Challenging Issues in Diagnosis and Screening of BK Virus Nephropathy in Kidney Transplant Recipients, A Multicenter Experience in Iranian Population.

INTRODUCTION: BK virus nephropathy (BKVN) is an important complication of kidney transplantation and kidney biopsy remains the gold standard for its diagnosis. Urine/serum polymerase chain reaction (PCR) is a more sensitive diagnostic method, although it has some potential limitations. METHODS: This study enrolled all kidney transplant recipients who underwent kidney transplant biopsy, collected from three medical centers. Urine and serum PCR results of the patients were also collected from the molecular laboratories. The cut-off value for positive viral DNA load in serum and urine were > 104 and > 107 copies/mL, respectively. Sensitivity, specifity, positive and negative predictive values (PPV, NPV) and cut off values for PCR results were compared with pathologic diagnosis among laboratories. RESULTS: Among 369 biopsy samples, 33 (8.9%) had definite diagnosis of BKVN. PCR results were available for 138 cases. Three patients with definite BKVN had negative PCR results. In 22 patients, PCR was positive without evidence of BKVN. The overall sensitivity, specificity, PPV and NPV of PCR for detecting BKVN, based on a unique cut-off value, were 88, 81, 51, and 97%; respectively. The overall accuracy of PCR in all laboratories was high (82 to 86%), however significant inter-laboratory differences in sensitivity and specificity was found . A 2-log difference in threshold value for positive results was observed in one laboratory. CONCLUSION: PCR may show a significant variability between different laboratories. Interpretation of PCR results using a single cut-off value for all laboratories, may decrease the sensitivity for the diagnosis and screening of BKVN.  DOI: 10.52547/ijkd.7143.

wde, calpA, if, dap160, and poe genes knock down Drosophila models exhibit neurofunctional deficit.

Intellectual disability (ID) is a heterogeneous disorder with high prevalence and remarkable social and cost burdens. Novel genetic variants of ATF7IP, CAPN9, ITGAV, ITSN1, and UBR4 genes are reported to be associated with the ID among Iranian families. However, in vivo validation is required to confirm the functional role of these variants in ID development. Drosophila melanogaster is a convenient model for such functional investigations as its genome bears ortholog of more than 75% of the disease-causing genes in human and represents numerous approaches to study defects in neuronal function. In this connection, RNAi gene silencing was applied to wde, calpA, if, dap160, and poe genes, the Drosophila ortholog of the selected human genes, and then consequent structural and functional changes in neurons were studied by means of immunohistochemistry and confocal microscopy of mushroom bodies (MBs) and validated behavioural assays including larvae and adult conditioning learning and memories, and ethanol sensitivity. Down-regulation of these genes led to neuronal loss which was evident by decline in total fluorescent signal intensity in micrographs of MBs structure. The gene silencing caused neuronal dysfunction and induction of ID-like symptoms manifested by deficits in larval preference learning, and short-term olfactory memory and courtship suppression learning in adults. Moreover, the RNAi flies showed higher sensitivity to ethanol vapour. Interestingly, the poe knock-down flies exhibited the most severe phenotypes among other genes. Altogether, we believe this study is first-of-its-kind and findings are highly applicable to confirm pathogenecity of the selected ID gene variants in Iranian population.

Association analysis of physiological traits in spring barley (Hordeum vulgare L.) under water-deficit conditions.

In the present study, 148 commercial barley cultivars were assessed by 14 AFLP primer combinations and 32 SSRs primer pairs. Population structure, linkage disequilibrium, and genomic regions associated with physiological traits under drought stress were investigated. The phenotypic results showed a high level of diversity between studied cultivars. The studied barley cultivars were divided into two subgroups. Linkage disequilibrium analysis revealed that r 2 values among all possible marker pairs have an average value of 0.0178. The mixed linear model procedure showed that totally, 207 loci had a significant association with investigated traits. 120 QTLs out of 207 were detected for traits under normal conditions, and 90 QTLs were detected for traits under drought stress conditions. Identified QTLs after validation and transferring to SCAR markers in the case of AFLPs can be used to develop MAS strategies for barley breeding programs. Some common markers were identified for a particular trait or some traits across normal and drought stress conditions. These markers show low interaction with environmental conditions (stable markers); therefore, selection by them for a trait under normal conditions will improve the trait value under stress conditions, too.

Plasma Cytokines Profile in Subjects with Alzheimer's Disease: Interleukin 1 Alpha as a Candidate for Target Therapy.

Background: Alzheimer's disease (AD) is the main cause of the neurodegenerative disorder, which is not detected unless the cognitive deficits are manifested. An early prediagnostic specific biomarker preferably detectable in plasma and hence non-invasive is highly sought-after. Various hypotheses refer to AD, with amyloid-beta (Aß) being the most studied hypothesis and inflammation being the most recent theory wherein pro-and anti-inflammatory cytokines are the main culprits. Materials and Methods: In this study, the cognitive performance of AD patients (n=39) was assessed using mini-mental state examination (MMSE), AD assessment scale-cognitive subscale (ADAS-cog), and clinical dementia rating (CDR). Their neuropsychiatric symptoms were evaluated through neuropsychiatric inventory-questionnaire (NPI-Q). Moreover, plasma levels of routine biochemical markers, pro-/anti-inflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin-1 α (IL-1α), IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-12p70, IL-10, Interferon-gamma, chemokines, including prostaglandin E2 (PGE-2), monocyte chemoattractant protein-1, interferon gamma-induced protein 10, Aß peptide species (42, 40) and Transthyretin (TTR) were measured. Results: Our results revealed that Aß 42/40 ratio and TTR were correlated (r=0.367, P=0.037). IL-1α was directly correlated with ADAS-cog (r=0.386, P=0.017) and Aß 40 (r=0.379, P=0.019), but was inversely correlated with IL-4 (r=-0.406, P=0.011). Negative correlations were found between MMSE and PGE2 (r=-0.405, P=0.012) and TNF-α/ IL-10 ratio (r=-0.35, P=0.037). CDR was positively correlated with both PGE2 (r=0.358, P=0.027) and TNF-α (r=0.416, P=0.013). There was a positive correlation between NPI-caregiver distress with CDR (r=0.363, P=0.045) and ADAS-cog (r=0.449, P=0.019). Conclusion: Based on the observed correlation between IL-1α, as a clinical moiety, and ADAS-cog, as a clinical manifestation of AD, anti-IL-1α therapy in AD could be suggested.

Contribution of Iran in Elucidating the Genetic Causes of Autosomal Recessive Intellectual Disability.

Many genes with different inheritance modes contribute to the pathogenicity of intellectual disability (ID) making it the most known genetically heterogeneous disorder. Advanced next-generation sequencing (NGS) technologies have helped researchers identify genes underlying ID at an exponential pace. As a consanguineous country, Iran is a hotspot for discovering novel autosomal recessive intellectual disability (ARID) genes. Here, we aimed to review and compare reported ARID gene discovery both in Iran and globally, and pinpoint the research areas that need to be developed in future. We studied published articles and reviews on all known ID genes. In parallel, the gene-discovery research carried out on the Iranian population were also reviewed to determine the contribution of Iran to identifying novel ID genes. Also we tried to find supporting evidence on the causative role of novel genes identified in Iran including confirmatory functional studies and existence of more affected families. We also briefly reviewed the current therapeutic approaches under development for a subset of eligible ID cases. In total, 8% of all ID and 11.5% of all ARID genes described so far have been identified via studies on Iranian population. Functional studies have been performed on 29% of the genes identified in Iran. More than one affected family has been reported for many of these genes, supporting their causative role in ID pathogenesis. Despite the notable contribution of Iran in gene-discovery research, further functional studies on the identified genes are required.

GWAS analysis in spring barley (Hordeum vulgare L.) for morphological traits exposed to drought.

Association analysis based on linkage disequilibrium has become a common and powerful approach for detection of QTLs underlying complex agronomic traits including drought tolerance. To determine marker/trait association, 148 modern European spring barley cultivars were evaluated under drought stress. Associations of morphological traits with AFLP/SSR markers were investigated based on the mixed linear model using the TASSEL3.0. Population structure was estimated using various methods including Bayesian clustering model by STRUCTURE software, PCoA analysis, NJ dendrogram and Hierarchical Clustering. Linkage disequilibrium patterns were explored among the whole genome and each chromosome separately. All the analysis for population structure divided the population into two sub-groups. Linkage disequilibrium analysis showed that by increasing genetic distance, LD decreases. Totally, 167 significant marker trait associations were found which delineated into 65 QTLs in both treatments. Two stable QTLs on 5H at 86.880 cM were detected for Internode Length and on 3H at 126.421 cM for flag leaf length in drought stress treatment. Fourteen QTLs were co-localized with previously reported QTLs and others were novel. The results indicate that these putative genomic regions contain genes that have pleiotropic effects on morphological traits in drought condition.