Small molecule inhibitors of the HPV16-E6 interaction with caspase 8

High-risk strains of human papillomaviruses (HPVs) cause nearly all cases of cervical cancer as well as a growing number of head and neck cancers. The oncogenicity of these viruses can be attributed to the activities of their two primary oncoproteins, E6 and E7. The E6 protein has among its functions the ability to prevent apoptosis of infected cells through its binding to FADD and caspase 8. A small molecule library was screened for candidates that could inhibit E6 binding to FADD and caspase 8. Flavonols were found to possess this activity with the rank order of myricetin > morin > quercetin > kaempferol = galangin ? (apigenin, 7-hydroxyflavonol, rhamnetin, isorhamnetin, geraldol, datiscetin, fisetin, 6-hydroxyflavonol). Counter screening, where the ability of these chosen flavonols to inhibit caspase 8 binding to itself was assessed, demonstrated that myricetin, morin and quercetin inhibited GST-E6 and His-caspase 8 binding in a specific manner. The structure–activity relationships suggested by these data are unique and do not match prior reports on flavonols in the literature for a variety of anticancer assays.     

Type specimens of argasid and ixodid ticks (Ixodoidea: Argasidae, Ixodidae) in the collection of the Zoological Institute, Russian Academy of Sciences (St. Petersburg)

The catalogue contains data on type specimens of 79 species and subspecies of argasid and ixodid ticks. The data on 32 holotypes, 35 lectotypes, and 2 neotypes are given; paratypes and paralectotypes of 47 taxa are present in the collection. Within each family, type specimens are listed in alphabetical order.     

Individual and population variation in cercariae of bird schistosomes of the <Emphasis Type="Italic">Trichobilharzia ocellata</Emphasis> species group as revealed with the polymerase chain reaction

The polymerase chain reaction with arbitrary (RAPD-PCR) or specific primers was used to study the population variation and to identify the species in cercariae of schistosomes of the Trichobilharzia ocellata species group (Trematoda, Schistosomatidae). In total, 28 cercariae were obtained from two spontaneously invaded mollusks Lymnaea stagnalis (LS) and L. ovata (LO), which were collected in different ponds of Moscow. RAPD-PCR was carried out with two arbitrary primers, OPA9 and OPB11, which each detected different levels of individual and among-group variation and revealed considerable genetic differentiation of cercariae from different host mollusks. To check whether the cercariae of the two samples belong to one species, sequencing was performed with a region corresponding to intergenic transcribed spacer 2 (ITS2), which was earlier proposed for cercaria identification in three European species of bird schistosomes of the genus Trichobilharzia (T. franki, T. regenti, and T. szidati). The ITS2 sequences of two LO cercariae were identical, each consisted of 319 bp, and showed 100% homology to the T. franki ITS2 sequence. The ITS2 sequences of two LS cercariae were identical, each consisted of 323 bp, and showed 99.4% homology to the T. szidati counterpart. The causes of genetic variation in cercariae and prospects of using RAPD markers to study different stages of the life cycle in trematodes are discussed.Translated from Genetika, Vol. 41, No. 1, 2005, pp. 17–22.Original Russian Text Copyright © 2005 by Semyenova, Chrisanfova, Filippova, Beer, Voronin, Ryskov.     

Morphology and ultrastructure of the anterior end of Diplocirrus longisetosus Marenzeller, 1890 (Flabelligeridae, Polychaeta, Annelida)

The morphology and ultrastructure of the sedentary polychaete Diplocirrus longisetosus Marenzeller, 1890, collected from the White Sea, were studied using dissection, histological methods, light microscopy, and both scanning and transmission electron microscopy. The prostomium and peristomium carry a pair of palps, eight branchiae, a pair of nuchal organs and two nephridiopores, ciliated folds and the mouth. The prostomium, peristomium and the first chaetigerous segment with all appendages comprise the so-called siphon complex. The mouth leads to a pharyngeal organ that is closed ventrally and composed of a ventral muscle bulb adjoined dorsally by two folds projecting into the pharyngeal lumen. These parts are connected and enveloped by the longitudinal investing muscle. No tongue-like organ is present. The nervous system of the siphonal part comprises the brain, the circum-oesophageal connectives and the ganglia of the peristomium and first chaetigerous segment.     

土壤中棉花黄萎病菌SYBR Green Ⅰ荧光RT-PCR定量检测技术研究

为实现田间土壤棉花黄萎病菌的早期检测,建立了土壤中棉花黄萎病菌的SYBR Green I荧光定量PCR检测方法。以含342bp PCR扩增产物的阳性质粒为参考,构建了标准曲线,并对该曲线的特异性、敏感性、可重复性进行了评价。结果表明,该方法具有快速、特异性强、敏感度高等特点。检测范围在3.8×103-3.8×108copies/μL之间有良好的线性关系,相关系数R2为0.996,扩增效率为101.5%,灵敏度比常规PCR方法高102倍。     

Morphological inversions during the ontogenesis of the ixodid ticks (Acari: Ixodidae) from the viewpoint of the hypermorphosis conception and their significance for systematics

Morphological inversions during the ontogenesis of the ixodid ticks consist in the deranges of species-specific tendencies in the development of some external structures by the female line. The inversions, which included a wide range of organs and their fine structures, have been described for the first time in 14 species of 4 from 7 Palearctic ixodid genera. Emphasis is placed on the study of the structures, which serve as differential characters for closely related species. It is shown, that the using of the structures subjected to inversions is unavoidable in systematics because of the great similarity of closely related species, especially in immature stages. It is established by the data on the variability of all active stages in the species distribution ranges, that the degree of the inversions manifestation may somewhat fluctuate in different subspecies or geographic morphotypes of the same species, but the peculiarity of the inversions always remains a species-specific character. The cause of inversions origin is the evolution of the Ixodidae by the way of morpho-ecological specialization, namely hypertrophic, giantism, the growth of teguments in the period of nutrition act by pasture ambushing, which led to the derange of the development coordination of the organs during ontogenesis. Biological implication of the inversions is a guarantee of the adaptive potential of species during the process of microevolution. Even though the inversions make identification of closely related species difficult, their substantial importance is that they form integral species-specific character for the whole active part of the species ontogenesis.     

Age-related macular degeneration: a high-resolution genome scan for susceptibility loci in a population enriched for late-stage disease

Age-related macular degeneration (AMD) is a complex multifactorial disease that affects the central region of the retina. AMD is clinically heterogeneous, leading to geographic atrophy (GA) and/or choroidal neovascularization (CNV) at advanced stages. Considerable data exists in support of a genetic predisposition for AMD. Recent linkage studies have provided evidence in favor of several AMD susceptibility loci. We have performed a high-resolution (5-cM) genome scan of 412 affected relative pairs that were enriched for late-stage disease (GA and/or CNV). Nonparametric linkage analysis was performed using two different diagnostic criteria and also by dividing the affected individuals according to GA or CNV phenotype. Our results demonstrate evidence of linkage in regions that were suggested in at least one previous study at chromosomes 1q (236-240 cM in the Marshfield genetic map), 5p (40-50 cM), and 9q (111 cM). Multipoint analysis of affected relatives with CNV provided evidence of additional susceptibility loci on chromosomes 2p (10 cM) and 22q (25 cM). A recently identified Gln5345Arg change in HEMICENTIN-1 on chromosome 1q25 was not detected in 274 affected members in the restricted group with AMD, 346 additional patients with AMD, and 237 unaffected controls. Our results consolidate the chromosomal locations of several AMD susceptibility loci and, together with previous reports, should facilitate the search for disease-associated sequence variants.