Differential migration of in vivo primed B and T lymphocytes to lymphoid and non-lymphoid organs.

Our study describes tissue-specific migration of T and B cells during a localized anti-viral immune response. After mouse mammary tumor virus (MMTV) injection, B lymphocytes of the draining lymph node become infected and present a retroviral superantigen to CD4(+) T lymphocytes. Infected B cells receive superantigen-mediated help in a fashion comparable to classical immune responses. To investigate the fate of T and B lymphocytes that had interacted via cognate help in the same peripheral lymph node microenvironment we adoptively transferred them into naive recipients. Here we show that MMTV-infected B cells and superantigen-stimulated T cells were programmed to migrate to distinct sites of the body. Plasmablasts but not T cells migrated to the mammary gland and activated alpha4beta1 integrins were found to have a crucial role in the migration to the mammary gland. In contrast, T cells had a much higher affinity for secondary lymphoid organs and large intestine. This demonstrates that upon antigen-driven B and T lymphocyte interaction in the local draining lymph node a subset-specific homing program for B and T lymphocytes is induced.

Viral superantigen drives extrafollicular and follicular B cell differentiation leading to virus-specific antibody production.

Mouse mammary tumor virus (MMTV[SW]) encodes a superantigen expressed by infected B cells. It evokes an antibody response specific for viral envelope protein, indicating selective activation of antigen-specific B cells. The response to MMTV(SW) in draining lymph nodes was compared with the response to haptenated chicken gamma globulin (NP-CGG) using flow cytometry and immunohistology. T cell priming occurs in both responses, with T cells proliferating in association with interdigitating dendritic cells in the T zone. T cell proliferation continues in the presence of B cells in the outer T zone, and B blasts then undergo exponential growth and differentiation into plasma cells in the medullary cords. Germinal centers develop in both responses, but those induced by MMTV(SW) appear later and are smaller. Most T cells activated in the T zone and germinal centers in the MMTV(SW) response are superantigen specific and these persist for weeks in lymph nodes draining the site MMTV(SW) injection: this contrasts with the selective loss of superantigen-specific T cells from other secondary lymphoid tissues. The results indicate that this viral superantigen, when expressed by professional antigen-presenting cells, drives extrafollicular and follicular B cell differentiation leading to virus-specific antibody production.

The small species of Belostoma Latreille (Heteroptera, Belostomatidae). III. A revision of oxyurum group, with a new species from Brazil and description of the male of B. noualhieri Montandon

Species of the oxyurum group (sensu Lauck) consist of five extant Neotropical small species, whose lengths range 15.0 to 20.0 mm. The anterior interocular width about 1.5 times the width of an eye and ventral diverticulum of phallus flattened, circular, and large are, in combination, diagnostic. The small species of the oxyurum group were included in the Lauck´s key to the identification of the species groups, without dealing with the species included in it because many of them are very similar in appearance. Therefore here we redescribe and key the Belostoma species of the oxyurum group. Belostoma oxyurum (Dufour) is newly recorded from Brazil (Paraná and Rio Grande do Sul). Holotype and lectotype are designated for B. oxyurum and B. sanctulum Montandon, respectively. The aspect of the prosternal keel, the ratio between the width of the ventral diverticulum of phallus and its length in ventral view, and the aspect of dorsal arms of ventral diverticulum have proven useful for better species delimitation. Based on specimens from Pará State (N. Brazil), Belostoma carajaensis Ribeiro & Estévez, sp. nov. is described and illustrated. This new species differs from B. sanctulum in having anteoculus shorter than interoculus and the dorsal arms of ventral diverticulum divergent and large. A male specimen of B. noualhieri Montandon was collected in São Paulo State and based mainly on features of male genitalia, this species is here also included under oxyurum group.

Requirement for CARMA1 in antigen receptor-induced NF-kappa B activation and lymphocyte proliferation.

Ligation of antigen receptors (TCR, BCR) on T and B lymphocytes leads to the activation of new transcriptional programs and cell cycle progression. Antigen receptor-mediated activation of NF-kappa B, required for proliferation of B and T cells, is disrupted in T cells lacking PKC theta and in B and T cells lacking Bcl10, a caspase recruitment domain (CARD)-containing adaptor protein. CARMA1 (also called CARD11 and Bimp3), the only lymphocyte-specific member in a family of membrane-associated guanylate kinase (MAGUK) scaffolding proteins that interact with Bcl10 by way of CARD-CARD interactions, is required for TCR-induced NF-kappa B activation in Jurkat T lymphoma cells. Here we show that T cells from mice lacking CARMA1 expression were defective in recruitment of Bcl10 to clustered TCR complexes and lipid rafts, in activation of NF-kappa B, and in induction of IL-2 production. Development of CD5(+) peritoneal B cells was disrupted in these mice, as was B cell proliferation in response to both BCR and CD40 ligation. Serum immunoglobulin levels were also markedly reduced in the mutant mice. Together, these results show that CARMA1 has a central role in antigen receptor signaling that results in activation and proliferation of both B and T lymphocytes.

Dominant Role of CD80-CD86 Over CD40 and ICOSL in the Massive Polyclonal B Cell Activation Mediated by LAT(Y136F) CD4(+) T Cells.

Coordinated interactions between T and B cells are crucial for inducing physiological B cell responses. Mutant mice in which tyrosine 136 of linker for activation of T cell (LAT) is replaced by a phenylalanine (Lat(Y136F)) exhibit a strong CD4(+) T cell proliferation in the absence of intended immunization. The resulting effector T cells produce high amounts of T(H)2 cytokines and are extremely efficient at inducing polyclonal B cell activation. As a consequence, these Lat(Y136F) mutant mice showed massive germinal center formations and hypergammaglobulinemia. Here, we analyzed the involvement of different costimulators and their ligands in such T-B interactions both in vitro and in vivo, using blocking antibodies, knockout mice, and adoptive transfer experiments. Surprisingly, we showed in vitro that although B cell activation required contact with T cells, CD40, and inducible T cell costimulator molecule-ligand (ICOSL) signaling were not necessary for this process. These observations were further confirmed in vivo, where none of these molecules were required for the unfolding of the LAT CD4(+) T cell expansion and the subsequent polyclonal B cell activation, although, the absence of CD40 led to a reduction of the follicular B cell response. These results indicate that the crucial functions played by CD40 and ICOSL in germinal center formation and isotype switching in physiological humoral responses are partly overcome in Lat(Y136F) mice. By comparison, the absence of CD80-CD86 was found to almost completely block the in vitro B cell activation mediated by Lat(Y136F) CD4(+) T cells. The role of CD80-CD86 in T-B cooperation in vivo remained elusive due to the upstream implication of these costimulatory molecules in the expansion of Lat(Y136F) CD4(+) T cells. Together, our data suggest that CD80 and CD86 costimulators play a key role in the polyclonal B cell activation mediated by Lat(Y136F) CD4(+) T cells even though additional costimulatory molecules or cytokines are likely to be required in this process.

Brief cognitive assessment instruments in schizophrenia and bipolar patients, and healthy control subjects: A comparison study between the Brief Cognitive Assessment Tool for Schizophrenia (B-CATS) and the Screen for Cognitive Impairment in Psychiatry (SCIP)

Cognitive impairment in schizophrenia and psychosis is ubiquitous and acknowledged as a core feature of clinical expression, pathophysiology, and prediction of functioning. However, assessment of cognitive functioning is excessively time-consuming in routine practice, and brief cognitive instruments specific to psychosis would be of value. Two screening tools have recently been created to address this issue, i.e., the Brief Cognitive Assessment Tool for Schizophrenia (B-CATS) and the Screen for Cognitive Impairment in Psychiatry (SCIP). The aim of this research was to examine the comparative validity of these two brief instruments in relation to a global cognitive score. 161 patients with psychosis (96 patients diagnosed with schizophrenia and 65 patients diagnosed with bipolar disorder) and 76 healthy control subjects were tested with both instruments to examine their concurrent validity relative to a more comprehensive neuropsychological assessment battery. Scores from the B-CATS and the SCIP were highly correlated in the three diagnostic groups, and both scales showed good to excellent concurrent validity relative to a Global Cognitive Composite Score (GCCS) derived from the more comprehensive examination. The SCIP-S showed better predictive value of global cognitive impairment than the B-CATS. Partial and semi-partial correlations showed slightly higher percentages of both shared and unique variance between the SCIP-S and the GCCS than between the B-CATS and the GCCS. Brief instruments for assessing cognition in schizophrenia and bipolar disorders, such as the SCIP-S and B-CATS, seem to be reliable and promising tools for use in routine clinical practice.

Directional and fluctuating asymmetry in finger and a-b ridge counts in psychosis: a case-control study

Background: Several studies have reported alterations in finger and a-b ridge counts, and theirderived measures of asymmetry, in schizophrenia compared to controls. Because ridges are fully formed by the end of the second trimester, they may provide clues to disturbed early development. The aim of this study was to assess these measures in a sample of patients with psychosis and normal controls.Methods: Individuals with psychosis (n = 240), and normal controls (n = 228) were drawn from a catchment-area case-control study. Differences in finger and a-b ridge count and Fluctuating Asymmetry were assessed in three group comparisons (non-affective psychosis versus controls; affective psychosis versus controls; non-affective psychosis versus affective psychosis). The analyses were performed separately for males and females. Results: There were no significant group differences for finger nor a-b ridge counts. While there were no group difference for Directional Asymmetry, for Fluctuating Asymmetry measures men with non-affective psychosis had significantly higher fluctuating asymmetry of the index finger ridge count (a) when compared to controls (FA-correlation score, p = 0.02), and (b) when compared to affective psychosis (adjusted FA-difference score, p = 0.04). Conclusion: Overall, measures of finger and a-b ridge counts, and their derived measures of directional and fluctuating asymmetry were not prominent features of psychosis in this sample. While directional asymmetry in cerebral morphology is reduced in schizophrenia, this is not reflected in dermatoglyphic variables.

Screening of breast lesions: a comparative study between mammography, B-mode ultrasonography, sonoelastography and histological results

Objective To compare the capacity of mammography, sonoelastography, B-mode ultrasonography and histological analysis to differentiate benign from malignant breast lesions. Materials and Methods A total of 12 histopathologically confirmed breast lesions were documented. The lesions were assessed by means of mammography, B-mode ultrasonography and sonoelastography, and histopathological analysis was utilized as a gold standard. Sensitivity and specificity were calculated. A receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic performance of the mentioned techniques. Results Sensitivity and specificity in the differentiation between benign and malignant lesions were respectively 100% and 50% for mammography, 100% and 71% for B-mode ultrasonography, and 67% and 83% for sonoelastography. The area under the ROC curve was calculated for the three imaging modalities and corresponded to 0.792 for mammography, 0.847 for B-mode ultrasonography, and 0.806 for sonoelastography. Conclusion Sonoelastography demonstrated higher specificity and lower sensitivity as compared with mammography and B-mode ultrasonography. On the other hand, B-mode ultrasonography had the largest area under the ROC curve. Sonoelastography has demonstrated to be a promising technique to detect and evaluate breast lesions, and could potentially reduce the number of unnecessary biopsies.

The Shiga toxin 2 B subunit inhibits net fluid absorption in human colon and elicits fluid accumulation in rat colon loops

Shiga toxin (Stx)-producing Escherichia coli (STEC) colonizes the large intestine causing a spectrum of disorders, including watery diarrhea, bloody diarrhea (hemorrhagic colitis), and hemolytic-uremic syndrome. It is estimated that hemolytic-uremic syndrome is the most common cause of acute renal failure in infants in Argentina. Stx is a multimeric toxin composed of one A subunit and five B subunits. In this study we demonstrate that the Stx2 B subunit inhibits the water absorption (Jw) across the human and rat colonic mucosa without altering the electrical parameters measured as transepithelial potential difference and short circuit current. The time-course Jw inhibition by 400 ng/ml purified Stx2 B subunit was similar to that obtained using 12 ng/ml Stx2 holotoxin suggesting that both, A and B subunits of Stx2 contributed to inhibit the Jw. Moreover, non-hemorrhagic fluid accumulation was observed in rat colon loops after 16 h of treatment with 3 and 30 ng/ml Stx2 B subunit. These changes indicate that Stx2 B subunit induces fluid accumulation independently of A subunit activity by altering the usual balance of intestinal absorption and secretion toward net secretion. In conclusion, our results suggest that the Stx2 B subunit, which is non-toxic for Vero cells, may contribute to the watery diarrhea observed in STEC infection. Further studies will be necessary to determine whether the toxicity of Stx2 B subunit may have pathogenic consequences when it is used as a component in an acellular STEC vaccine or as a vector in cancer vaccines.

BAFF promotes regulatory T-cell apoptosis and blocks cytokine production by activating B cells in primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology. A number of questions regarding its etiology are unclear. CD4+CD25+ regulatory T cells (Tregs) play a critical role in self-tolerance and, for unknown reasons, their relative number is reduced in PBC patients. B-cell-activating factor (BAFF) is a key survival factor during B-cell maturation and its concentration is increased in peripheral blood of PBC patients. It has been reported that activated B cells inhibit Treg cell proliferation and there are no BAFF receptors on Tregs. Therefore, we speculated that excessive BAFF may result in Treg reduction via B cells. To prove our hypothesis, we isolated Tregs and B cells from PBC and healthy donors. BAFF and IgM concentrations were then analyzed by ELISA and CD40, CD80, CD86, IL-10, and TGF-β expression in B cells and Tregs were measured by flow cytometry. BAFF up-regulated CD40, CD80, CD86, and IgM expression in B cells. However, BAFF had no direct effect on Treg cell apoptosis and cytokine secretion. Nonetheless, we observed that BAFF-activated B cells could induce Treg cell apoptosis and reduce IL-10 and TGF-β expression. We also showed that BAFF-activated CD4+ T cells had no effect on Treg apoptosis. Furthermore, we verified that bezafibrate, a hypolipidemic drug, can inhibit BAFF-induced Treg cell apoptosis. In conclusion, BAFF promotes Treg cell apoptosis and inhibits cytokine production by activating B cells in PBC patients. The results of this study suggest that inhibition of BAFF activation is a strategy for PBC treatment.

'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)