Double cropping in Vitis vinifera L. cv. Pinot Noir: agronomical and physiological validation

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PTP4A1 promotes TGFβ signaling and fibrosis in systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of skin and internal organs. Protein tyrosine phosphatases have received little attention in the study of SSc or fibrosis. Here, we show that the tyrosine phosphatase PTP4A1 is highly expressed in fibroblasts from patients with SSc. PTP4A1 and its close homolog PTP4A2 are critical promoters of TGFβ signaling in primary dermal fibroblasts and of bleomycin-induced fibrosis in vivo. PTP4A1 promotes TGFβ signaling in human fibroblasts through enhancement of ERK activity, which stimulates SMAD3 expression and nuclear translocation. Upstream from ERK, we show that PTP4A1 directly interacts with SRC and inhibits SRC basal activation independently of its phosphatase activity. Unexpectedly, PTP4A2 minimally interacts with SRC and does not promote the SRC-ERK-SMAD3 pathway. Thus, in addition to defining PTP4A1 as a molecule of interest for TGFβ-dependent fibrosis, our study provides information regarding the functional specificity of different members of the PTP4A subclass of phosphatases

Complement C3d Conjugation to Anthrax Protective Antigen Promotes a Rapid, Sustained, and Protective Antibody Response

B. anthracis is the causative agent of anthrax. Pathogenesis is primarily mediated through the exotoxins lethal factor and edema factor, which bind protective antigen (PA) to gain entry into the host cell. The current anthrax vaccine (AVA, Biothrax™) consists of aluminum-adsorbed cell-free filtrates of unencapsulated B. anthracis, wherein PA is thought to be the principle target of neutralization. In this study, we evaluated the efficacy of the natural adjuvant, C3d, versus alum in eliciting an anti-PA humoral response and found that C3d conjugation to PA and emulsion in incomplete Freund's adjuvant (IFA) imparted superior protection from anthrax challenge relative to PA in IFA or PA adsorbed to alum. Relative to alum-PA, immunization of mice with C3d-PA/IFA augmented both the onset and sustained production of PA-specific antibodies, including neutralizing antibodies to the receptor-binding portion (domain 4) of PA. C3d-PA/IFA was efficacious when administered either i.p. or s.c., and in adolescent mice lacking a fully mature B cell compartment. Induction of PA-specific antibodies by C3d-PA/IFA correlated with increased efficiency of germinal center formation and plasma cell generation. Importantly, C3d-PA immunization effectively protected mice from intranasal challenge with B. anthracis spores, and was approximately 10-fold more effective than alum-PA immunization or PA/IFA based on dose challenge. These data suggest that incorporation of C3d as an adjuvant may overcome shortcomings of the currently licensed aluminum-based vaccine, and may confer protection in the early days following acute anthrax exposure

Preliminary structural studies on the leucine-zipper homology region of the human protein Bap31

A leucine-zipper with properties as apoptotic regulator in the ER has been crystallized. X-ray data to 2.5 Å resolution were collected, molecular replacement solutions were identified and refinement has been started

The Crystal Structure of Bacillus subtilis YycI Reveals a Common Fold for Two Members of an Unusual Class of Sensor Histidine Kinase Regulatory Proteins

YycI and YycH are two membrane-anchored periplasmic proteins that regulate the essential Bacillus subtilis YycG histidine kinase through direct interaction. Here we present the crystal structure of YycI at a 2.9-Å resolution. YycI forms a dimer, and remarkably the structure resembles that of the two C-terminal domains of YycH despite nearly undetectable sequence homology (10%) between the two proteins

J. Bacteriol. doi:10.1128/JB.01937-06 Copyright © 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved. 1 2 3 4 5 6 7 8

The crystal structure of Bacillus subtilis YycI reveals a common fold for two members of an unusual class of sensor histidine kinase regulatory protein

C3d is a functional adjuvant in adolescent mice.

<p>3-week old A/J mice were immunized with PA-Av/IFA (○), PA-Av-Alum (□), or PA-Av-C3d₃/IFA (▵). (A) PA-specific IgG or (B) domain-4 specific IgG was measured by ELISA up to 20 days after primary immunization. Error bars indicate average of 2 mice/group, and was repeated twice.</p

PA-Av-C3d₃ is an effective immunogen delivered i.p., s.c or i.m.

<p>PA-Av-C3d₃ was injected i.p. (▵), s.c. (▪), or i.m. (♦) and (A) PA- or (B) Domain 4-specific IgG was measured by ELISA. Relative efficacy of PA-Av-C3d₃ (▪,♦) and PA-Av-alum (□,⋄) was compared following (C) s.c. or (D) i.m. administration of immunogen (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001044#s2" target="_blank">methods</a>). Error bars indicate SEM (*p≤0.05, ** p≤0.01, *** p≤0.005, n = 3).</p