A Hypermutable Region in the DISP2 Gene Links to Natural Selection and Late-Onset Neurocognitive Disorders in Humans.

(CCG) short tandem repeats (STRs) are predominantly enriched in genic regions, mutation hotspots for C to T truncating substitutions, and involved in various neurological and neurodevelopmental disorders. However, intact blocks of this class of STRs are widely overlooked with respect to their link with natural selection. The human neuron-specific gene, DISP2 (dispatched RND transporter family member 2), contains a (CCG) repeat in its 5' untranslated region. Here, we sequenced this STR in a sample of 448 Iranian individuals, consisting of late-onset neurocognitive disorder (NCD) (N = 203) and controls (N = 245). We found that the region spanning the (CCG) repeat was highly mutated, resulting in several flanking (CCG) residues. However, an 8-repeat of the (CCG) repeat was predominantly abundant (frequency = 0.92) across the two groups. While the overall distribution of genotypes was not different between the two groups (p > 0.05), we detected four genotypes in the NCD group only (2% of the NCD genotypes, Mid-p = 0.02), consisting of extreme short alleles, 5- and 6-repeats, that were not detected in the control group. The patients harboring those genotypes received the diagnoses of probable Alzheimer's disease and vascular dementia. We also found six genotypes in the control group only (2.5% of the control genotypes, Mid-p = 0.01) that consisted of the 8-repeat and extreme long alleles, 9- and 10-repeats, of which the 10-repeat was not detected in the NCD group. The (CCG) repeat specifically expanded in primates. In conclusion, we report an indication of natural selection at a novel hypermutable region in the human genome and divergent alleles and genotypes in late-onset NhCDs and controls. These findings reinforce the hypothesis that a collection of rare alleles and genotypes in a number of genes may unambiguously contribute to the cognition impairment component of late-onset NCDs.

Dyads of GGC and GCC form hotspot colonies that coincide with the evolution of human and other great apes.

BACKGROUND: GGC and GCC short tandem repeats (STRs) are of various evolutionary, biological, and pathological implications. However, the fundamental two-repeats (dyads) of these STRs are widely unexplored. RESULTS: On a genome-wide scale, we mapped (GGC)2 and (GCC)2 dyads in human, and found monumental colonies (distance between each dyad < 500 bp) of extraordinary density, and in some instances periodicity. The largest (GCC)2 and (GGC)2 colonies were intergenic, homogeneous, and human-specific, consisting of 219 (GCC)2 on chromosome 2 (probability < 1.545E-219) and 70 (GGC)2 on chromosome 9 (probability = 1.809E-148). We also found that several colonies were shared in other great apes, and directionally increased in density and complexity in human, such as a colony of 99 (GCC)2 on chromosome 20, that specifically expanded in great apes, and reached maximum complexity in human (probability 1.545E-220). Numerous other colonies of evolutionary relevance in human were detected in other largely overlooked regions of the genome, such as chromosome Y and pseudogenes. Several of the genes containing or nearest to those colonies were divergently expressed in human. CONCLUSION: In conclusion, (GCC)2 and (GGC)2 form unprecedented genomic colonies that coincide with the evolution of human and other great apes. The extent of the genomic rearrangements leading to those colonies support overlooked recombination hotspots, shared across great apes. The identified colonies deserve to be studied in mechanistic, evolutionary, and functional platforms.

Novel islands of GGC and GCC repeats coincide with human evolution.

BACKGROUND: Because of high mutation rate, overrepresentation in genic regions, and link with various neurological, neurodegenerative, and movement disorders, GGC and GCC short tandem repeats (STRs) are prone to natural selection. Among a number of lacking data, the 3-repeats of these STRs remain widely unexplored. RESULTS: In a genome-wide search in human, here we mapped GGC and GCC STRs of ≥3-repeats, and found novel islands of up to 45 of those STRs, populating spans of 1 to 2 kb of genomic DNA. RGPD4 and NOC4L harbored the densest (GGC)3 (probability 3.09061E-71) and (GCC)3 (probability 1.72376E-61) islands, respectively, and were human-specific. We also found prime instances of directional incremented density of STRs at specific loci in human versus other species, including the FOXK2 and SKI GGC islands. The genes containing those islands significantly diverged in expression in human versus other species, and the proteins encoded by those genes interact closely in a physical interaction network, consequence of which may be human-specific characteristics such as higher order brain functions. CONCLUSION: We report novel islands of GGC and GCC STRs of evolutionary relevance to human. The density, and in some instances, periodicity of these islands support them as a novel genomic entity, which need to be further explored in evolutionary, mechanistic, and functional platforms.

A GCC repeat in RAB26 undergoes natural selection in human and harbors divergent genotypes in late-onset Alzheimer's disease.

Although mainly located in genic regions and being mutation hotspots, intact blocks of CG-rich trinucleotide short tandem repeats (STRs) are largely overlooked with respect to their link with natural selection. The human RAB26 (member RAS oncogene family) directs synaptic and secretory vesicles into preautophagosomal structures, inhibition of which specifically disrupts axonal transport of degradative organelles and leads to an axonal dystrophy, resembling Alzheimer's disease (AD). Human RAB26 contains a GCC repeat in the top 1st percent in respect of length. Here we sequenced this STR in 441 Iranian individuals, consisting of late-onset neurocognitive disorder (NCD) (N = 216) and controls (N = 225). In both groups, the 12-repeat allele and the 12/12 genotype were predominantly abundant. We found excess of homozygosity for non-12 alleles in the NCD group (Mid-P exact = 0.027). Furthermore, divergent genotypes were detected that were specific to the NCD group (2.8% of genotypes) (Mid-P exact = 0.006) or controls (3.1% of genotypes) (Mid-P exact = 0.004). The patients harboring divergent genotypes received the diagnosis of AD. Based on the predominant abundance of the 12-repeat and 12/12 genotype in both groups, excess of non-12 homozygosity in the NCD group, and divergent genotypes across the NCD and control groups, we propose natural selection at this locus and link with late-onset AD. Our findings strengthen the hypothesis that a collection of rare genotypes unambiguously contribute to the pathogenesis of late-onset NCDs, such as AD.

Relationship between self-esteem and subjective vitality among older people in Iran.

Today, aging of the population is considered one of the most fundamental challenges worldwide. One of the important factors in active aging is paying attention to psychological variables and related factors. This study was conducted aimed to determine the relationship between self-esteem and subjective vitality of the older people in Iran, Sirjan in 2020. In this descriptive-analytical study, 200 older people aged 60 years and older were selected from comprehensive health centers in Sirjan by a two-stage random sampling method. The data were collected using the validated Rosenberg Self-Esteem Scale, and validated Subjective Vitality Scale. The data were analyzed using SPSS software version 20 using descriptive and inferential statistics, including the Mann-Whitney test, Kruskal-Wallis test, Post Hoc tests, and Spearman correlation coefficient. The mean age of the older people was 65,66±3,9 years. The the mean and standard deviation of self-esteem score was 36,34±4,62 and 21,80±2,85 for subjective vitality score. There was a positive and significant correlation between self-esteem and subjective vitality R=0,58 (p˂0,001 ). Also, gender, marital status and employment status were associated with subjective vitality (p˂0,05). Therefore, planners and policymakers should consider self-esteem and subjective vitality in designing and prioritizing interventions related to improving the health of the older people.

Corrigendum to "Estimation of Isentropic Compressibility of Biodiesel Using ELM Strategy: Application in Biofuel Production Processes".

[This corrects the article DOI: 10.1155/2021/7332776.].

Employing computational fluid dynamics technique for analyzing the PACK-1300XY with methanol and isopropanol mixture.

In this study, an innovative wire gauze structured packing, namely PACK-1300XY with a specific surface area of 1300 m2/m3 has been characterized by performing computational fluid dynamics (CFD) approach. Indeed, different features of this packing (height equivalent to a theoretical plate, wet/dry pressure drop, and mass transfer efficiency) were analyzed by analyzing the flow regime using the three-dimensional CFD approach with the Eulerian-Eulerian multiphase scenario. The results showed the mean relative deviation of 16% (for wet pressure drop), 14% (for dry pressure drop), and 17% (for mass transfer efficiency) between the CFD predictions and experimental measurements. These excellent levels of consistency between the numerical findings and experimental observations approve the usefulness of the CFD-based approach for reliable simulation of separation processes.

Upregulation of hsa-miR-625-5p Inhibits Invasion of Acute Myeloid Leukemia Cancer Cells through ILK/AKT Pathway.

Objective: Acute myeloid leukemia (AML) is characterized by abnormalities of differentiation and growth of primary hematopoietic stem cells (HSCs) in the blood and bone marrow. In many studies, miR-625-5p has been shown to inhibit downstream pathways from affecting the metastasis and invasion of the integrin-linked kinase (ILK) signaling pathway. It has been proved that the expression of miR-625-5p decreases in AML cell lines. This study aimed to investigate the effect of miR-625-5p upregulation on the invasion of KG1 ell line in vitro. Materials and Methods: In this experimental study, we investigated the impact of upregulation of miR-625-5p on invasion via the ILK/AKT pathway in the KG1 cell line. After transfection using the viral method, the cellular invasion was assessed by invasion assay and the levels of miR-625-5p genes and protein were evaluated by quantitative polymerase chain reaction (qPCR) and western blotting. Moreover, CXCR4 level was assessed by flow cytometry. Results: The invasion significantly reduced in MiR-625-5p-transfected KG1 cells (P<0.01) that was concomitant with remarkably decreasing in the expression levels of ILK, NF-κB, and COX2 genes compare with the control group (P<0.01). Incontrast, MMP9, AP1, and AKT significantly increased (P<0.01, P<0.001 and P<0.01, respectively) and GSK3ß did not change significantly in MiR-625-5p-transfected KG1 cells. The protein level of NF-κB decreased (P<0.01) and MMP9 increased, however it was not significant. Moreoever, the expression of CXCR4 was significantly lower (P<0.01) in comparison with the control group. Conclusion: miR-625-5p leads to a reduction in cell invasion in the AML cell line through ILK pathway. Therefore, it could be a breakthrough in future AML-related research. However, further studies are needed to support this argument.

Factors Affecting the Life Satisfaction of the older adult: The Role of Place attachment.

This study examined the association between life satisfaction and place attachment in the older adult. A total of 200 subjects of Kerman city, Iran, responded to questionnaires on life satisfaction and place attachment. The data were analyzed using chi-square, analysis of variance, correlation, and hierarchical multiple regression analysis by the SPSS software version 18. Approximately 51,4% of the subjects had intermediate life satisfaction. The Life satisfaction mean was significantly lower in subjects over 80 of the male gender, single marital status, with more than 3 chronic diseases and bad self-rated health. The majority of respondents had intermediate levels of place attachment (56,6%). There was a significant correlation between life satisfaction and place attachment. Independent variables accounted for 34,2% of the variance in life satisfaction. Individuals with higher attachment had higher levels of life satisfaction than those with lower place attachment. Place attachment is an appropriate strategy to increase life satisfaction in aging.

Comprehensive investigations of mixed convection of Fe-ethylene-glycol nanofluid inside an enclosure with different obstacles using lattice Boltzmann method.

In the present paper, nanofluid mixed convection is investigated in a square cavity with an adiabatic obstacle by using the Lattice Boltzmann method (LBM). This enclosure contains Fe-ethylene-glycol nanofluid and three constant temperature thermal sources at the left wall and bottom of the enclosure through a lateral wall. The fluid is incompressible, laminar, and Newtonian. The obtained results are presented in the constant Ra = 104 and a Pr = 0.71 for different Ri = 0.1, 1, and 10. The effects of the slope of the enclosure, volume fraction of nanoparticles [Formula: see text], the location of adiabatic obstacles, and nanoparticle diameter in the fluid are investigated on the value of heat transfer. A change in the attack angle of the enclosure leads to changes in the movement distance for fluid between hot and cold sources and passing fluid through case E, which affects the flow pattern strongly. In each attack angle, on colliding with an obstacle, the fluid heat transfers between two sources, which leads to uniform heat transfer in the enclosure. By increasing the velocity of the lid, the Richardson number decreases leading to improvement of the convective heat transfer coefficient and Nusselt number enhancement. The results so obtained reveal that by augmenting [Formula: see text] value the effect of Richardson number reduction can augment Nusselt number and the amount of absorbed heat from the hot surface. Consequently, in each state where a better flow mixture and lower depreciation of fluid velocity components, due to the penetration of lid movement and buoyancy force, occurs higher heat transfer rate is accomplished. Furthermore, it is shown that when Ri = 0.1, the effect of cavity angle is more important but when Ri = 10, the effect of the position of obstacle is more visible.

Estimation of Isentropic Compressibility of Biodiesel Using ELM Strategy: Application in Biofuel Production Processes.

Isentropic compressibility is one of the significant properties of biofuel. On the other hand, the complexity related to the experimental procedure makes the detection process of this parameter time-consuming and hard. Thus, we propose a new Machine Learning (ML) method based on Extreme Learning Machine (ELM) to model this important value. A real database containing 483 actual datasets is compared with the outputs predicted by the ELM model. The results of this comparison show that this ML method, with a mean relative error of 0.19 and R 2 values of 1, has a great performance in calculations related to the biodiesel field. In addition, sensitivity analysis exhibits that the most efficient parameter of input variables is the normal melting point to determine isentropic compressibility.

An insight into the estimation of drilling fluid density at HPHT condition using PSO-, ICA-, and GA-LSSVM strategies.

The present study evaluates the drilling fluid density of oil fields at enhanced temperatures and pressures. The main objective of this work is to introduce a set of modeling and experimental techniques for forecasting the drilling fluid density via various intelligent models. Three models were assessed, including PSO-LSSVM, ICA-LSSVM, and GA-LSSVM. The PSO-LSSVM technique outperformed the other models in light of the smallest deviation factor, reflecting the responses of the largest accuracy. The experimental and modeled regression diagrams of the coefficient of determination (R2) were plotted. In the GA-LSSVM approach, R2 was calculated to be 0.998, 0.996 and 0.996 for the training, testing and validation datasets, respectively. R2 was obtained to be 0.999, 0.999 and 0.998 for the training, testing and validation datasets, respectively, in the ICA-LSSVM approach. Finally, it was found to be 0.999, 0.999 and 0.999 for the training, testing and validation datasets in the PSO-LSSVM method, respectively. In addition, a sensitivity analysis was performed to explore the impacts of several variables. It was observed that the initial density had the largest impact on the drilling fluid density, yielding a 0.98 relevancy factor.

Apigenin Enhanced Radiation-Induced Apoptosis/Necrosis by Sensitization of LNCaP Prostate Cancer Cells to 6 MV Photon Beams.

OBJECTIVE: Whereas prostate cancer (PrCa) may be unresponsive or moderately responsive to radiation therapy (RT)- most common modality for treatment of PrCa- patients must receive a high dose of RT In order to achieve appropriate tumour control. However, this increase in radiation dose may lead to severe adverse effects in normal tissues. Sensitization of PrCa to radiation provides an alternate approach to improve the therapeutic efficacy of RT. This study aims to assess the radiosensitisation effect of apigenin (Api) on a prostate cancer cell line (LNCaP). MATERIALS AND METHODS: In this experimental study, LNCaP cells were treated with 0-80 µM Api to investigate its effect on LNCaP cell viability and determine its half-maximal inhibitory concentration (IC50). Next, the cells were divided into four groups: i. Control, ii. Cells treated with the IC50 concentration of Api, iii. Cells treated with 2 Gy ionizing radiation (IR), and cells co-treated with Api and IR. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, real-time polymerase chain reaction (PCR), and an Annexin V-FITC/PI assay were performed to assess cell survival, Bax and Bcl-2 expressions, and presence of apoptosis and necrosis. RESULTS: Api inhibited cell survival in a dose-dependent, but not time-dependent manner. Cells treated with Api had increased amounts of early apoptosis, late apoptosis, and secondary necrosis compared to the control group. This group also had decreased Bcl-2 gene expression and up-regulated Bax gene expression. Co-treatment with Api and IR significantly inhibited cell survival, and increased early apoptosis, late apoptosis and secondary necrosis compared to the other groups. There was a significant decrease in Bcl-2 gene expression along with up-regulation of Bax gene expression, and Bax/Bcl-2 ratio changes that favoured apoptosis. CONCLUSION: Api inhibited PrCa cell survival and induced apoptosis as a single agent. In addition, Api significantly sensitized the LNCaP cells to IR and enhanced radiation-induced apoptosis.

Risk of obstructive pulmonary diseases and occupational exposure to pesticides: a systematic review and meta-analysis.

OBJECTIVE: This meta-analysis study was performed to examine the relationship between occupational exposure to pesticides and the risk of obstructive pulmonary diseases such as chronic obstructive pulmonary disease (COPD) and chronic bronchitis. STUDY DESIGN: This is a systematic review and meta-analysis study. METHODS: PubMed and Scopus databases were searched for English-language publications. Eight cohort studies and one case-control study were included in the pooled analysis. RESULTS: These studies had a total of 101,353 participants from eleven different countries and were published between 2006 and 2018. The heterogeneity among the studies was high (P < 0.001, I2 = 68.7%). In a random-effects model meta-analysis, a pooled odds ratio (OR) analysis showed that there was a direct relationship between occupational exposure to the pesticides and obstructive pulmonary diseases (OR = 1.33, 95% confidence interval [CI]: 1.21-1.47). A positive significant relationship was also observed between exposure to the pesticides and risk of chronic bronchitis (OR = 1.27, 95% CI: 1.23-1.31). Also, there was a significant relationship between occupational exposure to the pesticides and an increased risk of COPD (OR = 1.44, 95% CI: 1.14-1.81). No evidence of publication bias was found among the studies according to the results of the Egger's test (P of bias = 0.157). CONCLUSIONS: Findings of this study show that occupational exposure to pesticides can be associated with an increased risk of obstructive lung diseases including chronic bronchitis and COPD.

Decoding material-specific memory reprocessing during sleep in humans.

Neuronal learning activity is reactivated during sleep but the dynamics of this reactivation in humans are still poorly understood. Here we use multivariate pattern classification to decode electrical brain activity during sleep and determine what type of images participants had viewed in a preceding learning session. We find significant patterns of learning-related processing during rapid eye movement (REM) and non-REM (NREM) sleep, which are generalizable across subjects. This processing occurs in a cyclic fashion during time windows congruous to critical periods of synaptic plasticity. Its spatial distribution over the scalp and relevant frequencies differ between NREM and REM sleep. Moreover, only the strength of reprocessing in slow-wave sleep influenced later memory performance, speaking for at least two distinct underlying mechanisms between these states. We thus show that memory reprocessing occurs in both NREM and REM sleep in humans and that it pertains to different aspects of the consolidation process.

Survey of clinical and pathological characteristics and outcomes of patients with prostate cancer.

INTRODUCTION: The importance of implementation: Prostate cancer is the most common malignancy in men and the second leading cause of cancer death in developed countries. Therefore, further studies about the protests of disease, diagnosis and timely treatment are essential. STUDY METHOD: In this study, 80 prostate cancer patients admitted to Imam Khomeini Hospital, Urmia in Iran from 2000 to 2008 were reviewed. Patients were studied according to their age, clinical protests, Gleason scoring, positive family history, smoking, type of treatment and post-treatment conditions. Questionnaires were adjusted based on the objectives and the data were extracted from the medical records of patients and the desired results were achieved. RESULTS: In this study, the most common age group for prostate cancer is older than 60 years (92/5%). The most common type of pathology for prostate cancer is adenocarcinoma that 93.75% of cases are included. Secondary TCC with secondary source is present in 5% and sarcoma in 1.25% of cases. 46.25% of patients with prostate cancer are smokers. The most common clinical symptoms among patients are obstructive symptoms (56.25%), and irritation of the urinary tract (52.81%). Hematuria in 26.25% and urinary incontinence in 5% of cases have been recorded. 16.3% of patients referred with metastatic symptoms. Most patients with prostate cancer have Gleason score 5-7 (40%). All patients were undergoing prostatectomy (82.5% TURP and 17.5% SPP) and 47.5% of cases were bilateral orchiectomy. The cases reviewed, 22 were followed that included 27.5% of cases. Among them, 6 people have died due prostate cancer (27.27%) that the mean age of the patients after diagnosis until death was 34.4 months. 2 others died from other causes (9.09%). The remaining 14 cases were elder patients with a mean follow-up duration of 44 months. CONCLUSION: According to the results obtained in the present study, the most common type of prostate cancer pathology is adenocarcinoma that is included 93.75% of cases. Prostate sarcoma is present at 1.25% and secondary bladder TCC at 5% of cases more over the incidence of prostate sarcoma is reported in a lower age group than adenocarcinoma, which the results obtained in a similar study in Iran in other centers. Regarding the relationship between smoking and prostate cancer it can be considered one of the important factors in this regard. 

Clonal spread of vancomycin resistance Enterococcus faecalis in an Iranian referral pediatrics center.

Vancomycin-resistant enterococci (VRE) represent as an immediate threat to public health. Since few active compounds are available for VRE infections, rapid identification of these isolates are essential. In the absence of any report on the genetic relatedness of Enterococcus faecalis especially Vancomycin-resistant E. faecalis (VREF) isolates in Iran, we undertook this study to characterize these isolates using random amplification of polymorphic DNA (RAPD-PCR) genotyping method. In this study, E. faecalis strains isolated from various samples collected from different wards of Children Medical Hospital (Tehran, Iran). These isolates were identified by standard laboratory procedures and tested for antimicrobial resistance to vancomycin and teicoplanin. The genetic similarity of the strains was investigated by amplification of the RAPD-PCR. In our study among 91 E. faecalis isolates, 15 (16%) were identified as VREF. The similarity pattern built for E. faecalis isolates by RAPD-PCR, demonstrated the presence of four distinct clusters (A, B, C, D). It is of interest to note that 100% of VREF isolates belonged to Clusters A, indicating that there may have occurred horizontal transmission of the same strain between patients. In conclusion, rapid spread of VREF from a clonal origin calls for implementation of careful isolation and infection control measures. Therefore, environmental control by routine disinfection of patient area as well as screening of high risk patients and isolation of colonized patients should be imposed in order to diminish risk of acquiring nosocomial VRE.

Effects of combination of intrathecal lidocaine and two doses of intrathecal midazolam on post-operative pain in patients undergoing herniorrhaphy: a randomized controlled trial.

Assessment of the effect of combination of intrathecal midazolam and lidocaine on postoperative pain was the aim of this study. This randomized controlled trial was performed during 2007 in a teaching hospital of Arak University of Medical Sciences. Forty five male patients who were candidates for elective inguinal herniorrhaphy entered the study and randomly divided into three groups of control (lidocaine 5% plus normal saline), M 0.5 (lidocaine 5% and midazolam 0.5 mg) and M 1.0 (lidocaine 5% and midazolam 1 mg) according intrathecal solution injected for spinal anesthesia. Mean arterial blood pressure, heart rate, post-operative pain, narcotic requirements and complications (nausea, vomiting, pruritic, headache, hypotension and bradycardia) were recorded. The severity of post-operative pain was lowest in M 1.0 group in all postoperative measurements except at 2 h after operation. With regard of complications, only there was significant difference in vomiting between three groups which had the highest frequency in M 0.5 group. No severe hypotension was seen; though, bradycardia occurred in one patient in M 0.5 group which needed treatment. Present findings suggest that administration of intrathecal midazolam (especially 1 mg) together with lidocaine is effective in reducing post-operative pain in patients undergoing open inguinal herniorrhaphy and is not associated with adverse effect.