bluuebunny/crossref_metadata_2025_split huggingface dataset:
NOD mouse model for Sjögren's syndrome: lack of longitudinal stability
Authors: Lodde BM , Mineshiba F , Kok MR , Wang J , Zheng C , Schmidt M , Cotrim AP , Kriete M , Tak PP , Baum BJ 
Published: October 2006

Objectives:  The non‐obese diabetic (NOD) mouse is not only a widely used model for diabetes mellitus type I, but also for the chronic autoimmune disease Sjögren's syndrome (SS), mainly affecting salivary and lacrimal glands. We studied the efficacy of local recombinant serotype 2 adeno‐associated viral (rAAV2) vector transfer of immunomodulatory transgenes to alter the SS‐like disease in NOD mice. Data collected over a 2‐year period indicated a changing SS phenotype in these mice and this phenomenon was investigated.Methods:  1010 particles rAAV2LacZ/gland were delivered to both submandibular glands (SMGs) of NOD/LtJ mice at 8 weeks (before sialadenitis onset) of age. Salivary flow rates were determined at 8 weeks and time of killing. Blood glucose levels and body weights were measured weekly. After killing, saliva and SMGs were harvested. Analyses of salivary output, inflammatory infiltrates (focus score), SMG cytokine profile, body weight, and diabetes mellitus status were performed. Data from six different experimental studies over 2 years were analyzed and compared.Results:  Salivary flow rate, focus score, and SMG cytokines interleukin (IL)‐2, IL‐4, IL‐6, IL‐10, IL‐12(p70), tumor necrosis factor‐α and IFNγ showed changes over time. There were no differences for body weight, diabetes mellitus prevalence, or blood glucose level of non‐diabetic mice.Conclusion:  This retrospective report is the first to describe longitudinal variability in the NOD mouse as a model for SS. We advise other investigators to continuously monitor the SS phenotype parameters and include appropriate controls when studying this disease in NOD mice.
An assessment of the impact of floodplain woodland on flood flows
Authors: Thomas H. , Nisbet T. R. 
Published: October 2006

AbstractThis paper examines the potential role of floodplain woodland in flood alleviation. In theory, the presence of trees and associated woody debris on the floodplain increases the hydraulic roughness, thus slowing down flood flows and enhancing flood storage. One and two‐dimensional models were used to simulate a 2.2 km reach of river in south‐west England to test this theory for a 1 in 100 year flood using appropriate roughness parameters. Both models predicted a reduction in water velocity within the woodland, increasing water level by up to 270 mm and creating a backwater effect that extended nearly 400 m upstream. Flood storage increased by 15 and 71%, while flood peak travel time was increased by 30 and 140 min for the two scenarios simulated. The results suggest that there is considerable scope for using strategically placed floodplain woodland to alleviate downstream flooding. In particular, it offers a means of tackling the increased flood risk associated with climate change.
Learning from the extreme River Tyne flood in January 2005
Authors: Archer David R. , Leesch Francois , Harwood Kirsty 
Published: October 2006

AbstractExtreme floods often demonstrate unanticipated characteristics that pose problems for management and response. The floods on the Tyne and Eden in January 2005 provided numerous examples of such unexpected response. This paper describes characteristics of storm rainfall and runoff generation on the River Tyne catchment, flood effects and damage. Unusual aspects of hydrological behaviour are highlighted as a basis for assessing what lessons can be learned for flood risk management. These include problems associated with coincidence of extreme wind speeds and rainfall, the retarding influence of floodplain storage on flood wave travel time in extreme flows, the influence of critical storm duration on the severity of the resulting flood on headwaters and main river, and the variety of mechanisms of flood occurrence. The occurrence of such an extreme flood provides the opportunity to validate and enhance the review process of the Environment Agency's flood zone maps.
Human skeletal muscle fibre type variations correlate with PPARα, PPARδ and PGC‐1α mRNA
Authors: Krämer D. K. , Ahlsén M. , Norrbom J. , Jansson E. , Hjeltnes N. , Gustafsson T. , Krook A. 
Published: October 2006

AbstractAims:  Studies from genetically modified animals have been instrumental in highlighting genes and their products involved in the regulation of muscle fibre type and oxidative phenotypes; however, evidence in humans is limited. Our aim was therefore to investigate expression of those genes implicated in the regulation of oxidative fibre phenotypes in humans.Methods:  Using quantitative polymerase chain reaction we determined mRNA expression of selected genes in skeletal muscle from three different groups, displaying physiological and pathological variations in muscle fibre type, activity and skeletal muscle metabolism respectively: (i) elite athletes (cyclists), with an increased proportion of type I slow twitch, oxidative fibres, (ii) normally active subjects with an average fibre type distribution, and (iii) spinal cord‐injured subjects with a low proportion of type I fibres.Results:  Skeletal muscle mRNA expression of calcineurin Aα and Aβ, peroxisome proliferator‐activated receptor (PPAR)‐α and ‐δ, and PPAR gamma coactivator (PGC)‐1α and ‐1β was determined. Calcineurin Aα and calcineurin Aβ mRNA expression was similar between groups. In contrast, mRNA expression of PPARα, PPARδ, PGC‐1α and ‐1β was increased in athletes, when compared with normally active subjects. Furthermore, mRNA expression of PPARα, PPARδ, PGC‐1α and ‐1β was reduced in spinal cord‐injured subjects. Additionally, PPARα, PPARδ and PGC‐1α correlated with oxidative fibre content.Conclusion:  Skeletal muscle mRNA expression of PPARα, PPARδ, PGC‐1α and ‐1β reflects differences in type I muscle fibres associated with pathologically and physiologically induced skeletal muscle fibre type differences.
Porphyromonas gingivalis
Genes Involved in Community Development with
Streptococcus gordonii
Authors: Simionato M. Regina , Tucker Chelsea M. , Kuboniwa Masae , Lamont Gwyneth , Demuth Donald R. , Tribble Gena D. , Lamont Richard J. 
Published: October 2006

ABSTRACT

Porphyromonas gingivalis
, one of the causative agents of adult periodontitis, develops biofilm microcolonies on substrata of
Streptococcus gordonii
but not on
Streptococcus mutans. P. gingivalis
genome microarrays were used to identify genes differentially regulated during accretion of
P. gingivalis
in heterotypic biofilms with
S. gordonii
. Thirty-three genes showed up- or downregulation by array analysis, and differential expression was confirmed by quantitative reverse transcription-PCR. The functions of the regulated genes were predominantly related to metabolism and energy production. In addition, many of the genes have no current known function. The roles of two upregulated genes,
ftsH
(PG0047) encoding an ATP-dependent zinc metallopeptidase and
ptpA
(PG1641) encoding a putative tyrosine phosphatase, were investigated further by mutational analysis. Strains with mutations in these genes developed more abundant biofilms with
S. gordonii
than the parental strain developed.
ftsH
and
ptpA
may thus participate in a regulatory network that constrains
P. gingivalis
accumulation in heterotypic biofilms. This study provided a global analysis of
P. gingivalis
transcriptional responses in an oral microbial community and also provided insight into the regulation of heterotypic biofilm development.
Role of
lgtC
in Resistance of Nontypeable
Haemophilus influenzae
Strain R2866 to Human Serum
Authors: Erwin Alice L. , Allen Simon , Ho Derek K. , Bonthius Paul J. , Jarisch Justin , Nelson Kevin L. , Tsao David L. , Unrath William C. T. , Watson Michael E. , Gibson Bradford W. , Apicella Michael A. , Smith Arnold L. 
Published: October 2006

ABSTRACT

We are investigating a nontypeable
Haemophilus influenzae
(NTHI) strain, R2866, isolated from a child with meningitis. R2866 is unusually resistant to killing by normal human serum. The serum 50% inhibitory concentration (IC
50
) for this strain is 18%, approaching that of encapsulated
H. influenzae
. R3392 is a derivative of R2866 that was found to have increased sensitivity to human serum (IC
50
, 1.5%). Analysis of tetrameric repeat regions within lipooligosaccharide (LOS) biosynthetic genes in both strains indicated that the glycosyltransferase gene
lgtC
was out of frame (“off”) in most colonies of R3392 but in frame with its start codon (“on”) in most colonies of the parent. We sought antigenic and biochemical evidence for modification of the LOS structure. In a whole-cell enzyme-linked immunosorbent assay, strain R3392 displayed reduced binding of the Galα1,4Gal-specific monoclonal antibody 4C4. Mass spectrometry analysis of LOS from strain R2866 indicated that the primary oligosaccharide glycoform contained four heptose and four hexose residues, while that of R3392 contained four heptose and three hexose residues. We conclude that the R2866
lgtC
gene encodes a galactosyltransferase involved in synthesis of the 4C4 epitope, as in other strains, and that expression of
lgtC
is associated with the high-level serum resistance that has been observed for this strain. This is the first description of the genetic basis of high-level serum resistance in NTHI, as well as the first description of LOS composition in an NTHI strain for which the complete genome sequence has been determined.
Complex Role of Hemoglobin and Hemoglobin-Haptoglobin Binding Proteins in
Haemophilus influenzae
Virulence in the Infant Rat Model of Invasive Infection
Authors: Seale Thomas W. , Morton Daniel J. , Whitby Paul W. , Wolf Roman , Kosanke Stanley D. , VanWagoner Timothy M. , Stull Terrence L. 
Published: October 2006

ABSTRACT

Haemophilus influenzae
requires an exogenous heme source for aerobic growth in vitro. Hemoglobin or hemoglobin-haptoglobin satisfies this requirement. Heme acquisition from hemoglobin-haptoglobin is mediated by proteins encoded by
hgp
genes. Both Hgps and additional proteins, including those encoded by the
hxu
operon, provide independent pathways for hemoglobin utilization. Recently we showed that deletion of the set of three
hgp
genes from a nontypeable strain (86-028NP) of
H. influenzae
attenuated virulence in the chinchilla otitis media model of noninvasive disease. The present study was undertaken to investigate the role of the
hgp
genes in virulence of the wild-type serotype b clinical isolate HI689 in the infant rat model of hematogenous meningitis, an established model of invasive disease requiring aerobic growth. Bacteremia of high titer and long duration (>14 days) and histopathologically confirmed meningitis occurred in >95% of infant rats challenged at 5 days of age with strain HI689. While mutations disrupting either the Hgp- or Hxu-mediated pathway of heme acquisition had no effect on virulence in infant rats, an isogenic mutant deficient for both pathways was unable to sustain bacteremia or produce meningitis. In contrast, mutations disrupting either pathway decreased the limited ability of
H. influenzae
to initiate and sustain bacteremia in weanling rats. Biochemical and growth studies also indicated that infant rat plasma contains multiple heme sources that change with age. Taken together, these data indicate that both the
hgp
genes and the
hxuC
gene are virulence determinants in the rat model of human invasive disease.
Clinical and Pathologic Changes in a Guinea Pig Aerosol Challenge Model of Acute Q Fever
Authors: Russell-Lodrigue K. E. , Zhang G. Q. , McMurray D. N. , Samuel J. E. 
Published: October 2006

ABSTRACT

Acute Q fever is a zoonotic disease caused by the obligate intracellular bacterium
Coxiella burnetii
and can manifest as a flu-like illness, pneumonia, or hepatitis. A need exists in Q fever research for animal models mimicking both the typical route of infection (inhalation) and the clinical illness seen in human cases of Q fever. A guinea pig aerosol challenge model was developed using
C. burnetii
Nine Mile phase I (RSA 493), administered using a specialized chamber designed to deliver droplet nuclei directly to the alveolar spaces. Guinea pigs were given 10
1
to 10
6
organisms and evaluated for 28 days postinfection. Clinical signs included fever, weight loss, respiratory difficulty, and death, with the degree and duration of response corresponding to the dose of organism delivered. Histopathologic evaluation of the lungs of animals infected with a high dose showed coalescing panleukocytic bronchointerstitial pneumonia at 7 days postinfection that resolved to multifocal lymphohistiocytic interstitial pneumonia by 28 days. Guinea pigs receiving a killed whole-cell vaccine prior to challenge with the highest dose of
C. burnetii
were protected against lethal infection and did not develop fever. Clinical signs and pathological changes noted for these guinea pigs were comparable to those seen in human acute Q fever, making this an accurate and valuable animal model of human disease.
Serologic Evidence for Effective Production of Cytolysin A in
Salmonella enterica
Serovars Typhi and Paratyphi A during Human Infection
Authors: von Rhein Christine , Hunfeld Klaus-Peter , Ludwig Albrecht 
Published: October 2006

ABSTRACT

ClyA
STy
and ClyA
SPaA
are closely related pore-forming cytolysins of
Salmonella enterica
serovars Typhi and Paratyphi A whose expression is strongly repressed under standard in vitro growth conditions. We show here that human infections by these pathogens cause a specific antibody response to ClyA, indicating effective toxin production during infection.
Role of Host Protein Tyrosine Phosphatase SHP-1 inLeishmania donovani-Induced Inhibition of Nitric Oxide Production
Authors: Forget Geneviève , Gregory David J. , Whitcombe Lorie A. , Olivier Martin 
Published: October 2006

ABSTRACTIn order to survive within the macrophages of its host organism, the protozoan parasiteLeishmaniainhibits a number of critical, gamma interferon (IFN-γ)-inducible, macrophage functions, including the generation of nitric oxide. We have previously shown that the protein tyrosine phosphatase SHP-1 (Src-homology 2 domain containing phosphatase-1) is activated duringLeishmaniainfection and plays an important role in both the survival ofLeishmaniawithin cultured macrophages and disease progression in vivo by inhibiting nitric oxide production. Here we use a SHP-1−/−macrophage cell line derived frommotheatenmice to address the mechanisms by which SHP-1 prevents IFN-γ-dependent nitric oxide production duringLeishmania donovaniinfection. We show thatLeishmaniainhibits nitric oxide production in response to IFN-γ poorly in SHP-1-deficient macrophages. This correlates with the inability ofLeishmaniato alter JAK2 and mitogen-activated protein kinase extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation and to prevent nuclear translocation of transcription factors NF-κB and AP-1, although the latter two to a lesser extent. Surprisingly,Leishmaniainactivated the transcription factor STAT1 to a similar extent in SHP-1-deficient and wild-type macrophages, so STAT1 is not necessary for nitric oxide production by infected macrophages. Overall, this study demonstrates that induction of SHP-1 byLeishmaniais vital for inhibition of nitric oxide generation and that this inhibition occurs through the inactivation of JAK2 and ERK1/2, and transcription factors NF-κB and AP-1.
Penicillin-Binding Protein 1a Promotes Resistance of Group B Streptococcus to Antimicrobial Peptides
Authors: Hamilton Andrea , Popham David L. , Carl David J. , Lauth Xavier , Nizet Victor , Jones Amanda L. 
Published: October 2006

ABSTRACTEvasion of host immune defenses is critical for the progression of invasive infections caused by the leading neonatal pathogen, group B streptococcus (GBS). Upon characterizing the factors required for virulence in a neonatal rat sepsis model, we found that a surface-associated penicillin-binding protein (PBP1a), encoded byponA, played an essential role in resistance of GBS to phagocytic clearance. In order to elucidate how PBP1a promotes resistance to innate immunity, we compared the susceptibility of wild-type GBS and an isogenicponAmutant to the bactericidal components of human neutrophils. The isogenic strains were found to be equally capable of blocking complement activation on the bacterial surface and equally associated with phagocytes and susceptible to oxidative killing. In contrast, theponAmutant was significantly more susceptible to killing by cationic antimicrobial peptides (AMPs) of the cathelicidin and defensin families, which are now recognized as integral components of innate host defense against invasive bacterial infection. These observations may help explain the sensitivity to phagocytic killing and attenuated virulence of theponAmutant. This novel function for PBP1a in promoting resistance of GBS to AMP did not involve an alteration in bacterial surface charge or peptidoglycan cross-linking. While the peptidoglycan polymerization and cross-linking activity of PBPs are essential for bacterial survival, our study is the first to identify a role for a PBP in resistance to host AMPs.
Discordance in the Effects ofYersinia pestison the Dendritic Cell Functions Manifested by Induction of Maturation and Paralysis of Migration
Authors: Velan Baruch , Bar-Haim Erez , Zauberman Ayelet , Mamroud Emanuelle , Shafferman Avigdor , Cohen Sara 
Published: October 2006

ABSTRACTThe encounter between invading microorganisms and dendritic cells (DC) triggers a series of events which include uptake and degradation of the microorganism, induction of a maturation process, and enhancement of DC migration to the draining lymph nodes. Various pathogens have developed strategies to counteract these events as a measure to evade the host defense. In the present study we found that interaction of theYersinia pestisEV76 strain with DC has no effect on cell viability and is characterized by compliance with effective maturation, which is manifested by surface display of major histocompatibility complex class II, of costimulatory markers, and of the chemokine receptor CCR7. This is in contrast to maturation inhibition and cell death induction exerted by the related speciesYersinia enterocoliticaWA O:8.Y. pestisinteractions with DC were found, however, to impair functions related to cytoskeleton rearrangement. DC pulsed withY. pestisfailed to adhere to solid surfaces and to migrate toward the chemokine CCL19 in an in vitro transmembrane assay. Both effects were dependent on the presence of the pCD1 virulence plasmid and on a bacterial growth shift to 37°C prior to infection. Moreover, while instillation of a pCD1-curedY. pestisstrain into mouse airways triggered effective transport of alveolar DC to the mediastinal lymph node, instillation ofY. pestisharboring the plasmid failed to do so. Taken together, these results suggest that virulence plasmid-dependent impairment of DC migration is the major mechanism utilized byY. pestisto subvert DC function.
Protease Activity, Secretion, Cell Entry, Cytotoxicity, and Cellular Targets of Secreted Autotransporter Toxin of Uropathogenic
Escherichia coli
Authors: Maroncle Nathalie M. , Sivick Kelsey E. , Brady Rebecca , Stokes Faye-Ellen , Mobley Harry L. T. 
Published: October 2006

ABSTRACT

The secreted autotransporter toxin (Sat), found predominantly in uropathogenic
Escherichia coli
, is a member of the SPATE (serine protease autotransporters of
Enterobacteriaceae
) family and, as such, has serine protease activity and causes cytopathic effects on various cell types. To assess the contribution of the serine protease active site to the mechanism of action of Sat, mutations were made in the first (S256I), in the second (S258A), or in both (S256I/S258A) serine residues within the active site motif. Mutations in the first or both serines reduced protease activity to background levels (
P
< 0.001); a single mutation in the second serine reduced activity by 60% compared to wild type (
P
< 0.001). After reversion of the S256I mutation to wild type (I256S), we confirmed S
256
as the catalytically active serine. None of these mutations affected secretion of the mature passenger domain or release into the supernatant. The S256I mutation, however, abrogated the cytotoxicity of Sat on human bladder (UM-UC-3) and kidney (HEK 293) epithelial cells, characterized by rounding and elongation, respectively, and a high level of cell detachment. Moreover, S
256
is essential for Sat to mediate cytoskeletal contraction and actin loss in host cells as well as to degrade specific membrane/cytoskeletal (fodrin and leukocyte function-associated molecule 1) and nuclear [microtubule-associated proteins, LIM domain-only protein 7, Rap GTPase-activating protein, poly(ADP-ribose) polymerase] proteins in vitro. Lastly, Sat was internalized by host cells and localized to the cytoskeletal fraction where membrane/cytoskeletal target proteins reside.
Cytosolic Entry Controls CD8+-T-Cell Potency during Bacterial Infection
Authors: Bahjat Keith S. , Liu Weiqun , Lemmens Edward E. , Schoenberger Stephen P. , Portnoy Daniel A. , Dubensky Thomas W. , Brockstedt Dirk G. 
Published: October 2006

ABSTRACTInteraction with host immunoreceptors during microbial infection directly impacts the magnitude of the ensuing innate immune response. How these signals affect the quality of the adaptive T-cell response remains poorly understood. Utilizing an engineered strain of the intracellular pathogenListeria monocytogenesthat infects cells but fails to escape from the phagosome, we demonstrate the induction of long-lived memory T cells that are capable of secondary expansion and effector function but are incapable of providing protective immunity. We demonstrate that microbial invasion of the cytosol is required for dendritic cell activation and integration of CD40 signaling, ultimately determining the ability of the elicited CD8+-T-cell pool to protect against lethal wild-typeL. monocytogeneschallenge. These results reveal a crucial role for phagosomal escape, not for delivery of antigen to the class I major histocompatibility complex pathway but for establishing the appropriate cellular context during CD8+-T-cell priming.
The Innate Immune Responses of Colonic Epithelial Cells toTrichuris murisAre Similar in Mouse Strains That Develop a Type 1 or Type 2 Adaptive Immune Response
Authors: deSchoolmeester Matthew L. , Manku Harinder , Else Kathryn J. 
Published: October 2006

ABSTRACTTrichuris murisresides in intimate contact with its host, burrowing within cecal epithelial cells. However, whether the enterocyte itself responds innately toT. murisis unknown. This study investigated for the first time whether colonic intestinal epithelial cells (IEC) produce cytokines or chemokines followingT. murisinfection and whether divergence of the innate response could explain differentially polarized adaptive immune responses in resistant and susceptible mice. Increased expression of mRNA for the proinflammatory cytokines gamma interferon (IFN-γ) and tumor necrosis factor and the chemokine CCL2 (MCP-1) were seen after infection of susceptible and resistant strains, with the only difference in expression being a delayed increase in CCL2 in BALB/c IEC. These increases were ablated in MyD88−/−mice, and NF-κB p65 was phosphorylated in response toT. murisexcretory/secretory products in the epithelial cell line CMT-93, suggesting involvement of the MyD88-NF-κB signaling pathway in IEC cytokine expression. These data reveal that IEC respond innately toT. muris. However, the minor differences identified between resistant and susceptible mice are unlikely to underlie the subsequent development of a susceptible type 1 (IFN-γ-dominated) or resistant type 2 (interleukin-4 [IL-4]/IL-13-dominated) adaptive immune response.