A newly identified c.1824_1828dupATACG mutation in exon 13 of the GAA gene in infantile-onset glycogen storage disease type II (Pompe disease)

Pompe disease or glycogen storage disease type II is a glycogen storage disorder associated with malfunction of the acid α-glucosidase enzyme (GAA; EC.3.2.1.3) leading to intracellular aggregations of glycogenin muscles. The infantile-onset type is the most life-threatening form of this disease, in which most of patients suffer from cardiomyopathy and hypotonia in early infancy. In this study, a typical case of Pompe disease was reported in an Iranian patient using molecular analysis of the GAA gene. Our results revealed a new c.1824_1828dupATACG mutation in exon 13 of the GAA gene. In conclusion, with the finding of this novel mutation, the genotypic spectrum of Iranian patients with Pompe disease has been extended, facilitating the definition of disease-related mutations.     

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.     

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.     

Three new species of mygalomorph and filistatid spiders from Iran (Araneae,Cyrtaucheniidae, Nemesiidae and Filistatidae)

Three new spider species are described from Iran: Anemesia koponeni sp. n. (♂, Cyrtaucheniidae); Raveniola mazandaranica sp. n. (♂, Nemesiidae) and Sahastata sinuspersica sp. n. (♀, Filistatidae). Cyrtaucheniidae and Sahastata Benoit, 1968 are reported from Iran for the fisrt time.     

Groove-type Recognition of Chlamydiaceae-specific Lipopolysaccharide Antigen by a Family of Antibodies Possessing an Unusual Variable Heavy Chain N-Linked Glycan

The structure of the antigen binding fragment of mAb S25-26, determined to 1.95 Å resolution in complex with the Chlamydiaceae family-specific trisaccharide antigen Kdo(2→8)Kdo(2→4)Kdo (Kdo = 3-deoxy-α-d-manno-oct-2-ulopyranosonic acid), displays a germ-line-coded paratope that differs significantly from previously characterized Chlamydiaceae-specific mAbs despite being raised against the identical immunogen. Unlike the terminal Kdo recognition pocket that promotes cross-reactivity in S25-2-type antibodies, S25-26 and the closely related S25-23 utilize a groove composed of germ-line residues to recognize the entire trisaccharide antigen and so confer strict specificity. Interest in S25-23 was sparked by its rare high μm affinity and strict specificity for the family-specific trisaccharide antigen; however, only the related antibody S25-26 proved amenable to crystallization. The structures of three unliganded forms of S25-26 have a labile complementary-determining region H3 adjacent to significant glycosylation of the variable heavy chain on asparagine 85 in Framework Region 3. Analysis of the glycan reveals a heterogeneous mixture with a common root structure that contains an unusually high number of terminal αGal-Gal moieties. One of the few reported structures of glycosylated mAbs containing these epitopes is the therapeutic antibody Cetuximab; however, unlike Cetuximab, one of the unliganded structures in S25-26 shows significant order in the glycan with appropriate electron density for nine residues. The elucidation of the three-dimensional structure of an αGal-containing N-linked glycan on a mAb variable heavy chain has potential clinical interest, as it has been implicated in allergic response in patients receiving therapeutic antibodies.     

The effect of local bending on gating of MscL using a representative volume element and finite element simulation

Many physiological processes such as cell division, endocytosis and exocytosis cause severe local curvature of the cell membrane. Local curvature has been shown experimentally to modulate numerous mechanosensitive (MS) ion channels. In order to quantify the effects of local curvature we introduced a coarse grain representative volume element for the bacterial mechanosensitive ion channel of large conductance (MscL) using continuum elasticity. Our model is designed to be consistent with the channel conformation in the closed and open states to capture its major continuum rheological behavior in response to the local membrane curvature. Herein we show that change in the local curvature of the lipid bilayer can modulate MscL activity considerably by changing both bilayer thickness and lateral pressure profile. Intriguingly, although bending in any direction results in almost the same free-energy cost, inward (cytoplasmic) bending favors channel opening, whereas outward (periplasmic) bending facilitates closing of the narrowest part of the MscL pore. This quantitative study using MscL as a model channel may have wide reaching consequences for the effect of local curvature on the physiological function of other types of prokaryotic and eukaryotic membrane proteins.     

Up-regulation of Arl4a gene expression by broccoli aqueous extract is associated with improved spermatogenesis in mouse testes

Introduction: Broccoli (Brassica oleracea) is well known for its properties as an anticancer, antioxidant, and scavenger of free radicals. However, its benefits in enhancing spermatogenesis have not been well established.Objective: To study broccoli aqueous extract effects on sperm factors and the expression of genes Catsper1, Catsper2, Arl4a, Sox5, and Sox9 in sperm factors in mice.Material and methods: Male mice were divided randomly into six groups: (1) Control; (2) cadmium (3 mg/kg of mouse body weight); (3) orally treated with 200 µl broccoli aqueous extract (1 g ml^-1); (4) orally treated with 400 µl of broccoli aqueous extract; (5) orally treated with 200 broccoli aqueous extract plus cadmium, and (6) orally treated with 400 µl of broccoli aqueous extract plus cadmium. We analyzed the sperms factors and Catsper1, Catsper2, Arl4a, Sox5, and Sox9 gene expression.Results: An obvious improvement in sperm count and a slight enhancement in sperm motility were observed in mice treated with broccoli extract alone or with cadmium. Sperm viability was reduced by broccoli extract except for the 200 µl dose with cadmium, which significantly increased it. Interestingly, Arl4a gene expression increased in the 400 µl broccoli- treated group. Likewise, the Arl4a mRNA level in mice treated with cadmium and 200 µl of broccoli extract was higher than in the cadmium-treated mice. Furthermore, broccoli extract enhanced the mRNA level of Catsper2 and Sox5 genes in mice treated with 200 µl and 400 µl broccoli extract plus cadmium compared with the group treated solely with cadmium.Conclusion: The higher sperm count in broccoli-treated mice opens the way for the development of pharmaceutical products for infertile men.