131 results on '"Mojarrad M"'
Search Results
2. Influence of a phase-space extension of nuclear forces on the sharp baryon-quark phase transition in hybrid neutron stars
- Author
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Ghaemmaghami, S. A., Khoshi, M. R., and Mojarrad, M. Ghazanfari
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- 2023
- Full Text
- View/download PDF
3. Hot dense nuclear matter with the Thomas-Fermi approximation
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Razavi, N.S. and Ghazanfari Mojarrad, M.
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- 2023
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4. A statistical model for the thermodynamic instabilities of asymmetric nuclear matter
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Ghaemmaghami, S. A. and Mojarrad, M. Ghazanfari
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- 2022
- Full Text
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5. Thomas–Fermi approximation in the phase transition of neutron star matter from [formula omitted]-stable nuclear matter to quark matter
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Ghazanfari Mojarrad, M. and Ranjbar, J.
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- 2020
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6. Experimental study of nutrient removal in an anaerobic hybrid upflow sludge blanket filtration bioreactor using response surface methodology
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Hashtroudi, H., Mojarrad, M., Noroozi, A., and Mahmoodi, Peyman
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- 2019
- Full Text
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7. Proto-neutron stars in the Thomas-Fermi theory
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Ghazanfari Mojarrad, M. and Razavi, N.S.
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- 2019
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8. Thomas–Fermi approximation for β-stable nuclear matter in the Landau Fermi-liquid theory
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Ghazanfari Mojarrad, M., Razavi, N.S., and Vaezzade, S.
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- 2018
- Full Text
- View/download PDF
9. Overexpression of functional human FLT3 ligand in Pichia pastoris
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Karimi, E., Faraji, H., Hamidi Alamdari, D., Souktanloo, M., Mojarrad, M., Ashman, L. K., and Mashkani, B.
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- 2017
- Full Text
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10. Identification of a Rare Mutation in the SRD5A2 Gene in an Iranian Family with Sex Development Disorder.
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Ataei, A., Eshraghi, P., Eslahi, A., Khazaei, Z., Rasool, M. Ale, Jamali, S., Ghadamyari, F., and Mojarrad, M.
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TESTOSTERONE ,SEX differentiation disorders ,GENITALIA ,PERIODIC health examinations ,ULTRASONIC imaging - Abstract
5 α-Reductase type 2 deficiency, caused by mutations in the SRD5A2 gene, leads to an autosomal recessive disorder of sex differentiation (DSD) in 46, XY persons. A 2 years old female with ambiguous genitalia was referred to Genetic Foundation of Khorasan Razavi (GFKR), IRAN. Her secondary sex characteristics, level of sex hormones, the development of reproductive system and karyotype were assessed. Whole-exome sequencing (WES) was preformed to find the pathogenic genetic variations associated with ambiguous genitalia. Also, Sanger sequencing was used to verify the WES results in the patient. Segregation analysis was performed to confirm mutation in the parents and other relatives. Physical examination and ultrasonography data demonstrated that the patient have testis in the left labium majus and right groin but does not have a uterus or ovaries. Sex hormone examination revealed that hormone therapy was successful and the level of FSH, LH, testosterone, and dihydrotestostron (DHT) was 2.8 mlu/ml, 2.4 mlu/ml, 15ng/dl, 21pg/ml, respectively. Cytogenetic study showed 46XY compatible to normal male karyotype. According to WES result and Sanger sequencing a homozygote loss of function mutation (c.16C>T; p.Gln6Ter) in SRD5A2 has been detected. Segregation analysis confirmed the mutation in the family. Homozygote mutation in SRD5A2 is the main cause of disorders of sex development in this family. [ABSTRACT FROM AUTHOR]
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- 2023
11. Hybrid neutron stars with the Thomas-Fermi approximation and nonlocal Nambu–Jona-Lasinio model
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Ranjbar, J., primary and Ghazanfari Mojarrad, M., additional
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- 2021
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12. Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants
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Neuray, C., Maroofian, R., Scala, M., Sultan, T., Pai, G. S., Mojarrad, M., Khashab, H. E., Deholl, L., Yue, W., Alsaif, H. S., Zanetti, M. N., Bello, O., Person, R., Eslahi, A., Khazaei, Z., Feizabadi, M. H., Efthymiou, S., El-Bassyouni, H. T., Soliman, D. R., Tekes, S., Ozer, L., Baltaci, V., Khan, S., Beetz, C., Amr, K. S., Salpietro, V., Jamshidi, Y., Alkuraya, F. S., Houlden, H., Groppa, S., Karashova, B. M., Nachbauer, W., Boesch, S., Arning, L., Timmann, D., Cormand, B., Perez-Duenas, B., Synaps, Group, Di Rosa, G., Aguennouz, M., Goraya, J. S., Mine, J., Avdjieva, D., Kathom, H., Tincheva, R., Banu, S., Pineda-Marfa, M., Veggiotti, P., Ferrari, M. D., Verrotti, A., Marseglia, G., Savasta, S., Garcia-Silva, M., Ruiz, A. M., Garavaglia, B., Borgione, E., Portaro, S., Sanchez, B. M., Boles, R., Papacostas, S., Vikelis, M., Papanicolaou, E. Z., Dardiotis, E., Maqbool, S., Ibrahim, S., Kirmani, S., Rana, N. N., Atawneh, O., Koutsis, G., Breza, M., Mangano, S., Scuderi, C., Morello, G., Stojkovic, T., Zollo, M., Heimer, G., Dauvilliers, Y. A., Striano, P., Al-Khawaja, I., Al-Mutairi, F., Sherifa, H., Neuray C., Maroofian R., Scala M., Sultan T., Pai G.S., Mojarrad M., Khashab H.E., deHoll L., Yue W., Alsaif H.S., Zanetti M.N., Bello O., Person R., Eslahi A., Khazaei Z., Feizabadi M.H., Efthymiou S., El-Bassyouni H.T., Soliman D.R., Tekes S., Ozer L., Baltaci V., Khan S., Beetz C., Amr K.S., Salpietro V., Jamshidi Y., Alkuraya F.S., Houlden H., Mangano S., Dicle Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Tıbbi Biyoloji Ana Bilim Dalı, Tekeş, Selahattin, University College of London [London] (UCL), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), University of Genoa (UNIGE), IRCCS Istituto Giannina Gaslini [Genoa, Italy], Children's Hospital [Lahore], Institute of Child Health [Lahore], Medical University of South Carolina [Charleston] (MUSC), Mashhad University of Medical Sciences, Ain Shams University (ASU), University of Oxford [Oxford], GeneDx [Gaithersburg, MD, USA], Khorasan Razavi Agricultural and Natural Resources Research and Education Center, National Research Centre [Cairo, Egypt], Benha University (BU), Dicle University, CENTOGENE AG, University of London [London], King Faisal Specialist Hospital [Riyadh, Saudi Arabia] (Research Centre), and SYNaPS Study Group: Stanislav Groppa, Blagovesta Marinova Karashova, Wolfgang Nachbauer, Sylvia Boesch, Larissa Arning, Dagmar Timmann, Bru Cormand, Belen Pérez-Dueñas, Gabriella Di Rosa, Jatinder S Goraya, Tipu Sultan, Jun Mine, Daniela Avdjieva, Hadil Kathom, Radka Tincheva, Selina Banu, Mercedes Pineda-Marfa, Pierangelo Veggiotti, Michel D Ferrari, Alberto Verrotti, Giangluigi Marseglia, Salvatore Savasta, Mayte García-Silva, Alfons Macaya Ruiz, Barbara Garavaglia, Eugenia Borgione, Simona Portaro, Benigno Monteagudo Sanchez, Richard Boles, Savvas Papacostas, Michail Vikelis, Eleni Zamba Papanicolaou, Efthymios Dardiotis, Shazia Maqbool, Shahnaz Ibrahim, Salman Kirmani, Nuzhat Noureen Rana, Osama Atawneh, George Koutsis, Marianthi Breza, Salvatore Mangano, Carmela Scuderi, Eugenia Borgione, Giovanna Morello, Tanya Stojkovic, Massimi Zollo, Gali Heimer, Yves A Dauvilliers, Pasquale Striano, Issam Al-Khawaja, Fuad Al-Mutairi, Hamed Sherifa
- Subjects
Male ,0301 basic medicine ,Glutamate decarboxylase ,Malalties cerebrals ,Neurotransmissors ,Neurodevelopmental delay ,Epilepsy ,0302 clinical medicine ,MESH: Child ,Age of Onset ,Child ,cleft palate ,GAD1 ,AcademicSubjects/SCI01870 ,Glutamate Decarboxylase ,Glutamate receptor ,Muscle weakness ,purl.org/becyt/ford/3.1 [https] ,Neurotransmitters ,MESH: Infant ,Hypotonia ,muscle weakne ,Cleft palate ,MESH: Epilepsy ,Child, Preschool ,Muscle Hypotonia ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,purl.org/becyt/ford/3 [https] ,Female ,Brain diseases ,Abnormalities ,medicine.symptom ,Multiple ,medicine.drug ,epilepsy ,muscle weakness ,neurodevelopmental delay ,MESH: Glutamate Decarboxylase ,medicine.medical_specialty ,MESH: Abnormalities, Multiple ,MESH: Mutation ,MESH: Age of Onset ,Biology ,Inhibitory postsynaptic potential ,GAD1, cleft palate, epilepsy, muscle weakness, neurodevelopmental delay ,gamma-Aminobutyric acid ,03 medical and health sciences ,Excitatory synapse ,Internal medicine ,medicine ,Humans ,Abnormalities, Multiple ,Preschool ,Alleles ,MESH: Neurodevelopmental Disorders ,MESH: Humans ,MESH: Muscle Hypotonia ,MESH: Alleles ,MESH: Child, Preschool ,Infant ,medicine.disease ,MESH: Male ,Epilèpsia ,Editor's Choice ,030104 developmental biology ,Endocrinology ,Neurodevelopmental Disorders ,Mutation ,AcademicSubjects/MED00310 ,Neurology (clinical) ,MESH: Female ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,030217 neurology & neurosurgery ,Reports - Abstract
Mice lacking GAD1 show neonatal mortality, but the human phenotype associated with GAD1 disruption is poorly characterized. Neuray et al. describe six patients with biallelic GAD1 mutations, presenting with early-infantile onset epilepsy, neurodevelopmental delay, muscle weakness and non-CNS manifestations., Gamma-aminobutyric acid (GABA) and glutamate are the most abundant amino acid neurotransmitters in the brain. GABA, an inhibitory neurotransmitter, is synthesized by glutamic acid decarboxylase (GAD). Its predominant isoform GAD67, contributes up to ∼90% of base-level GABA in the CNS, and is encoded by the GAD1 gene. Disruption of GAD1 results in an imbalance of inhibitory and excitatory neurotransmitters, and as Gad1−/− mice die neonatally of severe cleft palate, it has not been possible to determine any potential neurological dysfunction. Furthermore, little is known about the consequence of GAD1 disruption in humans. Here we present six affected individuals from six unrelated families, carrying bi-allelic GAD1 variants, presenting with developmental and epileptic encephalopathy, characterized by early-infantile onset epilepsy and hypotonia with additional variable non-CNS manifestations such as skeletal abnormalities, dysmorphic features and cleft palate. Our findings highlight an important role for GAD1 in seizure induction, neuronal and extraneuronal development, and introduce GAD1 as a new gene associated with developmental and epileptic encephalopathy.
- Published
- 2020
13. Thomas–Fermi approximation in the phase transition of neutron star matter from β-stable nuclear matter to quark matter
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Ghazanfari Mojarrad, M., primary and Ranjbar, J., additional
- Published
- 2020
- Full Text
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14. Cloning of K26 Hydrophilic Antigen from Iranian Strain of Leishmania infantum
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Hosseini Farash, B. R., Mohebali, M., Kazemi, B., Hajjaran, H., Akhoundi, B., Reza Raoofian, Fata, A., Mojarrad, M., and Sharifi-Yazdi, M. K.
- Subjects
Visceral leishmaniasis ,lcsh:Public aspects of medicine ,parasitic diseases ,lcsh:RA1-1270 ,Original Article ,K26 immunodominant antigen ,Leishmania infantum - Abstract
Background: Visceral leishmaniasis (VL) caused by Leishmania infantum is the most severe form of leishmaniasis in Iran, which causes a high mortality rate in the case of inaccurate diagnosis and treatment. This study aimed to clone of K26 gene from Iranian strain of L. infantum and register the sequencing results in Genbank to facilitate the preparation a new K26 antigen for the detection of L. infantum infection. Methods: L. infantum was obtained from an infected domestic dog in Meshkin-Shahr area from northwestern Iran in 2015. Canine visceral leishmaniasis was confirmed by direct agglutination test (DAT), rK39 dipstick and parasitological methods. L. infantum was confirmed by N-acetyl glucosamine -1-phosphate transferase (nagt)–PCR and its sequencing. The band of interest for k26 form Iranian strain of L. infantum was purified by gel extraction kit after PCR amplification and then ligated into pBluescript II SK (+) and pET-32a (+), respectively. The sequences of recombinant plasmids were analyzed and submitted to Genbank. Results: The submission of rk26 nucleotide sequence was performed to the GeneBank/NCBI Data Base under accession number KY212883. The related gene was showed a homology about 99% to L. chagasi and L. infantum k26 gene, while the level of homology in comparison with different strains of L. donovani ranged from 84-94%. Conclusion: The successful rk26 cloning into an expression vector performed in this study could help to produce a new recombinant antigen for serodiagnosis of VL especially in areas where L. infantum is the main causative agent.
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- 2017
15. PRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment
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Zollo, M, Ahmed, M, Ferrucci, V, Salpietro, V, Asadzadeh, F, Carotenuto, M, Maroofian, R, Al-Amri, A, Singh, R, Scognamiglio, I, Mojarrad, M, Musella, L, Duilio, A, Di Somma, A, Karaca, E, Rajab, A, Al-Khayat, A, Mohan Mohapatra, T, Eslahi, A, Ashrafzadeh, F, Rawlins, LE, Prasad, R, Gupta, R, Kumari, P, Srivastava, M, Cozzolino, F, Kumar Rai, S, Monti, M, Harlalka, GV, Simpson, MA, Rich, P, Al-Salmi, F, Patton, MA, Chioza, BA, Efthymiou, S, Granata, F, Di Rosa, G, Wiethoff, S, Borgione, E, Scuderi, C, Mankad, K, Hanna, MG, Pucci, P, Houlden, H, Lupski, JR, Crosby, AH, Baple, EL, Zollo, Massimo, Ahmed, M., Ferrucci, Veronica, Salpietro, V., Asadzadeh, F., Carotenuto, Marianeve, Maroofian, R., Al Amri, A., Singh, R., Scognamiglio, I., Mojarrad, M., Musella, L., Duilio, Angela, Di Somma, Angela, Karaca, E., Rajab, A., Al Khayat, A., Mohapatra, T. M., Eslahi, A., Ashrafzadeh, F., Rawlins, L. E., Prasad, R., Gupta, R., Kumari, P., Srivastava, M, Cozzolino, Flora, Rai, S. K., Monti, Maria, Harlalka, G. V., Simpson, M. A., Rich, P., Al Salmi, F., Patton, M. A., Chioza, B. A., Efthymiou, S., Granata, F., Di Rosa, G., Wiethoff, S., Borgione, E., Scuderi, C., Mankad, K., Hanna, M. G., Pucci, Pietro, Houlden, H., Lupski, J. R., Crosby, A. H., and Baple, E. L.
- Subjects
Male ,Adolescent ,Developmental delay ,Developmental Disabilities ,Nervous System ,Microtubules ,Normal brain development ,Young Adult ,Cell Movement ,Recessive ,Humans ,microcephaly ,Child ,Preschool ,Cytoskeleton ,Cerebral Cortex ,normal brain development ,fungi ,Brain ,Infant ,Cell Differentiation ,Original Articles ,Microtubule polymerization ,PRUNE1, developmental delay, microcephaly, microtubule polymerization, tubulinopathy, normal brain development ,Microcephaly ,PRUNE1 ,Tubulinopathy ,Carrier Proteins ,Child, Preschool ,Female ,Genes, Recessive ,Heredodegenerative Disorders, Nervous System ,Mutation ,Pedigree ,microtubule polymerization, tubulinopathy ,developmental delay ,Genes ,nervous system ,Heredodegenerative Disorders - Abstract
Zollo et al. report that mutations in PRUNE1, a phosphoesterase superfamily molecule, underlie primary microcephaly and profound global developmental delay in four unrelated families from Oman, India, Iran and Italy. The study highlights a potential role for prune during microtubule polymerization, suggesting that prune syndrome may be a tubulinopathy., PRUNE is a member of the DHH (Asp-His-His) phosphoesterase protein superfamily of molecules important for cell motility, and implicated in cancer progression. Here we investigated multiple families from Oman, India, Iran and Italy with individuals affected by a new autosomal recessive neurodevelopmental and degenerative disorder in which the cardinal features include primary microcephaly and profound global developmental delay. Our genetic studies identified biallelic mutations of PRUNE1 as responsible. Our functional assays of disease-associated variant alleles revealed impaired microtubule polymerization, as well as cell migration and proliferation properties, of mutant PRUNE. Additionally, our studies also highlight a potential new role for PRUNE during microtubule polymerization, which is essential for the cytoskeletal rearrangements that occur during cellular division and proliferation. Together these studies define PRUNE as a molecule fundamental for normal human cortical development and define cellular and clinical consequences associated with PRUNE mutation.
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- 2017
16. Hybrid neutron stars in the Thomas-Fermi theory
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Ghazanfari Mojarrad, M., primary and Ranjbar, J., additional
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- 2019
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17. P04.20 Analysis of HORMAD1, FTHL17 and ADAM29 Cancer/testis specific genes expression in Glioblastoma
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Anvari, K, primary, Mojarrad, M, additional, Gholamin, M, additional, Fathi, M, additional, Tabatabaii, A, additional, and Eslahi, A, additional
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- 2018
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18. P04.73 Detection of protein markers of two IDH1 gene mutation (R132H, R132S) by immunohistochemistry in brain Astrocytomas
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Anvari, K, primary, Tabatabaii, A, additional, Gholamin, M, additional, Mojarrad, M, additional, and Nikkhah, N, additional
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- 2018
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19. SUN-P061: Effects of L-Carnitine Supplementation on Body Composition in Patients with Nonalcoholic Steatohepatitis
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Amiri-Moghadam, S., primary, Nematy, M., additional, Eghtesadi, S., additional, Khalili, M., additional, Mojarrad, M., additional, Jazayeri, S., additional, Vosooghinia, H., additional, Khosravi, A., additional, Salehi, M., additional, Beheshti-Namdar, A., additional, and Mehdizadeh Hakkak, A., additional
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- 2017
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20. Detecting shoreline changes in Chabahar Bay by processing satellite images
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Zeinali, S., primary, Dehghani, M., additional, Rastegar, M.A., additional, and Mojarrad, M., additional
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- 2017
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21. Thomas–Fermi approximation for the equation of state of nuclear matter: A semi-classical approach from the Landau Fermi-Liquid theory
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Ghazanfari Mojarrad, M., primary and Mousavi Khoroshtomi, S. K., additional
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- 2017
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22. Hyperon-rich matter in a two-solar-mass neutron star within the Thomas-Fermi approximation
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Ghazanfari Mojarrad, M., primary and Arabsaeidi, R., additional
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- 2016
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23. Hybrid neutron stars in the Thomas-Fermi theory.
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Mojarrad, M. Ghazanfari and Ranjbar, J.
- Subjects
- *
NEUTRON stars , *NAMBU-Jona-Lasinio model , *QUARK matter , *EQUATIONS of state , *PHASE transitions , *PULSARS , *QUARKS - Abstract
The baryon-quark phase transition is studied for the equation of state (EOS) of neutron star (NS) matter. The Thomas-Fermi (TF) approximation is employed in a semiclassical mean-field (MF) model for the EOS of baryonic matter including hyperons. The EOS of quark matter is also extracted from the Nambu-Jona-Lasinio (NJL) model. The phase transition from baryons to quarks is considered in the NS structure under the Maxwell and Gibbs constructions. Our findings for the maximum mass of NSs, as compared with the almost 2M⊙ pulsars J1614-2230 and J0348+0432, indicate that a region of baryon-quark mixed phase can exist in the inner core of NSs, while the existence of a pure phase is not allowed. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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24. Genetic landscape of hearing loss in prelingual deaf patients of eastern Iran: Insights from exome sequencing analysis.
- Author
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Alerasool M, Eslahi A, Vona B, Kahaei MS, Mojaver NK, Rajati M, Pasdar A, Ghasemi MM, Saburi E, Ardehaie RM, Aval MH, Tale MR, Nourizadeh N, Afzalzadeh MR, Niknezhad HT, and Mojarrad M
- Abstract
Hearing loss is one of the most prevalent genetic disorders in humans. Locus and allelic heterogeneity cause fundamental challenges in hearing loss genetic diagnosis and management of patients and their families. This study examined the genetic profile of patients with prelingual hearing loss who were referred to the Genetic Foundation of Khorasan Razavi spanning over a decade. Deleterious variants in GJB2 were evaluated through Sanger sequencing among 745 non-syndromic hearing loss patients. Furthermore, exome sequencing was applied in 250 patients with negative GJB2 sequencing results and 30 patients with syndromic hearing loss. The findings revealed a relatively low frequency of GJB2 variants among the studied patients. Exome sequencing successfully identified the genetic causes of hearing loss in 70% of the patients. Moreover, variants in 10 genes, namely SLC26A4, MYO15A, TMPRSS3, TMC1, OTOF, CDH23, PJVK, MYO7A, TECTA, and PCDH15, accounted for 66% of the positive exome sequencing findings in this study. At least three prevalent founder alleles in the hearing-impaired population of eastern Iran were identified. This study emphasizes the efficiency of exome sequencing as a powerful tool for determining the etiology of prelingual hearing loss in the eastern Iranian population., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2024
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25. Enhancing Temozolomide (TMZ) chemosensitivity using CRISPR-dCas9-mediated downregulation of O 6 -methylguanine DNA methyltransferase (MGMT).
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Yousefi Y, Nejati R, Eslahi A, Alizadeh F, Farrokhi S, Asoodeh A, and Mojarrad M
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- Humans, DNA Repair Enzymes genetics, DNA Repair Enzymes metabolism, Brain Neoplasms genetics, Brain Neoplasms drug therapy, Brain Neoplasms pathology, DNA Modification Methylases genetics, DNA Modification Methylases metabolism, Tumor Suppressor Proteins genetics, Tumor Suppressor Proteins metabolism, HEK293 Cells, Drug Resistance, Neoplasm genetics, DNA Methylation drug effects, Gene Expression Regulation, Neoplastic drug effects, Cell Line, Tumor, Promoter Regions, Genetic, Temozolomide pharmacology, Antineoplastic Agents, Alkylating pharmacology, Antineoplastic Agents, Alkylating therapeutic use, CRISPR-Cas Systems, Down-Regulation, Glioblastoma genetics, Glioblastoma drug therapy
- Abstract
Purpose: Glioblastoma (GBM) stands out as the most prevalent and aggressive intracranial tumor, notorious for its poor prognosis. The current standard-of-care for GBM patients involves surgical resection followed by radiotherapy, combined with concurrent and adjuvant chemotherapy using Temozolomide (TMZ). The effectiveness of TMZ primarily relies on the activity of O
6 -methylguanine DNA methyltransferase (MGMT), which removes alkyl adducts from the O6 position of guanine at the DNA level, thereby counteracting the toxic effects of TMZ., Method: In this study, we employed fusions of catalytically-inactive Cas9 (dCas9) to DNA methyltransferases (dCas9-DNMT3A) to selectively downregulation MGMT transcription by inducing methylation at MGMT promoter and K-M enhancer., Result: Our findings demonstrate a significant reduction in MGMT expression, leading to intensified TMZ sensitivity in the HEK293T cell line., Conclusion: This study serves as a proof of concept for the utilization of CRISPR-based gene suppression to overcome TMZ resistance and enhance the lethal effect of TMZ in glioblastoma tumor cells., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)- Published
- 2024
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26. Contrast flow in CT-guided lumbar interlaminar epidural steroid injections: does needle position effect the laterality of contrast flow?
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Mojarrad M, Wieschhoff GG, and Mandell JC
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- Humans, Injections, Epidural methods, Female, Middle Aged, Adult, Male, Aged, Retrospective Studies, Aged, 80 and over, Steroids administration & dosage, Contrast Media administration & dosage, Radiography, Interventional methods, Tomography, X-Ray Computed methods, Lumbar Vertebrae diagnostic imaging, Needles
- Abstract
Purpose: To evaluate the effect of needle position on the laterality of contrast flow in CT-guided lumbar interlaminar epidural steroid injections., Materials and Methods: A retrospective review of consecutive CT-guided interlaminar lumbar epidural steroid injections was performed. The terminal needle tip position (midline or lateral) and the laterality of epidural contrast were evaluated by two readers. Contrast flow pattern was classified as ipsilateral to needle trajectory, bilateral, or contralateral. Bilateral flow was further divided into asymmetric, symmetrical, or asymmetric to the contralateral side. Inter-reader agreement was calculated with the kappa statistic. The relationship of needle position to contrast laterality was calculated with the chi statistic. Pain scores were compared for bilateral and unilateral flows with a two-tailed T test for independent means., Results: A total of 250 injections were included in 204 patients, with an age range of 24 to 93 years. The most commonly injected level (145/250) was L4-L5. Agreement between the two readers was almost perfect and substantial (kappa 0.751-0.880). The majority of injections (154/250) demonstrated contrast flow ipsilateral to the needle trajectory, 90/250 demonstrated bilateral flow, and 6/250 had contralateral flow. Of the 90 cases with bilateral flow, 80% were performed with a midline terminal needle position (p < 0.001). There was no difference in immediate post-procedure pain scores between patients with ipsilateral or bilateral contrast flow., Conclusion: For interlaminar epidural steroid injections, a midline terminal needle tip position has a greater probability of producing bilateral contrast flow compared to a lateral terminal needle tip position., (© 2024. The Author(s), under exclusive licence to International Skeletal Society (ISS).)
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- 2024
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27. Identification of a novel mutation of Platelet-Derived Growth Factor-C (PDGFC) gene in a girl with Non-Syndromic cleft lip and palate.
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Rahnama M, Movahedi T, Eslahi A, Kaseb-Mojaver N, Alerasool M, Adabi N, and Mojarrad M
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- Humans, Female, Animals, Child, Preschool, Iran, Mutation, Platelet-Derived Growth Factor genetics, Cleft Lip genetics, Cleft Palate genetics
- Abstract
Background: Cleft lip with or without cleft palate (CL/CP) is a prevalent congenital malformation. Approximately 16 candidate loci for CL/CP have been identified in both animal models and humans through association or genetic linkage studies. One of these loci is the platelet-derived growth factor-C (PDGFC) gene. In animal models, a mutation in the PDGFC gene has been shown to lead to CL/CP, with PDGF-C protein serving as a growth factor for mesenchymal cells, playing a crucial role in embryogenesis during the induction of neural crest cells. In this study, we present the identification of a novel frameshift mutation in the PDGFC gene, which we hypothesize to be associated with CL/CP, within a consanguineous Iranian family., Case Presentation: The proband was a 3-year-old girl with non-syndromic CL/CP. A history of craniofacial clefts was present in her family. Following genetic counseling, karyotype analysis and whole-exome sequencing (WES) were performed. Cytogenetic analysis revealed normal results, while WES analysis showed that the proband carried a homozygous c.546dupA (p.L183fs) mutation in the PDGFC gene. Sanger sequencing confirmed that her parents were carriers of the mutation., Conclusion: The c.546dupA (p.L183fs) mutation of PDGFC has not been previously reported and was not found in human genome databases. We speculate that the c.546dupA mutation of the PDGFC gene, identified in the Iranian patient, may be responsible for the phenotype of non-syndromic CL/CP (ns-CL/CP). Further studies are warranted to explore the specific pathogenesis of the PDGFC mutation in ns-CL/CP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)
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- 2024
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28. Production of Duchenne muscular dystrophy cellular model using CRISPR-Cas9 exon deletion strategy.
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Alizadeh F, Abraghan YJ, Farrokhi S, Yousefi Y, Mirahmadi Y, Eslahi A, and Mojarrad M
- Subjects
- Humans, Gene Editing methods, Cell Line, Sequence Deletion, Mutation, Muscular Dystrophy, Duchenne genetics, Muscular Dystrophy, Duchenne therapy, Muscular Dystrophy, Duchenne metabolism, Muscular Dystrophy, Duchenne pathology, CRISPR-Cas Systems, Exons, Dystrophin genetics, Dystrophin metabolism
- Abstract
Duchenne Muscular Dystrophy (DMD) is a progressive muscle wasting disorder caused by loss-of-function mutations in the dystrophin gene. Although the search for a definitive cure has failed to date, extensive efforts have been made to introduce effective therapeutic strategies. Gene editing technology is a great revolution in biology, having an immediate application in the generation of research models. DMD muscle cell lines are reliable sources to evaluate and optimize therapeutic strategies, in-depth study of DMD pathology, and screening the effective drugs. However, only a few immortalized muscle cell lines with DMD mutations are available. In addition, obtaining muscle cells from patients also requires an invasive muscle biopsy. Mostly DMD variants are rare, making it challenging to identify a patient with a particular mutation for a muscle biopsy. To overcome these challenges and generate myoblast cultures, we optimized a CRISPR/Cas9 gene editing approach to model the most common DMD mutations that include approximately 28.2% of patients. GAP-PCR and sequencing results show the ability of the CRISPR-Cas9 system to efficient deletion of mentioned exons. We showed producing truncated transcript due to the targeted deletion by RT-PCR and sequencing. Finally, mutation-induced disruption of dystrophin protein expression was confirmed by western blotting. All together, we successfully created four immortalized DMD muscle cell lines and showed the efficacy of the CRISPR-Cas9 system for the generation of immortalized DMD cell models with the targeted deletions., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2024
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29. Technical and cost analysis of zero-emission high-speed ferries: Retrofitting from diesel to green hydrogen.
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Mojarrad M, Thorne RJ, and Rødseth KL
- Abstract
This paper proposes a technical and cost analysis model to assess the change in costs of a zero-emission high-speed ferry when retrofitting from diesel to green hydrogen. Both compressed gas and liquid hydrogen are examined. Different scenarios explore energy demand, energy losses, fuel consumption, and cost-effectiveness. The methodology explores how variation in the ferry's total weight and equipment efficiency across scenarios impact results. Applied to an existing diesel high-speed ferry on one of Norway's longest routes, the study, under certain assumptions, identifies compressed hydrogen gas as the current most economical option, despite its higher energy consumption. Although the energy consumption of the compressed hydrogen ferry is slightly more than the liquid hydrogen counterpart, its operating expenses are considerably lower and comparable to the existing diesel ferry on the route. However, constructing large hydrogen liquefaction plants could reduce liquid hydrogen's cost and make it competitive with both diesel and compressed hydrogen gas. Moreover, liquid hydrogen allows the use of a superconducting motor to enhance efficiency. Operating the ferry with liquid hydrogen and a superconducting motor, besides its technical advantages, offers promising economic viability in the future, comparable to diesel and compressed hydrogen gas options. Reducing the ferry's speed and optimizing equipment improves fuel efficiency and economic viability. This research provides valuable insights into sustainable, zero-emission high-speed ferries powered by green hydrogen., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)
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- 2024
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30. Design Principles of a Novel Construct for HBB Gene-Editing and Investigation of Its Gene-Targeting Efficiency in HEK293 Cells.
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Lotfi M, Ashouri A, Mojarrad M, Mozaffari-Jovin S, and Abbaszadegan MR
- Subjects
- Humans, RNA, Guide, CRISPR-Cas Systems, HEK293 Cells, Gene Editing methods, Recombinational DNA Repair, CRISPR-Cas Systems, beta-Thalassemia genetics
- Abstract
Beta-thalassemia is one of the most common monogenic inherited disorders worldwide caused by different mutations in the hemoglobin subunit beta (HBB) gene. Genome-editing based on clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 system (CRISPR/Cas9) has raised the hope for life-long gene therapy of beta-thalassemia. In a proof-of-concept study, we describe the detailed design and assess the efficacy of a novel homology-directed repair (HDR)-based CRISPR construct for targeting the HBB locus. The selected sgRNAs were designed and cloned into an optimized CRISPR plasmid. The HDR donor templates containing a reporter and a selection marker flanked by the piggyBac Inverted Tandem Repeat (ITRs), the homology arms and the delta thymidine kinase (ΔTK) gene for negative selection were constructed. The efficiency of on-target mutagenesis by the eSpCas9/sgRNAs was assessed by mismatch assays. HDR-positive cells were isolated by treatment with G418 or selection based on truncated Neuron Growth Factor Receptor (tNGFR) expression using the Magnetic Activated Cell Sorting (MACS) method followed by ganciclovir (GCV) treatment to eliminate cells with random genomic integration of the HDR donor template. In-out PCR and sanger sequencing confirmed HDR in the isolated cells. Our data showed ~ 50% efficiency for co-transfection of CRISPR/donor template plasmids in HEK293 cells and following G418 treatment, the HDR efficiency was detected at ~ 37.5%. Moreover, using a clinically-relevant strategy, HDR events were validated after selection for tNGFR+ cells followed by negative selection for ΔTK by GCV treatment. Thus, our HDR-based gene-editing strategy could efficiently target the HBB locus and enrich for HDR-positive cells., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2024
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31. Characterizing Homozygous Variants in Bardet-Biedl Syndrome-Associated Genes Within Iranian Families: Unveiling a Founder Variant in BBS2, c.471G>A.
- Author
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Feizabadi MH, Alerasool M, Eslahi A, Esmaeilzadeh E, Mehrjardi MYV, Saket M, Farokhi S, Fattahi Z, Khorshid HRK, and Mojarrad M
- Abstract
Bardet-Biedl syndrome (BBS) is a rare inherited ciliopathy disorder characterized by a broad spectrum of clinical symptoms such as retinal dystrophy, obesity, polydactyly, genitourinary and kidney anomalies, learning disability, and hypogonadism. The understanding of the variants involved in BBS-causing genes remains incomplete, highlighting the need for further research to develop a molecular diagnostic strategy for this syndrome. Singleton whole-exome sequencing (WES) was performed on sixteen patients. Our study revealed (1) nine patients carried eight homozygous pathogenic variants with four of them being novel (2) Specifically, a synonymous splicing variant (c.471G > A) in BBS2 gene in six patients with Baloch ethnicity. The identification of runs of homozygosity (ROH) calling was performed using the BCFtools/RoH software on WES data of patients harboring c.471G > A variant. The presence of shared homozygous regions containing the identified variant was confirmed in these patients. In-silico analysis predicted the effect of the c.471G > A variants on BBS2 mRNA splicing. This variant results in disrupted wild-type donor site and intron retention in the mature mRNA. (3) And a deletion of exons 14 to 17 in the BBS1 gene was identified in one patient by Copy-Number Variation (CNV) analysis using the ExomeDepth pipeline. Our results identified the founder variant c.471G > A in the BBS2 gene in the Baloch ethnicity of the Iranian population. This finding can guide the diagnostic approach of this syndrome in future studies., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2024
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32. Bi-allelic genetic variants in the translational GTPases GTPBP1 and GTPBP2 cause a distinct identical neurodevelopmental syndrome.
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Salpietro V, Maroofian R, Zaki MS, Wangen J, Ciolfi A, Barresi S, Efthymiou S, Lamaze A, Aughey GN, Al Mutairi F, Rad A, Rocca C, Calì E, Accogli A, Zara F, Striano P, Mojarrad M, Tariq H, Giacopuzzi E, Taylor JC, Oprea G, Skrahina V, Rehman KU, Abd Elmaksoud M, Bassiony M, El Said HG, Abdel-Hamid MS, Al Shalan M, Seo G, Kim S, Lee H, Khang R, Issa MY, Elbendary HM, Rafat K, Marinakis NM, Traeger-Synodinos J, Ververi A, Sourmpi M, Eslahi A, Khadivi Zand F, Beiraghi Toosi M, Babaei M, Jackson A, Bertoli-Avella A, Pagnamenta AT, Niceta M, Battini R, Corsello A, Leoni C, Chiarelli F, Dallapiccola B, Faqeih EA, Tallur KK, Alfadhel M, Alobeid E, Maddirevula S, Mankad K, Banka S, Ghayoor-Karimiani E, Tartaglia M, Chung WK, Green R, Alkuraya FS, Jepson JEC, and Houlden H
- Subjects
- Animals, Humans, Drosophila melanogaster genetics, GTP Phosphohydrolases genetics, Phenotype, Drosophila Proteins genetics, GTP-Binding Proteins genetics, Microcephaly, Nervous System Malformations, Neurodevelopmental Disorders genetics
- Abstract
The homologous genes GTPBP1 and GTPBP2 encode GTP-binding proteins 1 and 2, which are involved in ribosomal homeostasis. Pathogenic variants in GTPBP2 were recently shown to be an ultra-rare cause of neurodegenerative or neurodevelopmental disorders (NDDs). Until now, no human phenotype has been linked to GTPBP1. Here, we describe individuals carrying bi-allelic GTPBP1 variants that display an identical phenotype with GTPBP2 and characterize the overall spectrum of GTP-binding protein (1/2)-related disorders. In this study, 20 individuals from 16 families with distinct NDDs and syndromic facial features were investigated by whole-exome (WES) or whole-genome (WGS) sequencing. To assess the functional impact of the identified genetic variants, semi-quantitative PCR, western blot, and ribosome profiling assays were performed in fibroblasts from affected individuals. We also investigated the effect of reducing expression of CG2017, an ortholog of human GTPBP1/2, in the fruit fly Drosophila melanogaster. Individuals with bi-allelic GTPBP1 or GTPBP2 variants presented with microcephaly, profound neurodevelopmental impairment, pathognomonic craniofacial features, and ectodermal defects. Abnormal vision and/or hearing, progressive spasticity, choreoathetoid movements, refractory epilepsy, and brain atrophy were part of the core phenotype of this syndrome. Cell line studies identified a loss-of-function (LoF) impact of the disease-associated variants but no significant abnormalities on ribosome profiling. Reduced expression of CG2017 isoforms was associated with locomotor impairment in Drosophila. In conclusion, bi-allelic GTPBP1 and GTPBP2 LoF variants cause an identical, distinct neurodevelopmental syndrome. Mutant CG2017 knockout flies display motor impairment, highlighting the conserved role for GTP-binding proteins in CNS development across species., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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33. Design of a rapid electrochemical biosensor based on MXene/Pt/C nanocomposite and DNA/RNA hybridization for the detection of COVID-19.
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Bolourinezhad M, Rezayi M, Meshkat Z, Soleimanpour S, Mojarrad M, Zibadi F, Aghaee-Bakhtiari SH, and Taghdisi SM
- Subjects
- Humans, SARS-CoV-2 genetics, RNA, Oligonucleotides, DNA, COVID-19 diagnosis, Biosensing Techniques methods, Nanocomposites
- Abstract
Since the rapid spread of the SARS-CoV-2 (2019), the need for early diagnostic techniques to control this pandemic has been highlighted. Diagnostic methods based on virus replication, such as RT-PCR, are exceedingly time-consuming and expensive. As a result, a rapid and accurate electrochemical test which is both available and cost-effective was designed in this study. MXene nanosheets (Ti
3 C2 Tx) and carbon platinum (Pt/C) were employed to amplify the signal of this biosensor upon hybridization reaction of the DNA probe and the virus's specific oligonucleotide target in the RdRp gene region. By the differential pulse voltammetry (DPV) technique, the calibration curve was obtained for the target with varying concentrations ranging from 1 aM to 100 nM. Due to the increase in the concentration of the oligonucleotide target, the signal of DPV increased with a positive slope and a correlation coefficient of 0.9977. Therefore, at least a limit of detection (LOD) was obtained 0.4 aM. Furthermore, the specificity and sensitivity of the sensors were evaluated with 192 clinical samples with positive and negative RT-PCR tests, which revealed 100% accuracy and sensitivity, 97.87% specificity and limit of quantification (LOQ) of 60 copies/mL. Besides, various matrices such as saliva, nasopharyngeal swabs, and serum were assessed for detecting SARS-CoV-2 infection by the developed biosensor, indicating that this biosensor has the potential to be used for rapid Covid-19 test detection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)- Published
- 2023
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34. Generation of Zebrafish Models of Human Retinitis Pigmentosa Diseases Using CRISPR/Cas9-Mediated Gene Editing System.
- Author
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Mirzaei F, Eslahi A, Karimi S, Alizadeh F, Salmaninejad A, Rezaei M, Mozaffari S, Hamzehloei T, Pasdar A, and Mojarrad M
- Abstract
Generating animal models can explore the role of new candidate genes in causing diseases and the pathogenicity of a specific mutation in the underlying genes. These animals can be used to identify new pharmaceutical or genetic therapeutic methods. In the present experiment, we developed a rpe65a knock out (KO) zebrafish as a retinitis pigmentosa (RP) disease model. Using the CRISPR/Cas9 system, the rpe65a gene was KO in zebrafish. Two specific single-guide RNAs (sgRNAs) were designed for the zebrafish rpe65a gene. SgRNAs were cloned into the DR274 plasmid and synthesized using in vitro transcription method. The efficiency of Ribonucleoprotein (synthesized sgRNA and recombinant Cas9) was evaluated by in vitro digestion experiment. Ribonucleoprotein complexes were microinjected into one to four-celled eggs of the TU zebrafish strain. The effectiveness of sgRNAs in KO the target gene was determined using the Heteroduplex mobility assay (HMA) and Sanger sequencing. Online software was used to determine the percent of mosaicism in the sequenced samples. By examining the sequences of the larvae that showed a mobility shift in the HMA method, the presence of indels in the binding region of sgRNAs was confirmed, so the zebrafish model for RP disease established. Zebrafish is an ideal animal model for the functional study of various diseases involving different genes and mutations and used for evaluating different therapeutic approaches in human diseases. This study presents the production of rpe65a gene KO zebrafish models using CRISPR/Cas9 technology. This model can be used in RP pathophysiology studies and preclinical gene therapy experiments., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2023
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35. Recent Advances in CRISPR/Cas9 Delivery Approaches for Therapeutic Gene Editing of Stem Cells.
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Lotfi M, Morshedi Rad D, Mashhadi SS, Ashouri A, Mojarrad M, Mozaffari-Jovin S, Farrokhi S, Hashemi M, Lotfi M, Ebrahimi Warkiani M, and Abbaszadegan MR
- Subjects
- Humans, Gene Editing, Cell Differentiation, Stem Cell Transplantation, CRISPR-Cas Systems genetics, Pluripotent Stem Cells
- Abstract
Rapid advancement in genome editing technologies has provided new promises for treating neoplasia, cardiovascular, neurodegenerative, and monogenic disorders. Recently, the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system has emerged as a powerful gene editing tool offering advantages, including high editing efficiency and low cost over the conventional approaches. Human pluripotent stem cells (hPSCs), with their great proliferation and differentiation potential into different cell types, have been exploited in stem cell-based therapy. The potential of hPSCs and the capabilities of CRISPR/Cas9 genome editing has been paradigm-shifting in medical genetics for over two decades. Since hPSCs are categorized as hard-to-transfect cells, there is a critical demand to develop an appropriate and effective approach for CRISPR/Cas9 delivery into these cells. This review focuses on various strategies for CRISPR/Cas9 delivery in stem cells., (© 2023. The Author(s).)
- Published
- 2023
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36. Lunapark deficiency leads to an autosomal recessive neurodevelopmental phenotype with a degenerative course, epilepsy and distinct brain anomalies.
- Author
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Accogli A, Zaki MS, Al-Owain M, Otaif MY, Jackson A, Argilli E, Chandler KE, De Goede CGEL, Cora T, Alvi JR, Eslahi A, Asl Mohajeri MS, Ashtiani S, Au PYB, Scocchia A, Alakurtti K, Pagnamenta AT, Toosi MB, Karimiani EG, Mojarrad M, Arab F, Duymuş F, Scantlebury MH, Yeşil G, Rosenfeld JA, Türkyılmaz A, Sağer SG, Sultan T, Ashrafzadeh F, Zahra T, Rahman F, Maqbool S, Abdel-Hamid MS, Issa MY, Efthymiou S, Bauer P, Zifarelli G, Salpietro V, Al-Hassnan Z, Banka S, Sherr EH, Gleeson JG, Striano P, Houlden H, Severino M, and Maroofian R
- Abstract
LNPK encodes a conserved membrane protein that stabilizes the junctions of the tubular endoplasmic reticulum network playing crucial roles in diverse biological functions. Recently, homozygous variants in LNPK were shown to cause a neurodevelopmental disorder (OMIM#618090) in four patients displaying developmental delay, epilepsy and nonspecific brain malformations including corpus callosum hypoplasia and variable impairment of cerebellum. We sought to delineate the molecular and phenotypic spectrum of LNPK -related disorder. Exome or genome sequencing was carried out in 11 families. Thorough clinical and neuroradiological evaluation was performed for all the affected individuals, including review of previously reported patients. We identified 12 distinct homozygous loss-of-function variants in 16 individuals presenting with moderate to profound developmental delay, cognitive impairment, regression, refractory epilepsy and a recognizable neuroimaging pattern consisting of corpus callosum hypoplasia and signal alterations of the forceps minor ('ear-of-the-lynx' sign), variably associated with substantia nigra signal alterations, mild brain atrophy, short midbrain and cerebellar hypoplasia/atrophy. In summary, we define the core phenotype of LNPK -related disorder and expand the list of neurological disorders presenting with the 'ear-of-the-lynx' sign suggesting a possible common underlying mechanism related to endoplasmic reticulum-phagy dysfunction., Competing Interests: The Department of Molecular and Human Genetics at Baylor College of Medicine receives revenue from clinical genetic testing completed at Baylor Genetics Laboratories., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)
- Published
- 2023
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37. Broadening the phenotypic and molecular spectrum of FINCA syndrome: Biallelic NHLRC2 variants in 15 novel individuals.
- Author
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Sczakiel HL, Zhao M, Wollert-Wulf B, Danyel M, Ehmke N, Stoltenburg C, Damseh N, Al-Ashhab M, Balci TB, Osmond M, Andrade A, Schallner J, Porrmann J, McDonald K, Liao M, Oppermann H, Platzer K, Dierksen N, Mojarrad M, Eslahi A, Bakaeean B, Calame DG, Lupski JR, Firoozfar Z, Seyedhassani SM, Mohammadi SA, Anwaar N, Rahman F, Seelow D, Janz M, Horn D, Maroofian R, and Boschann F
- Subjects
- Humans, Disease Progression, Fibrosis, HEK293 Cells, Phenotype, Seizures genetics, Syndrome, Intellectual Disability genetics, Movement Disorders
- Abstract
FINCA syndrome [MIM: 618278] is an autosomal recessive multisystem disorder characterized by fibrosis, neurodegeneration and cerebral angiomatosis. To date, 13 patients from nine families with biallelic NHLRC2 variants have been published. In all of them, the recurrent missense variant p.(Asp148Tyr) was detected on at least one allele. Common manifestations included lung or muscle fibrosis, respiratory distress, developmental delay, neuromuscular symptoms and seizures often followed by early death due to rapid disease progression.Here, we present 15 individuals from 12 families with an overlapping phenotype associated with nine novel NHLRC2 variants identified by exome analysis. All patients described here presented with moderate to severe global developmental delay and variable disease progression. Seizures, truncal hypotonia and movement disorders were frequently observed. Notably, we also present the first eight cases in which the recurrent p.(Asp148Tyr) variant was not detected in either homozygous or compound heterozygous state.We cloned and expressed all novel and most previously published non-truncating variants in HEK293-cells. From the results of these functional studies, we propose a potential genotype-phenotype correlation, with a greater reduction in protein expression being associated with a more severe phenotype.Taken together, our findings broaden the known phenotypic and molecular spectrum and emphasize that NHLRC2-related disease should be considered in patients presenting with intellectual disability, movement disorders, neuroregression and epilepsy with or without pulmonary involvement., (© 2023. The Author(s).)
- Published
- 2023
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38. New advancements in CRISPR based gene therapy of Duchenne muscular dystrophy.
- Author
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Eslahi A, Alizadeh F, Avan A, Ferns GA, Moghbeli M, Reza Abbaszadegan M, and Mojarrad M
- Subjects
- Humans, Dystrophin genetics, CRISPR-Cas Systems, Gene Editing, Genetic Therapy, Muscular Dystrophy, Duchenne genetics, Muscular Dystrophy, Duchenne therapy
- Abstract
Duchenne muscular dystrophy (DMD) is caused by the dystrophin gene mutations and is one of the most common and lethal human hereditary disorders. A novel therapeutic approach using CRISPR technology has gained attention in the treatment of DMD. Gene replacement strategies are being proposed as a promising therapeutic option to compensate the loss of function mutations. Although, the large size of the dystrophin gene and the limitations of the existing gene replacement approach, could mean the gene delivery of shortened versions of dystrophin such as midystrophin and microdystrophins. There are also other approaches: including Targeted removal of dystrophin exons to restore the reading-frame; Dual sgRNA-directed DMD exon deletion, CRISPR-SKIP strategy; reframing of dystrophin using Prime Editing technology; exon removal using twin prime technology; TransCRISTI technology to targeted exon integration into dystrophin gene. Here we provide an overview of recent progresses in dystrophin gene editing using updated versions of CRISPR to introduce novel opportunities in DMD gene therapy. Overall, the novel CRISPR based technologies are improving and expanding to allow the application of more precise gene editing for the treatment of DMD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)
- Published
- 2023
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39. CRISPR-Based Fluorescent Reporter (CBFR) Assay for Sensitive, Specific, Inexpensive, and Visual Detection of a Specific EGFR Exon 19 Deletion in NSCLC.
- Author
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Salehipour P, Mahdiannasser M, Sedaghat Shayegan G, Shankaie K, Tabrizi M, Mojarrad M, and Modarressi MH
- Subjects
- Humans, Mutation, ErbB Receptors genetics, Coloring Agents, Exons, Carcinoma, Non-Small-Cell Lung genetics, Lung Neoplasms genetics
- Abstract
Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein receptor with intracellular tyrosine kinase activity. Mutations in the EGFR gene, including deletions in exon 19 and the mutation L858R, induce responsiveness of non-small cell lung cancer (NSCLC) to a group of drugs known as tyrosine kinase inhibitors. Here, we report the development of the CRISPR-based fluorescent reporter (CBFR) assay including a two-step strategy combining PCR amplification and Cas12a-driven cleavage to detect the delE746_A750 subtype of EGFR exon 19 deletions. Sensitivity and specificity of the CBFR assay were analyzed with different concentrations of fluorescence reporter and different amounts of PCR product. The results demonstrated that increasing the fluorescent reporter to 4 μM and the PCR product to 5 μl enhanced sensitivity. The CBFR assay could detect EGFR exon 19 deletion even with a frequency of 1% in samples. In clinical NSCLC samples, optimized CBFR assay enabled visual detection of the delE746_A750 subtype in less than 1 h. The CBFR assay provides a sensitive, specific, and simple strategy designed based on a straightforward and inexpensive process. We suggest that the CBFR assay could serve as a diagnostic approach to detect mutations, deletions, and pathogens in underequipped laboratories and promote personalized therapeutic approaches., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2023
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40. Bioaugmentation with marine sediment-derived microbial consortia in mesophilic anaerobic digestion for enhancing methane production under ammonium or salinity stress.
- Author
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Duc LV, Nagao S, Mojarrad M, Miyagawa Y, Li ZY, Inoue D, Tajima T, and Ike M
- Subjects
- Bioreactors, Anaerobiosis, Sodium Chloride pharmacology, Methane, Geologic Sediments, Salt Stress, Microbial Consortia, Ammonium Compounds
- Abstract
Ammonium (NH
4 + ) and salinity (NaCl) inhibit CH4 production in anaerobic digestion. However, whether bioaugmentation using marine sediment-derived microbial consortia can relieve the inhibitory effects of NH4 + and NaCl stresses on CH4 production remains unclear. Thus, this study evaluated the effectiveness of bioaugmentation using marine sediment-derived microbial consortia in alleviating the inhibition of CH4 production under NH4 + or NaCl stress and elucidated the underlying mechanisms. Batch anaerobic digestion experiments under 5 gNH4 -N/L or 30 g/L NaCl were performed with or without augmentation using two marine sediment-derived microbial consortia pre-acclimated to high NH4 + and NaCl. Compared with non-bioaugmentation, bioaugmentation reinforced CH4 production. Network analysis revealed the joint effects of microbial connections by Methanoculleus, which promoted the efficient consumption of propionate accumulated under NH4 + and NaCl stresses. In conclusion, bioaugmentation with pre-acclimated marine sediment-derived microbial consortia can mitigate the inhibition under NH4 + or NaCl stress and enhance CH4 production in anaerobic digestion., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)- Published
- 2023
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41. Targeted Cell Labeling and Sorting of Prokaryotes for Cultivation and Omics Approaches.
- Author
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Sturm G, Mojarrad M, and Kaster AK
- Subjects
- Genome, Cell Separation, Metagenomics methods, Prokaryotic Cells
- Abstract
To date, the vast majority of prokaryotic organisms escapes detailed characterization because they cannot be isolated in axenic cultures. These organisms are referred to as microbial dark matter. Targeted labelling and sorting of these microorganisms pave the way for single-cell, enrichment, or cultivation approaches. In this review, we describe an array of different methods ranging from labeling-free to specific labelling techniques. In addition, different cell sorting methods and their combinations with targeting strategies are summarized and downstream applications like sequencing and cultivation are reviewed. Recent advances, challenges, and limitations of the particular methods are discussed with respect to cell viability, genome integrity as well as throughput, in order to help researchers select the most suitable methods for their specific research questions., (© 2023 The Author(s). Published by S. Karger AG, Basel.)
- Published
- 2023
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42. Posterior Cruciate Ligament and Patellar Tendon Can Predict Anterior Cruciate Ligament Size for Planning During ACL Reconstruction in Pediatric Patients.
- Author
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Strada NA, Vutescu ES, Mojarrad M, Harrington R, Orman S, Evangelista P, and Cruz AI Jr
- Abstract
Purpose: To establish correlations between the anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), and patellar tendon in normal pediatric knees to inform surgical planning for ACL reconstruction graft size., Methods: Magnetic resonance imaging scans of patients ages 8 to 18 years were assessed. Measurements included ACL and PCL length, thickness, and width, and ACL footprint thickness and width at the tibial insertion. Interrater reliability was assessed with a random set of 25 patients. Pearson correlation coefficients were used to assess the correlation between ACL, PCL, and patellar tendon measurements. Linear regression models were used to test whether the relationships differed by sex or age., Results: Magnetic resonance imaging scans of 540 patients were assessed. Interrater reliability was high for all measurements except PCL thickness at midsubstance. Sample equations for estimating ACL size are as follows: ACL length = 22.61 + 1.55∗PCL origin width (R
2 = 0.46; 8- to 11-year-old male patients), ACL length = 12.37 + 0.58∗PCL length + 2.29∗PCL origin thickness - 0.90∗PCL insertion width (R2 = 0.68; 8- to 11-year-old female patients), ACL midsubstance thickness = 4.95 + 0.25∗PCL midsubstance thickness + 0.04∗PCL insertion thickness - 0.08∗PCL insertion width (R2 = 0.12; 12- to 18-year-old male patients), and ACL midsubstance width = 0.57 + 0.23∗PCL midsubstance thickness + 0.07∗PCL midsubstance width + 0.16∗PCL insertion width (R2 = 0.24; 12- to 18-year-old female patients)., Conclusions: We found correlations between ACL, PCL, and patellar tendon measurements that can be used to create equations that predict ACL size in various dimensions based on PCL and patellar tendon measurements., Clinical Relevance: There is a lack of consensus on the ideal ACL graft diameter for pediatric ACL reconstruction. The findings from this study can assist orthopaedic surgeons to individualize ACL graft size for specific patients., (© 2022 The Authors.)- Published
- 2022
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43. CFTR mutations causing congenital unilateral absence of the vas deferens (CUAVD) and congenital absence of the uterus (CAU) in a consanguineous family.
- Author
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Ghouchanatigh MD, Khan R, Mojarrad M, Hameed U, Zubair M, Waqas A, Jalali M, Kalantari M, Shamsa A, Zhang H, and Shi QH
- Subjects
- Consanguinity, Cystic Fibrosis Transmembrane Conductance Regulator genetics, Female, Humans, Iran, Male, Mutation, Urogenital Abnormalities, Uterus abnormalities, Vas Deferens abnormalities, Azoospermia genetics, Azoospermia pathology, Cystic Fibrosis
- Abstract
Cystic fibrosis (CF) is one of the most common recessive genetic diseases, with a wide spectrum of phenotypes, ranging from infertility to severe pulmonary disease. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are considered the main genetic cause for CF. In this study, we recruited a consanguineous Iranian pedigree with four male patients diagnosed with congenital unilateral absence of the vas deferens (CUAVD), and one female patient diagnosed with congenital absence of the uterus (CAU). Testicular biopsy of one patient was performed, and hematoxylin and eosin (H and E) staining of testis sections displayed the presence of germ cell types ranging from spermatogonia to mature spermatids, indicating obstructive azoospermia. To explore the underlying genetic factor in this familial disorder, we therefore performed whole-exome sequencing (WES) on all available family members. WES data filtration and CFTR haplotype analysis identified compound heterozygous mutations in CFTR among four patients (two CUAVD patients carried p.H949Y and p.L997F, and one CUAVD and the female CAU patient carried p.H949Y and p.I148T). All these mutations were predicted to be deleterious by at least half of the prediction software programs and were confirmed by Sanger sequencing. Our study reported that CFTR compound heterozygous mutations in a consanguineous Iranian family cause infertility in both sexes., Competing Interests: None
- Published
- 2022
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44. Sensitive and specific clinically diagnosis of SARS-CoV-2 employing a novel biosensor based on boron nitride quantum dots/flower-like gold nanostructures signal amplification.
- Author
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Hatamluyi B, Rezayi M, Amel Jamehdar S, Rizi KS, Mojarrad M, Meshkat Z, Choobin H, Soleimanpour S, and Boroushaki MT
- Subjects
- Boron Compounds, Gold, Humans, RNA, Viral genetics, SARS-CoV-2 genetics, Sensitivity and Specificity, Biosensing Techniques methods, COVID-19 diagnosis, Nanostructures, Quantum Dots
- Abstract
The sudden increase of the COVID-19 outbreak and its continued growth with mutations in various forms has created a global health crisis as well as devastating social and economic effects over the past two years. In this study, a screen-printed carbon electrode reinforced with boron nitride quantum dots/flower-like gold nanostructures (BNQDs/FGNs/SPCE) and functionalized by highly specific antisense DNA oligonucleotide presents an alternative and promising solution for targeting SARS-CoV-2 RNA without nucleic acid amplification. The platform was tested on 120 SARS-CoV-2 RNA isolated from real clinical samples (60 positive and 60 negative confirmed by conventional RT-PCR method). Based on obtained quantitative results and statistical analysis (box-diagram, cutoff value, receiver operating characteristic curve, and t-test), the biosensor revealed a significant difference between the two positive and negative groups with 100% sensitivity and 100% specificity. To evaluate the quantitation capacity and detection limit of the biosensor for clinical trials, the detection performance of the biosensor for continuously diluted RNA isolated from SARS-CoV-2-confirmed patients was compared to those obtained by RT-PCR, demonstrating that the detection limit of the biosensor is lower than or comparable to that of RT-PCR. The ssDNA/BNQDs/FGNs/SPCE showed negligible cross-reactivity with RNA fragments isolated from Influenza A (IAV) clinical samples and also remained stable for up to 14 days. In conclusion, the fabricated biosensor may serve as a promising tool for point-of-care applications., (Copyright © 2022 Elsevier B.V. All rights reserved.)
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- 2022
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45. Challenges of expressing recombinant human tissue factor as a secreted protein in Pichia pastoris .
- Author
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Jalili-Nik M, Soukhtanloo M, Mojarrad M, Sadeghian MH, and Mashkani B
- Subjects
- Codon genetics, Codon metabolism, Humans, Recombinant Proteins metabolism, Saccharomycetales, Pichia genetics, Pichia metabolism, Thromboplastin genetics, Thromboplastin metabolism
- Abstract
Tissue factor (TF) is the core reagent in the prothrombin time (PT) assay. In this study, expression and α-factor mediated secretion of three forms of tissue factor (full-length TF (Full-TF), extracellular plus transmembrane domain (TED-TF), and only extracellular domain (ED-TF) were investigated in Pichia pastoris . The amino acid sequence of TF was obtained from the UniProt database, back-translated and codon-optimized for expression in Pichia pastoris . The Full-TF sequence was synthesized but the ED-TF, TED-TF coding fragments were extracted from the Full-TF by PCR. All the coding sequences were cloned into pPICZαA vector in-frame with the α-factor; and electroporated into KM71H. The culture supernatants and the cell lysates were analyzed using SDS-PAGE, dot-blotting, and Western-blotting for expression of TF. The Full-TF and TED-TF expression vector pPICZαA were successfully inserted into the KM71H, but the product was not detected in the SDS-PAGE analysis of the culture supernatant. However, ED-TF expression and secretion was verified by SDS-PAGE, dot blotting, and Western blotting. It seems that the TM domain in the Full-TF and TED-TF have an important role in impairing α-factor-mediated secretion of TF. Therefore, further investigation is necessary to overcome challenges of expressing Full-TF as a heterologous protein in P. pastoris .
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- 2022
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- View/download PDF
46. MicroRNA-96: A therapeutic and diagnostic tumor marker.
- Author
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Rahimi HR, Mojarrad M, and Moghbeli M
- Abstract
Cancer has been always considered as one of the main human health challenges worldwide. One of the main causes of cancer-related mortality is late diagnosis in the advanced stages of the disease, which reduces the therapeutic efficiency. Therefore, novel non-invasive diagnostic methods are required for the early detection of tumors and improving the quality of life and survival in cancer patients. MicroRNAs (miRNAs) have pivotal roles in various cellular processes such as cell proliferation, motility, and neoplastic transformation. Since circulating miRNAs have high stability in body fluids, they can be suggested as efficient noninvasive tumor markers. MiR-96 belongs to the miR-183-96-182 cluster that regulates cell migration and tumor progression as an oncogene or tumor suppressor by targeting various genes in solid tumors. In the present review, we have summarized all of the studies that assessed the role of miR-96 during tumor progression. This review clarifies the molecular mechanisms and target genes recruited by miR-96 to regulate tumor progression and metastasis. It was observed that miR-96 mainly affects tumorigenesis by targeting the structural proteins and FOXO transcription factors., Competing Interests: The authors declare that they have no conflicts of interest.
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- 2022
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47. Whole exome sequencing in 17 consanguineous Iranian pedigrees expands the mutational spectrum of inherited retinal dystrophies.
- Author
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Rehman AU, Sepahi N, Bedoni N, Ravesh Z, Salmaninejad A, Cancellieri F, Peter VG, Quinodoz M, Mojarrad M, Pasdar A, Asad AG, Ghalamkari S, Piran M, Piran M, Superti-Furga A, and Rivolta C
- Subjects
- DNA Mutational Analysis, Eye Diseases, Hereditary diagnosis, Eye Proteins genetics, Female, Gene Frequency, Guanylate Cyclase genetics, Humans, Iran, Male, Mutation, Pedigree, Receptors, Cell Surface genetics, Retinal Dystrophies diagnosis, Exome Sequencing, Consanguinity, Eye Diseases, Hereditary genetics, Retinal Dystrophies genetics
- Abstract
Inherited retinal dystrophies (IRDs) constitute one of the most heterogeneous groups of Mendelian human disorders. Using autozygome-guided next-generation sequencing methods in 17 consanguineous pedigrees of Iranian descent with isolated or syndromic IRD, we identified 17 distinct genomic variants in 11 previously-reported disease genes. Consistent with a recessive inheritance pattern, as suggested by pedigrees, variants discovered in our study were exclusively bi-allelic and mostly in a homozygous state (in 15 families out of 17, or 88%). Out of the 17 variants identified, 5 (29%) were never reported before. Interestingly, two mutations (GUCY2D:c.564dup, p.Ala189ArgfsTer130 and TULP1:c.1199G > A, p.Arg400Gln) were also identified in four separate pedigrees (two pedigrees each). In addition to expanding the mutational spectrum of IRDs, our findings confirm that the traditional practice of endogamy in the Iranian population is a prime cause for the appearance of IRDs., (© 2021. The Author(s).)
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- 2021
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48. PLA2G6 gene mutation and infantile neuroaxonal degeneration; report of three cases from Iran.
- Author
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Jafarzadeh Esfehani R, Eslahi A, Beiraghi Toosi M, Sadr-Nabavi A, Kerachian MA, Asl Mohajeri MS, Farjami M, Alizade F, and Mojarrad M
- Abstract
Objectives: Infantile neuroaxonal degeneration (INAD) is a rare subgroup of neurodegeneration with brain iron accumulation (NBIA) disorders. This progressive disorder may develop during the early years of life. Affected individuals mostly manifest developmental delay and/or psychomotor regression as well as other neurological deficits. In the present study, we discussed 3 INAD patients diagnosed before the age of 10 by using Whole-Exome Sequencing (WES)., Materials and Methods: We evaluated 3 pediatric patients with clinical phenotypes of INAD who underwent WES. Sanger sequencing was performed for co-segregation analysis of the variants in the families. An in-silico study was conducted for identification of the molecular function of the identified genetic variants in the PLA2G6 gene., Results: We detected three novel genetic variants in the PLA2G6 gene including a homozygous missense (NM_003560.2; c.1949T>C; p.Phe650Ser), a splicing (NM_001349864; c.1266-1G>A) and a frameshift variant (NM_003560.4; c.1547_1548dupCG; p.Gly517ArgfsTer29). Since the variants were not previously reported in literature or population databases, we performed in-silico studies for these variants and demonstrated their potential pathogenicity., Conclusion: The current study reports novel genetic variants in the PLA2G6 gene in the Iranian population, emphasizing the importance of high-throughput genetic testing in rare diseases., Competing Interests: The authors do not have any conflict of intrest to declare.
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- 2021
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49. Association of tensor fascia lata hypertrophy and fatty infiltration in the presence of abductor tendon tears: a radiographic study.
- Author
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Quinn M, Levins J, Mojarrad M, O'Donnell R, DeFroda S, Haggerty E, Evangelista P, and Tabaddor R
- Abstract
Hip abductor tendon tears of the gluteus medius and minimus are becoming a well-recognized source of pain and dysfunction, primarily in middle-age females. Like the rotator cuff, fatty infiltration (FI) can occur after tearing of these tendons. While the association of TFL hypertrophy after abductor tendon tears has been established, its association with FI has not been well studied. Our hypothesis is that hypertrophy of the TFL will be associated with FI of the abductors. All patients >18 years old undergoing primary surgical repair for a confirmed tears on MRI, without a history of prior hip surgery or osteoarthritis, were included. The following measurements were obtained from MRI: TFL cross-sectional area, TFL:sartorius volume ratio, and modified Goutallier grade of gluteus medius and minimus. Seventy patients met inclusion criteria and were divided in two groups, those with ( n = 28) and those without FI ( n = 42) of the abductors. The FI group was on average older (65 versus 58 years, P < 0.00016). TFL hypertrophy and TFL:sartorius volume ratio were significantly associated with FI ( P = 0.00069). Following abductor tendon tear and subsequent FI, there exists significant TFL hypertrophy in patients without a prior history of hip surgery in our patient cohort., (© The Author(s) 2021. Published by Oxford University Press.)
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- 2021
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50. Fragile X Syndrome in a Female With Homozygous Full-Mutation Alleles of the FMR1 Gene.
- Author
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Vafaeie F, Alerasool M, Kaseb Mojaver N, and Mojarrad M
- Abstract
Fragile X syndrome (FXS) has been reported as the leading cause of mental retardation (MR) that predominantly involves males compared to females. An over-expansion of CGG repeats in the 5' untranslated region of the FMR1 gene plays the primary role in this disease. In this study, we encountered a homozygote female patient affected by FMR1 expansion mutation. Surprisingly, she had inherited her full-mutated alleles from two different ancestors. This condition is an extremely rare case of FXS. After accurate genetic counseling, family members were referred to the laboratory for genetic testing. Karyotype with two X chromosomes was the finding after the G-banding study of the proband. Molecular analysis indicated that she was a female with full-mutated or pre-mutated alleles on both of her X chromosomes. It is a rare phenomenon that we detected in this patient. We have concluded that a combination of allele instability during oogenesis and inheritance of two alleles are the leading cause of MR in the presented case., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Vafaeie et al.)
- Published
- 2021
- Full Text
- View/download PDF
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