Shashi XLMR syndrome: report of a second family

This report describes a family with mental retardation in two brothers. The pedigree is consistent with either X-linked mental retardation or autosomal recessive inheritance. The clinical features consist of coarse face, prominent lower lip, large testes, and obesity. This same constellation of findings was observed in a family with X-linked mental retardation (XLMR) reported by Shashi et al. [2000: Am J Hum Genet 66:469-479]. Furthermore, haplotype analysis was consistent with localization of the Shashi XLMR syndrome in Xq26-q27. Thus, the family likely represents a second occurrence of the Shashi XLMR syndrome.     

A porcine G9 rotavirus strain shares neutralization and VP7 phylogenetic sequence lineage 3 characteristics with contemporary human G9 rotavirus strains

Of five globally important VP7 (G) serotypes (G1-4 and 9) of group A rotaviruses (the single most important etiologic agents of infantile diarrhea worldwide), G9 continues to attract considerable attention because of its unique natural history. Serotype G9 rotavirus was isolated from a child with diarrhea first in the United States in 1983 and subsequently in Japan in 1985. Curiously, soon after their detection, G9 rotaviruses were not detected for about a decade in both countries and then reemerged in both countries in the mid-1990s. Unexpectedly, however, such reemerged G9 strains were distinct genetically and molecularly from those isolated in the 1980s. Thus, the origin of the reemerged G9 viruses remains an enigma. Sequence analysis has demonstrated that the G9 rotavirus VP7 gene belongs to one of at least three phylogenetic lineages: lineage 1 (strains isolated in the 1980s in the United States and Japan), lineage 2 (strains first isolated in 1986 and exclusively in India thus far), and lineage 3 (strains that emerged/reemerged in the mid-1990s). Currently, lineage 3 G9 viruses are the most frequently detected G9 strains globally. We characterized a porcine rotavirus (A2 strain) isolated in the United States that was known to belong to the P[7] genotype but had not been serotyped by neutralization. The A2 strain was found to bear serotype G9 and P9 specificities as well as NSP4 [B] and subgroup I characteristics. By VP7-specific neutralization, the porcine G9 strain was more closely related to lineage 3 viruses than to lineage 1 or 2 viruses. Furthermore, by sequence analysis, the A2 VP7 was shown to belong to lineage 3 G9. These findings raise intriguing questions regarding possible explanations for the emergence of variations among the G9 strains.     

Novel sequence variants in the TMC1 gene in Pakistani families with autosomal recessive hearing impairment

Though many hearing impairment genes have been identified, only a few of these genes have been screened in population studies. For this study, 168 Pakistani families with autosomal recessive hearing impairment not due to mutations in the GJB2 (Cx26) gene underwent a genome scan. Two-point and multipoint parametric linkage analyses were carried out. Twelve families had two-point or multipoint LOD scores of 1.4 or greater within the transmembrane cochlear expressed gene 1 (TMC1) region and were subjected to further screening with direct DNA sequencing. Five novel putatively functional non-synonymous sequence variants, c.830A>G (p.Y277C), c.1114G>A (p.V372M), c.1334G>A (p.R445H), c.2004T>G (p.S668R), and c.2035G>A (p.E679K), were found to segregate within seven families, but were not observed in 234 Pakistani control chromosomes. The variants c.830A>G (p.Y277C), c.1114G>A (p.V372M), and c.1334G>A (p.R445H) occurred at highly conserved regions and were predicted to lie within hydrophobic transmembrane domains, while non-synonymous variants c.2004T>G (p.S668R) and c.2035G>A (p.E679K) occurred in extracellular regions that were not highly conserved. There is evidence that the c.2004T>G (p.S668R) variant may have occurred at a phosphorylation site. One family has the known splice site mutation c.536 -8T>A. The prevalence of non-syndromic hearing impairment due to TMC1 in this Pakistani population is 4.4% (95%CI: 1.9, 8.6%). The TMC1 protein might have an important function in K(+) channels of inner hair cells, which would be consistent with the hypothetical structure of protein domains in which sequence variants were identified.     

From rafts to crafts: membrane asymmetry in moving cells

Many important biological events, including the leukocyte-mediated immune response, wound repair, axon guidance and developmental patterning, involve persistent cell movement towards a directional signal, a process termed chemotaxis. Establishment of functional and spatial cell polarity is an absolute requirement for this response. We propose that redistribution of specific membrane microdomains, termed rafts, during cell migration is a pivotal step in achieving polarity. On the one hand, partitioning of molecules into rafts might help to localize proteins at the front or the rear of moving cells, and on the other hand, rafts might function as platforms for local activation and coordination of the signaling pathways involved in cell migration.     

Immune response in human visceral leishmaniasis: analysis of the correlation between innate immunity cytokine profile and disease outcome

We investigated the cytokine profile of cells of the innate immune response and its association with active (ACT), asymptomatic (AS) and cured (CUR) human visceral leishmaniasis (VL), as well as noninfected (NI) subjects. The frequency of cytokine-producing cells was determined after short-term in vitro incubation of whole peripheral blood samples with soluble Leishmania antigen (SLA). Our data demonstrated a predominant type 2 cytokine profile in NI and ACT. In NI, we observed an increase of IL-4+ neutrophils, IL-10+ eosinophils besides a decrease of tumour necrosis factor (TNF)-alpha+ eosinophils/monocytes. Yet in ACT, we observed an increase of IL-4+ neutrophils and natural killer (NK) cells and IL-10+ monocytes, a reduced frequency of IL-12+ and IFN-gamma+ eosinophils and lower levels of TNF-alpha+ and IL-12+ monocytes. AS presented a mixed profile, characterized by an increase of IFN-gamma+ neutrophils/eosinophils and NK cells, of IL-12+ eosinophils/monocytes, as well as increase of IL-4+ neutrophils and NK cells and IL-10+ eosinophils/monocytes. In contrast, CUR was characterized by a type 1 response with an increase of IFN-gamma+ neutrophils/eosinophils and NK cells, associated with an increase in IL-12+ monocytes. In conclusion, we show a correlation between innate immune cytokine patterns and clinical status of VL, suggesting that these cells, in addition to other factors, may contribute to the cytokine microenvironment in which Leishmania-specific T cells are primed and to disease outcome.     

Outer membrane proteins from rough strains of four Brucella species.

Outer membrane proteins from 15 rough strains of Brucella abortus, B. ovis, B. canis, and B. melitensis were extracted with a dipolar detergent, and outer membrane proteins from selected strains were purified by anion exchange chromatography and gel filtration (Verstreate et al., Infect. Immun. 35:979-989, 1982). Outer membrane proteins produced two types of profiles on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. One type, demonstrated by B. abortus, B. ovis, and B. canis strains, contained the three predominant protein groups present in smooth B. abortus strains (Verstreate et al., Infect. Immun. 35:979-989, 1982): groups 1, 2 (porin [Douglas et al., Infect. Immun. 44:16-21]), and 3. B. melitensis strains demonstrated the second profile type, in which there was an additional band between groups 1 and 2. The relative proportion of porin was considerably lower in B. ovis, B. canis, and B. melitensis than in B. abortus. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis profiles could be used to distinguish B. abortus and B. melitensis from each other and from B. canis and B. ovis. The amino acid compositions of groups 2 and 3 from rough strains of B. abortus, B. canis, and B. melitensis were similar to those of corresponding proteins from smooth B. abortus strains. Zwittergent-soluble fractions from most rough strains contained antigen [b], which cross-reacted with group 2 from smooth B. abortus strains, and antigens [c] and [d], which cross-reacted with group 3 from smooth B. abortus strains. Antigen [a], shared by groups 2 and 3 (D. R. Verstreate and A. J. Winter, Infect. Immun. 46:182-187, 1984), was detected in most rough strains. None of these antigens were related to either rough or smooth lipopolysaccharide.     

Assessment of a rapid HIV test strategy during labor: a pilot study from Rio de Janeiro, Brazil

OBJECTIVES: To use two rapid human immunodeficiency virus (HIV) tests at labor, measure test acceptance and performance, and measure HIV prevalence in these women. METHODS: Between February and October 2000, two rapid tests (Determine; Abbott, Chicago, IL, U.S.A. and Double Check; Orgenics, Yavne, Israel) were used in three public maternities in Rio de Janeiro, Brazil. Enzyme-linked immunosorbent assay (ELISA) and Western blot (WB) analysis confirmed positive and discordant results. RESULTS: Of the 858 patients who were enrolled, the mean gestational age was 36 weeks (median = 39, mode = 40) and 17 (2%) refused testing. Of the 841 patients tested, 13 were positive by both tests, which represents a 1.5% prevalence (95% confidence interval: 0.7%-2.3%); all were confirmed by ELISA and WB analysis. Seven samples gave discordant results by the rapid tests; of these, six were ELISA-negative/WB-negative and one was ELISA-negative/WB-indeterminate. The positive predictive value for samples that were positive by both rapid tests simultaneously was 100%. CONCLUSIONS: Two rapid HIV tests used at labor were well accepted (98%). When the combined results of the two rapid tests (but not a single rapid test) were analyzed, this strategy was as efficient as the standard ELISA and WB HIV strategy for correctly classifying individuals.     

Evaluation of anhydride oligomers within polymer microsphere blends and their impact on bioadhesion and drug delivery in vitro

The effect of the addition of small molecular weight anhydride oligomers to polymer microspheres was evaluated and increased bioadhesion of the composite was demonstrated. Blends of low molecular weight anhydride oligomers with thermoplastic poly(fumaric-co-sebacic anhydride) [p(FASA)] and polycaprolactone were examined. The effects of anhydride oligomers on polymer microsphere degradation, crystallinity, and surface morphology were also explored. The results demonstrated that fumaric anhydride oligomer remained within polymer microspheres for several hours after exposure to phosphate buffer, formed a homogenous crystalline blend, increased bioadhesion as measured on rat intestine, and enhanced drug delivery in vitro as measured by the everted sac technique.     

Genome diversity in temperate bacteriophages of Oenococcus oeni

Summary.  The genome structure of six bacteriophages of Oenococcus oeni was compared. Two distinct groups with no apparent restriction site conservation were defined. In members of the α group (fOgML34, fOg4029, fOg30 and fOg218) a 7.5 kb region containing the origin of DNA packaging (cos) was highly conserved. Stretches of DNA heterogeneity could also be assigned to particular regions and were mostly evident in the right area of the genomes. fOg44 and fOgPSU1 (β group) were indistinguishable in the left half of their genomes, including cos, but were markedly dissimilar in other regions. Strong labelling signals detected in cross-hybridizations involving members of different groups were confined to fragments centrally located in their physical maps. The attachment site (attP) of fOg44 was assigned to this conserved region. It is suggested that recombination events at this location may have been important in generating the observed diversity of oenophage genomes. Accepted October 15, 1997 Received August 11, 1997     

Pattern of mtDNA Variation in Three Populations from São Tomé e Príncipe

We have analysed the matrilineal genetic composition of three self‐reported ethnic groups from São Tomé e Príncipe (Gulf of Guinea), an African archipelago whose settlement begun in the late fifteenth century. Sequence data from the hypervariable segments I (HVS‐I) and II (HVS‐II) were obtained for 30 Angolares, 35 Forros and 38 Tongas. The repertory of mtDNA lineages in São Tomé e Príncipe denoted a fully African maternal pool, primarily arisen from a Central/Southwestern substratum. The absence of any lineages of putative European descent means that the European impact at the mitochondrial pool was virtually nil. Angolares showed a clear reduction of mtDNA diversity and a slight genetic differentiation relative to Tongas or Forros, whereas the latter two groups did not present any signs of genetic boundaries between each other. The data obtained here reinforce the depiction of genetic substructuring in São Tomé e Príncipe previously derived from Y‐chromosome STRs. In addition, the crossing of mtDNA and Y‐STR information led to the inference that the female mediated gene flow within the archipelago was less restricted than the male, a pattern that could be framed in the cultural traditions and socio‐historical interactions among the groups.