Evolving evidence on a link between the ZMYM3 exceptionally long GA-STR and human cognition

The human X-linked zinc finger MYM-type protein 3 (ZMYM3) contains the longest GA-STR identified across protein-coding gene 5� UTR sequences, at 32-repeats. This exceptionally long GA-STR is located at a complex string of GA-STRs with a human-specific formula across the complex as follows: (GA)8-(GA)4-(GA)6-(GA)32 (ZMYM3-207 ENST00000373998.5). ZMYM3 was previously reported among the top three genes involved in the progression of late-onset Alzheimer�s disease. Here we sequenced the ZMYM3 GA-STR complex in 750 human male subjects, consisting of late-onset neurocognitive disorder (NCD) as a clinical entity (n = 268) and matched controls (n = 482). We detected strict monomorphism of the GA-STR complex, except of the exceptionally long STR, which was architecturally skewed in respect of allele distribution between the NCD cases and controls F (1, 50) = 12.283; p = 0.001. Moreover, extreme alleles of this STR at 17, 20, 42, and 43 repeats were detected in seven NCD patients and not in the control group (Mid-P exact = 0.0003). A number of these alleles overlapped with alleles previously found in schizophrenia and bipolar disorder patients. In conclusion, we propose selective advantage for the exceptional length of the ZMYM3 GA-STR in human, and its link to a spectrum of diseases in which major cognition impairment is a predominant phenotype. © 2020, The Author(s)

The Effect of Practical Application of Intimate Relationship Skills (PAIRS) on Enhancing Sexual Satisfaction and Marital Happiness in Married Wives

The aim of this research was investigating the effect of Practical Application of Intimate Relationship Skills (PAIRS) training program on enhancing sexual satisfaction and marital happiness in married women. The method of the study was semi-experimental with pre-test, post-test and follow-up with control group. For this purpose, 22 married wives were randomly selected and assigned in to two experimental and control groups, each one 11 subjects. The Index of Sexual Satisfaction (ISS) )Hudson, Harrison & Crosscup( and Marital Happiness Scale (MHS) )Azrin, Naster, & Jones( were used to gather the data. The training sessions of intimate relationship skills was delivered for 8 weeks, each session lasting two hours. The control group has not delivered training. After finishing of training sessions, post-test was done for both groups. The results showed that the training of practical application of intimate relationship program had significantly improved both sexual satisfaction (eta2=44%) and marital happiness (eta2=37%) in experimental group. The Follow up has shown an effect size of 42% for sexual satisfaction and 36% for marital happiness. The results of this research similar to other researchers showed that marital happiness and sexual satisfaction were enhanced by the training of intimate relationship skills, in married wives, hence this program can be suggested to enhance couple's quality of relationship

The Measurement of Rigidity in Elbow Joint: An Objective Method for the Evaluation of Parkinson's disease

Introduction: One of the most common syndromes in Parkinson's disease (PD) is rigidity. Currently, an index is used to evaluate the level of PD by the clinical measurement of rigidity in the upper extremity. The index uses a subjective method called Unified Parkinson's Disease Rating System (UPDRS). The subjective nature of this method makes the influence of physician in the measurement of rigidity possible. Hence, the development of a new standard method based on objective indices is needed. Materials and Methods: In this research, a new device was fabricated and used to measure the viscous and elastic indices and the range of motion during passive movement of elbow joint. The relation between each index and the level of illness was analyzed. The parameters were measured on 41 patients and 11 controls. The indices were extracted using Matlab-R14 software and the statistical analysis was performed using Spss-13. Results: Although there were significant differences in both the viscous and elastic indices between the pair groups and also among the UPDRS groups, but better correlations of the viscous ones and UPDRS were found.  The range of motion by itself has no good correlation with the level of the disease. Discussion and Conclusion: Based on the obtained results, it can be inferred that using viscous indices of rigidity may have an advantage over the elastic ones for the evaluation of Parkinson’s disease. Upon conducting more trials and also considering the sub indices in different parts of the range of motion, the method used here may become a standard objective method for the evaluation of Parkinson's disease

Natural Selection at the NHLH2 Core Promoter Exceptionally Long CA-Repeat in Human and Disease-Only Genotypes in Late-Onset Neurocognitive Disorder

Background: Approximately 2 of the human core promoter short tandem repeats (STRs) reach lengths of �6 repeats, which may in part be a result of adaptive evolutionary processes and natural selection. A single-exon transcript of the human nescient helix loop helix 2 (NHLH2) gene is flanked by the longest CA-repeat detected in a human protein-coding gene core promoter (Ensembl transcript ID: ENST00000369506.1). NHLH2 is involved in several biological and pathological pathways, such as motivated exercise, obesity, and diabetes. Methods: The allele and genotype distribution of the NHLH2 CA-repeat were investigated by sequencing in 655 Iranian subjects, consisting of late-onset neurocognitive disorder (NCD) as a clinical entity (n = 290) and matched controls (n = 365). The evolutionary trend of the CA-repeat was also studied across vertebrates. Results: The allele range was between 9 and 25 repeats in the NCD cases, and 12 and 24 repeats in the controls. At the frequency of 0.56, the 21-repeat allele was the predominant allele in the controls. While the 21-repeat was also the predominant allele in the NCD patients, we detected significant decline of the frequency (p < 0.0001) and homozygosity (p < 0.006) of this allele in this group. Furthermore, 12 genotypes were detected across 16 patients (5.5 of the entire NCD sample) and not in the controls (disease-only genotypes; p < 0.0003), consisting of at least one extreme allele. The extreme alleles were at 9, 12, 13, 18, and 19 repeats (extreme short end), and 23, 24, and 25 repeats (extreme long end), and their frequencies ranged between 0.001 and 0.04. The frequency of the 21-repeat allele significantly dropped to 0.09 in the disease-only genotype compartment (p < 0.0001). Evolutionarily, while the maximum length of the NHLH2 CA-repeat was 11 repeats in non-primates, this CA-repeat was �14 repeats in primates and reached maximum length in human. Conclusion: We propose a novel locus for late-onset NCD at the NHLH2 core promoter exceptionally long CA-STR and natural selection at this locus. Furthermore, there was indication of genotypes at this locus that unambiguously linked to late-onset NCD. This is the first instance of natural selection in favor of a predominantly abundant STR allele in human and its differential distribution in late-onset NCD. © 2020 The Author(s) Published by S. Karger AG, Basel