RORA and Autism in The Isfahan Population: Is There An Epigenetic Relationship.

OBJECTIVE Autism is a neurodevelopmental disorder characterized by difficulty in verbal and non-verbal communication, impaired social interaction, and restricted and repetitive behavior. It has been recently introduced as a multigenic disorder with significant epigenetic effects on its pathology. Recently, epigenetic silencing of retinoic acid receptor- related orphan receptor alpha (RORα) gene (which has an essential role in neural tissue development) was shown to have occurred in autistic children due to methylation of its promoter region. This may thus explain a significant part of the molecular pathogenesis of autism. Therefore, we aimed to confirm this finding by implementing a case-control (experimental) study in the population of Isfahan. MATERIALS AND METHODS The methylation status of a 136 bp sequence of a GpG island (encompassing 13 CpG sites) in the RORA promoter region (positions -200 to -64) as an experimental study was examined in the lymphocyte cells of 30 autistic children after sodium bisulfite treatment using the melting curve analysis-methylation (MCA-Meth) assay compared with normal children. Also, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis was used to estimate the level of mRNA transcripts and to evaluate MCA-Meth analysis results. RESULTS This study revealed no methylation in the examined promoter regions in both autistic and normal children, with the melting curve of all studied samples being comparable to that of the non-methylated control. The results of MCA-Meth analysis were also consistent with qRT-PCR results. We therefore observed no significant difference in the levels of RORα transcripts in the blood lymphocytes between autistic and healthy children. CONCLUSION The methylation of the RORA promoter region may not be considered as a common epigenetic risk factor for autism in all populations. Hence, the molecular pathogenesis of autism remains unclear in the population investigated

Decoding the genetics of speech and language: Genetic insight into the functional elements

زمینه و هدف: مدت زمان مدیدی است که تصور می‌شود توانایی انسان برای کسب قابلیت زبان توسط ساختار ژنتیکی او کد می‌شود. با این حال، تنها به تازگی شواهد ژنتیکی متعددی برای اثبات اساس ژنتیکی احتمالی ِزبان در دسترس است. در طول دهه گذشته، واریانت‌های ژنتیکی مختلفی شناسایی شده‌اند که ممکن است افراد را به جنبه‌های مختلف اختلالات زبان مستعد کنند. اختلالات زبان و گفتار طیف گسترده‌ای از شرایط با فنوتیپ‌های هتروژن و همپوشان را پوشش می‌دهند که می‌توانند علل پیچیده‌ی ژنتیکی و محیطی داشته باشند. ر‌وش بررسی: در این مطالعه مروری، جستجوی نظام ‌مندی در پایگاه‌های الکترونیکی معتبر (Googlescholar, Pubmed, Sciencedirect و Scopus) انجام شد و مقالات انگلیسی مرتبط با موضوع به وسیله‌ی انتخاب کلمات کلیدی زبان، ژنتیک، ژن FOXP2، ژن‌های کاندید و غیره مورد جستجو و استخراج قرار گرفتند. یافته ‌ها: در این مقاله‌ی مروری، بحث می‌کنیم که چگونه شناسایی و مطالعه‌ی ژن‌های خاص، از جمله: FOXP2، CNTNAP2، FOXP1، DCDC2، DYX1C1، ROBO1، KIAA0319، ATP2C2، CMIP، CYP19A1، SRPX2، MRPL19، C2ORF3 و DOCK4، می‌تواند درک ما از سبب‌شناسی اختلالات تکلم و اساس بیولوژیکی اکتساب زبان را افزایش دهد. نتیجه ‌گیری: شناسایی ژن‌های مرتبط با فنوتیپ‌های زبان و تکلم، و توصیف عملکردهای طبیعی و نابجای این ژن‌ها در سال‌های اخیر، جزئیات پیچیده‌ی مکانیسم‌های مولکولی و شناختی را مشخص کرده و دیدگاه ارزشمندی از اساس بیولوژیکی زبان ارائه کرده است

An overview on the evolution of language and genetics of speech disorders

Language, as an exclusive salient of human kind, is the requisite of development and formation of the human society; thus, it is at the topmost of human evolutionary features. Language and speech can be studied in various fields such as biology. Biolinguistics is an interdisciplinary field in which biological development of language is studied. It aims to find the functioning cycle in mind that enables humans to perceive the principles and bases of language. Language genetics, a subfield of biolinguistics, traces genetic factors in the formation and perception of language. Although a variety of theories have been introduced to explain the origins of language, considering recent studies, acquiring essential genetic abilities for speaking are undoubtedly of the most crucial necessities of this skill. Researchers have recently found defective genes in a wide spectrum of language disorders, through which they strongly confirm that speech systems rely on these genes to function properly. However, there is no report on a study which answers this question clearly: considering the origins of language and human evolution, is the proper function of genes, genetic structures, and general requirements necessary for speaking? The evolution of language and genetics of speech disorders along with the outstanding improvements and recent studies are discussed in this review article. © 2014, Isfahan University of Medical Sciences(IUMS). All rights reserved

RORA and Autism in Isfahan population: Is there an epigenetic relationship

Objective: Autism is a neurodevelopmental disorder characterized by difficulty in verbal and non-verbal communication, impaired social interaction, and restricted and repetitive behavior. It has been recently introduced as a multigenic disorder with significant epigenetic effects on its pathology. Recently, epigenetic silencing of retinoic acid receptorrelated orphan receptor alpha (RORα) gene (which has an essential role in neural tissue development) was shown to have occurred in autistic children due to methylation of its promoter region. This may thus explain a significant part of the molecular pathogenesis of autism. Therefore, we aimed to confirm this finding by implementing a case-control (experimental) study in the population of Isfahan. Materials and Methods: The methylation status of a 136 bp sequence of a GpG island (encompassing 13 CpG sites) in the RORA promoter region (positions - 200 to - 64) as an experimental study was examined in the lymphocyte cells of 30 autistic children after sodium bisulfite treatment using the melting curve analysis-methylation (MCA-Meth) assay compared with normal children. Also, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis was used to estimate the level of mRNA transcripts and to evaluate MCA-Meth analysis results. Results: This study revealed no methylation in the examined promoter regions in both autistic and normal children, with the melting curve of all studied samples being comparable to that of the non-methylated control. The results of MCA-Meth analysis were also consistent with qRT-PCR results. We therefore observed no significant difference in the levels of RORα transcripts in the blood lymphocytes between autistic and healthy children. Conclusion: The methylation of the RORA promoter region may not be considered as a common epigenetic risk factor for autism in all populations. Hence, the molecular pathogenesis of autism remains unclear in the population investigated

Evaluation of the Effect of Tooth Type and Canal Configuration on Crown Size in Mandibular Premolars by Cone-Beam Computed Tomography

Introduction: To achieve success in treatment, one cannot ignore the knowledge of pulp anatomy. Mandibular premolars are considered to be the most difficult teeth for endodontic therapy due to high variability in their canal morphology. It is possible that a relation exists between the crown size and the number of extra canals in these teeth, so this in vitro study aims to investigate the relationship between the crown size and the uncommon morphology of mandibular premolars using Cone-Beam Computed Tomography (CBCT). Materials and Methods: Eighty three extracted mandibular human premolars were exposed to radiation using the CBCT device. Root canal configuration was categorized according to the Vertucci’s classification. The crown size was measured in three axial, coronal and sagittal sections. Finally, the relation between these two factors was evaluated with variance analysis (two-way ANOVA) and chi-square. Results: The most common canal type in the mandibular first and second premolars are type I (71% and 76%, respectively), followed by type V (29% and 22%, respectively). No significant relationship was found between the crown size and extra canals in mandibular premolars (P>0.05). Conclusion: In this in vitro study, the average crown size in two-canalled second premolars was less than that in first premolars with a single canal; although the difference was not statistically significant. The research hypothesis was therefore rejected in both first and second mandibular premolars

Autism and Probable Prerequisites: Severe and Scheduled Prenatal Stresses at Spotligh

Background: Due to the importance of prenatal maternal stress as environmental factor on autism, the influ-ence of prenatal maternal psychological agitations was assessed in relation with the risk of autism. Methods: In this case-control study, some mothers of autistic children in Isfahan, central Iran, in 2014, were retrospectively compared with control mothers in terms of quantity, quality, andschedule of exposure to 45 stressful events in a 15-month period. In addition, dividing the stressors into two groups of genome-dependent/independent events, their prevalence was separately scrutinized and compared among patient and control families. Results: Although the child’s risk of autism increases significantly with the increase of maternal stress during months 4-7 of pregnancy, the increased stress during months 2-3 of pregnancy can lead to a significant increase in the severity of autism affliction as well as a slight but significant increase in the possibility of LFA in afflicted children (P<0.05). The overall prevalence of genome-dependent stressful events among two patient and control groups was significantly higher than that of genome-independent events (P=0.000), but genome-dependent events led to more stress inpatient families. Conclusion: Although the present study consistent with recent findings in the fields of epigenetics and gene-environment interactions can confirm the role of severe and scheduled prenatal stresses in causing autism, it does not deny the necessity of a perspective and wider study in Isfahan and Iran

The <em>Bifidobacterim bifidum</em> (BIB2) Probiotic Increased Immune System Factors in Men Sprint Athletes

Foods supplemented with probiotics enhance athletes’ immune system functions, improve body health and consequently decreases athlete’s health maintenance costs. Probiotics improve immune system function against pathogens via affecting on innate immune system, humeral immunity and cytokines. The effects of consumption of Iranian probiotic Bifidobactrium bifidum (BIB2) on athletes’ immune system functions were evaluated. The results showed studied immune system factors were significantly different between test and control groups, so that IgA, IgM, lymphocyte and monocytes percentage and CD4 measurements of test group were higher than control. The Bifidobacterim bifidum (BIB2) probiotic consumption can affect some immune system factors; therefore its ability to improved general health should be studied more

Methylation Analysis of 5&apos;UTR Promoter Region of DBC2 as a Biomarker in the Peripheral Bloods of Some Iranian Women with Sporadic Breast Cancer

ABSTRAC

Molecular and microscopy detection of Pneumocystis jirovecii in hospitalized patients during the COVID-19 pandemic

IntroductionEarly detection of Pneumocystis jirovecii as an opportunistic pathogen that may endanger predisposed persons, including COVID-19 patients, may help to choose the optimal management.MethodsIn this study, 585, including 530 COVID-19 patients, with clinical and radiological evidence of respiratory diseases, were investigated for P. jirovecii screening. Clinical specimens were examined by direct microscopy and PCR, and randomly selected positive PCR products were confirmed through DNA sequence analysis.ResultsThirty-one (5.3%) samples were positive in P. jirovecii-specific nested-PCR, while by direct microscopic tests, Pneumocystis was observed in 22 (3.76%) samples. Males (61.7%) and patients over 50 years old (75.6%) were more commonly affected than others, and malaise and fatigue (84%), and wheezing (75%) were the most common symptoms, followed by fever (40.48%) and dyspnea (39.51%). Among the Pneumocystis-positive patients, three cases had coinfection with Aspergillus fumigatus, A. flavus, and A. niger (each n = 1), as documented by direct microscopy, culture, and species identification by PCR-sequencing.ConclusionPneumocystis pneumonia is still a diagnostic challenge; therefore, additional large-scale studies are needed to clarify the epidemiology of the disease in immunocompromised or COVID-19 patients