scholarly journals A (GCC) Repeat in the Untranslated Region of Human SBF1 Departs from Hardy-Weinberg Equilibrium in Human and Links to Late-onset Neurocognitive Disorder.

Author(s):  
Mina Ohadi ◽  
Safoura Khamse ◽  
Samira Alizadeh ◽  
Stephan H Bernhart ◽  
Hossein Afshar ◽  
...  

Abstract The human SBF1 (SET binding factor 1) gene, alternatively known as MTMR5, is predominantly expressed in the brain, and its epigenetic dysregulation is linked to late-onset neurocognitive disorders (NCDs), such as Alzheimer’s disease. This gene contains a (GCC)-repeat at the interval between +1 and +60 of the transcription start site (SBF1-202 ENST00000380817.8). Sequencing of the SBF1 (GCC)-repeat in a sample of 542 Iranian individuals, consisting of late-onset NCDs (N=260) and controls (N=282) revealed a predominantly bi-allelic locus for this STR, consisting of 8 and 9 repeats, with allele frequencies ranging from 0.39 to 0.55, and four other alleles with frequencies of <0.03 across the two groups. Overall heterozygosity for the observed alleles was significantly less than expected in the NCD and control groups, at 22.3% and 16.31%, respectively (p=0.000). Specifically, the heterozygous 8/9 genotype was significantly less than expected in both case and control groups (Hardy-Weinberg disequilibrium, p=0.000), and significantly enriched in the NCD group (Yates corrected p=0.001). Skewed heterozygous genotypes were also detected for other allele combinations, such as 6/8 vs 6/9 across groups (p=0.000). Bioinformatics studies revealed that the number of (GCC)-repeats may change the RNA secondary structure and interaction sites across human exon 1. This STR was specifically expanded beyond 2-repeats in primates. In conclusion, we report a novel biological phenomenon in which there is indication of purifying selection against heterozygous genotypes at a STR locus in human, and skewed genotype compartment in late-onset NCD vs. controls. In view of the location of this STR in the 5′ UTR, RNA/RNA or RNA/DNA heterodimer formation of the involved genotypes and possible deleterious downstream events should be considered.

2009 ◽  
Vol 24 (5) ◽  
pp. 383-386 ◽  
Author(s):  
Cecília Maria de Carvalho Xavier Holanda ◽  
Monique Batista da Costa ◽  
Natália Chilinque Zambão da Silva ◽  
Maurício Ferreira da Silva Júnior ◽  
Vanessa Santos de Arruda Barbosa ◽  
...  

PURPOSE: Aloe vera is a tropical plant popularly known in Brazil as babosa. We have investigated the effect of aqueous extract of Aloe vera on the biodistribution of Na99mTcO4 and laboratorial parameters in Wistar rats. METHODS: Twelve animals were divided into treated and control groups. In the treated group, Aloe vera was given by gavage (5mg/mL/day) during 10 days. The control group received sorbitol by the same way and period. One hour after the last dose, we injected 0.1mL of Na99mTcO4 by orbital plexus. After 60 min, all the animals were killed. Samples were harvested from the brain, liver, heart, muscle, pancreas, stomach, femur, kidneys, blood, testis and thyroid and the percentage of radioactivity (%ATI/g) was determined. Biochemical dosages were performed. RESULTS: There was a significant increase of %ATI/g in blood, femur, kidneys, liver, stomach, testis and thyroid and also in blood levels of AST and ALT. A significant decrease in levels of glucose, cholesterol, triglycerides, creatinine and urea occurred. The statistical analyses were performed by Mann-Whitney test and T-Student test (p<0.05). CONCLUSION: The aqueous extract of Aloe vera facilitated the uptake of Na99mTcO4 in organs of rats and it was responsible to a high increase of levels of AST and ALT.


Endocrinology ◽  
2005 ◽  
Vol 146 (9) ◽  
pp. 4074-4081 ◽  
Author(s):  
Sutada Lotinun ◽  
Jean D. Sibonga ◽  
Russell T. Turner

Abstract We examined proliferation of cells associated with PTH-induced peritrabecular bone marrow fibrosis in rats as well as the fate of those cells after withdrawal of PTH. Time-course studies established that severe fibrosis was present 7 d after initiation of a continuous sc PTH infusion (40 μg/kg·d). To ascertain cell proliferation, rats were coinfused for 1 wk with PTH (treated) or vehicle (control) and [3H]thymidine (1.5 mCi/rat). Groups of control and treated rats were killed immediately (d 0) and 1 wk (d 7) later. Few osteoblasts (Obs) and osteocytes in treated and control groups were radiolabeled on d 0. Peritrabecular cells expressing a fibroblastic (Fb) phenotype and surrounded by an extracellular matrix were not present in controls on either d 0 or d 7. Multiple cell layers of Fbs lined most (70%) of the bone surface on d 0 in treated rats and nearly all (85%) of the Fbs were radiolabeled. Fbs had entirely disappeared from bone surfaces on d 7. Eighty-five percent of the Obs on and 73% of the osteocytes within the active remodeling sites were radiolabeled. Immunohistochemistry revealed that Fbs induced by PTH treatment produced osteocalcin, osteonectin, and core binding factor-α1. These data provide compelling evidence that Fbs recruited to bone surfaces in response to a continuous PTH infusion undergo extensive proliferation, express osteoblast-specific proteins, and produce an extracellular matrix that is similar to osteoid. After restoration of normal PTH levels, Fbs differentiated to Obs, providing further evidence that Fbs are preosteoblasts.


2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Wei-zhen Lou ◽  
Fang Jiang ◽  
Jing Hu ◽  
Xiao-xu Chen ◽  
Ying-na Song ◽  
...  

The ratio of soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1/PlGF) is elevated and proved to be useful in preeclampsia (PE) diagnosis. Its value in differential diagnosis with other pregnancy complications and prediction of pregnancy duration has yet to be clarified in Chinese population. We retrospectively analyzed 118 singleton pregnancies with suspected or diagnosed PE at the Peking Union Medical College Hospital (PUMCH) in China. Among these, 62 pregnancies were diagnosed as PE (48 early onsets and 14 late onsets, with 39 and 5 severe PE, respectively), 12 gestational hypertension (GH), 15 chronic hypertension (chrHTN), 16 autoimmune diseases, and 13 pregnancies with uncomplicated proteinuria. And 76 normal pregnancies were included as control. The results showed (1) the sFlt-1/PlGF ratio in early onset PE subgroup was significantly higher than that in GH, chrHTN, and control groups; the sFlt-1/PlGF ratio in late onset PE subgroup was significantly higher than that in chrHTN and control groups, but similar as GH group; the sFlt-1/PlGF ratio was similar among GH, chrHTN, and control groups. (2) The sFlt-1/PlGF ratio was significantly increased in the PE group compared with autoimmune disease and uncomplicated proteinuria pregnancies. (3) By ROC curve analysis, the cutoff value of the sFlt-1/PlGF ratio was less than 21.5 to rule out PE and higher than 97.2 to confirm the diagnosis of PE. (4) The sFlt-1/PlGF ratio was higher in PE pregnancies delivering within 7 days than those more than 7 days, either in early onset PE or severe PE. In conclusion, we show that maternal sFlt-1/PlGF ratio is an efficient biomarker in the diagnosis and differential diagnosis of PE. This ratio can be used to predict the timing of delivery for PE pregnancies.


2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
M. Ohadi ◽  
Y. Heshmati ◽  
A. Mirabzadeh ◽  
H.R. Khorram Khorshid ◽  
K. Kamali

Crucial interaction of caveolin-1 (CAV1) with beta- and gamma-secretases, and aberrant expression of the gene encoding this protein in Alzheimer's disease (AD) support a role for CAV1 in the pathophysiology of this disease.We report a novel polymorphic purine complex stretching ~150 bp of genomic DNA at the 1.5 kb upstream region of the human CAV1 gene, alleles and genotypes of which are associated with sporadic late-onset AD. Extra-short alleles were observed in the case group that were absent in the control subjects. Increased homozygosity for haplotypes was also observed at this region in the Alzheimer's cases, for those alleles and allele lengths shared by the case and control groups [(c2=30.75, df=1, p< .000, OR=4.54, CI 95% (2.56-8.3)]. This region contains GGAA and GAAA motifs, the consensus binding sites for the Ets and IRF family transcription factors, respectively, and is highly conserved in distantly-related non-human primates in respect with location and motif sequence. The effect of this complex sequence on the expression of CAV1, and the related mechanisms in the pathophysiology of AD remain to be clarified.


2022 ◽  
Vol 04 (01) ◽  
pp. 686-701
Author(s):  
Magda Hamid KAMBASH ◽  
Nidal Fadel ABBAS ◽  
Esraa Fadel ABBAS

The use of modern teaching strategies aims to develop the practices of ‎female learners inside and outside the classroom, which contributes to ‎changing the role of the student from a negative role to a positive role in ‎general. Therefore, learning strategies have become involved in the ‎application of many educational and teaching programs and curricula, as ‎they greatly help in conveying information to the learner. With less ‎effort and time, except that the material to be learned is theoretical or ‎practical. In light of what the current era is witnessing of a huge ‎knowledge explosion and a wide technological revolution that covered ‎various areas of life, it has become necessary for researchers to be ‎interested in searching for ways to ensure the development of thinking ‎among learners, which is one of the foundations of correct learning, ‎some strategies, means and methods used in the learning process help. ‎To bring the learner to a stage where he can access knowledge on their ‎own by applying that knowledge and using it to overcome the problems ‎they face in their daily lives. He has to use different and multiple ‎methods and methods, and this requires him to be familiar with how ‎learning takes place, and how the teaching methods and means used ‎affect the speed of achieving the goal of the learning process and the ‎success of applying the educational curriculum and achieving its goals‏.‏ One of the features of the modern era is technological progress in ‎various fields and situations of life, as rapid change has become a feature ‎of the era in which we live. There is no doubt that its use affects all ‎aspects of life, including education and teaching, and with this clear ‎progress in the level of mastery of learning skills in sports events around ‎the world, it has become necessary to use learning strategies in ‎programs and curricula for teaching and teaching physical education and ‎learning basic skills for all games and events Sports, including volleyball‏.‏ The researchers found the lack of use of modern strategies in the ‎educational process, and despite their active role in learning basic skills ‎using modern methods, it requires the presence of exercises that ‎contribute to learning basic skills in volleyball, whose weakness emerged ‎from the research sample, which casts a clear shadow on the ‎performance and levels of learners. The aim of the research is to prepare ‎special exercises According to the brain-based learning strategy in ‎learning some basic volleyball skills for students of the second average, ‎and to identify the effect of special exercises according to the brain-‎based learning strategy in learning some basic volleyball skills for ‎students of the second average, and to identify the preference of the ‎experimental and control groups in learning some basic volleyball skills ‎for female students. The second is average. The researchers used the ‎experimental approach for the experimental and control groups, and the ‎research sample was represented by (30) students, then the sample was ‎divided into an experimental group of (15) female students and a control ‎group of (15) female students.


2016 ◽  
Vol 38 (4) ◽  
pp. 1406-1414 ◽  
Author(s):  
Xiaoyan Ren ◽  
Mingzhen Guo ◽  
Caili Liu ◽  
Tao Huang ◽  
Qiang Li ◽  
...  

Background/Aims: Preeclampsia (PE) is a systemic inflammatory response syndrome involving varieties of cytokines, and previous studies have shown that IL-33 and its receptor IL-1RL1 play pivotal roles in the development of it. As a polygenetic hereditary disease, it is necessary to study the gene analysis for PE. Therefore, the present study was to determine whether IL-33 rs3939286 and IL-1RL1 rs13015714 associated with susceptibility to PE in Chinese Han women. Methods: 1,031 PE patients and 1,298 controls were enrolled and the genotyping for rs3939286 in IL-33 and rs13015714 in IL-1RL1 was performed by TaqMan allelic discrimination real-time PCR. Hardy-Weinberg equilibrium (HWE) was examined to ensure the group representativeness and Pearson's chi-square test was used to compare the differences in genetic distributions between the two groups. Results: No significant differences in genotypic and allelic frequencies of the two polymorphisms loci were observed between cases and controls. There were also no significant differences in genetic distributions between mild/severe and early/late-onset PE and control groups. Conclusion: Although our data suggested that the polymorphisms of IL-33 rs3939286 and IL-1RL1 rs13015714 might not be critical risk factors for PE in Chinese Han women, the results need to be validated in different nations.


2017 ◽  
Vol 59 (8) ◽  
pp. 973-979 ◽  
Author(s):  
Terhi Tuokkola ◽  
Juha Koikkalainen ◽  
Riitta Parkkola ◽  
Mira Karrasch ◽  
Jyrki Lötjönen ◽  
...  

Background Brain atrophy is associated with mild cognitive impairment (MCI), and by using volumetric and visual analyzing methods, it is possible to differentiate between individuals with progressive MCI (MCIp) and stable MCI (MCIs). Automated analysis methods detect degenerative changes in the brain earlier and more reliably than visual methods. Purpose To detect and evaluate structural brain changes between and within the MCIs, MCIp, and control groups during a two-year follow-up period. Material and Methods Brain magnetic resonance imaging (MRI) scans of 11 participants with MCIs, 18 participants with MCIp, and 84 controls were analyzed by the visual rating method (VRM) and tensor-based morphometry (TBM). Results At baseline, both VRM and TBM differentiated the whole MCI group (combined MCIs and MCIp) and the MCIp group from the control group, but they did not differentiate the MCIs group from the control group. At follow-up, both methods differentiated the MCIp group from the control group, but minor differences between the MCIs and control groups were only seen by TBM. Neuropsychological tests did not find differences between the MCIs and control groups at follow-up. Neither method revealed relevant signs of brain atrophy progression within or between MCI subgroups during the follow-up time. Conclusion Both methods are equally good in the evaluation of structural brain changes in MCI if the groups are sufficiently large and the disease progresses to AD. Only TBM disclosed minor atrophic changes in the MCIs group compared to controls at follow-up. The results need to be confirmed with a large patient group and longer follow-up time.


2019 ◽  
Vol 8 (10) ◽  
pp. 1703
Author(s):  
Seung-Jae Lim ◽  
Chan-Woo Park ◽  
Dong-Uk Kim ◽  
Kwangjoon Han ◽  
Minkyu Seo ◽  
...  

Corticosteroids have been widely used in patients with brain tumors to reduce tumor-associated edema and neurological deficits. This study examined the outcomes of total hip arthroplasty (THA) in patients with osteonecrosis of the femoral head (ONFH) following brain tumor surgery. We identified 34 THAs performed in 26 patients with steroid-induced ONFH among 9254 patients undergoing surgical treatment for primary brain tumors. After propensity score matching with demographics, 68 THAs (52 patients) in ONFH unrelated to brain tumors were selected as the control group. At the time of THA, 54% of brain tumor patients had neurological sequelae and 46% had adrenal insufficiency. After THA, patients with brain tumor required longer hospital stay, reported a lower functional score, and showed a higher rate of heterotopic ossification compared to the control group. However, hip pain score improved significantly after THA in the brain tumor group, and did not differ from that of the control group (P-value = 0.168). Major complication rates were similar (2.9% and 1.5% for the brain tumor and control groups, respectively; P-value = 1.000), and implant survivorships were not different at 7 years (100% and 98.1% for the brain tumor and control groups, respectively; P-value = 0.455). Our findings suggest that THA can be safely performed to reduce hip pain in patients with steroid-induced ONFH after surgical treatment of primary brain tumors.


1991 ◽  
Vol 70 (2) ◽  
pp. 590-593 ◽  
Author(s):  
Y. Honda ◽  
I. Hashizume

Steady-state CO2-ventilation response curves with hyperoxia (end-tidal PO2 greater than 200 Torr) and mild hypoxia (end-tidal PO2 approximately equal to 60 Torr) were compared in five carotid body-resected (BR) patients and five control patients. The data were analyzed by fitting a linear equation, V = S(PETCO2-B), where V is minute ventilation S is the response curve slope. PETCO2 is end-tidal PCO2, and B is the response curve threshold. S slightly increased from hyperoxia to hypoxia in both BR and control groups. On the other hand, B moderately increased with hypoxia in BR patients, whereas it slightly decreased in controls. These changes were all not significant. However, in accordance with the change in B, the response curve to hypoxia at V of 10 1/min was significantly shifted in opposite directions in the two groups, i.e., rightward and leftward shift in BR and control groups, respectively. Thus the average magnitude of V calculated at PETCO2 of 40 Torr in hypoxia was significantly lower in BR patients than in controls (P less than 0.01). We conclude that this hypoxic depression of the CO2-ventilation response found in BR patients may have resulted, at least in part, from modulation of the brain stem neural mechanisms that were elicited by loss of afferent discharges from the carotid body.


1976 ◽  
Vol 6 (2) ◽  
pp. 307-311 ◽  
Author(s):  
J. C. Shaw

SynopsisIndependent studies which showed a difference between the EEG frequency spectra of test and control groups have been compared. Some of the test groups included schizophrenic patients, others comprised groups with dyslexia, reading disability and left preference. The EEG differences between the test and control groups are shown to be similar across the studies. It is suggested that the common attribute of the test groups relates to the functional organisation of the brain and that investigation of EEG correlates of this phenomenon may be of value to research into the biological basis of psychiatric illness.


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