18 results on '"Firoz Kabir"'
Search Results
2. The Wound Infection Following Caesarean Section
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Sheikh Firoz Kabir, Sabina Parveen, Binoy Krishna Golder, Begum Shamsun Naher Shirin, Fatema Ruhane, and Rawshan Ara Khanam
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medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,medicine ,Caesarean section ,General Medicine ,business ,Wound infection ,Surgery - Published
- 2020
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Catalog
3. A genomic deletion encompassing CRYBB2-CRYBB2P1 is responsible for autosomal recessive congenital cataracts
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Bushra Irum, Firoz Kabir, Nadav Shoshany, Shahid Y. Khan, Bushra Rauf, Muhammad Asif Naeem, Tanveer A. Qaiser, Sheikh Riazuddin, J. Fielding Hejtmancik, and S. Amer Riazuddin
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Genetics ,Molecular Biology ,Biochemistry - Abstract
Here we report a consanguineous Pakistani family with multiple affected individuals with autosomal recessive congenital cataract (arCC). Exclusion analysis established linkage to chromosome 22q, and Sanger sequencing coupled with PCR-based chromosome walking identified a large homozygous genomic deletion. Our data suggest that this deletion leads to CRYBB2-CRYBB2P1 fusion, consisting of exons 1–5 of CRYBB2 and exon 6 of CRYBB2P1, the latter of which harbors the c.463 C > T (p.Gln155*) mutation, and is responsible for arCC. more...
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- 2022
4. Robust identification of common genomic biomarkers from multiple gene expression profiles for the prognosis, diagnosis, and therapies of pancreatic cancer
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Md Bayazid Hossen, Md Ariful Islam, Md Selim Reza, Md Kaderi Kibria, Md Abu Horaira, Khanis Farhana Tuly, Md Omar Faruqe, Firoz Kabir, and Md Nurul Haque Mollah
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Health Informatics ,Computer Science Applications - Abstract
Pancreatic cancer (PC) is one of the leading causes of cancer-related death globally. So, identification of potential molecular signatures is required for diagnosis, prognosis, and therapies of PC. In this study, we detected 71 common differentially expressed genes (cDEGs) between PC and control samples from four microarray gene-expression datasets (GSE15471, GSE16515, GSE71989, and GSE22780) by using robust statistical and machine learning approaches, since microarray gene-expression datasets are often contaminated by outliers due to several steps involved in the data generating processes. Then we detected 8 cDEGs (ADAM10, COL1A2, FN1, P4HB, ITGB1, ITGB5, ANXA2, and MYOF) as the PC-causing key genes (KGs) by the protein-protein interaction (PPI) network analysis. We validated the expression patterns of KGs between case and control samples by box plot analysis with the TCGA and GTEx databases. The proposed KGs showed high prognostic power with the random forest (RF) based prediction model and Kaplan-Meier-based survival probability curve. The KGs regulatory network analysis detected few transcriptional and post-transcriptional regulators for KGs. The cDEGs-set enrichment analysis revealed some crucial PC-causing molecular functions, biological processes, cellular components, and pathways that are associated with KGs. Finally, we suggested KGs-guided five repurposable drug molecules (Linsitinib, CX5461, Irinotecan, Timosaponin AIII, and Olaparib) and a new molecule (NVP-BHG712) against PC by molecular docking. The stability of the top three protein-ligand complexes was confirmed by molecular dynamic (MD) simulation studies. The cross-validation and some literature reviews also supported our findings. Therefore, the finding of this study might be useful resources to the researchers and medical doctors for diagnosis, prognosis and therapies of PC by the wet-lab validation. more...
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- 2023
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5. Genome Sequence of a SARS-CoV-2 P.1 Variant of Concern (20J/501Y.V3) from Bangladesh
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Sharif Akhteruzzaman, Abu Sayeed Mohammad Mahmud, M. Saddam Hossain, Barna Goswami, Mohammad Samir Uzzaman, M. Ahashan Habib, Firoz Kabir, Mukhlesur Rahman, Tanjina Akhtar Banu, Mohammad Fazle Alam Rabbi, M. Salim Khan, M. Abdul Khaleque, Shahina Akter, Murshed Hasan Sarkar, Kazi Nadim Hasan, Eshrar Osman, and Iffat Jahan more...
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Whole genome sequencing ,2019-20 coronavirus outbreak ,Phylogenetic tree ,Coronavirus disease 2019 (COVID-19) ,Oropharyngeal swab (specimen) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,viruses ,Genome Sequences ,virus diseases ,Biology ,Virology ,Immunology and Microbiology (miscellaneous) ,Genetics ,Molecular Biology - Abstract
This study reports the coding-complete genome sequence, with variant identifications and phylogenetic analysis, of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) P.1 variant (20J/501Y.V3), obtained from an oropharyngeal swab specimen from a female Bangladeshi patient diagnosed with coronavirus disease 2019 (COVID-19) with no travel history. more...
- Published
- 2021
6. A missense allele of PEX5 is responsible for the defective import of PTS2 cargo proteins into peroxisomes
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Saima Riazuddin, S. Amer Riazuddin, Michael L. Robinson, Xiaodong Jiao, Muhammad Ali, Mohsin Shahzad, Muhammad Hassaan Ali, Bushra Rauf, Asma A. Khan, Tânia Francisco, Jorge E. Azevedo, Azra Mehmood, Bushra Irum, Hang Qi, Javed Akram, Shehla Javed Akram, J. Fielding Hejtmancik, Muhammad Zaman Khan Assir, Myriam Baes, Firoz Kabir, Khaled K. Abu-Amero, Shahid Y. Khan, Tony A. Rodrigues, Sheikh Riazuddin, and Muhammad Asif Naeem more...
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Male ,Peroxisome-Targeting Signal 1 Receptor ,Genetic Linkage ,Mutant ,Mutation, Missense ,Biological Transport, Active ,Chromosomal translocation ,Biology ,Cataract ,Peroxisomal Targeting Signals ,03 medical and health sciences ,Consanguinity ,Mice ,Peroxisomal disorder ,Lens, Crystalline ,Sequestosome-1 Protein ,Exome Sequencing ,Genetics ,medicine ,Peroxisomes ,Missense mutation ,Animals ,Humans ,Genetics (clinical) ,030304 developmental biology ,Mice, Knockout ,0303 health sciences ,Chromosomes, Human, Pair 12 ,Peroxisomal Targeting Signal 1 ,030305 genetics & heredity ,Peroxisome Targeting Signal 2 ,Peroxisome ,medicine.disease ,Cell biology ,Cytosol ,ATP-Binding Cassette Transporters ,Female - Abstract
Peroxisomes, single-membrane intracellular organelles, play an important role in various metabolic pathways. The translocation of proteins from the cytosol to peroxisomes depends on peroxisome import receptor proteins and defects in peroxisome transport result in a wide spectrum of peroxisomal disorders. Here, we report a large consanguineous family with autosomal recessive congenital cataracts and developmental defects. Genome-wide linkage analysis localized the critical interval to chromosome 12p with a maximum two-point LOD score of 4.2 (θ = 0). Next-generation exome sequencing identified a novel homozygous missense variant (c.653 T > C; p.F218S) in peroxisomal biogenesis factor 5 (PEX5), a peroxisome import receptor protein. This missense mutation was confirmed by bidirectional Sanger sequencing. It segregated with the disease phenotype in the family and was absent in ethnically matched control chromosomes. The lens-specific knockout mice of Pex5 recapitulated the cataractous phenotype. In vitro import assays revealed a normal capacity of the mutant PEX5 to enter the peroxisomal Docking/Translocation Module (DTM) in the presence of peroxisome targeting signal 1 (PTS1) cargo protein, be monoubiquitinated and exported back into the cytosol. Importantly, the mutant PEX5 protein was unable to form a stable trimeric complex with peroxisomal biogenesis factor 7 (PEX7) and a peroxisome targeting signal 2 (PTS2) cargo protein and, therefore, failed to promote the import of PTS2 cargo proteins into peroxisomes. In conclusion, we report a novel missense mutation in PEX5 responsible for the defective import of PTS2 cargo proteins into peroxisomes resulting in congenital cataracts and developmental defects. more...
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- 2020
7. Comparative transcriptome analysis of hESC- and iPSC-derived lentoid bodies
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Firoz Kabir, Yinghong Ma, S. Amer Riazuddin, Michael Delannoy, Caihong Qiu, Shahid Y. Khan, Muhammad Ali, and Jason J. Thomson
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0301 basic medicine ,Male ,Embryonic stem cells ,Human Embryonic Stem Cells ,Induced Pluripotent Stem Cells ,Primary Cell Culture ,lcsh:Medicine ,RNA-Seq ,Biology ,Article ,Cell Line ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,Lens, Crystalline ,Humans ,Lentoid ,lcsh:Science ,Induced pluripotent stem cell ,Transcriptomics ,Aged ,Regulation of gene expression ,Multidisciplinary ,lcsh:R ,Gene Expression Regulation, Developmental ,Cell Differentiation ,Cellular Reprogramming ,Embryonic stem cell ,Cell biology ,030104 developmental biology ,Fiber cell ,Cell culture ,030221 ophthalmology & optometry ,Leukocytes, Mononuclear ,lcsh:Q - Abstract
The ocular lens serves as an excellent system to investigate the intricate details of development and differentiation. Generation of lentoid bodies or lens-like structures using pluripotent stem cells is important for understanding the processes critical for lens morphogenesis and the mechanism of cataractogenesis. We previously reported the generation of peripheral blood mononuclear cell (PBMC)-originated, induced pluripotent stem cells (iPSCs). Here, we report generation of lentoid bodies from human embryonic stem cells (hESCs) and (PBMC)-originated, iPSCs employing the “fried egg” method with brief modifications. The ultrastructure analysis of hESC- and iPSC-derived lentoid bodies identified closely packed lens epithelial- and differentiating fiber-like cells. In addition, we performed RNA sequencing (RNA-Seq) based transcriptome profiling of hESC- and iPSC-derived lentoid bodies at differentiation day 25. Next-generation RNA sequencing (RNA-Seq) of hESC- and iPSC-derived lentoid bodies detected expression (≥0.659 RPKM) of 13,975 and 14,003 genes, respectively. Comparative transcriptome analysis of hESC- and iPSC-derived lentoid bodies revealed 13,563 (>96%) genes common in both datasets. Among the genes common in both transcriptome datasets, 12,856 (~95%) exhibited a quantitatively similar expression profile. Next, we compared the mouse lens epithelial and fiber cell transcriptomes with hESC- and iPSC-derived lentoid bodies transcriptomes and identified > 96% overlap with lentoid body transcriptomes. In conclusion, we report first-time comparative transcriptome analysis of hESC- and iPSC-derived lentoid bodies at differentiation day 25. more...
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- 2019
8. Mutation in the intracellular chloride channel CLCC1 associated with autosomal recessive retinitis pigmentosa
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Michel Michaelides, Sheikh Riazuddin, Yan Ma, Lin Li, Muhammad Ali, Muhammad Imran Khan, Ralph Nelson, Ahmed Salman, S. Amer Riazuddin, J. Fielding Hejtmancik, Siying Lin, Andrew H. Crosby, Zeynep Coban Akdemir, Longhua Zhang, James Fasham, Gavin Arno, Abdul Hameed, Chi-Chao Chan, Paul A. Sieving, Raheel Qamar, Sarah Hull, Muhammad Asif Naeem, John K. Chilton, Frans P.M. Cremers, Shalini N. Jhangiani, Xiaodong Jiao, Firoz Kabir, Barry A. Chioza, Ilaria D'Atri, James R. Lupski, Zhiwei Ma, Radha Ayyagari, Fumihito Ono, Naoki Nakaya, Xiaoying Cai, Gaurav V. Harlalka, Jay E. Self, Emma L. Baple, Javed Akram, Anthony T. Moore, Holly Hardy, and Mundlos, Stefan more...
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0301 basic medicine ,Cancer Research ,Cytoplasm ,genetic structures ,Neurodegenerative ,Eye ,Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12] ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Retinal Rod Photoreceptor Cells ,2.1 Biological and endogenous factors ,Pakistan ,Aetiology ,Zebrafish ,Genetics (clinical) ,Mice, Knockout ,biology ,Homozygote ,medicine.anatomical_structure ,Chloride channel ,Retinal Cone Photoreceptor Cells ,Erg ,Intracellular ,Retinitis Pigmentosa ,Asian Continental Ancestry Group ,lcsh:QH426-470 ,Knockout ,Mutation, Missense ,Retina ,Cell Line ,03 medical and health sciences ,All institutes and research themes of the Radboud University Medical Center ,Rare Diseases ,Asian People ,Chloride Channels ,medicine ,Genetics ,Animals ,Humans ,Eye Proteins ,Molecular Biology ,Eye Disease and Disorders of Vision ,Ecology, Evolution, Behavior and Systematics ,CLCC1 ,Wild type ,Neurosciences ,Retinal ,biology.organism_classification ,Molecular biology ,eye diseases ,lcsh:Genetics ,030104 developmental biology ,HEK293 Cells ,chemistry ,Mutation ,biology.protein ,sense organs ,Missense ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
We identified a homozygous missense alteration (c.75C>A, p.D25E) in CLCC1, encoding a presumptive intracellular chloride channel highly expressed in the retina, associated with autosomal recessive retinitis pigmentosa (arRP) in eight consanguineous families of Pakistani descent. The p.D25E alteration decreased CLCC1 channel function accompanied by accumulation of mutant protein in granules within the ER lumen, while siRNA knockdown of CLCC1 mRNA induced apoptosis in cultured ARPE-19 cells. TALEN KO in zebrafish was lethal 11 days post fertilization. The depressed electroretinogram (ERG) cone response and cone spectral sensitivity of 5 dpf KO zebrafish and reduced eye size, retinal thickness, and expression of rod and cone opsins could be rescued by injection of wild type CLCC1 mRNA. Clcc1+/-KO mice showed decreased ERGs and photoreceptor number. Together these results strongly suggest that intracellular chloride transport by CLCC1 is a critical process in maintaining retinal integrity, and CLCC1 is crucial for survival and function of retinal cells. more...
- Published
- 2018
9. Cyber security challenges: An efficient intrusion detection system design
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Sven Hartmann and M. Firoz Kabir
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Random indexing ,Network administrator ,Computer science ,ComputerSystemsOrganization_COMPUTER-COMMUNICATIONNETWORKS ,Search engine indexing ,Real-time computing ,Denial-of-service attack ,Deep packet inspection ,Intrusion detection system ,Flooding (computer networking) ,Buffer overflow - Abstract
The importance of accurate intrusion detection is growing tremendously as the malicious network traffic activities have also grown significantly. Intrusion Detection Systems (IDSs) provide automatic detection for security violation like denial of service (DoS), virus, port scans, buffer overflows, CGI attacks, clogging or flooding etc. For network and host based systems, the most widely used and effective approach is data analysis with signature-based detection methods. Thus, the success of the detection system depends on the real appearance of the security violation, detection of the violation and response time. We are working on highly efficient real time network intrusion detection systems (NIDS) which will solve the detection efficiency problem such as real time detection rate, false positive etc in distributed environments. In this work, we propose a concept IDS to investigate the experimental performance of Snort based NIDS. We have used an open source network intrusion detection and prevention system Snort to implement our two different indexing methods. We used Snort version 2.9.7.5 which has almost 26k Snort rules and very efficient for online network auditing. We implemented prefix and random indexing method to all Snort rules to create primary patterns that reduce packet inspection time. Since all highly sensitive positive alerts need instant action from network administrator, our concept IDS also reduces the false positive (wrong alert) rate even at high network traffic. By combining the concept IDS and a data mining technique indexing will improve the accuracy of the intrusion detection in real time. We also present our experimental data and results of our IDS prototype. more...
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- 2018
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10. Comparative transcriptome analysis of hESC- and iPSC-derived corneal endothelial cells
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John D. Gottsch, Shahid Y. Khan, Firoz Kabir, S. Amer Riazuddin, and Muhammad Ali
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0301 basic medicine ,Male ,Corneal endothelium ,Cellular differentiation ,Cell ,Human Embryonic Stem Cells ,Induced Pluripotent Stem Cells ,Biology ,Peripheral blood mononuclear cell ,Transcriptome ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,medicine ,Humans ,Microscopy, Phase-Contrast ,Induced pluripotent stem cell ,Aged ,Gene Expression Profiling ,Endothelium, Corneal ,High-Throughput Nucleotide Sequencing ,Cell Differentiation ,Cadherins ,Embryonic stem cell ,Sensory Systems ,Cell biology ,Gene expression profiling ,Ophthalmology ,030104 developmental biology ,medicine.anatomical_structure ,cardiovascular system ,Zonula Occludens-1 Protein ,Biomarkers - Abstract
The corneal endothelium (CE), a monolayer of hexagonal cells constitutes the innermost layer of the cornea that is critical in maintaining clarity by mediating hydration through barrier and pump functions. Corneal endothelial cells (CECs) have limited proliferative potential and therefore generation of CECs has been undertaken by many groups. We previously reported generation of CECs from peripheral blood mononuclear cell (PBMC)-originated, induced pluripotent stem cells (iPSCs). In here, we extend our analysis through next-generation seqeuncing based transcriptome profiling of H9 human embryonic stem cell (hESC)- and human PBMC-originated, iPSC-derived CECs. The differentiating CECs on day 20 (D20) exhibited a tightly packed hexagonal/polygonal shape expressing zona occludens-1 (ZO-1) and N-cadherin at the cell boundaries. Next-generation RNA sequencing of hESC- and iPSC-derived CECs detected expression (≥0.659 RPKM) of 13,546 and 13,536 genes, respectively. Comparative transcriptome analysis of hESC- and iPSC-derived CECs revealed 13,208 (>96%) genes common in both transcriptomes. Among the 13,208 genes common in these transcriptomes, 12,580 (>95%) exhibited a quantitatively similar expression. To the best of our knowledge, this is the first report presenting comparative transcriptome analysis of hESC- and iPSC-derived CECs. more...
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- 2018
11. Whole genome sequencing data for two individuals of Pakistani descent
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Shahid Y. Khan, Sheikh Riazuddin, Oussama M’Hamdi, Muhammad Asif Naeem, Shaheen N. Khan, S. Amer Riazuddin, Xiaodong Jiao, Firoz Kabir, and J. Fielding Hejtmancik
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0301 basic medicine ,Statistics and Probability ,South asia ,dbSNP ,Library and Information Sciences ,Biology ,Genome ,Polymorphism, Single Nucleotide ,Deep sequencing ,Education ,03 medical and health sciences ,Data sequences ,Asian People ,Polymorphism (computer science) ,Humans ,Family ,Pakistan ,Whole genome sequencing ,Genetics ,Whole Genome Sequencing ,Genome, Human ,High-Throughput Nucleotide Sequencing ,Computer Science Applications ,genomic DNA ,030104 developmental biology ,Statistics, Probability and Uncertainty ,Information Systems - Abstract
Here we report next-generation based whole genome sequencing of two individuals (H1 and H2) from a family of Pakistani descent. The genomic DNA was used to prepare paired-end libraries for whole-genome sequencing. Deep sequencing yielded 706.49 and 778.12 million mapped reads corresponding to 70.64 and 77.81 Gb sequence data and 23× and 25× average coverage for H1 and H2, respectively. Notably, a total of 448,544 and 470,683 novel variants, not present in the single nucleotide polymorphism database (dbSNP), were identified in H1 and H2, respectively. Comparative analysis identified 2,415,852 variants common in both genomes including 240,181 variants absent in the dbSNP. Principal component analysis linked the ancestry of both genomes with South Asian populations. In conclusion, we report whole genome sequences of two individuals from a family of Pakistani descent. more...
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- 2018
12. Pattern of Chemical Ocular Injury: A Clinical Study
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Md. Firoz Kabir, Subrata Das, Md. Wazed Chowdhury, Saiem Mohd Nurul Anwar, Joyabrata Das, Ahmed Abdul Hannan, and Rajib Mothey
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medicine.medical_specialty ,education.field_of_study ,Visual acuity ,business.industry ,Population ,Visual disability ,Context (language use) ,Alkali burn ,Surgery ,Clinical study ,Good visual acuity ,Internal medicine ,Medicine ,General Materials Science ,medicine.symptom ,Male to female ,business ,education - Abstract
Background: Chemical ocular injury is a common injury among the population of Bangladesh. This present study in aimed to evaluate the pattern of chemical ocular injury in our context.Methods: This cross-sectional observational study was done among 50 patients of chemical ocular injury by different substances between January and June 2013. After initial evaluation patients were also followed up for next 3 months to evaluate the visual outcome.Results: Male to female ratio was 1.7:1. Males between 21-30 years and 41-50 years were mostly affected whereas females of 41-50 were affected most. Most commonly affected occupation was service (36%) followed by housewives (22%) and majority (58%) were from low socio-economic conditions. Thirty five (70%) cases were alkali burn and remainder 15 (30%) were acid burn. Among alkali, hydrated lime Ca (OH)2 had highest percentage 82.8%. Most (46%) patients with good visual acuity i.e. 6/12 6/24 belongs to early (less than six hours) reporting time interval. It was found that 48% were grade I and 34% cases were grade II injury and other grades were not pronounced. Study showed that improvement of visual acuity after initial management and subsequent treatment was significant.Conclusion: Alkali burn is the common pattern of ocular injury in our country where lime is the common chemical substance. Early intervention is essential to avoid long term visual disability.DOI: http://dx.doi.org/10.3329/cmoshmcj.v13i1.19418 more...
- Published
- 2014
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13. A spectrum of CYP1B1 mutations associated with primary congenital glaucoma in families of Pakistani descent
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Sheikh Riazuddin, Javed Akram, Firoz Kabir, Shaheen N. Khan, Tayyab Husnain, Bushra Rauf, Sabika Firasat, Bushra Irum, S. Amer Riazuddin, and Muhammad Asif Naeem
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0301 basic medicine ,Genetics ,Sanger sequencing ,Genetic heterogeneity ,Nonsense mutation ,Locus (genetics) ,Disease ,Biology ,Bioinformatics ,Biochemistry ,Frameshift mutation ,body regions ,03 medical and health sciences ,symbols.namesake ,030104 developmental biology ,0302 clinical medicine ,Data Report ,030221 ophthalmology & optometry ,symbols ,Microsatellite ,Missense mutation ,Molecular Biology - Abstract
Glaucoma is the second leading cause of blindness, affecting ~65 million people worldwide. We identified and ascertained a large cohort of inbred families with multiple individuals manifesting cardinal symptoms of primary congenital glaucoma (PCG) to investigate the etiology of the disease at a molecular level. Ophthalmic examinations, including slit-lamp microscopy and applanation tonometry, were performed to characterize the causal phenotype and confirm that affected individuals fulfilled the diagnostic criteria for PCG. Subsequently, exclusion analysis was completed with fluorescently labeled short tandem repeat markers, followed by Sanger sequencing to identify pathogenic variants. Exclusion analysis suggested linkage to the CYP1B1 locus, with positive two-point logarithm of odds scores in 23 families, while Sanger sequencing identified a total of 11 variants, including two novel mutations, in 23 families. All mutations segregated with the disease phenotype in their respective families. These included the following seven missense mutations: p.Y81N, p.E229K, p.R368H, p.R390H, p.W434R, p.R444Q and p.R469W, as well as one nonsense mutation, p.Q37*, and three frameshift mutations, p.W246Lfs81*, p.T404Sfs30* and p.P442Qfs15*. In conclusion, we identified a total of 11 mutations, reconfirming the genetic heterogeneity of CYP1B1 in the pathogenesis of PCG. To the best of our knowledge, this is the largest study investigating the contribution of CYP1B1 to the pathogenesis of PCG in the Pakistani population. more...
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- 2016
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14. Mutations in phosphodiesterase 6 identified in familial cases of retinitis pigmentosa
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S. Amer Riazuddin, Inayat Ullah, Sheikh Riazuddin, Shaheen N. Khan, Clare Brooks S. Gottsch, Aditya A. Guru, Radha Ayyagari, Firoz Kabir, Muhammad Asif Naeem, and Javed Akram
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0301 basic medicine ,Retinal Disorder ,Biology ,Neurodegenerative ,Eye ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Rare Diseases ,Locus heterogeneity ,PDE6B ,Retinitis pigmentosa ,medicine ,Data Report ,Genetics ,2.1 Biological and endogenous factors ,Aetiology ,Molecular Biology ,Eye Disease and Disorders of Vision ,030102 biochemistry & molecular biology ,Human Genome ,Neurosciences ,Phosphodiesterase ,Retinal ,medicine.disease ,Phenotype ,3. Good health ,chemistry ,030221 ophthalmology & optometry ,Human genome - Abstract
To delineate the genetic determinants associated with retinitis pigmentosa (RP), a hereditary retinal disorder, we recruited four large families manifesting cardinal symptoms of RP. We localized these families to regions on the human genome harboring the α and β subunits of phosphodiesterase 6 and identified mutations that were absent in control chromosomes. Our data suggest that mutations in PDE6A and PDE6B are responsible for the retinal phenotype in these families. more...
- Published
- 2016
15. Loss of function mutations in RP1 are responsible for retinitis pigmentosa in consanguineous familial cases
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Firoz, Kabir, Inayat, Ullah, Shahbaz, Ali, Alexander D H, Gottsch, Muhammad Asif, Naeem, Muhammad Zaman, Assir, Shaheen N, Khan, Javed, Akram, Sheikh, Riazuddin, Radha, Ayyagari, J Fielding, Hejtmancik, and S Amer, Riazuddin more...
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Male ,Base Sequence ,Genetic Linkage ,DNA Mutational Analysis ,Exons ,Polymerase Chain Reaction ,eye diseases ,Pedigree ,Consanguinity ,Young Adult ,Loss of Function Mutation ,Mutation ,Electroretinography ,Humans ,Female ,sense organs ,Lod Score ,Eye Proteins ,Microtubule-Associated Proteins ,Retinitis Pigmentosa ,Genome-Wide Association Study ,Research Article - Abstract
Purpose This study was undertaken to identify causal mutations responsible for autosomal recessive retinitis pigmentosa (arRP) in consanguineous families. Methods Large consanguineous families were ascertained from the Punjab province of Pakistan. An ophthalmic examination consisting of a fundus evaluation and electroretinography (ERG) was completed, and small aliquots of blood were collected from all participating individuals. Genomic DNA was extracted from white blood cells, and a genome-wide linkage or a locus-specific exclusion analysis was completed with polymorphic short tandem repeats (STRs). Two-point logarithm of odds (LOD) scores were calculated, and all coding exons and exon–intron boundaries of RP1 were sequenced to identify the causal mutation. Results The ophthalmic examination showed that affected individuals in all families manifest cardinal symptoms of RP. Genome-wide scans localized the disease phenotype to chromosome 8q, a region harboring RP1, a gene previously implicated in the pathogenesis of RP. Sanger sequencing identified a homozygous single base deletion in exon 4: c.3697delT (p.S1233Pfs22*), a single base substitution in intron 3: c.787+1G>A (p.I263Nfs8*), a 2 bp duplication in exon 2: c.551_552dupTA (p.Q185Yfs4*) and an 11,117 bp deletion that removes all three coding exons of RP1. These variations segregated with the disease phenotype within the respective families and were not present in ethnically matched control samples. Conclusions These results strongly suggest that these mutations in RP1 are responsible for the retinal phenotype in affected individuals of all four consanguineous families. more...
- Published
- 2015
16. Proteome Profiling of Developing Murine Lens Through Mass Spectrometry
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Santosh Renuse, Shahid Y. Khan, S. Amer Riazuddin, C. Conover Talbot, Sean F. Hackett, Chan Hyun Na, Firoz Kabir, and Muhammad Ali
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0301 basic medicine ,Proteome ,Biology ,Tandem mass tag ,Mass Spectrometry ,law.invention ,Transcriptome ,Lens protein ,Mice ,Lens ,03 medical and health sciences ,Protein sequencing ,law ,Lens, Crystalline ,medicine ,Animals ,RNA, Messenger ,Eye Proteins ,Gene Expression Profiling ,Trypsin ,Embryonic stem cell ,Cell biology ,Lens (optics) ,030104 developmental biology ,Animals, Newborn ,Models, Animal ,lens proteins ,medicine.drug - Abstract
Purpose We previously completed a comprehensive profile of the mouse lens transcriptome. Here, we investigate the proteome of the mouse lens through mass spectrometry-based protein sequencing at the same embryonic and postnatal time points. Methods We extracted mouse lenses at embryonic day 15 (E15) and 18 (E18) and postnatal day 0 (P0), 3 (P3), 6 (P6), and 9 (P9). The lenses from each time point were preserved in three distinct pools to serve as biological replicates for each developmental stage. The total cellular protein was extracted from the lens, digested with trypsin, and labeled with isobaric tandem mass tags (TMT) for three independent TMT experiments. Results A total of 5404 proteins were identified in the mouse ocular lens in at least one TMT set, 4244 in two, and 3155 were present in all three TMT sets. The majority of the proteins exhibited steady expression at all six developmental time points; nevertheless, we identified 39 proteins that exhibited an 8-fold differential (higher or lower) expression during the developmental time course compared to their respective levels at E15. The lens proteome is composed of diverse proteins that have distinct biological properties and functional characteristics, including proteins associated with cataractogenesis and autophagy. Conclusions We have established a comprehensive profile of the developing murine lens proteome. This repository will be helpful in identifying critical components of lens development and processes essential for the maintenance of its transparency. more...
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- 2018
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17. A Common Ancestral Mutation in CRYBB3 Identified in Multiple Consanguineous Families with Congenital Cataracts
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Xiaodong Jiao, S. Amer Riazuddin, David Li, J. Fielding Hejtmancik, Asma A. Khan, Firoz Kabir, Arif O. Khan, Tayyab Husnain, Bushra Irum, Qiwei Wang, Sheikh Riazuddin, and Javed Akram
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Male ,0301 basic medicine ,Chromosomes, Human, Pair 22 ,lcsh:Medicine ,Database and Informatics Methods ,Consanguinity ,Mice ,0302 clinical medicine ,beta-Crystallin B Chain ,Medicine and Health Sciences ,Missense mutation ,lcsh:Science ,Exome ,Lens (Anatomy) ,Genetics ,Sanger sequencing ,Mammalian Genomics ,Slit Lamp ,Multidisciplinary ,Chromosome Biology ,Genomics ,Genomic Databases ,Pedigree ,3. Good health ,Congenital cataracts ,symbols ,Female ,Anatomy ,Research Article ,Genetic Markers ,Ocular Anatomy ,Single-nucleotide polymorphism ,Biology ,Research and Analysis Methods ,Polymorphism, Single Nucleotide ,Chromosomes ,Cataract ,03 medical and health sciences ,symbols.namesake ,Genomic Medicine ,Ocular System ,Genetic linkage ,Lens, Crystalline ,medicine ,Animals ,Humans ,Family ,Alleles ,Evolutionary Biology ,Population Biology ,Base Sequence ,Cataracts ,Gene Expression Profiling ,lcsh:R ,Haplotype ,Biology and Life Sciences ,Computational Biology ,Cell Biology ,Genome Analysis ,medicine.disease ,eye diseases ,Ophthalmology ,Biological Databases ,030104 developmental biology ,Haplotypes ,Animal Genomics ,Genetic Loci ,Lens Disorders ,Mutation ,030221 ophthalmology & optometry ,lcsh:Q ,Lod Score ,Population Genetics ,Microsatellite Repeats - Abstract
Purpose This study was performed to investigate the genetic determinants of autosomal recessive congenital cataracts in large consanguineous families. Methods Affected individuals underwent a detailed ophthalmological examination and slit-lamp photographs of the cataractous lenses were obtained. An aliquot of blood was collected from all participating family members and genomic DNA was extracted from white blood cells. Initially, a genome-wide scan was performed with genomic DNAs of family PKCC025 followed by exclusion analysis of our familial cohort of congenital cataracts. Protein-coding exons of CRYBB1, CRYBB2, CRYBB3, and CRYBA4 were sequenced bidirectionally. A haplotype was constructed with SNPs flanking the causal mutation for affected individuals in all four families, while the probability that the four familial cases have a common founder was estimated using EM and CHM-based algorithms. The expression of Crybb3 in the developing murine lens was investigated using TaqMan assays. Results The clinical and ophthalmological examinations suggested that all affected individuals had nuclear cataracts. Genome-wide linkage analysis localized the causal phenotype in family PKCC025 to chromosome 22q with statistically significant two-point logarithm of odds (LOD) scores. Subsequently, we localized three additional families, PKCC063, PKCC131, and PKCC168 to chromosome 22q. Bidirectional Sanger sequencing identified a missense variation: c.493G>C (p.Gly165Arg) in CRYBB3 that segregated with the disease phenotype in all four familial cases. This variation was not found in ethnically matched control chromosomes, the NHLBI exome variant server, or the 1000 Genomes or dbSNP databases. Interestingly, all four families harbor a unique disease haplotype that strongly suggests a common founder of the causal mutation (p more...
- Published
- 2016
- Full Text
- View/download PDF
18. The role of the mitochondrial outer membrane in energy metabolism of tumor cells
- Author
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Firoz Kabir and B. Dean Nelson
- Subjects
Voltage-dependent anion channel ,Porins ,Saccharomyces cerevisiae ,Oxidative phosphorylation ,Mitochondrion ,Biochemistry ,Ion Channels ,chemistry.chemical_compound ,Adenosine Triphosphate ,Cytosol ,Hexokinase ,Animals ,Glycolysis ,biology ,Intracellular Membranes ,Neoplasms, Experimental ,General Medicine ,Plants ,Mitochondria ,Cell biology ,Neurospora ,chemistry ,Porin ,biology.protein ,Energy Metabolism ,Bacterial outer membrane ,Bacterial Outer Membrane Proteins - Abstract
Summary The outer mitochondrial membrane contains a pore structure which is composed of a 30 000 Da protein, porin. The pore has an internal diameter of 2 nm and exhibits a molecular-sieving exclusion limit between 3000 and 6000 Da. These pores, therefore, provide the exit/entrance port for metabolites moving between mitochondria and the cytosol. Hexokinase binds to porin on the outer surface of mitochondria. The location of hexokinase has evoked a number of theories in which bound hexokinase is given a central role in regulating glycolysis, and, perhaps, the metabolic communication between oxidative and glycolytic metabolism. This is of particular importance in rapidly growing tumor cells in which the aerobic production of lactate and hexokinase activity are highly induced. In the present paper, we summarize the suggested roles of the outer membrane and bound hexokinase in regulation glycolysis of tumor cells. Experiments attemping to elucidate the role of hexokinase binding in the regulation of tumor cell metabolism are presented. more...
- Published
- 1986
- Full Text
- View/download PDF
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