Contribution of receptor editing to the antibody repertoire

Receptor editing, clonal deletion, and anergy are the mechanisms by which B cells maintain tolerance to self antigens. To determine the extent to which receptor editing shapes the normal antibody repertoire, we generated an immunoglobulin kappa polymorphism that facilitates the detection of editing of immunoglobulin light chains in vivo. We found that B cells are targeted for editing during a 2-hour delay in development at the pre-BII cell stage, and that about 25% of all antibody molecules are produced by gene replacement. These results suggest that receptor editing represents a major force in shaping the antibody repertoire.     

Survey for viruses-particularly begomoviruses-infecting pepper crops in China.

Viruses are considered the most important constraint to hot and sweet pepper （Capsicum sp.） production in China, from which nine viruses have been reported （Wang X.P. et al., 2002）. However, so far no information has been available about the presence of begomoviruses in peppers. From 1999 to 2005, 762 leaf tissue samples were collected from farmers＇ fields in 13 provinces, namely Yunnan, Guangxi, Hainan, Guangdong and Guizhou in the south, Sichuan, Chongqing, Hunan, Jiangxi, Shaanxi and Henan in the central region, and Hebei and Heilongjiang in the north, and showed typical virus symptoms such as mottling, mosaic, yellowing and leaf deformations including leafcurling. Polymerase chain reaction with the degenerate primer pair PAL1 v 1978/PARlc 715 （M.R.Rojas et al., 1993） was used to test DNA extracts for the presence of begomoviruses. Leaf homogenates were tested by DAS-ELISA for the presence of other common chilli-infecting viruses such as Cucumber mosaic virus （CMV）, Chilli veinal mottle virus （ChiVMV）, Potato virus Y （PVY）, Tomato mosaic virus （ToMV）, Pepper mild mottle virus （PMMV） and Pepper veinal mottle virus （PVMV）, the latter reportedly known to occur throughout Africa （Dafalla G.A., 2003）.     

Intron existence predated the divergence of eukaryotes and prokaryotes

Nucleotide sequences for the nuclear genes encoding chloroplast (GapA and GapB) and cytosolic (GapC) glyceraldehyde-3-phosphate dehydrogenases (GAPDHs) from Arabidopsis thaliana were determined. Comparison of nucleotide sequences indicates that the divergence of chloroplast and cytosolic GAPDH genes preceded the divergence of prokaryotes and eukaryotes. In addition, some intron-exon junctions are conserved among GapB, GapC, and chicken GAPDH genes. These results provide evidence at the molecular level to support the idea that introns existed before the divergence of prokaryotes and eukaryotes.     

Isovaleric and -methylbutyric acidemias induced by hypoglycin A: mechanism of Jamaican vomiting sickness

Hypoglycin A, the causative agent of the Jamaican vomiting sickness, produced a marked increase in concentration of isovaleric acid in the plasma of rats, when administered in a single dose. alpha-Methylbutyric acid, a position isomer, also accumulated. The use of hypoglycin A reproduced some features of human isovaleric acidemia. Accumulation of these branched pentanoic acids may be another factor contributing to the pathogenesis of the Jamaican vomiting sickness.     

Downregulation of L3T4+ cytotoxic T lymphocytes by interleukin-2

Proliferation of activated cytotoxic T lymphocytes (CTLs) that recognize foreign histocompatibility antigens is induced by interleukin-2, a potent immunoregulatory molecule originally described as T cell growth factor. Interleukin-2 (IL-2) is widely used to isolate and induce clonal expansion of CTLs for functional studies in vitro and in vivo. However, in studies with CTLs specific for class I and class II histocompatibility antigens, IL-2 rapidly downregulated the lytic activity of some class II-specific CTLs in a time- and dose-dependent manner. Lytic activity of L3T4+ CTLs specific for the murine class II antigen I-Ek was repeatedly up- and downregulated in vitro by alternate exposure to specific (alloantigen) and nonspecific (recombinant IL-2) signals, respectively. These results demonstrate that some CTLs modulate their functional property (cytolysis) while undergoing IL-2-driven cell proliferation without loss of antigen specificity or ability to revert to a lytic phenotype.     

Steroid control of longevity in Drosophila melanogaster

Ecdysone, the major steroid hormone of Drosophila melanogaster, is known for its role in development and reproduction. Flies that are heterozygous for mutations of the ecdysone receptor exhibit increases in life-span and resistance to various stresses, with no apparent deficit in fertility or activity. A mutant involved in the biosynthesis of ecdysone displays similar effects, which are suppressed by feeding ecdysone to the flies. These observations demonstrate the importance of the ecdysone hormonal pathway, a new player in regulating longevity.     

Suppression of HIV infection in AZT-treated SCID-hu mice

The SCID-hu mouse, engrafted with human hematolymphoid organs, is permissive for infection with the human immunodeficiency virus (HIV). This mouse model was used to test compounds for antiviral efficacy. Two weeks after infection with HIV, 100 percent (40/40) of SCID-hu mice were positive for HIV by the polymerase chain reaction. When first treated with 3'-azido-3'-deoxythymidine (AZT), none (0/17) were HIV-positive by this assay. However, AZT-treated SCID-hu mice did have a few infected cells; after AZT treatment was stopped, viral spread was detected by polymerase chain reaction in such mice. Thus, the SCID-hu mouse provides a means to directly compare new antiviral compounds with AZT and to further improve antiviral efficacy.     

Chlorella 11-Peptide Inhibits the Production of Macrophage-Induced Adhesion Molecules and Reduces Endothelin-1 Expression and Endothelial Permeability

The inflammation process in large vessels involves the up-regulation of vascular adhesion molecules such as endothelial cell selectin (E-selectin), intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) which are also known as the markers of atherosclerosis. We have reported that Chlorella 11-peptide exhibited effective anti-inflammatory effects. This peptide with an amino sequence Val-Glu-Cys-Tyr-Gly-Pro-Asn-Arg-Pro-Gln-Phe was further examined for its potential in preventing atherosclerosis in this study. In particular, the roles of Chlorella 11-peptide in lowering the production of vascular adhesion molecules, monocyte chemoattractant protein (MCP-1) and expression of endothelin-1 (ET-1) from endothelia (SVEC4-10 cells) were studied. The production of E-selectin, ICAM-1, VCAM-1 and MCP-1 in SVEC4-10 cells was measured with ELISA. The mRNA expression of ET-1 was analyzed by RT-PCR and agarose gel. Results showed that Chlorella 11-peptide significantly suppressed the levels of E-selectin, ICAM, VCAM, MCP-1 as well as ET-1 gene expression. The inhibition of ICAM-1 and VCAM-1 production by Chlorella 11-peptide was reversed in the presence of protein kinase A inhibitor (H89) which suggests that the cAMP pathway was involved in the inhibitory cause of the peptide. In addition, this peptide was shown to reduce the extent of increased intercellular permeability induced by combination of 50% of lipopolysaccharide (LPS)-activated RAW 264.7 cells medium and 50% normal SEVC cell culture medium (referred to as 50% RAW-conditioned medium). These data demonstrate that Chlorella 11-peptide is a promising biomolecule in preventing chronic inflammatory-related vascular diseases.     

Cardiopulmonary effects of a new inspiratory impedance threshold device in anesthetized hypotensive dogs

ObjectiveTo compare the hemodynamic and respiratory effects of an inspiratory impedance threshold device (ITD) in anesthetized normotensive and hypotensive dogs.Study designProspective randomized study.AnimalsTen adult dogs.MethodsDogs were anesthetized with propofol followed by isoflurane. During spontaneous ventilation, tidal volume ( $\dot{\mathrm{V}}$), systolic (SAP), mean (MAP) and diastolic arterial blood pressure, central venous pressure, gastric PCO₂ as an indicator of gastric perfusion, subcutaneous oxygen tension, subcutaneous blood flow, cardiac index (CI), systemic vascular resistance and blood lactate were monitored. To monitor respiratory compliance (RC) and resistance (ResR), animals were briefly placed on mechanical ventilation. Dogs were studied under four different conditions: 1) normotension (MAP > 60 mmHg) with and without the ITD and 2) hypotension (target MAP = 40 mmHg) with and without ITD. These four conditions were performed during one anesthetic period, allowing for stabilization of parameters for each condition. Data were analyzed by anova repeated measure mixed models.ResultsNo cardiovascular changes were detected between no ITD and ITD in the normotensive state. During hypotension, CI was higher with the ITD (5 ± 1.0 L minute^?1 m^?2) compared with no ITD (4 ± 1.3 L minute^?1 m^?2). During hypotension, SAP was increased with ITD (80 ± 14 mmHg) versus without ITD (67 ± 13 mmHg). There was an increase in ResR and decreased RC with the ITD in both normotensive and hypotensive state.Conclusion and clinical relevanceImpedance threshold device in dogs during isoflurane-induced hypotension improved CI and SAP but had negative effects on RC and ResR.