Rab GTPases as well as kinesin engines throughout endosomal trafficking

17p13.3 microduplications are rare copy number variations (CNVs) associated with variable phenotypes, including facial dysmorphism, developmental delay, intellectual disability, and autism. see more Typically, when a recognized pathogenic CNV is identified, other genetic factors are not considered. We investigated via whole-exome sequencing the presence of additional variants in four carriers of class I 17p13.3 microduplications. A 730 kb 17p13.3 microduplication was identified in two half-brothers with intellectual disability, but not in a third affected half-brother or blood cells from their normal mother (Family A), thus leading to the hypothesis of maternal germline mosaicism. No additional pathogenic variants were detected in Family A. Two affected siblings carried maternally inherited 450 kb 17p13.3 microduplication (Family B); the three carriers of the microduplication exhibited microcephaly and learning disability/speech impairment of variable degrees. Exome analysis revealed a variant of uncertain significance in RORA, a gene already linked to autism, in the autistic boy; his sister was heterozygous for a CYP1B1 pathogenic variant that could be related to her congenital glaucoma. Besides, both siblings carried a loss-of-function variant in DIP2B, a candidate gene for intellectual disability, which was inherited from their father, who also exhibited learning disability in childhood. In conclusion, additional pathogenic variants were revealed in two affected carriers of class I 17p13.3 microduplication (Family B), probably adding to their phenotypes. These results provided new evidence regarding the contribution of RORA and DIP2B to neurocognitive deficits, and highlighted the importance of full genetic investigation in carriers of CNV syndromes with variable expressivity. Finally, we suggest that microcephaly may be a rare clinical feature also related to the presence of the class I 17p13.3 microduplication.Infertility is known as one of the most common problems among couples. In this regard, generation of male germ cells from adult stem ones are among the current promising priorities of researchers. Mesenchymal stromal cells (MSCs) were previously induced to differentiate into germ-like progenitors in vitro. Monophosphoryl lipid A (MPLA) is a detoxified derivative of lipopolysaccharides (LPS) that lacks many of the endotoxic properties of LPS. Our present study aimed to investigate the expression of migration genes (CXCR4, VCAM1, VEGF, MMP2, and VLA4), and differentiation markers during human umbilical mesenchymal stromal cells (hUMSCs) culture in the presence of retinoic acid (RA) and MPLA-treated acellular testis. Accordingly, the high expression levels of deleted in azoospermia-like (DAZL), piwi-like RNA-mediated gene silencing 2 (PIWIL2) transcripts as well as protein were consequently observed in treated hUMSCs. It was concluded that combination treatment (i.e., MPLA/RA) had more prominent results than each of the treatments alone, even though MPLA and RA could be regarded as inducer of migration and differentiation, respectively. Ultimately, it was suggested to introduce the use of combination treatment as a more effective strategy to improve therapies in regenerative medicine.Integration of human papilloma virus (HPV) in human genome is a random event, and fragile sites are one of the most susceptible sites for viral integrations. WWOX (WW-domain containing oxidoreductase) gene harbours the second most common fragile site, FRA16D, and can be an important candidate for HPV integration and cervical carcinogenesis. Our aim was to evaluate the potential role of WWOX in cervical carcinogenesis. Presence of HPV and its genotype was detected by PCR in normal cervix tissues and human cervical carcinoma. The expression of WWOX transcript and its protein was examined by RT-PCR, RNA in situ hybridization, and immunoblotting. Southern blotting and sequencing were used to determine the alternative transcripts of WWOX. Statistical analysis were performed by Mann Whitney U-test, Pearson correlation coefficient test at significance level of P value less then 0.05. Prevalence of HPV was observed in cervicitis (40%), cervical intraepithelial neoplasia patients (50%), and invasive cervical carcinoma patients (89.6%). Clinicopathological findings suggested a correlation of reduced level of WWOX protein and progression of cervical carcinoma deciphering its role in tumorigenesis. Furthermore, we observed aberrant WWOX transcript having deleted exon 6-8 region in invasive cervical cancer tissues as well as normal cervix samples. More than 60% of cervical carcinoma samples showed reduced protein level with an increase in wild type transcript level suggesting the involvement of a negative regulator, pAck1 (activated Cdc42- associated kinase) which might ubiquitinate WWOX protein leading to its degradation. Also, nuclear retention of WWOX transcript in invasive cervical carcinoma tissues suggests its regulation at post-transcriptional level. Our findings suggest that WWOX acts as a tumor suppressor in cervical carcinoma and could act as a potential therapeutic target for the disease.Although colorectal cancer (CRC) is one of the most common cancers, the exact molecular mechanism of this cancer is not yet known. Circular RNAs (circRNAs), a class of non-coding RNAs, are newly identified and their role in the pathogenesis of various cancers has been shown. In this research, we studied the expression pattern and clinical importance of hsa_circ_000425 in CRC patients. After evaluation of hsa_circ_000425 expression rate in 4 CRC cell lines and 100 paired CRC tissues, the potential correlation between hsa_circ_000425 expression rate and clinicopathological parameters of CRC patients was analyzed. Additionally, receiver operating characteristic (ROC) curve was drawn to study the diagnostic value of hsa_circ_000425. A significant downregulation of hsa_circ_000425 was observed in both CRC tissues and cell lines. In addition, this downregulation was significantly associated with differentiation and lymphatic metastasis. The area under the ROC curve of hsa_circ_000425 was 0.839 (P less then 0.001).