Prenatal allergen and diesel exhaust exposure and their effects on allergy in adult offspring mice

Multiple studies have suggested that prenatal exposure to either allergens or air pollution may increase the risk for the development of allergic immune responses in young offspring. However, the effects of prenatal environmental exposures on adult offspring have not been well-studied. We hypothesized that combined prenatal exposure to Aspergillus fumigatus (A. fumigatus) allergen and diesel exhaust particles will be associated with altered IgE production, airway inflammation, airway hyperreactivity (AHR), and airway remodeling of adult offspring. Following sensitization via the airway route to A. fumigatus and mating, pregnant BALB/c mice were exposed to additional A. fumigatus and/or diesel exhaust particles. At age 9-10 weeks, their offspring were sensitized and challenged with A. fumigatus. We found that adult offspring from mice that were exposed to A. fumigatus or diesel exhaust particles during pregnancy experienced decreases in IgE production. Adult offspring of mice that were exposed to both A. fumigatus and diesel exhaust particles during pregnancy experienced decreases in airway eosinophilia. These results suggest that, in this model, allergen and/or diesel administration during pregnancy may be associated with protection from developing systemic and airway allergic immune responses in the adult offspring

Charged pion form factor between Q2Q^2=0.60 and 2.45 GeV2^2. I. Measurements of the cross section for the 1{^1}H(e,e′π+e,e'\pi^+)nn reaction

Cross sections for the reaction ${^1}$H($e,e'\pi^+$)$n$ were measured in Hall C at Thomas Jefferson National Accelerator Facility (JLab) using the CEBAF high-intensity, continous electron beam in order to determine the charged pion form factor. Data were taken for central four-momentum transfers ranging from $Q^2$=0.60 to 2.45 GeV$^2$ at an invariant mass of the virtual photon-nucleon system of $W$=1.95 and 2.22 GeV. The measured cross sections were separated into the four structure functions $\sigma_L$, $\sigma_T$, $\sigma_{LT}$, and $\sigma_{TT}$. The various parts of the experimental setup and the analysis steps are described in detail, including the calibrations and systematic studies, which were needed to obtain high precision results. The different types of systematic uncertainties are also discussed. The results for the separated cross sections as a function of the Mandelstam variable $t$ at the different values of $Q^2$ are presented. Some global features of the data are discussed, and the data are compared with the results of some model calculations for the reaction ${^1}$H($e,e'\pi^+$)$n$.Comment: 26 pages, 23 figure

Separated Response Function Ratios in Exclusive, Forward pi^{+/-} Electroproduction

The study of exclusive $\pi^{\pm}$ electroproduction on the nucleon, including separation of the various structure functions, is of interest for a number of reasons. The ratio $R_L=\sigma_L^{\pi^-}/\sigma_L^{\pi^+}$ is sensitive to isoscalar contamination to the dominant isovector pion exchange amplitude, which is the basis for the determination of the charged pion form factor from electroproduction data. A change in the value of $R_T=\sigma_T^{\pi^-}/\sigma_T^{\pi^+}$ from unity at small $-t$, to 1/4 at large $-t$, would suggest a transition from coupling to a (virtual) pion to coupling to individual quarks. Furthermore, the mentioned ratios may show an earlier approach to pQCD than the individual cross sections. We have performed the first complete separation of the four unpolarized electromagnetic structure functions above the dominant resonances in forward, exclusive $\pi^{\pm}$ electroproduction on the deuteron at central $Q^2$ values of 0.6, 1.0, 1.6 GeV$^2$ at $W$=1.95 GeV, and $Q^2=2.45$ GeV$^2$ at $W$=2.22 GeV. Here, we present the $L$ and $T$ cross sections, with emphasis on $R_L$ and $R_T$, and compare them with theoretical calculations. Results for the separated ratio $R_L$ indicate dominance of the pion-pole diagram at low $-t$, while results for $R_T$ are consistent with a transition between pion knockout and quark knockout mechanisms.Comment: 6 pages, 3 figure

Lack of association between mutations of gene-encoding mitochondrial D310 (displacement loop) mononucleotide repeat and oxidative stress in chronic dialysis patients in Taiwan

<p>Abstract</p> <p>Background</p> <p>Mitochondria (mt) are highly susceptible to reactive oxygen species (ROS). In this study, we investigated the association between a region within the displacement loop (D-loop) in mtDNA that is highly susceptible to ROS and oxidative stress markers in chronic dialysis patients. We enrolled 184 chronic dialysis patients and 213 age-matched healthy subjects for comparison. Blood levels of oxidative stress markers, such as thiobarbituric acid reactive substances (TBARS) and free thiol, and the mtDNA copy number were determined. A mononucleotide repeat sequence (CCCC...CCCTCCCCCC) between nucleotides 303 and 316-318 (D310) was identified in mtDNA.</p> <p>Results</p> <p>Depending on alterations in the D310 mononucleotide repeat, subjects were categorized into 4 subgroups: 7-C, 8-C, 9 or 10-C, and T-to-C transition. Oxidative stress was higher in chronic dialysis patients, evidenced by higher levels of TBARS and mtDNA copy number, and a lower level of free thiol. The distribution of 7-C, 8-C, and 9-10C in dialysis and control subjects was as follows: 7-C (38% <it>vs. </it>31.5%), 8-C (35.3% <it>vs. </it>43.2%), and 9-10C (24.5% <it>vs. </it>22.1%). Although there were significant differences in levels of TBARS, free thiol, and the mtDNA copy number in the D310 repeat subgroups (except T-to-C transition) between dialysis patients and control subjects, post hoc analyses within the same study cohort revealed no significant differences.</p> <p>Conclusion</p> <p>Although oxidative stress was elevated in chronic dialysis patients and resulted in a compensatory increase in the mtDNA copy number, homopolymeric C repeats in the mtDNA region (D310), susceptible to ROS, were not associated with oxidative stress markers in these patients.</p

Charged pion form factor between Q^2=0.60 and 2.45 GeV^2. II. Determination of, and results for, the pion form factor

The charged pion form factor, Fpi(Q^2), is an important quantity which can be used to advance our knowledge of hadronic structure. However, the extraction of Fpi from data requires a model of the 1H(e,e'pi+)n reaction, and thus is inherently model dependent. Therefore, a detailed description of the extraction of the charged pion form factor from electroproduction data obtained recently at Jefferson Lab is presented, with particular focus given to the dominant uncertainties in this procedure. Results for Fpi are presented for Q^2=0.60-2.45 GeV^2. Above Q^2=1.5 GeV^2, the Fpi values are systematically below the monopole parameterization that describes the low Q^2 data used to determine the pion charge radius. The pion form factor can be calculated in a wide variety of theoretical approaches, and the experimental results are compared to a number of calculations. This comparison is helpful in understanding the role of soft versus hard contributions to hadronic structure in the intermediate Q^2 regime.Comment: 18 pages, 11 figure

Association of the MAOA promoter uVNTR polymorphism with suicide attempts in patients with major depressive disorder

<p>Abstract</p> <p>Background</p> <p>The MAOA uVNTR polymorphism has been documented to affect the MAOA gene at the transcriptional level and is associated with aggressive impulsive behaviors, depression associated with suicide (depressed suicide), and major depressive disorder (MDD). We hypothesized that the uVNTR polymorphism confers vulnerability to MDD, suicide or both. The aim of this study was to explore the association between the MAOA uVNTR and depressed suicide, using multiple controls.</p> <p>Methods</p> <p>Four different groups were included: 432 community controls, 385 patients with MDD who had not attempted suicide, 96 community subjects without mental disorders who had attempted suicide, and 109 patients with MDD who had attempted suicide. The MAOA uVNTR polymorphism was genotyped by a PCR technique. The symptom profiles and personal characteristics in each group were also compared.</p> <p>Results</p> <p>The MAOA 4R allele was more frequent in males with MDD than in male community controls (χ²= 4.182, p = 0.041). Logistic regression analysis showed that, among the depressed subjects, those younger in age, more neurotic or who smoked had an increased risk of suicide (β = -0.04, p = 0.002; β = 0.15, p = 0.017; β = 0.79, p = 0.031, respectively). Moreover, among those who had attempted suicide, those younger in age, with more paternal overprotection, and more somatic symptoms were more likely to be in the MDD group than in the community group (β = -0.11, p < 0.001; β = 0.15, p = 0.026; β = 1.11, p < 0.001). Structural equation modeling (SEM) showed that nongenetic factors, such as age, paternal overprotection, and somatic symptoms, were associated with MDD, whereas depressed suicide were associated with severity of depression, personality traits, age, marital status, and inversely associated with anxiety symptoms. However, depression did not affect suicidal behavior in the community group.</p> <p>Conclusion</p> <p>The MAOA 4R allele is associated with enhanced vulnerability to suicide in depressed males, but not in community subjects. The MAOA 4R allele affects vulnerability to suicide through the mediating factor of depressive symptoms. Further large-scale studies are needed to verify the psychopathology of the relationships among MAOA uVNTR polymorphism, symptom profiles, and suicidal behavior.</p

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that have diverse roles in tissue morphogenesis and patho-physiological remodeling, in inflammation and in vascular biology. The human family includes 19 members that can be sub-grouped on the basis of their known substrates, namely the aggrecanases or proteoglycanases (ADAMTS1, 4, 5, 8, 9, 15 and 20), the procollagen N-propeptidases (ADAMTS2, 3 and 14), the cartilage oligomeric matrix protein-cleaving enzymes (ADAMTS7 and 12), the von-Willebrand Factor proteinase (ADAMTS13) and a group of orphan enzymes (ADAMTS6, 10, 16, 17, 18 and 19). Control of the structure and function of the extracellular matrix (ECM) is a central theme of the biology of the ADAMTS, as exemplified by the actions of the procollagen-N-propeptidases in collagen fibril assembly and of the aggrecanases in the cleavage or modification of ECM proteoglycans. Defects in certain family members give rise to inherited genetic disorders, while the aberrant expression or function of others is associated with arthritis, cancer and cardiovascular disease. In particular, ADAMTS4 and 5 have emerged as therapeutic targets in arthritis. Multiple ADAMTSs from different sub-groupings exert either positive or negative effects on tumorigenesis and metastasis, with both metalloproteinase-dependent and -independent actions known to occur. The basic ADAMTS structure comprises a metalloproteinase catalytic domain and a carboxy-terminal ancillary domain, the latter determining substrate specificity and the localization of the protease and its interaction partners; ancillary domains probably also have independent biological functions. Focusing primarily on the aggrecanases and proteoglycanases, this review provides a perspective on the evolution of the ADAMTS family, their links with developmental and disease mechanisms, and key questions for the future

Functions of Some Capsular Polysaccharide Biosynthetic Genes in Klebsiella pneumoniae NTUH K-2044

The growing number of Klebsiella pneumoniae infections, commonly acquired in hospitals, has drawn great concern. It has been shown that the K1 and K2 capsular serotypes are the most detrimental strains, particularly to those with diabetes. The K1 cps (capsular polysaccharide) locus in the NTUH-2044 strain of the pyogenic liver abscess (PLA) K. pneumoniae has been identified recently, but little is known about the functions of the genes therein. Here we report characterization of a group of cps genes and their roles in the pathogenesis of K1 K. pneumoniae. By sequential gene deletion, the cps gene cluster was first re-delimited between genes galF and ugd, which serve as up- and down-stream ends, respectively. Eight gene products were characterized in vitro and in vivo to be involved in the syntheses of UDP-glucose, UDP-glucuronic acid and GDP-fucose building units. Twelve genes were identified as virulence factors based on the observation that their deletion mutants became avirulent or lost K1 antigenicity. Furthermore, deletion of kp3706, kp3709 or kp3712 (ΔwcaI, ΔwcaG or Δatf, respectively), which are all involved in fucose biosynthesis, led to a broad range of transcriptional suppression for 52 upstream genes. The genes suppressed include those coding for unknown regulatory membrane proteins and six multidrug efflux system proteins, as well as proteins required for the K1 CPS biosynthesis. In support of the suppression of multidrug efflux genes, we showed that these three mutants became more sensitive to antibiotics. Taken together, the results suggest that kp3706, kp3709 or kp3712 genes are strongly related to the pathogenesis of K. pneumoniae K1

Lipopolysaccharide O1 Antigen Contributes to the Virulence in Klebsiella pneumoniae Causing Pyogenic Liver Abscess

Klebsiella pneumoniae is the common cause of a global emerging infectious disease, community-acquired pyogenic liver abscess (PLA). Capsular polysaccharide (CPS) and lipopolysaccharide (LPS) are critical for this microorganism's ability to spread through the blood and to cause sepsis. While CPS type K1 is an important virulence factor in K. pneumoniae causing PLA, the role of LPS in PLA is not clear. Here, we characterize the role of LPS O antigen in the pathogenesis of K. pneumoniae causing PLA. NTUH-K2044 is a LPS O1 clinical strain; the presence of the O antigen was shown via the presence of 1,3-galactan in the LPS, and of sequences that align with the wb gene cluster, known to produce O-antigen. Serologic analysis of K. pneumoniae clinical isolates demonstrated that the O1 serotype was more prevalent in PLA strains than that in non-tissue-invasive strains (38/42 vs. 9/32, P<0.0001). O1 serotype isolates had a higher frequency of serum resistance, and mutation of the O1 antigen changed serum resistance in K. pneumoniae. A PLA-causing strain of CPS capsular type K2 and LPS serotype O1 (i.e., O1:K2 PLA strain) deleted for the O1 synthesizing genes was profoundly attenuated in virulence, as demonstrated in separate mouse models of septicemia and liver abscess. Immunization of mice with the K2044 magA-mutant (K1− O1) against LPS O1 provided protection against infection with an O1:K2 PLA strain, but not against infection with an O1:K1 PLA strain. Our findings indicate that the O1 antigen of PLA-associated K. pneumoniae contributes to virulence by conveying resistance to serum killing, promoting bacterial dissemination to and colonization of internal organs after the onset of bacteremia, and could be a useful vaccine candidate against infection by an O1:K2 PLA strain

Heterostructures for High Performance Devices

Contains table of contents for Part I, table of contents for Section 1, an introduction, reports on eighteen research projects and a list of publications.Charles S. Draper Laboratories Contract DL-H-418483DARPA/NCIPTJoint Services Electronics Program Contract DAAL03-89-C-0001Joint Services Electronics Program Contract DAAL03-92-C-0001IBM Corporation FellowshipNational Science Foundation FellowshipVitesse SemiconductorGTE LaboratoriesCharles S. Draper LaboratoriesElectronics and Telecommunications Research Institute (ETRI) FellowshipNational Science Foundation/Northeastern UniversityTRW SystemsU.S. Army Research OfficeNational Science FoundationAT&T Bell Laboratories FellowshipNational Science Foundation Grant ECS 90-0774