate by inhibiting translation initiation of their own mRNAs. Conclusions: Overall, we show that mRNA selection for translation initiation is not as uniformly regimented as previously anticipated. Components of the closed loop complex are highly relevant for many mRNAs, but some heavily translated mRNAs interact poorly with this machinery. Therefore, alternative, possibly Pab1p-dependent mechanisms likely exist to load ribosomes effectively onto mRNAs. Finally, these studies identify and characterize a complex self-regulatory circuit for the yeast 4E-BPs.
Molecular and Cellular Biology, 2004
Childhood ataxia with central nervous system hypomyelination (CACH), or vanishing white matter le... more Childhood ataxia with central nervous system hypomyelination (CACH), or vanishing white matter leukoencephalopathy (VWM), is a fatal brain disorder caused by mutations in eukaryotic initiation factor 2B (eIF2B). eIF2B is essential for protein synthesis and regulates translation in response to cellular stresses. We performed mutagenesis to introduce changes equivalent to 12 human CACH/VWM mutations in three subunits of the equivalent factor from yeast (Saccharomyces cerevisiae) and analyzed effects on cell growth, translation, and gene expression in response to stresses. None of the mutations is lethal or temperature sensitive, but almost all confer some defect in eIF2B function significant enough to alter growth or gene expression under normal or stress conditions. Biochemical analyses indicate that mutations analyzed in eIF2B␣ and-reduce the steady-state level of the affected subunit, while the most severe mutant tested, eIF2B V341D (human eIF2B V316D), forms complexes with reduced stability and lower eIF2B activity. eIF2B␦ is excluded from eIF2B V341D complexes. eIF2B v341D function can be rescued by overexpression of eIF2B␦ alone. Our findings imply CACH/VWM mutations do not specifically impair responses to eIF2 phosphorylation, but instead cause protein structure defects that impair eIF2B activity. Altered protein folding is characteristic of other diseases, including cystic fibrosis and neurodegenerative disorders such as Huntington, Alzheimer's, and prion diseases.
Translation Initiation: Cell Biology, High-Throughput Methods, and Chemical-Based Approaches, 2007
The eukaryotic initiation factor 2B (eIF2B) is a five-subunit guanine nucleotide exchange factor,... more The eukaryotic initiation factor 2B (eIF2B) is a five-subunit guanine nucleotide exchange factor, that functions during translation initiation to catalyze the otherwise slow exchange of GDP for GTP on its substrate eIF2. Assays to measure substrate interaction and guanine nucleotide release ability of eIF2B require the complex to be purified free of interacting proteins. We have also found that a subcomplex of two subunits, gamma and epsilon or the largest one, epsilon alone, promotes this activity. Within eIF2Bepsilon, the catalytic center requires the C-terminal 200 residues only. Here, we describe our protocols for purifying the Saccharomyces cerevisiae eIF2B complexes and the catalytic subunit using FLAG-tagged proteins overexpressed in yeast cells. Using commercially available FLAG-affinity resin and high salt buffer, we are able to purify active eIF2B virtually free of contaminants.