Recurrent distal 7q11.23 deletion including HIP1 and YWHAG identified in patients with intellectual disabilities, epilepsy, and neurobehavioral problems

We report 26 individuals from ten unrelated families who exhibit variable expression and/or incomplete penetrance of epilepsy, learning difficulties, intellectual disabilities, and/or neurobehavioral abnormalities as a result of a heterozygous microdeletion distally adjacent to the Williams-Beuren syndrome region on chromosome 7q11.23. In six families with a common recurrent ∼1.2 Mb deletion that includes the Huntingtin-interacting protein 1 (HIP1) and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma (YWHAG) genes and that is flanked by large complex low-copy repeats, we identified sites for nonallelic homologous recombination in two patients. There were no cases of this ∼1.2 Mb distal 7q11.23 deletion copy number variant identified in over 20,000 control samples surveyed. Three individuals with smaller, nonrecurrent deletions (∼180–500 kb) that include HIP1 but not YWHAG suggest that deletion of HIP1 is sufficient to cause neurological disease. Mice with targeted mutation in the Hip1 gene (Hip1^−/−) develop a neurological phenotype characterized by failure to thrive, tremor, and gait ataxia. Overall, our data characterize a neurodevelopmental and epilepsy syndrome that is likely caused by recurrent and nonrecurrent deletions, including HIP1. These data do not exclude the possibility that YWHAG loss of function is also sufficient to cause neurological phenotypes. Based on the current knowledge of Hip1 protein function and its proposed role in AMPA and NMDA ionotropic glutamate receptor trafficking, we believe that HIP1 haploinsufficiency in humans will be amenable to rational drug design for improved seizure control and cognitive and behavioral function.     

Protective Immunity to Sarcocystis capracanis-Induced Abortion in Dairy Goats1

ABSTRACT. Eleven female goats (Nos. 1 to 11) were each inoculated orally with 10⁴ sporocysts of Sarcocystis capracanis, and four female goats (Nos. 12 to 15) were not inoculated. Between 31 and 69 days after inoculation (DAI) goats were mated with a single buck; one goat (No. 5) did not breed. Eight inoculated goats were challenged with 10⁵or 10⁶ sporocysts, 135 DAI. Two of four goats challenged with 10⁶ sporocysts and one of three goats challenged with 10⁵ sporocysts aborted one month before the expected time of parturition. The three inoculated goats that were not challenged delivered healthy kids. All inoculated goats including the nonpregnant one (No. 5) were only mildly ill from the primary or challenge inoculations. Two of the four control goats challenged with 5 × 10⁴ or 10⁵ sporocysts aborted 21 days later, and both died of sarcocystosis 25 and 88 DAI. The two remaining control goats delivered normal kids. The results indicate that immunization prior to pregnancy protects some but not all goats from .Sarc0c.es/is-induced abortion.     

Age and Growth of Spotted Snakehead,Channa punctata from the Ganga River

Journal of Ichthyology - The present study was undertaken to estimate age and growth of the spotted snakehead Channa punctata (Bloch, 1793) from the Ganga River, based on 390 fish samples collected...     

Analysis of Binding Interaction Between Antibacterial Ciprofloxacin and Human Serum Albumin by Spectroscopic Techniques

To develop an efficient method for extracting and purifying the active ingredient, arctiin, from Fructus arctii and to investigate the protective effect of arctiin against glucose-induced rat aortic endothelial cell (RAEC) injury was investigated. Using a L9 (34) orthogonal array and two-step column chromatography (with AB-8 macroporous resin) arctiin extraction was optimized using a reflux method with 70 % ethanol. The RAECs were then treated with different concentrations of arctiin (1, 10, or 100 μg/ml). The effects of arctiin on cell viability in a high glucose medium, malondialdehyde (MDA) levels, and lactate dehydrogenase were measured using commercially available assays. After extraction, the purity of arctiin reached 95.7 %. In rats, arctiin was shown to stimulate the proliferation of RAECs in a high glucose medium in a dose-dependent manner. Exposure of RAECs to high glucose resulted in a significant increase in MDA and release of lactate dehydrogenase. This was accompanied by significant increase in nitric oxide release and expression of antiendothelial nitric oxide synthase. This technique resulted in relatively pure arctiin extraction. Furthermore, the results from this study suggest that arctiin could potentially function as a protector against vascular endothelial cell injury and further investigation is warranted.     

Expression of the entomotoxic Cocculus hirsutus trypsin inhibitor (ChTI) gene in transgenic chickpea enhances its underlying resistance against the infestation of Helicoverpa armigera and Spodoptera litura

Plant Cell, Tissue and Organ Culture (PCTOC) - A trypsin inhibitor from Cocculus hirsutus, commonly known as “Farid Buti” has been demonstrated to exhibit insecticidal, fungicidal, as...     

Nanoparticle-induced morphological transition of Bombyx mori nucleopolyhedrovirus: a novel method to treat silkworm grasserie disease

Grasserie, a polyorganotrophic disease caused by Bombyx mori nucleopolyhedrovirus (BmNPV), accounts for lethal infection to fifth instar silkworm larvae. It was found that nanoparticle (NP)-induced morphological transformation of BmNPV polyhedra could reduce the infectivity of BmNPV both in cell line and in silkworm larvae. Initially, 11 NPs were screened for evaluation of their nature of interaction with polyhedra surface through scanning electron microscopy. Amongst these NPs, lipophilically coated silica nanoparticle (SNPL), alumina nanoparticles in the hexagonal close-packed α structure and aspartate capped gold nanoparticle transformed polyhedra were tested for their infectivity in B. mori cell line using cytopathic effect and plaque reduction assay. SNPL was evaluated for its bio-efficacy in fifth instar silkworm larvae. The study of polyhedra morphology as a function of NP concentration showed severe ‘roughening’ of the polyhedra with replacement of the regular facets by a large number of irregular ones by SNPL, and this caused transition of highly infectious polyhedra into a nearly spherical, non-infectious structure. A moderate polyhedra roughening was observed for alumina NPs, and no roughening was noticed for gold NPs. The morphological changes could be correlated with reduction of virus-induced cytopathic effect and plaque formation, and increased survival rate of SNPL transformed polyhedra infected silkworm larvae to 70.09?±?6.61 % after 96 h. In this group, 61.04?±?8.03 % larvae formed normal cocoons from which moths eclosed, laid eggs and larvae emerged. This study could lead to open up newer pathways for designing nano pharmaceuticals to combat other viral diseases.     

Recent admixture in an Indian population of African ancestry

Identification and study of genetic variation in recently admixed populations not only provides insight into historical population events but also is a powerful approach for mapping disease loci. We studied a population (OG-W-IP) that is of African-Indian origin and has resided in the western part of India for 500 years; members of this population are believed to be descendants of the Bantu-speaking population of Africa. We have carried out this study by using a set of 18,534 autosomal markers common between Indian, CEPH-HGDP, and HapMap populations. Principal-components analysis clearly revealed that the African-Indian population derives its ancestry from Bantu-speaking west-African as well as Indo-European-speaking north and northwest Indian population(s). STRUCTURE and ADMIXTURE analyses show that, overall, the OG-W-IPs derive 58.7% of their genomic ancestry from their African past and have very little inter-individual ancestry variation (8.4%). The extent of linkage disequilibrium also reveals that the admixture event has been recent. Functional annotation of genes encompassing the ancestry-informative markers that are closer in allele frequency to the Indian ancestral population revealed significant enrichment of biological processes, such as ion-channel activity, and cadherins. We briefly examine the implications of determining the genetic diversity of this population, which could provide opportunities for studies involving admixture mapping.