A single nucleotide polymorphism in BCAT1 gene is associated with type 2 diabetes mellitus

The level of circulatory branched chain amino acids (BCAAs) is often increased in type 2 diabetes mellitus (T2DM). Catabolism of BCAAs involves a transamination reaction mediated by the branched chain amino acid aminotransferase (BCAT1) enzyme. Differences in the level of BCAT1 were found to be linked with hypertension, obesity, and cancer. Herein, using a case control design, we tested the association of rs9668920 and rs12321766 polymorphisms in BCAT1 gene with T2DM. Three hundred subjects were recruited in the study. Genotyping of the indicated polymorphisms was achieved using restriction fragment length polymorphism technique after amplification of the target sequences. The results showed that, under a recessive inheritance model, the GG genotype of rs9668920 increased the risk of T2DM (P=0.026; OR 2.60; 95% CI 1.119–6.048). This effect was independent of the age, body mass index, waist circumference, serum glucose, cholesterol, triglycerides, and BCAAs (P>0.05). In conclusion, The GG genotype of BCAT1 rs9668920 SNP might be a risk factor of T2DM. More studies are required to confirm this finding.

Common ALDH3A1 Gene Variant Associated with Keratoconus Risk in the Polish Population

Background: ALDH3A1 protein is important in maintaining corneal physiology and protecting the eye from UV damage. However, none of the genome-wide association studies has indicated that the ALDH3A1 locus is associated with keratoconus. In this study, we examined the potential role of ALDH3A1 variants as risk factors for keratoconus incidence and severity in a large group of Polish keratoconus patients. Methods: In the first stage we analyzed the coding region sequence of the ALDH3A1 in a subgroup of keratoconus. Then, we genotyped three selected ALDH3A1 variants in a larger KC group of patients (n = 261) and healthy controls (n = 317). Results: We found that the rs1042183 minor allele A is a risk factor for keratoconus in the dominant model (OR = 2.06, 95%CI = 1.42–2.98, p = 0.00013). The rs2228100 variant genotypes appear to be associated with an earlier age of KC diagnosis in the Polish population (p = 0.055 for comparison of three genotypes and p = 0.022 for the dominant inheritance model). Conclusions: The rs1042183 variant in ALDH3A1 is associated with keratoconus risk in the Polish population. The differences in the allele frequency between both populations could be partially responsible for the difference in the disease prevalence.

VITAMIN D AND UROLITHIASIS IN CHILDREN

Background. Urolithiasis is currently one of the topical issues of contemporary urology and medicine in general. This is primarily due to the high prevalence of urolithiasis; according to several population studies it ranges from 3.5 to 9.6%. At the same time, there is a steady increase in its incidence. Therefore, the matter of urolithiasis is one of the most urgent in present-day medicine. Objectives. The aim of the research was to study the content of a polymorphic genetic marker of the vitamin D receptor gene related to development and relapse of urolithiasis in children. Methods. The content of a polymorphic genetic marker of the vitamin D receptor gene related to development and relapse of urolithiasis in 100 children was investigated. Results. The results of the study prove that the vitamin D receptor gene assists in revealing disorders that promote urolithiasis development. Conclusion. Comparative analysis of the frequency of distribution of Fok1 genotypes of the vitamin D receptor gene polymorphism showed that statistical significance of the association (p=0.02) of f allele according to the dominant inheritance model (total Ff+ff genotypes) was established in the group of patients with urolithiasis compare to the corresponding indicator of the control group (63%).

The Evolution of Moral Cognition

<p>Many modern approaches to the evolution of mind have claimed that the fundamental drivers of our cognitive capacities and cultures are genetically specified psychological adaptations, which evolved in response to evolutionary pressures deep within our lineage's history. Many of our cognitive capacities are innate. Recent approaches to moral cognition have similarly argued that moral cognition is innate. In this thesis, I argue that even though our capacity for moral cognising is an adaptation, it is a learned adaptation. Moral cognition is not innate. In arguing this thesis I will question many of the assumptions of traditional cognitive science and evolutionary approaches to the mind. By incorporating theory and evidence from cognitive science and the philosophy of mind, I apply the explanatory frameworks of embodied and extended cognition to the domain of morality: moral cognition is both embodied and extended cognition. This places particular importance on the role of our bodies and world in the fundamental structuring and scaffolding of the development and execution of moral cognition. Putting this in an evolutionary framework, I develop a dual inheritance model of the non-nativist evolution of moral cognition focusing on the roles of niche construction, biased learning and active learning in the transfer of moral phenotypes between generations. Morality is a learned adaptation that evolved through the dynamic and reciprocal interaction between genes and culture.</p>

The Evolution of Moral Cognition

<p>Many modern approaches to the evolution of mind have claimed that the fundamental drivers of our cognitive capacities and cultures are genetically specified psychological adaptations, which evolved in response to evolutionary pressures deep within our lineage's history. Many of our cognitive capacities are innate. Recent approaches to moral cognition have similarly argued that moral cognition is innate. In this thesis, I argue that even though our capacity for moral cognising is an adaptation, it is a learned adaptation. Moral cognition is not innate. In arguing this thesis I will question many of the assumptions of traditional cognitive science and evolutionary approaches to the mind. By incorporating theory and evidence from cognitive science and the philosophy of mind, I apply the explanatory frameworks of embodied and extended cognition to the domain of morality: moral cognition is both embodied and extended cognition. This places particular importance on the role of our bodies and world in the fundamental structuring and scaffolding of the development and execution of moral cognition. Putting this in an evolutionary framework, I develop a dual inheritance model of the non-nativist evolution of moral cognition focusing on the roles of niche construction, biased learning and active learning in the transfer of moral phenotypes between generations. Morality is a learned adaptation that evolved through the dynamic and reciprocal interaction between genes and culture.</p>

Prepositional Phrases in Modern Standard Arabic: An Agree-Based Analysis

Prepositions, in Arabic traditional grammar literature, have been analyzed as Genitive Case assigners (Hasan, 1976; Sibaweihi, n.d.). This paper presents a phase-based analysis for prepositions (Ps) in Modern Standard Arabic (MSA). The analysis is built on Chomsky's (2005, 2008) Feature-Inheritance model of Agree. In this proposed analysis, Prepositional Phrases (PPs) in MSA are analyzed as phases, where a Probe-Goal relation is established between the prepositional Probe p-P and the DP in its searching domain (i.e., its complement). The outcome of this relation is valuation of the unvalued Case feature on this DP complement (i.e., Genitive Case), and a similar valuation to the unvalued phi-features (φ-fs) on the Probe p-P.

A Review on the Expression Pattern of Non-coding RNAs in Patients With Schizophrenia: With a Special Focus on Peripheral Blood as a Source of Expression Analysis

Schizophrenia is a destructive neuropsychiatric disease with a median prevalence of 4.0 per 1,000 during the whole life. Genome-wide association studies have shown the role of copy number variants (generally deletions) and certain alleles of common single nucleotide polymorphisms in the pathogenesis of schizophrenia. This disorder predominantly follows the polygenic inheritance model. Schizophrenia has also been linked with various alterations in the transcript and protein content of the brain tissue. Recent studies indicate that alterations in non-coding RNAs (ncRNAs) signature underlie a proportion of this dysregulation. High throughput microarray investigations have demonstrated momentous alterations in the expression of long non-coding RNAs (lncRNA) and microRNAs (miRNAs) in the circulation or post-mortem brain tissues of patients with schizophrenia compared with control samples. While Gomafu, PINT, GAS5, TCONS_l2_00021339, IFNG-AS1, FAS-AS1, PVT1, and TUG1 are among down-regulated lncRNAs in schizophrenia, MEG3, THRIL, HOXA-AS2, Linc-ROR, SPRY4-IT1, UCA1, and MALAT1 have been up-regulated in these patients. Moreover, several miRNAs, such as miR-30e, miR-130b, hsa-miR-130b, miR-193a-3p, hsa-miR-193a-3p, hsa-miR-181b, hsa-miR-34a, hsa-miR-346, and hsa-miR-7 have been shown to be dysregulated in blood or brain samples of patients with schizophrenia. Dysregulation of these transcripts in schizophrenia not only provides insight into the pathogenic processes of this disorder, it also suggests these transcripts could serve as diagnostic markers for schizophrenia. In the present paper, we explore the changes in the expression of miRNAs and lncRNAs in patients with schizophrenia.

IL17F: A Possible Risk Marker for Spondyloarthritis in HLA-B*27 Negative Brazilian Patients

HLA-B*27 is an important marker for spondyloarthritis (SpA), however, many SpA patients are HLA-B*27 negative. Thus, the aim of this study was to investigate the influence of IL17, TNF and VDR gene polymorphisms in SpA patients who were HLA-B*27 negative. This case-control study was conducted in 158 patients [102 patients with ankylosing spondylitis (AS) and 56 with psoriatic arthritis (PsA)] and 184 controls. HLA-B*27 genotyping was performed using PCR-SSP and IL17A (rs2275913), IL17F (rs763780), TNF-308 (rs1800629), TNF-238 (rs361525), FokI C>T (rs2228570), TaqI C>T (rs731236), ApaI A>C (rs7975232), and BsmI C>T (rs1544410) using PCR-RFLP. Statistical analyses were performed by Chi-square and logistic regression using OpenEpi and SNPStats software. The IL17F C allele frequency was higher in patients with SpA, AS and PsA compared to controls. The IL17F T/C genotype frequency was higher in SpA patients in an overdominant inheritance model and when men and women were separately analyzed. IL17A_IL17F AC haplotype was significantly associated to the risk for SpA patients. As for VDR, the ApaI a/a was a potential risk factor for SpA in men. In conclusion, IL17F C variant contributed to the risk of SpA in Brazilian patients who were HLA-B*27 negative and could be a potential marker for SpA.

Oligogenic Inheritance of Monoallelic TRIP11, FKBP10, NEK1, TBX5, and NBAS Variants Leading to a Phenotype Similar to Odontochondrodysplasia

Skeletal dysplasias are often well characterized, and only a minority of the cases remain unsolved after a thorough analysis of pathogenic variants in over 400 genes that are presently known to cause monogenic skeletal diseases. Here, we describe an 11-year-old Finnish girl, born to unrelated healthy parents, who had severe short stature and a phenotype similar to odontochondrodysplasia (ODCD), a monogenic skeletal dysplasia caused by biallelic TRIP11 variants. The family had previously lost a fetus due to severe skeletal dysplasia. Exome sequencing and bioinformatic analysis revealed an oligogenic inheritance of a heterozygous nonsense mutation in TRIP11 and four likely pathogenic missense variants in FKBP10, TBX5, NEK1, and NBAS in the index patient. Interestingly, all these genes except TBX5 are known to cause skeletal dysplasia in an autosomal recessive manner. In contrast, the fetus was found homozygous for the TRIP11 mutation, and achondrogenesis type IA diagnosis was, thus, molecularly confirmed, indicating two different skeletal dysplasia forms in the family. To the best of our knowledge, this is the first report of an oligogenic inheritance model of a skeletal dysplasia in a Finnish family. Our findings may have implications for genetic counseling and for understanding the yet unsolved cases of rare skeletal dysplasias.

Resistant Sources and Genetic Control of Resistance to ToLCNDV in Cucumber

Tomato leaf curl New Delhi virus (ToLCNDV) is a severe threat for cucurbit production worldwide. Resistance has been reported in several crops, but at present, there are no described accessions with resistance to ToLCNDV in cucumber (Cucumis sativus). C. sativus var. sativus accessions were mechanically inoculated with ToLCNDV and screened for resistance, by scoring symptom severity, tissue printing, and PCR (conventional and quantitative). Severe symptoms and high load of viral DNA were found in plants of a nuclear collection of Spanish landraces and in accessions of C. sativus from different geographical origins. Three Indian accessions (CGN23089, CGN23423, and CGN23633) were highly resistant to the mechanical inoculation, as well as all plants of their progenies obtained by selfing. To study the inheritance of the resistance to ToLCNDV, plants of the CGN23089 accession were crossed with the susceptible accession BGV011742, and F1 hybrids were used to construct segregating populations (F2 and backcrosses), which were mechanically inoculated and evaluated for symptom development and viral load by qPCR. The analysis of the genetic control fit with a recessive monogenic inheritance model, and after genotyping with SNPs distributed along the C. sativus genome, a QTL associated with ToLCNDV resistance was identified in chromosome 2 of cucumber.