Autophagy and senescence: A new insight in selected human diseases

Senescence and autophagy play important roles in homeostasis. Cellular senescence and autophagy commonly cause several degenerative processes, including oxidative stress, DNA damage, telomere shortening, and oncogenic stress; hence, both events are known to be interrelated. Autophagy is well known for its disruptive effect on human diseases, and it is currently proposed to have a direct effect on triggering senescence and quiescence. However, it is yet to be proven whether autophagy has a positive or negative impact on senescence. It is known that elevated levels of autophagy induce cell death, whereas inadequate autophagy can trigger cellular senescence. Both have important roles in human diseases such as aging, renal degeneration, neurodegenerative disorders, and cancer. Therefore, this review aims to highlight the relevance of senescence and autophagy in selected human ailments through a summary of recent findings on the connection and effects of autophagy and senescence in these diseases.     

Exploring genetic variations in threatened medicinal orchids using start codon targeted (SCoT) polymorphism and marker-association with seed morphometric traits

We aimed to study the genetic diversity and population structure of eight Iranian terrestrial orchid species, including Anacamptis coriophora (L.) R. M. Bateman, Pridgeon and M. W. Chase, Dactylorhiza umbrosa (Kar. & Kir.) Nevski, Himantoglossum affine (Boiss.) Schltr., Orchis collina Banks and Solander, Orchis mascula (L.) L., Orchis simia Lam., Ophrys schulzei Bornm. and Fleischm., and Ophrys straussii H. Fleischm. and Bornm. using start target codon markers (SCoT) and finding markers associated with seed morphometric traits. A total of 254 reproducible SCoT fragments were generated, of which 248 fragments were polymorphic (average polymorphism of 96.18%). The SCoT markers showed a narrow range of polymorphism information content (PIC) varied from 0.397 for S9 primer to 0.499 for S11 and S20 primers. Based on the population analysis results, the Orchis simia accessions collected from Paveh region (Os.P) represented the lowest observed number of alleles (Na) (1.13) and effective number of alleles (Ne) (1.09). At the same time, the highest Na (1.29) and Ne (1.18) values were obtained in O. schulzei collected from Javanrood (Oyst.JA). Shannon’s information index (I) was ranged from 0.03 for D. umbrosa accessions collected from Marivan (Du.M population) to 0.263 for Ha.Ja population (H. affine accessions collected from Javanrood). The UPGMA dendrogram obtained with the Jaccard similarity coefficient (r = 0.97295) divided 97 studied terrestrial orchid accessions into eight groups mainly based on species type and geographical origin. Based on the Bayesian statistical index, the highest probability of the data was achieved when accessions were divided into eight groups (K = 8). Multiple association analysis (MRA) revealed significant associations between some of SCoT bands with seed morphometric traits. Our findings can be useful for germplasm characterization, conservation, and improvement of Iranian terrestrial orchid species.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12298-021-00978-4.     

Let-7e enhances the radiosensitivity of colorectal cancer cells by directly targeting insulin-like growth factor 1 receptor

Abnormal expression of various microRNAs (miRNAs), as regulators of biological signaling pathways, has a strong association with cancer resistance to chemotherapy and radiotherapy. The let-7 family of miRNAs as tumor suppressors have shown to be downregulated in different types of human malignancies including colorectal cancer (CRC). However, the biological function of let-7 members in the processes of resistance to radiation in CRC has not yet been completely elucidated. Insulin-like growth factor 1 receptor (IGF-1R) signaling pathway is amplified in CRC and leads to its progression, development, and also radiation resistance. So, it seems like an attractive target for anticancer therapy. In this study, by using bioinformatics analysis, it has been revealed that IGF-1R is a direct target of the let-7e member. Consistent with this, we identified that increased levels of let-7e in CRC cells reduced IGF-1R protein level and subsequently its downstream signaling pathways, which resulted in the G1 cell cycle arrest and a significant reduction in the proliferation, survival and also resistance to radiation of CRC cells. Altogether, these results suggested that let-7e by targeting the IGF-1R signaling pathway might serve as therapeutics in anticancer therapy.     

Toll-like receptors signaling network in pre-eclampsia: An updated review

Toll-like receptors (TLRs) are innate immune cells receptors. They are expressed on leukocytes, epithelial cells, and more particularly on placental immune cells and chorion trophoblast. Upregulation of innate immune response occurs during normal pregnancy, but its excessive activity is involved in the pathology of pregnancy complications including pregnancy-induced hypertension and pre-eclampsia (PE). The recent studies about the overmuch inflammatory responses and aberrant placentation are associated with increased expression of TLRs in PE patients. This review has tried to focus on the relationship between some activities of TLRs and the risk of preeclampsia development.     

Population Genomic Analyses Based on 1 Million SNPs in Commercial Egg Layers

Identifying signatures of selection can provide valuable insight about the genes or genomic regions that are or have been under selective pressure, which can lead to a better understanding of genotype-phenotype relationships. A common strategy for selection signature detection is to compare samples from several populations and search for genomic regions with outstanding genetic differentiation. Wright''s fixation index, F_ST, is a useful index for evaluation of genetic differentiation between populations. The aim of this study was to detect selective signatures between different chicken groups based on SNP-wise F_ST calculation. A total of 96 individuals of three commercial layer breeds and 14 non-commercial fancy breeds were genotyped with three different 600K SNP-chips. After filtering a total of 1 million SNPs were available for F_ST calculation. Averages of F_ST values were calculated for overlapping windows. Comparisons of these were then conducted between commercial egg layers and non-commercial fancy breeds, as well as between white egg layers and brown egg layers. Comparing non-commercial and commercial breeds resulted in the detection of 630 selective signatures, while 656 selective signatures were detected in the comparison between the commercial egg-layer breeds. Annotation of selection signature regions revealed various genes corresponding to productions traits, for which layer breeds were selected. Among them were NCOA1, SREBF2 and RALGAPA1 associated with reproductive traits, broodiness and egg production. Furthermore, several of the detected genes were associated with growth and carcass traits, including POMC, PRKAB2, SPP1, IGF2, CAPN1, TGFb2 and IGFBP2. Our approach demonstrates that including different populations with a specific breeding history can provide a unique opportunity for a better understanding of farm animal selection.     

Initiation of mammalian O-mannosylation in vivo is independent of a consensus sequence and controlled by peptide regions within and upstream of the alpha-dystroglycan mucin domain

To reveal insight into the initiation of mammalian O-mannosylation in vivo, recombinant glycosylation probes containing sections of human alpha-dystroglycan (hDG) were expressed in epithelial cell lines. We demonstrate that O-mannosylation within the mucin domain of hDG occurs preferentially at Thr/Ser residues that are flanked by basic amino acids. Protein O-mannosylation is independent of a consensus sequence, but strictly dependent on a peptide region located upstream of the mucin domain. This peptide region cannot be replaced by other N-terminal peptides, however, it is not sufficient to induce O-mannosylation on a structurally distinct mucin domain in hybrid constructs. The presented in vivo evidence for a more complex regulation of mammalian O-mannosylation contrasts with a recent in vitro study of O-mannosylation in human alpha-dystroglycan peptides indicating the existence of an 18-meric consensus sequence. We demonstrate in vivo that the entire region p377-417 is necessary and sufficient for O-mannosylation initiation of hDG, but not of MUC1 tandem repeats. The feature of a doubly controlled initiation process distinguishes mammalian O-mannosylation from other types of O-glycosylation, which are largely controlled by structural properties of the substrate positions and their local peptide environment.     

Phylogenetic analysis of Aphanius from the endorheic Kor River Basin in the Zagros Mountains,South‐western Iran (Teleostei: Cyprinodontiformes: Cyprinodontidae)

Morphologically similar populations of Aphanius that are currently considered as A. sophiae inhabit the endorheic Kor River Basin in the Zagros Mountains. Using genetic analysis based on mtDNA (cytochrome b), combined with examination of morphology (morphometry, meristics, otoliths), we discovered that what is thought to be A. sophiae is actually two distinct species, one of which is described as A. shirini sp. n. The males of the new species can be distinguished from those of all other Iranian inland Aphanius species by having only 7–10 clearly defined white flank bars, which is the lowest number of flank bars among the Iranian inland Aphanius species. Both males and females differ from all other Iranian inland Aphanius species by having a significantly longer caudal peduncle and a smaller dorsal fin depth. Based on the PhyML and Bayesian likelihood trees, A. shirini is sister to A. vladykovi from the Karoun Basin in the Zagros Mountains. Our results indicate that an ancient exorheic Kor River Basin existed in the Late Miocene and Pliocene. The close phylogenetic relationship between A. shirini and A. vladykovi suggests that the pre‐Pliocene drainage in the ancient Kor River Basin was directed to the north‐west (to the Karoun Basin), and not to the south‐east as in the present‐day Kor Basin. Both A. shirini and A. vladykovi represent the highest altitude records for Aphanius. We conclude that the splits of A. shirini and A. vladykovi can be linked to tectonic events in the Middle to Late Miocene, which created the highest altitudes (>3000 m) in the Zagros Mountains, and led to isolation of populations. The present‐day endorheic Kor Basin is known to have formed in the Late Pleistocene or Early Holocene, and the ‘young’ age of A. sophiae is clearly related to this history. Our results contribute to elucidate the link between geological history and the present‐day species diversity in the tectonically still active Zagros Mountains of Iran.