B-lymphocyte effector functions in health and disease.

B-lymphocytes have traditionally been thought to contribute to immunity and autoimmune disease through terminal differentiation into plasma cells that secrete antibody. However, studies in mice and recent clinical studies have demonstrated that genetically altered B-cell function and B-cell-targeted therapies can significantly affect autoimmune diseases that were predominantly thought to be T-cell-mediated. B-cell depletion in mouse models of disease has also led to the identification of alternative B-cell effector functions that regulate normal immune responses and autoimmune disease. This review highlights multiple B-cell effector mechanisms, including the promotion of cellular immunity, the negative regulation of immune responses, and the production of pathogenic antibodies.

Neutralization activity in a geographically diverse East London cohort of human immunodeficiency virus type 1-infected patients: clade C infection results in a stronger and broader humoral immune response than clade B infection.

The array of human immunodeficiency virus (HIV) subtypes encountered in East London, an area long associated with migration, is unusually heterogeneous, reflecting the diverse geographical origins of the population. In this study it was shown that viral subtypes or clades infecting a sample of HIV type 1 (HIV-1)-positive individuals in East London reflect the global pandemic. The authors studied the humoral response in 210 treatment-naïve chronically HIV-1-infected (>1 year) adult subjects against a panel of 12 viruses from six different clades. Plasmas from individuals infected with clade C, but also plasmas from clade A, and to a lesser degree clade CRF02_AG and CRF01_AE, were significantly more potent at neutralizing the tested viruses compared with plasmas from individuals infected with clade B. The difference in humoral robustness between clade C- and B-infected patients was confirmed in titration studies with an extended panel of clade B and C viruses. These results support the approach to develop an HIV-1 vaccine that includes clade C or A envelope protein (Env) immunogens for the induction of a potent neutralizing humoral response.

Quantification of Hox and Surfactant Protein-B Transcription during Murine Lung Development.

Abstract BACKGROUND: Genetic processes underlying fetal lung development and maturation are incompletely understood. Better knowledge of these processes would provide insights into the causes of lung malformations and prevention of respiratory distress syndrome and the potential adverse effects of glucocorticoids. Hox genes are involved in the lung branching morphogenesis and maturation of respiratory epithelium, but their expression pattern remains to be defined. OBJECTIVES: We hypothesized that genes involved in lung branching would be downregulated during early development, whereas those involved in maturation would be unchanged or upregulated. METHODS: TaqMan real-time primers and probes were designed for all 39 murine Hox genes, and the murine SP-B gene and transcription profiles of these genes were obtained from whole lungs isolated at e14.5, e16.5, e18.5, e19.5 and postnatal days 1 and 20. RESULTS: Hox genes in clusters A and B, specifically those between paralog groups 3 and 7, were the most represented, with Hoxa4 and Hoxa5 being the most highly transcribed. A wave of reduced transcription in 16 Hox genes, coincident with increased SP-B transcription, was observed with advancing gestation. Consistently high transcription of Hoxa5 from e14.5 to postnatal day 20 may indicate that sustained transcription is required for normal lung maturation. When e15.5 lungs were cultured with dexamethasone, Hoxb6, Hoxb7 and Hoxb8 levels were significantly upregulated, creating the potential for modulation of diverse downstream target genes. CONCLUSIONS: Improved understanding of the genetic processes underlying lung development afforded by our Q-PCR platform may allow development of more specific methods for inducing fetal lung maturation.

Ginkgolide B and bilobalide block the pore of the 5-HT3 receptor at a location that overlaps the picrotoxin binding site

Extracts from the Ginkgo biloba tree are widely used as herbal medicines, and include bilobalide (BB) and ginkgolides A and B (GA and GB). Here we examine their effects on human 5-HT(3)A and 5-HT(3)AB receptors, and compare these to the effects of the structurally related compounds picrotin (PTN) and picrotoxinin (PXN), the two components of picrotoxin (PTX), a known channel blocker of 5-HT3, nACh and GABA(A) receptors. The compounds inhibited 5-HT-induced responses of 5-HT3 receptors expressed in Xenopus oocytes, with IC50 values of 470 mu M (BB), 730 mu M (GB), 470 mu M (PTN), 11 mu M (PXN) and > 1 mM (GA) in 5-HT(3)A receptors, and 3.1 mM (BB), 3.9 mM (GB), 2.7 mM (PTN), 62 mu M (PXN) and > 1 mM (GA) in 5-HT(3)AB receptors. Radioligand binding on receptors expressed in HEK 293 cells showed none of the compounds displaced the specific 5-HT3 receptor antagonist [H-3]granisetron, confirming that they do not act at the agonist binding site. Inhibition by GB at 5-HT(3)A receptors is weakly use-dependent, and recovery is activity dependent, indicating channel block. To further probe their site of action at 5-HT(3)A receptors, BB and GB were applied alone or in combination with PXN, and the results fitted to a mathematical model; the data revealed partially overlapping sites of action. We conclude that BB and GB block the channel of the 5-HT(3)A receptor. Thus these compounds have comparable, although less potent, behaviour than at some other Cys-loop receptors, demonstrating their actions are conserved across the family. (C) 2010 Published by Elsevier Ltd.

Recombinant Subgroup B Human Respiratory Syncytial Virus Expressing Enhanced Green Fluorescent Protein Efficiently Replicates in Primary Human Cells and Is Virulent in Cotton Rats

Human respiratory syncytial virus (HRSV) is the most important viral cause of severe respiratory tract disease in infants. Two subgroups (A and B) have been identified, which cocirculate during, or alternate between, yearly epidemics and cause indistinguishable disease. Existing in vitro and in vivo models of HRSV focus almost exclusively on subgroup A viruses. Here, a recombinant (r) subgroup B virus (rHRSV(B05)) was generated based on a consensus genome sequence obtained directly from an unpassaged clinical specimen from a hospitalized infant. An additional transcription unit containing the gene encoding enhanced green fluorescent protein (EGFP) was introduced between the phosphoprotein and matrix genes (position 5) of the genome to generate rHRSV(B05)EGFP(5). The recombinant viruses replicated efficiently in both HEp-2 cells and in well-differentiated normal human bronchial cells grown at air-liquid interface. Intranasal infection of cotton rats (Sigmodon hispidus) resulted in high numbers of EGFP(+) cells in epithelia of the nasal septum and conchae. When administered in a relatively large inoculum volume, the virus also replicated efficiently in bronchiolar epithelial cells and spread extensively in both the upper and lower respiratory tracts. Virus replication was not observed in ciliated epithelial cells of the trachea. This is the first virulent rHRSV strain with the genetic composition of a currently circulating wild-type virus. In vivo tracking of infected cells by means of EGFP fluorescence in the absence of cytopathic changes increases the sensitivity of virus detection in HRSV pathogenesis studies.

IMPORTANCE

Virology as a discipline has depended on monitoring cytopathic effects following virus culture in vitro. However, wild-type viruses isolated from patients often do not cause significant changes to infected cells, necessitating blind passage. This can lead to genetic and phenotypic changes and the generation of high-titer, laboratory-adapted viruses with diminished virulence in animal models of disease. To address this, we determined the genome sequence of an unpassaged human respiratory syncytial virus from a sample obtained directly from an infected infant, assembled a molecular clone, and recovered a wild-type recombinant virus. Addition of a gene encoding enhanced green fluorescent protein allowed this wild-type virus to be tracked in primary human cells and living animals in the absence of significant cytopathic effects. Imaging of fluorescent cells proved to be a highly valuable tool for monitoring the spread of virus and may help improve assays for evaluating novel intervention strategies.

'What ever happened to breakdancing?' : transnational b-boy/b-girl networks, underground video magazines and imagined affinities

In 1997, Paul Gilroy was able to write: "I have been asking myself, whatever happened to breakdancing" (21), a form of vernacular dance associated with urban youth that emerged in the 1970s. However, in the last decade, breakdancing has experienced a massive renaissance in movies (You Got Served), commercials ("Gotta Have My Pops!") and documentaries (the acclaimed Freshest Kids). In this thesis, 1 explore the historical development of global b-boy/bgirl culture through a qualitative study involving dancers and their modes of communication. Widespread circulation of breakdancing images peaked in the mid-1980s, and subsequently b-boy/b-girl culture largely disappeared from the mediated landscape. The dance did not reemerge into the mainstream of North American popular culture until the late 1990s. 1 argue that the development of major transnational networks between b-boys and b-girls during the 1990s was a key factor in the return of 'b-boying/b-girling' (known formerly as breakdancing). Street dancers toured, traveled and competed internationally throughout this decade. They also began to create 'underground' video documentaries and travel video 'magazines.' These video artefacts circulated extensively around the globe through alternative distribution channels (including the backpacks of traveling dancers). 1 argue that underground video artefacts helped to produce 'imagined affinities' between dancers in various nations. Imagined affinities are identifications expressed by a cultural producer who shares an embodied activity with other practitioners through either mediated texts or travels through new places. These 'imagined affinities' helped to sustain b-boy/b-girl culture by generating visual/audio representations of popularity for the dance movement across geographical regions.

Identification of Bartonella species in rodents, shrews and cats in Denmark: detection of two B-henselae variants, one in cats and the other in the long-tailed field mouse

Small mammals and stray cats were trapped in two areas of North Zealand, Denmark, and their blood cultured for hemotrophic bacteria. Bacterial isolates were recovered in pure culture and subjected to 16S rDNA gene sequencing. Bartonella species were isolated from five mammalian species: B. grahamii from Microtus agrestis (field vole) and Apodemus flavicollis (yellow-necked field mouse); B. taylorii from M. agrestis, A. flavicollis and A. sylvaticus (long-tailed field mouse); B. tribocorum from A. flavicollis; R vinsonii subsp. vinsonii from M. agrestis and A. sylvaticus; and B. birtlesii from Sorex vulgaris (common shrew). In addition, two variant types of B. henselae were identified: variant I was recovered from three specimens of A. sylvaticus, and B. henselae variant 11 from I I cats; in each case this was the only B. henselae variant found. No Bartonella species was isolated from Clethrionomys glareolus (bank vole) or Micromys minutus (harvest mouse). These results suggest that B. henselae occurs in two animal reservoirs in this region, one of variant I in A. sylvaticus, which may be transmitted between mice by the tick Ixodes ricinus, and another of variant 11 in cats, which may be transmitted by the cat flea (Ctenocephalides felis). To our knowledge, this is the first report of the occurrence of B. henselae and B. tribocorum in Apodemus mice.

Gradual Decline in Malaria-Specific Memory T Cell Responses Leads to Failure to Maintain Long-Term Protective Immunity to Plasmodium chabaudi AS Despite Persistence of B Cell Memory and Circulating Antibody

The mechanisms responsible for the generation and maintenance of immunological memory to Plasmodium are poorly understood and the reasons why protective immunity in humans is so difficult to achieve and rapidly lost remain a matter for debate. A possible explanation for the difficulty in building up an efficient immune response against this parasite is the massive T cell apoptosis resulting from exposure to high-dose parasite Ag. To determine the immunological mechanisms required for long-term protection against P. chabaudi malaria and the consequences of high and low acute phase parasite loads for acquisition of protective immunity, we performed a detailed analysis of T and B cell compartments over a period of 200 days following untreated and drug-treated infections in female C57BL/6 mice. By comparing several immunological parameters with the capacity to control a secondary parasite challenge, we concluded that loss of full protective immunity is not determined by acute phase parasite load nor by serum levels of specific IgG2a and IgG1. Abs, but appears to be a consequence of the progressive decline in memory T cell response to parasites, which occurs similarly in untreated and drug-treated mice with time after infection. Furthermore, by analyzing adoptive transfer experiments, we confirmed the major role of CD4(+) T cells for guaranteeing long-term full protection against P. chabaudi malaria. The Journal of Immunology, 2008, 181: 8344-8355.

CIE L*a*b*: comparison of digital images obtained photographically by manual and automatic modes

The aim of this study was to analyze the color alterations performed by the CIE L*a*b* system in the digital imaging of shade guide tabs, which were obtained photographically according to the automatic and manual modes. This study also sought to examine the observers' agreement in quantifying the coordinates. Four Vita Lumin Vaccum shade guide tabs were used: A3.5, B1, B3 and C4. An EOS Canon digital camera was used to record the digital images of the shade tabs, and the images were processed using Adobe Photoshop software. A total of 80 observations (five replicates of each shade according to two observers in two modes, specifically, automatic and manual) were obtained, leading to color values of L*, a* and b*. The color difference (AE) between the modes was calculated and classified as either clinically acceptable or unacceptable. The results indicated that there was agreement between the two observers in obtaining the L*, a* and b* values related to all guides. However, the B1, B3, and C4 shade tabs had AE values classified as clinically acceptable (Delta E = 0.44, Delta E = 2.04 and Delta E = 2.69, respectively). The A3.5 shade tab had a AE value classified as clinically unacceptable (Delta E = 4.17), as it presented higher values for luminosity in the automatic mode (L* = 54.0) than in the manual mode (L* = 50.6). It was concluded that the B1, B3 and C4 shade tabs can be used at any of the modes in digital camera (manual or automatic), which was a different finding from that observed for the A3.5 shade tab.

A linkage map for the B-genome of Arachis (Fabaceae) and its synteny to the A-genome

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Chromosomal mapping of repetitive DNAs in the beetle Dichotomius geminatus provides the first evidence for an association of 5S rRNA and histone H3 genes in insects, and repetitive DNA similarity between the B chromosome and A complement

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Analysis of the Hb(b)over-bar coupling constant and CP-violation effects at the future e(+)e(-) collider

The e(+)e(-)-->b (B) over bar nu(ν) over bar process, where nu is an electron, muon, or tau-lepton neutrino, is analyzed in detail for the general form of the coupling constant of a Higgs boson with b quarks, with the (m(b)/v)(a + igamma(5)b) parameterization of the Hb (b) over bar interaction. This process is shown to be highly sensitive to this coupling constant. Experiments at the future with roots = 500-GeV linear collider will provide limits of 2 and 20% for deviations of the parameters a and b, respectively, from their Standard Model values. Results concerning the e(+)e(-)-->b (b) over bar nu(ν) over bar process in combination with the independent measurements of the partial width Gamma(H --> b (b) over bar) can testify to the CP origin of the Higgs sector of the theory. (C) 2003 MAIK Nauka/Interperiodica.

Measurement of the CP-violation parameter of B-0 mixing and decay with p(p)over-bar ->mu mu X data

We measure the dimuon charge asymmetry A in p (p) over bar collisions at a center of mass energy root s=1960 GeV. The data was recorded with the D0 detector and corresponds to an integrated luminosity of approximately 1.0 fb(-1). Assuming that the asymmetry A is due to asymmetric B-0 <->(B) over bar (0) mixing and decay, we extract the CP-violation parameter of B-0 mixing and decay: ((epsilon B0))/(1+vertical bar epsilon B0 vertical bar 2)=(AB0)/(4)= -0.0023 +/- 0.0011(stat)+/- 0.0008(syst).A(B)(0) is the dimuon charge asymmetry from decays of B-0(B) over bar (0) pairs. The general case, with CP violation in both B-0 and B-s(0) systems, is also considered. Finally we obtain the forward-backward asymmetry that quantifies the tendency of mu(+) to go in the proton direction and mu(-) to go in the antiproton direction. The results are consistent with the standard model and constrain new physics.

Relative rates of B meson decays into psi(2S) and J/psi mesons

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Cytogenetic analysis of A-, B-chromosomes and ZZ/ZW sex chromosomes of Characidium gomesi (Teleostei, Characiformes, Crenuchidae)

Different cytogenetic techniques were used to analyze the chromosomes of Characidium gomesi with the main objective of comparing the base composition of ZZ/ZW sex-chromosomes, B-chromosomes and the heterochromatin of A-chromosomes. The results of digestion of chromosomes with AluI restriction endonuclease (RE), silver and CMA3 staining, C-banding and fluorescence in situ hybridization (FISH) with the 18S rDNA probe suggested the existence of compositional differences between the heterochromatin of ZZ/ZW sex-chromosomes, A- and B-chromosomes, and indicated the presence of different numbers and morphology of B-chromosomes in the samples of this population.