Additional deletion in sex-determining region of human Y chromosome resolves paradox of X,t(Y;22) female

Whether a human embryo develops as a male or a female is determined by the presence of the Y chromosome. The sex-determining function lies entirely in interval 1A, inasmuch as most XX individuals with descended testes and normal male external genitalia carry this small region of the Y chromosome. We have localized an essential part of the sex-determining function to a portion of interval 1A, on the basis of the discovery of a female with a reciprocal Y;22 translocation and part of 1A deleted at the translocation breakpoint. Recently, a paradox has arisen with the report of four partially masculinized XX individuals who carry only a portion of interval 1A--a portion that does not overlap the deletion in the X,t(Y;22) female. These recent findings imply that the sex-determining function lies in the portion of 1A present in the four XX intersexes and not in the portion deleted in the X,t(Y;22) female. To explain the X,t(Y;22) individual, it was proposed that she was female because of a chromosomal position effect or delayed development of the gonadal soma. Here we report that the X,t(Y;22) female has a deletion of a second portion of interval 1A--a portion corresponding closely to that present in the XX intersexes. This resolves the apparent contradiction. Nonetheless, phenotype-genotype correlations suggest that two or more genetic elements in interval 1A may contribute to the sex-determining function of the Y chromosome. The X,t(Y;22) female lacks the ZFY gene but does not exhibit the complex phenotype known as Turner's syndrome, arguing against the hypothesis that ZFY is the Turner's syndrome gene on the Y chromosome.     

HIV infection is blocked in vitro by recombinant soluble CD4

The T-cell surface glycoprotein, CD4 (T4), acts as the cellular receptor for human immunodeficiency virus, type 1 (HIV-1), the first member of the family of viruses that cause acquired immunodeficiency syndrome. HIV recognition of CD4 is probably mediated through the virus envelope glycoprotein (gp120) as shown by co-immunoprecipitation of CD4 and gp120 (ref.5) and by experiments using recombinant gp120 as a binding probe. Here we demonstrate that recombinant soluble CD4(rsT4) purified from the conditioned medium of a stably transfected Chinese hamster ovary cell line is a potent inhibitor of both virus replication and virus-induced cell fusion (syncytium formation). These results suggest that rsT4 is sufficient to bind HIV, and that it represents a potential anti-viral therapy for HIV infection.     

Discovery of novel avermectins with unprecedented insecticidal activity

Summary A new class of insecticidal and antiparasitic agents, 4-amino-4-deoxy avermectins, has been developed by chemical modification of avermectin B₁. The most effective of these compounds are 1500-fold more potent than avermectin B₁ (abamectin) against the beet armywormSpodoptera exigua and show similar potency against other lepidopteran larvae.     

Ant fauna (Hymenoptera: Formicidae) of the Socotra Archipelago (Yemen): zoogeography,distribution and description of a new species

The animal fauna of the Socotra Archipelago is influenced by three biogeographical regions, the Afrotropical, the Oriental and the Palaearctic. Consequently, the Archipelago shares faunal elements of these three regions in addition to unique endemic taxa. The ant fauna of Socotra Island was studied and is reviewed based on literature and newly collected material. In total, 28 species, belonging to 10 genera and four subfamilies, were collected from the main island. Eighteen of these (64%) are successful invasive species, seven are native (25%), and three are considered endemic (11%), Cardiocondyla longiceps Seifert, Monomorium elghazalyi sp. nov. and Monomorium nimihil Collingwood et al. Two genera are recorded for the first time from the island, Hypoponera Santschi, and Syllophopsis Santschi. Ten species are recorded for the first time, Cardiocondyla mauritanica Forel, Cardiocondyla minutior Forel, Monomorium atomum Forel, Monomorium dichroum Forel, Monomorium exiguum Forel, Pheidole pallidula (Nylander), Syllophopsis cryptobia (Santschi), Tetramorium pauper Forel, Tetramorium transformans Santschi and Hypoponera punctatissima (Roger). Ten invasive species are recorded from Socotra, reflecting human impacts on the Archipelago. These species are Tapinoma melanocephalum (Fabricius), Cardiocondyla emeryi Forel, Monomorium exiguum Forel, Pheidole indica Mayr, Syllophopsis cryptobia (Santschi), Tetramorium lanuginosum Mayr, Tetramorium simillimum (Smith), Tetramorium caldarium (Roger), Trichomyrmex destructor (Jerdon) and Trichomyrmex mayri (Forel). Our survey indicated a mixture of Afrotropical faunal elements (10 species, 36%), followed by cosmopolitan (nine species, 32%), Palaearctic (five species, 18%) and Oriental (four species, 14%) taxa. Two new synonyms of Monomorium exiguum Forel are proposed: Monomorium exiguum Forel = Monomorium baushare Collingwood & Agosti syn. nov. = Monomorium qarahe Collingwood & Agosti syn. nov. Tetramorium transformans Santschi is removed from synonymy with Tetramorium caldarium (Roger) and elevated to species rank. Ecological and biological notes for each species are given. Distribution maps for all species known from the Socotra Archipelago are provided.

http://zoobank/urn:lsid:zoobank.org:pub:89612083-9CE6-48E8-8975-1CE5334E098B     

Revertant mosaicism in genodermatoses

Inherited monogenic skin disorders include blistering disorders, inflammatory disorders, and disorders of differentiation or development. In most cases, the skin is broadly involved throughout the affected individual’s lifetime, but rarely, appearance of normal skin clones has been described. In these cases of revertant mosaicism, cells undergo spontaneous correction to ameliorate the effects of genetic mutation. While targeted reversion of genetic mutation would have tremendous therapeutic value, the mechanisms of reversion in the skin are poorly understood. In this review, we provide an overview of genodermatoses that demonstrate widespread reversion and their corrective mechanisms, as well as the current research aimed to understand this “natural gene therapy”.     

Effect of recombinant soluble CD4 in rhesus monkeys infected with simian immunodeficiency virus of macaques

The CD4 molecule is a high-affinity cell-surface receptor for the human immunodeficiency virus (HIV-1) and a soluble truncated form of CD4 produced by recombinant DNA technology is a potent inhibitor of HIV-1 replication and HIV-1-induced cell fusion in vitro. Rhesus monkeys infected with the simian immunodeficiency virus of macaques (SIVMAC), a virus closely related to HIV-1, develop an AIDS-like syndrome, and so provide an important model for the evaluation of potential AIDS therapies. We have assessed the therapeutic effect of recombinant soluble CD4 in SIVMAC-infected rhesus monkeys. Virus was readily isolated from peripheral blood lymphocytes and bone marrow cells of these animals before starting treatment with soluble CD4, but became difficult to isolate soon after treatment had begun. Moreover the diminished growth of both granulocyte-macrophage and erythrocyte progenitor colonies from the bone marrow of these monkeys rose to normal levels during treatment. These findings indicate that soluble CD4 could prove valuable in the treatment of AIDS.     

Visualizing spatially correlated dynamics that directs RNA conformational transitions

RNAs fold into three-dimensional (3D) structures that subsequently undergo large, functionally important, conformational transitions in response to a variety of cellular signals. RNA structures are believed to encode spatially tuned flexibility that can direct transitions along specific conformational pathways. However, this hypothesis has proved difficult to examine directly because atomic movements in complex biomolecules cannot be visualized in 3D by using current experimental methods. Here we report the successful implementation of a strategy using NMR that has allowed us to visualize, with complete 3D rotational sensitivity, the dynamics between two RNA helices that are linked by a functionally important trinucleotide bulge over timescales extending up to milliseconds. The key to our approach is to anchor NMR frames of reference onto each helix and thereby directly measure their dynamics, one relative to the other, using 'relativistic' sets of residual dipolar couplings (RDCs). Using this approach, we uncovered super-large amplitude helix motions that trace out a surprisingly structured and spatially correlated 3D dynamic trajectory. The two helices twist around their individual axes by approximately 53 degrees and 110 degrees in a highly correlated manner (R = 0.97) while simultaneously (R = 0.81-0.92) bending by about 94 degrees. Remarkably, the 3D dynamic trajectory is dotted at various positions by seven distinct ligand-bound conformations of the RNA. Thus even partly unstructured RNAs can undergo structured dynamics that directs ligand-induced transitions along specific predefined conformational pathways.