553 research outputs found
Elastic precursor of the transformation from glycolipid-nanotube to -vesicle
By the combination of optical tweezer manipulation and digital video
microscopy, the flexural rigidity of single glycolipid "nano" tubes has been
measured below the transition temperature at which the lipid tubules are
transformed into vesicles. Consequently, we have found a clear reduction of the
rigidity obviously before the transition as temperature increasing. Further
experiments of infrared spectroscopy (FT-IR) and differential scanning
calorimetry (DSC) have suggested a microscopic change of the tube walls,
synchronizing with the precursory softening of the nanotubes.Comment: 9 pages, 6 figure
Sliding Columnar Phase of DNA-Lipid Complexes
We introduce a simple model for DNA-cationic-lipid complexes in which
galleries between planar bilayer lipid lamellae contain DNA 2D smectic lattices
that couple orientationally and positionally to lattices in neighboring
galleries. We identify a new equilibrium phase in which there are long-range
orientational but not positional correlations between DNA lattices. We discuss
properties of this new phase such as its X-ray structure factor S(r), which
exhibits unusual exp(- const.ln^2 r) behavior as a function of in-plane
separation r.Comment: This file contains 4 pages of double column text and one postscript
figure. This version includes interactions between dislocations in a given
gallery and presents an improved estimate of the decoupling temperature. It
is the published versio
The Influence of B Cell Depletion Therapy on Naturally Acquired Immunity to Streptococcus pneumoniae
The anti-CD20 antibody Rituximab to deplete CD20+ B cells is an effective treatment for rheumatoid arthritis and B cell malignancies, but is associated with an increased incidence of respiratory infections. Using mouse models we have investigated the consequences of B cell depletion on natural and acquired humoral immunity to Streptococcus pneumoniae. B cell depletion of naïve C57Bl/6 mice reduced natural IgM recognition of S. pneumoniae, but did not increase susceptibility to S. pneumoniae pneumonia. ELISA and flow cytometry assays demonstrated significantly reduced IgG and IgM recognition of S. pneumoniae in sera from mice treated with B cell depletion prior to S. pneumoniae nasopharyngeal colonization compared to untreated mice. Colonization induced antibody responses to protein rather than capsular antigen, and when measured using a protein array B cell depletion prior to colonization reduced serum levels of IgG to several protein antigens. However, B cell depleted S. pneumoniae colonized mice were still partially protected against both lung infection and septicemia when challenged with S. pneumoniae after reconstitution of their B cells. These data indicate that although B cell depletion markedly impairs antibody recognition of S. pneumoniae in colonized mice, some protective immunity is maintained, perhaps mediated by cellular immunity
Genetic Resistance to Malaria Is Associated With Greater Enhancement of Immunoglobulin (Ig)M Than IgG Responses to a Broad Array of Plasmodium falciparum Antigens
Background. People of the Fulani ethnic group are more resistant to malaria compared with genetically distinct ethnic groups, such as the Dogon people, in West Africa, and studies suggest that this resistance is mediated by enhanced antibody responses to Plasmodium falciparum antigens. However, prior studies measured antibody responses to <0.1% of P falciparum proteins, so whether the Fulani mount an enhanced and broadly reactive immunoglobulin (Ig)M and IgG response to P falciparum remains unknown. In general, little is known about the extent to which host genetics influence the overall antigen specificity of IgM and IgG responses to natural infections. Methods. In a cross-sectional study in Mali, we collected plasma from asymptomatic, age-matched Fulani (n = 24) and Dogon (n = 22) adults with or without concurrent P falciparum infection. We probed plasma against a protein microarray containing 1087 P falciparum antigens and compared IgM and IgG profiles by ethnicity. Results. We found that the breadth and magnitude of P falciparum-specific IgM and IgG responses were significantly higher in the malaria-resistant Fulani versus the malaria-susceptible Dogon, and, unexpectedly, P falciparum-specific IgM responses more strongly distinguished the 2 ethnic groups. Conclusions. These findings point to an underappreciated role for IgM in protection from malaria, and they suggest that host genetics may influence the antigen specificity of IgM and IgG responses to infection
Genomic Organization, Splice Variants and Expression of CGMl, a CD66-related Member of the Carcinoembryonic Antigen Gene Family
The tumor marker carcinoembryonic antigen (CEA) belongs to a family of proteins which are composed of one immunogiobulin variable domain and a varying number of immunoglobulin constant-like domains. Most of the membrane-bound members, which are anchored either by a glycosylphosphatidylinositol moiety or a transmembrane domain, have been shown to convey cell adhesion in vitro. Here we describe two splice variants of CGMI. a transmembrane member of the CEA family without immunoglobulin constant.like domains. CGM1a and CGM1c contain cytopiasmic domains of 71 and 31 amino acids, respectively, The cytoplasmic region of CGM1a is encoded by four exons (Cyt1-Cyt4). Differential splicing of the Cyt1 exon (53 bp)..
Structural Properties of the Sliding Columnar Phase in Layered Liquid Crystalline Systems
Under appropriate conditions, mixtures of cationic and neutral lipids and DNA
in water condense into complexes in which DNA strands form local 2D smectic
lattices intercalated between lipid bilayer membranes in a lamellar stack.
These lamellar DNA-cationic-lipid complexes can in principle exhibit a variety
of equilibrium phases, including a columnar phase in which parallel DNA strands
from a 2D lattice, a nematic lamellar phase in which DNA strands align along a
common direction but exhibit no long-range positional order, and a possible new
intermediate phase, the sliding columnar (SC) phase, characterized by a
vanishing shear modulus for relative displacement of DNA lattices but a
nonvanishing modulus for compressing these lattices. We develop a model capable
of describing all phases and transitions among them and use it to calculate
structural properties of the sliding columnar phase. We calculate displacement
and density correlation functions and x-ray scattering intensities in this
phase and show, in particular, that density correlations within a layer have an
unusual dependence on separation r. We
investigate the stability of the SC phase with respect to shear couplings
leading to the columnar phase and dislocation unbinding leading to the lamellar
nematic phase. For models with interactions only between nearest neighbor
planes, we conclude that the SC phase is not thermodynamically stable.
Correlation functions in the nematic lamellar phase, however, exhibit SC
behavior over a range of length scalesComment: 28 pages, 4 figure
Identification of the Feline Humoral Immune Response to Bartonella henselae Infection by Protein Microarray
Background: Bartonella henselae is the zoonotic agent of cat scratch disease and causes potentially fatal infections in immunocompromised patients. Understanding the complex interactions between the host’s immune system and bacterial pathogens is central to the field of infectious diseases and to the development of effective diagnostics and vaccines. Methodology: We report the development of a microarray comprised of proteins expressed from 96 % (1433/1493) of the predicted ORFs encoded by the genome of the zoonotic pathogen Bartonella henselae. The array was probed with a collection of 62 uninfected, 62 infected, and 8 ‘‘specific-pathogen free’ ’ naïve cat sera, to profile the antibody repertoire elicited during natural Bartonella henselae infection. Conclusions: We found that 7.3 % of the B. henselae proteins on the microarray were seroreactive and that seroreactivity was not evenly distributed between predicted protein function or subcellular localization. Membrane proteins were significantly most likely to be seroreactive, although only 23 % of the membrane proteins were reactive. Conversely, we found that proteins involved in amino acid transport and metabolism were significantly underrepresented and did not contain any seroreactive antigens. Of all seroreactive antigens, 52 were differentially reactive with sera from infected cats, and 53 were equally reactive with sera from infected and uninfected cats. Thirteen of the seroreactive antigens were found to be differentially seroreactive between B. henselae type I and type II. Based on these results, we developed a classifier algorith
Contribution of noncanonical antigens to virulence and adaptive immunity in human infection with enterotoxigenic E. coli
Enterotoxigenic Escherichia coli (ETEC) contributes significantly to the substantial burden of infectious diarrhea among children living in low- and middle-income countries. In the absence of a vaccine for ETEC, children succumb to acute dehydration as well as nondiarrheal sequelae related to these infections, including malnutrition. The considerable diversity of ETEC genomes has complicated canonical vaccine development approaches defined by a subset of ETEC pathovar-specific antigens known as colonization factors (CFs). To identify additional conserved immunogens unique to this pathovar, we employed an “open-aperture” approach to capture all potential conserved ETEC surface antigens, in which we mined the genomic sequences of 89 ETEC isolates, bioinformatically selected potential surface-exposed pathovar-specific antigens conserved in more than 40% of the genomes (n = 118), and assembled the representative proteins onto microarrays, complemented with known or putative colonization factor subunit molecules (n = 52) and toxin subunits. These arrays were then used to interrogate samples from individuals with acute symptomatic ETEC infections. Surprisingly, in this approach, we found that immune responses were largely constrained to a small number of antigens, including individual colonization factor antigens and EtpA, an extracellular adhesin. In a Bangladeshi cohort of naturally infected children <2 years of age, both EtpA and a second antigen, EatA, elicited significant serologic responses that were associated with protection from symptomatic illness. In addition, children infected with ETEC isolates bearing either etpA or eatA genes were significantly more likely to develop symptomatic disease. These studies support a role for antigens not presently targeted by vaccines (noncanonical) in virulence and the development of adaptive immune responses during ETEC infections. These findings may inform vaccine design efforts to complement existing approaches
Systems Biology Approach Predicts Antibody Signature Associated with Brucella melitensis Infection in Humans
A complete understanding of the factors that determine selection of antigens recognized by the humoral immune response following infectious agent challenge is lacking. Here we illustrate a systems biology approach to identify the antibody signature associated with Brucella melitensis (Bm) infection in humans and predict proteomic features of serodiagnostic antigens. By taking advantage of a full proteome microarray expressing previously cloned 1406 and newly cloned 1640 Bm genes, we were able to identify 122 immunodominant antigens and 33 serodiagnostic antigens. The reactive antigens were then classified according to annotated functional features (COGs), computationally predicted features (e.g., subcellular localization, physical properties), and protein expression estimated by mass spectrometry (MS). Enrichment analyses indicated that membrane association and secretion were significant enriching features of the reactive antigens, as were proteins predicted to have a signal peptide, a single transmembrane domain, and outer membrane or periplasmic location. These features accounted for 67% of the serodiagnostic antigens. An overlay of the seroreactive antigen set with proteomic data sets generated by MS identified an additional 24%, suggesting that protein expression in bacteria is an additional determinant in the induction of Brucella-specific antibodies. This analysis indicates that one-third of the proteome contains enriching features that account for 91% of the antigens recognized, and after B. melitensis infection the immune system develops significant antibody titers against 10% of the proteins with these enriching features. This systems biology approach provides an empirical basis for understanding the breadth and specificity of the immune response to B. melitensis and a new framework for comparing the humoral responses against other microorganisms
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