bluuebunny/crossref_metadata_2025 huggingface dataset:
Virulence Genotype and Phylogenetic Origin in Relation to Antibiotic Resistance Profile among
Escherichia coli
Urine Sample Isolates from Israeli Women with Acute Uncomplicated Cystitis
Authors: Johnson James R. , Kuskowski Michael A. , O'Bryan Timothy T. , Colodner Raul , Raz Raul
Published: December 2004

To clarify the virulence and phylogenetic implications of antimicrobial agent resistance in
Escherichia coli
, 100
E. coli
isolates from urine samples of Israeli women with acute uncomplicated cystitis were analyzed by molecular phylotyping and virulence genotyping for comparison with resistance phenotypes. The differences between the isolates that were resistant and susceptible to trimethoprim-sulfamethoxazole and ampicillin were minimal. In contrast, ciprofloxacin resistance was associated with greatly reduced inferred virulence and categorical shifts away from the highly virulent phylogenetic group B2, which explained much of the virulence effect. The results of amplification fingerprinting suggested that most ciprofloxacin-resistant isolates represented unique clonal groups and were not derived from clonal groups with more highly virulent susceptible isolates. These findings suggest that virulence and antimicrobial resistance are not mutually exclusive in
E. coli
clinical isolates. Instead, the relationship between virulence and antimicrobial resistance varies according to the particular resistance phenotype; for ciprofloxacin resistance, the relationship is strongly influenced by phylogenetic background. The basis for the concentration of ciprofloxacin resistance in non-B2 phylogenetic groups remains unknown.
De Novo Generation of Cationic Antimicrobial Peptides: Influence of Length and Tryptophan Substitution on Antimicrobial Activity
Authors: Deslouches Berthony , Phadke Shruti M. , Lazarevic Vanja , Cascio Michael , Islam Kazi , Montelaro Ronald C. , Mietzner Timothy A.
Published: December 2004

Comparison of human immunodeficiency virus lentiviral lytic peptide 1 with other host-derived peptides indicates that antimicrobial properties of membrane-active peptides are markedly influenced by their cationic, hydrophobic, and amphipathic properties. Many common themes, such as Arg composition of the cationic face of an amphipathic helix and the importance of maintaining the hydrophobic face, have been deduced from these observations. These studies suggest that a peptide with these structural properties can be derived de novo by using only a few strategically positioned amino acids. However, the effects of length and helicity on antimicrobial activity and selectivity have not been objectively evaluated in the context of this motif. To address these structure-function issues, multimers of a 12-residue lytic base unit (LBU) peptide composed only of Arg and Val residues aligned to form idealized amphipathic helices were designed. Bacterial killing assays and circular dichroism analyses reveal a strong correlation between antibacterial activity, peptide length, and propensity to form a helix in solvent mimicking the environment of a membrane. Increasing peptide length beyond two LBUs (24-residue peptides) resulted in no appreciable increase in antimicrobial activity. Derivatives (WLBU) of the LBU series were further engineered by substituting Trp residues in the hydrophobic domains. The 24-residue WLBU2 peptide was active at physiologic NaCl concentrations againstStaphylococcus aureusand mucoid and nonmucoid strains ofPseudomonas aeruginosa. Further, WLBU2 displayed the highest antibacterial selectivity of all peptides evaluated in the present study by using a coculture model ofP. aeruginosaand primary human skin fibroblasts. These findings provide fundamental information toward the de novo design of an antimicrobial peptide useful for the management of infectious diseases.
Anti-Human Immunodeficiency Virus Type 1 Microbicide Cellulose Acetate 1,2-Benzenedicarboxylate in a Human In Vitro Model of Vaginal Inflammation
Authors: Fichorova R. N. , Zhou F. , Ratnam V. , Atanassova V. , Jiang S. , Strick N. , Neurath A. R.
Published: December 2004

The sexual transmission of human immunodeficiency virus type 1 (HIV-1) is facilitated by inflammation and related epithelial barrier perturbation. Microbicides for vaginal applications are currently being developed to reduce the risk of HIV-1 transmission. However, little is known about their interference with epithelial immune function. In recent clinical trials, nonoxynol-9 (N-9), a virucide with a long history of intravaginal use as a contraceptive, failed to protect against HIV-1 possibly due to mucosal inflammatory damage. Cellulose acetate 1,2-benzenedicarboxylate, also named CAP (for “controls AIDS pandemic”), is an anti-HIV-1 microbicide selected from pharmaceutical excipients that are regarded as safe for oral administration but have not been assessed for potential effects on inflammatory factors in the vaginal environment. Here we use a sensitive human cell culture system to evaluate proinflammatory profiles of soluble CAP in reference to N-9 and known epithelial activators such as tumor necrosis factor alpha (TNF-α) and bacterial lysates. Within 6 h of exposure, TNF-α and N-9 triggered NF-κB and AP-1/cFos activation and upregulated interleukins and an array of chemokines by vaginal and polarized cervical epithelial cells. The induced proinflammatory status continued after removal of stimuli and was confirmed by enhanced transepithelial neutrophil migration. While sustaining stability and anti-HIV-1 activity in the epithelial environment, CAP did not increase the production of proinflammatory mediators during or after exposure, nor did it modify the epithelial resistance to leukocyte traffic. CAP attenuated some TNF-α-induced responses but did not interfere with epithelial cytokine responsiveness to gonococcal determinants. The described system may be useful for predicting proinflammatory side effects of other microbicide candidates for vaginal application.
Real-Time In Vivo Bioluminescent Imaging for Evaluating the Efficacy of Antibiotics in a Rat
Staphylococcus aureus
Endocarditis Model
Authors: Xiong Yan Q. , Willard Julie , Kadurugamuwa Jagath L. , Yu Jun , Francis Kevin P. , Bayer Arnold S.
Published: December 2004

Therapeutic options for invasive
Staphylococcus aureus
infections have become limited due to rising antimicrobial resistance, making relevant animal model testing of new candidate agents more crucial than ever. In the present studies, a rat model of aortic infective endocarditis (IE) caused by a bioluminescently engineered, biofilm-positive
S. aureus
strain was used to evaluate real-time antibiotic efficacy directly. This strain was vancomycin and cefazolin susceptible but gentamicin resistant. Bioluminescence was detected and quantified daily in antibiotic-treated and control animals with IE, using a highly sensitive in vivo imaging system (IVIS). Persistent and increasing cardiac bioluminescent signals (BLS) were observed in untreated animals. Three days of vancomycin therapy caused significant reductions in both cardiac BLS (>10-fold versus control) and
S. aureus
densities in cardiac vegetations (
P
< 0.005 versus control). However, 3 days after discontinuation of vancomycin therapy, a greater than threefold increase in cardiac BLS was observed, indicating relapsing IE (which was confirmed by quantitative culture). Cefazolin resulted in modest decreases in cardiac BLS and bacterial densities. These microbiologic and cardiac BLS differences during therapy correlated with a longer time-above-MIC for vancomycin (>12 h) than for cefazolin (∼4 h). Gentamicin caused neither a reduction in cardiac
S. aureus
densities nor a reduction in BLS. There were significant correlations between cardiac BLS and
S. aureus
densities in vegetations in all treatment groups. These data suggest that bioluminescent imaging provides a substantial advance in the real-time monitoring of the efficacy of therapy of invasive
S. aureus
infections in live animals.
Interaction of Bismuth Subsalicylate with Fruit Juices, Ascorbic Acid, and Thiol-Containing Substrates To Produce Soluble Bismuth Products Active against
Clostridium difficile
Authors: Mahony D. E. , Woods A. , Eelman M. D. , Burford N. , Veldhuyzen van Zanten S. J. O.
Published: December 2004

Bismuth subsalicylate (BSS), the active ingredient of Pepto-Bismol, has been used for many years to treat various disorders of the gastrointestinal tract. Using mass spectrometry and the agar dilution method, we determined that insoluble BSS interacts with certain dietary components and organic substrates to produce water-soluble products with activity against
Clostridium difficile
.
Surface-Active Fungicidal
d
-Peptide Inhibitors of the Plasma Membrane Proton Pump That Block Azole Resistance
Authors: Monk Brian C. , Niimi Kyoko , Lin Susan , Knight Allison , Kardos Thomas B. , Cannon Richard D. , Parshot Rekha , King Amanda , Lun David , Harding David R. K.
Published: December 2004

A 1.8-million-member
d
-octapeptide combinatorial library was constructed in which each member comprised a diversity-containing N-terminal pentapeptide and a C-terminal amidated triarginine motif. The C-terminal motif concentrated the library members at the fungal cell surface. A primary screen for inhibitors of
Saccharomyces cerevisiae
and
Candida albicans
growth, together with an in vitro secondary screen with the
S. cerevisiae
plasma membrane ATPase (Pma1p) as a target, identified the antifungal
d
-octapeptide BM0 (
d
-NH
2
-RFWWFRRR-CONH
2
). Optimization of BM0 led to the construction of BM2 (
d
-NH
2
-RRRFWWFRRR-CONH
2
), which had broad-spectrum fungicidal activity against
S. cerevisiae
,
Candida
species, and
Cryptococcus neoformans
; bound strongly to the surfaces of fungal cells; inhibited the physiological activity of Pma1p; and appeared to target Pma1p, with 50% inhibitory concentrations in the range of 0.5 to 2.5 μM. At sub-MICs (<5 μM), BM2 chemosensitized to fluconazole (FLC)
S. cerevisiae
strains functionally hyperexpressing fungal lanosterol 14α-demethylase and resistance-conferring transporters of azole drugs. BM2 chemosensitized to FLC some FLC-resistant clinical isolates of
C. albicans
and
C. dubliniensis
and chemosensitized to itraconazole clinical isolates of
C. krusei
that are intrinsically resistant to FLC. The growth-inhibitory concentrations of BM2 did not cause fungal cell permeabilization, significant hemolysis of red blood cells, or the death of cultured HEp-2 epithelial cells. BM2 represents a novel class of broad-spectrum, surface-active, Pma1p-targeting fungicides which increases the potencies of azole drugs and circumvents azole resistance.
Comparison of Three PCR Primer Sets for Identification of
vanB
Gene Carriage in Feces and Correlation with Carriage of Vancomycin-Resistant Enterococci: Interference by
vanB
-Containing Anaerobic Bacilli
Authors: Ballard S. A. , Grabsch E. A. , Johnson P. D. R. , Grayson M. L.
Published: December 2004

We assessed the sensitivities and specificities of three previously described PCR primers on enrichment broth cultures of feces for the accurate detection of fecal carriage of vancomycin-resistant enterococci (VRE). In addition, we investigated specimens that were
vanB
PCR positive but VRE culture negative for the presence of other
vanB
-containing pathogens. Feces from 59 patients (12 patients carrying
vanB Enterococcus faecium
strains and 47 patients negative for VRE carriage) were cultured for 36 h in aerobic brain heart infusion (BHI) broth, anaerobic BHI (AnO
2
BHI) broth, or aerobic Enterococcosel (EC) broth. DNA was extracted from the cultures and tested for the presence of
vanB
by using the PCR primers of Dutka-Malen et al. (S. Dutka-Malen, S. Evers, and P. Courvalin, J. Clin. Microbiol. 33:24-27, 1995), Bell et al. (J. M. Bell, J. C. Paton, and J. Turnidge, J. Clin. Microbiol. 36:2187-2190, 1998), and Stinear et al. (T. P. Stinear, D. C. Olden, P. D. R. Johnson, J. K. Davies, and M. L. Grayson, Lancet 357:855-856, 2001). The sensitivity (specificity) of PCR compared with the results of culture on BHI, AnO
2
BHI, and EC broths were 67% (96%), 50% (94%), and 17% (100%), respectively, with the primers of Dutka-Malen et al.; 92% (60%), 92% (45%), and 92% (83%), respectively, with the primers of Bell et al.; and 92% (49%), 92% (43%), and 100% (51%) respectively, with the primers of Stinear et al. The primers of both Bell et al. and Stinear et al. were significantly more sensitive than those of Dutka-Malen et al. in EC broth (
P
= 0.001 and
P
< 0.001, respectively). The poor specificities for all primer pairs were due in part to the isolation and identification of six anaerobic gram-positive bacilli,
Clostridium hathewayi
(
n
= 3), a
Clostridium innocuum
-like organism (
n
= 1),
Clostridium bolteae
(
n
= 1), and
Ruminococcus lactaris
-like (
n
= 1), from five fecal specimens that were
vanB
positive but VRE culture negative. All six organisms were demonstrated to contain a
vanB
gene identical to that of VRE.
VanB-
containing bowel anaerobes may result in false-positive interpretation of PCR-positive fecal enrichment cultures as VRE, regardless of the primers and protocols used.
Role of EspA and Intimin in Expression of Proinflammatory Cytokines from Enterocytes and Lymphocytes by Rabbit Enteropathogenic
Escherichia coli
-Infected Rabbits
Authors: Ramirez Karina , Huerta Rocio , Oswald Eric , Garcia-Tovar Carlos , Hernandez Jose Manuel , Navarro-Garcia Fernando
Published: December 2004

Enteropathogenic
Escherichia coli
(EPEC) produces attaching and effacing (A/E) lesions and watery diarrhea, both of which are intimin and EspA dependent. In this work, we explored the mucosal immune response by detecting cytokine induction in rabbits with diarrhea caused by rabbit EPEC (REPEC). Orally inoculated rabbits exhibited weight loss and mucosal inflammation, developed watery diarrhea, and died (day 7). At day 6 postinoculation, animals were analyzed for the induction of proinflammatory cytokines in enterocytes. The role of lymphocyte-dependent immunity was determined through the expression of proinflammatory cytokines by lymphocytes from Peyer's patches (PP) and the spleen. EspA and intimin mutants were used to explore the role of A/E lesions in the expression of these cytokines. REPEC-infected rabbit enterocytes showed increased interleukin 1β (IL-1β), IL-6, IL-8, and tumor necrosis factor alpha (TNF-α) mRNA expression, but that of anti-inflammatory IL-10 was increased only slightly. In contrast, intimin mutant-infected rabbits were unable to produce this proinflammatory cytokine profile but did produce a remarkable increase in IL-10 expression. Bacteria lacking EspA increased the expression of IL-8 and TNF-α, but that of IL-10 was increased only slightly. PP lymphocytes also produced proinflammatory cytokines, which were dependent on EspA (except for TNF-α) and intimin, while IL-10 was induced by EspA and intimin mutants. In contrast, spleen lymphocytes (systemic compartment) were unable to produce IL-1β and TNF-α. These data show the importance of the proinflammatory cytokines secreted by enterocytes and those expressed locally by PP lymphocytes, which can activate effector mechanisms at the epithelium. Furthermore, this cytokine profile, including IL-6 and IL-1β, which may be involved in the diarrhea produced by EPEC, depends on intimin.
NF-κB Activation duringRickettsia rickettsiiInfection of Endothelial Cells Involves the Activation of Catalytic IκB Kinases IKKα and IKKβ and Phosphorylation-Proteolysis of the Inhibitor Protein IκBα
Authors: Clifton Dawn R. , Rydkina Elena , Freeman Robert S. , Sahni Sanjeev K.
Published: December 2004

Rocky Mountain spotted fever, a systemic tick-borne illness caused by the obligate intracellular bacteriumRickettsia rickettsii, is associated with widespread infection of the vascular endothelium.R. rickettsiiinfection induces a biphasic pattern of the nuclear factor-κB (NF-κB) activation in cultured human endothelial cells (ECs), characterized by an early transient phase at 3 h and a late sustained phase evident at 18 to 24 h. To elucidate the underlying mechanisms, we investigated the expression of NF-κB subunits, p65 and p50, and IκB proteins, IκBα and IκBβ. The transcript and protein levels of p50, p65, and IκBβ remained relatively unchanged during the course of infection, but Ser-32 phosphorylation of IκBα at 3 h was significantly increased over the basal level in uninfected cells concomitant with a significant increase in the expression of IκBα mRNA. The level of IκBα mRNA gradually returned toward baseline, whereas that of total IκBα protein remained lower than the corresponding controls. The activities of IKKα and IKKβ, the catalytic subunits of IκB kinase (IKK) complex, as measured by in vitro kinase assays with immunoprecipitates from uninfected andR. rickettsii-infected ECs, revealed significant increases at 2 h after infection. The activation of IKK and early phase of NF-κB response were inhibited by heat treatment and completely abolished by formalin fixation of rickettsiae. The IKK inhibitors parthenolide and aspirin blocked the activities of infection-induced IKKα and IKKβ, leading to attenuation of nuclear translocation of NF-κB. Also, increased activity of IKKα was evident later during the infection, coinciding with the late phase of NF-κB activation. Thus, activation of catalytic components of the IKK complex represents an important upstream signaling event in the pathway forR. rickettsii-induced NF-κB activation. Since NF-κB is a critical regulator of inflammatory genes and prevents host cell death during infection via antiapoptotic functions, selective inhibition of IKK may provide a potential target for enhanced clearance of rickettsiae and an effective strategy to reduce inflammatory damage to the host during rickettsial infections.
Development of Allergic Airway Disease in Mice following Antibiotic Therapy and Fungal Microbiota Increase: Role of Host Genetics, Antigen, and Interleukin-13
Authors: Noverr Mairi C. , Falkowski Nicole R. , McDonald Rod A. , McKenzie Andrew N. , Huffnagle Gary B.
Published: December 2004

Lending support to the hygiene hypothesis, epidemiological studies have demonstrated that allergic disease correlates with widespread use of antibiotics and alterations in fecal microbiota (“microflora”). Antibiotics also lead to overgrowth of the yeastCandida albicans, which can secrete potent prostaglandin-like immune response modulators, from the microbiota. We have recently developed a mouse model of antibiotic-induced gastrointestinal microbiota disruption that is characterized by stable increases in levels of gastrointestinal enteric bacteria andCandida. Using this model, we have previously demonstrated that microbiota disruption can drive the development of a CD4 T-cell-mediated airway allergic response to mold spore challenge in immunocompetent C57BL/6 mice without previous systemic antigen priming. The studies presented here address important questions concerning the universality of the model. To investigate the role of host genetics, we tested BALB/c mice. As with C57BL/6 mice, microbiota disruption promoted the development of an allergic response in the lungs of BALB/c mice upon subsequent challenge with mold spores. In addition, this allergic response required interleukin-13 (IL-13) (the response was absent in IL-13−/−mice). To investigate the role of antigen, we subjected mice with disrupted microbiota to intranasal challenge with ovalbumin (OVA). In the absence of systemic priming, only mice with altered microbiota developed airway allergic responses to OVA. The studies presented here demonstrate that the effects of microbiota disruption are largely independent of host genetics and the nature of the antigen and that IL-13 is required for the airway allergic response that follows microbiota disruption.
Differential Roles of Toll-Like Receptors 2 and 4 in In Vitro Responses of Macrophages toLegionella pneumophila
Authors: Akamine Morikazu , Higa Futoshi , Arakaki Noriko , Kawakami Kazuyoshi , Takeda Kiyoshi , Akira Shizuo , Saito Atsushi
Published: December 2004

The role of Toll-like receptors (TLRs) in innate immunity toLegionella pneumophila, a gram-negative facultative intracellular bacterium, was studied by using bone marrow-derived macrophages and dendritic cells from TLR2-deficient (TLR2−/−), TLR4−/−, and wild-type (WT) littermate (C57BL/6 × 129Sv) mice. Intracellular growth ofL. pneumophilawas enhanced within TLR2−/−macrophages compared to WT and TLR4−/−macrophages. There was no difference in the bacterial growth within dendritic cells from WT and TLR-deficient mice. Production of interleukin-12p40 (IL-12p40) and IL-10 after infection withL. pneumophilawas attenuated in TLR2−/−macrophages compared to WT and TLR4−/−macrophages. Induction of IL-12p40, IL-10, and tumor necrosis factor alpha secretion from macrophages by theL. pneumophila dotOmutant, which cannot multiply within macrophages, and heat-killed bacteria, was similar to that caused by a viable virulent strain. There was no difference between the WT and its mutants in susceptibility to the cytopathic effect of bacteria. AnL. pneumophilasonicated lysate induced IL-12p40 production by macrophages, but that of TLR2−/−macrophages was significantly lower than those of WT and TLR4−/−macrophages. Treatment ofL. pneumophilasonicated lysate with proteinase K and heating did not abolish TLR2-dependent IL-12p40 production. Our results show that TLR2, but not TLR4, is involved in murine innate immunity againstL. pneumophila, although other TLRs may also contribute to innate immunity against this organism.
Contribution of the
Helicobacter pylori
Thiol Peroxidase Bacterioferritin Comigratory Protein to Oxidative Stress Resistance and Host Colonization
Authors: Wang Ge , Olczak Adriana A. , Walton James P. , Maier Robert J.
Published: December 2004

Peroxiredoxins, the enzymes that catalyze the reduction of hydrogen peroxide and organic hydroperoxides, are ubiquitous proteins that protect organisms from damage by reactive oxygen species.
Helicobacter pylori
contains three members of the peroxiredoxin family: AhpC (alkyl hydroperoxide reductase), Tpx (thiol-specific peroxidase), and bacterioferritin comigratory protein (BCP). In this study, we characterized
H. pylori bcp
mutant strains and wild-type BCP. Compared to the parent strain and the
ahpC
mutant strain, the
bcp
mutant showed moderate sensitivity to the superoxide-generating agent paraquat and to organic hydroperoxides. Upon exposure of 10
8
cells to air for 10 h, 10
6
wild-type cells survived but none of the 10
8
bcp
mutant cells were recovered. Introduction of an intact
bcp
gene at an unrelated locus in the
bcp
strain restored the wild-type-like oxidative stress resistance phenotype. Purified BCP was shown to be a thiol peroxidase that depends on the reducing activity of thioredoxin and thioredoxin reductase. Among a series of peroxides tested, linoleic acid hydroperoxide was the preferred substrate of BCP. By examining the profiles of protein expression within
H. pylori
cells, we confirmed that AhpC is much more abundant than BCP. The overlapping functions and activities of BCP and AhpC probably explain why the
bcp
mutant displayed a relatively weak oxidative stress resistance phenotype. The
bcp
mutant strain could colonize mouse stomachs, although colonization by the wild-type strain was slightly better than that by the mutant strain at 1 week after host inoculation. However, at 3 weeks after inoculation, the colonization ability of the wild type was significantly greater than that of the
bcp
mutant; for example,
H. pylori
was recovered from 10 of 11 mouse stomachs inoculated with the wild-type strain but from only 4 of 12 mice that were inoculated with the
bcp
mutant strain. This indicates that
H. pylori
BCP plays a significant role in efficient host colonization.
Chemokine Expression in the Monocytic Cell Line THP-1 in Response to Purified Shiga Toxin 1 and/or Lipopolysaccharides
Authors: Harrison Lisa M. , van den Hoogen Christel , van Haaften Wilhelmina C. E. , Tesh Vernon L.
Published: December 2004

Infections with Shiga toxin (Stx)-producing bacteria are associated with bloody diarrhea and postdiarrheal sequelae, including hemolytic uremic syndrome and central nervous system (CNS) abnormalities. Stx-induced intestinal, renal, and CNS vascular lesions may involve a localized production of proinflammatory cytokines in target organs, as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) up-regulate Stx receptor globotriaosylceramide (Gb3) expression on vascular endothelial cells. However, leukocyte recruitment to injured sites may also exacerbate vascular damage. A cytokine macroarray analysis of transcripts derived from macrophage-like THP-1 cells treated with Stx1, lipopolysaccharides (LPS), or both demonstrated a consistent up-regulation ofTNF-α,IL-1β, and four genes encoding the chemokines interleukin-8 (IL-8), macrophage inflammatory protein-1α (MIP-1α), MIP-1β, and growth-related oncogene beta (GRO-β). Real-time PCR analysis verified the macroarray results. Northern blot analyses after the addition of the transcriptional inhibitor actinomycin D revealed increased IL-8 mRNA stability in THP-1 cells treated with Stx1 or Stx1 plus LPS. Finally, enzyme-linked immunosorbent assay data for Stx1- plus LPS-treated cells demonstrated a poor correlation between IL-8, MIP-1α, MIP-1β, and GRO-β mRNA levels and protein production, indicating a posttranscriptional regulatory effect. Our data suggest that in response to Stx1 and LPS, macrophages may be a source of chemokines that promote tissue damage through leukocyte recruitment and activation.
Ehrlichia chaffeensisExpresses Macrophage- and Tick Cell-Specific 28-Kilodalton Outer Membrane Proteins
Authors: Singu Vijayakrishna , Liu Haijie , Cheng Chuanmin , Ganta Roman R.
Published: December 2004

Ehrlichia chaffeensis, a tick-transmitted rickettsial agent, causes human monocyte/macrophage-tropic ehrlichiosis. In this study, proteomic approaches were used to demonstrate host cell-specific antigenic expression byE. chaffeensis. The differentially expressed antigens include those from the 28-kDa outer membrane protein (p28-Omp) multigene locus. The proteins expressed in infected macrophages are the products of p28-Omp19 and p28-Omp20 genes, whereas in tick cells, the protein expressed is the p28-Omp14 gene product. The differentially expressed proteins are posttranslationally modified by phosphorylation and glycosylation to generate multiple expressed forms. Host cell-specific protein expression is not influenced by growth temperatures and is reversible. Host cell-specific protein expression coupled with posttranslational modifications may be a hallmark for the pathogen's adaptation to a dual-host life cycle and its persistence.
A signalling role for muscle glycogen in the regulation of pace during prolonged exercise
Authors: Rauch H G L , St Clair Gibson A , Lambert E V , Noakes T D
Published: December 2004

Introduction:In this study we examined the pacing strategy and the end muscle glycogen contents in eight cyclists, once when they were carbohydrate loaded and once when they were non-loaded.

Methods:Cyclists completed 2 hours of cycling at ∼73% of maximum oxygen consumption, which included five sprints at 100% of peak sustained power output every 20 minutes, followed immediately by a 1 hour time trial. Muscle biopsies were performed before and immediately after exercise, while blood samples were taken during the 2 hour steady state rides and immediately after exercise.

Results:Carbohydrate loading improved mean power output during the 1 hour time trial (mean (SEM) 219 (17)v233 (15) W; p<0.05) and enabled subjects to use significantly more muscle glycogen than during the trial following their normal diet. Significantly, the subjects, kept blind to all feedback except for time, started both time trials at similar workloads (∼30 W), but after 1 minute of cycling, the workload average 14 W higher throughout the loaded compared with the non-loaded time trial. There were no differences in subjects’ plasma glucose and lactate concentrations and heart rates in the carbohydrate loaded versus the non-loaded trial. Of the eight subjects, seven improved their time trial performance after carbohydrate loading. Finishing muscle glycogen concentrations in these seven subjects were remarkably similar in both trials (18 (3)v20 (3) mmol/kg w/w), despite significantly different starting values and time trial performances (36.55 (1.47)v38.14 (1.27) km/h; p<0.05). The intra-subject coefficient of variation (CV) for end glycogen content in these seven subjects was 10%, compared with an inter-subject CV of 43%.

Conclusions:As seven subjects completed the time trials with the same end exercise muscle glycogen concentrations, diet induced changes in pacing strategies during the time trials in these subjects may have resulted from integrated feedback from the periphery, perhaps from glycogen content in exercising muscles.
Weight loss pressure on a 5 year old wrestler
Authors: Sansone R A , Sawyer R
Published: December 2004

The case is reported of a 5 year old boy who was pressured to lose weight in order to wrestle at a lower weight class. Although a minority of athletes engage in unhealthy weight management practices, this is an unusual case because of the age of the athlete and the influential role of a parent.
TORUS KNOTS AND 3-MANIFOLDS
Authors: KIM SOO HWAN , KIM YANGKOK
Published: December 2004

We consider a family of words in a free group of rank n which determine 3-manifolds ℳn(p,q). We prove that the fundamental groups of ℳn(p,q) are cyclically presented, and that ℳn(p,q) is the n-fold cyclic covering of the 3-sphere branched over the torus knots T(p,q) if p is odd and q≡±2( mod p). We also obtain an explicit Dunwoody parameters for the torus knots T(p,q) for odd p and q≡±2( mod p).
FACE PAIRING GRAPHS AND 3-MANIFOLD ENUMERATION
Authors: BURTON BENJAMIN A.
Published: December 2004

The face pairing graph of a 3-manifold triangulation is a 4-valent graph denoting which tetrahedron faces are identified with which others. We present a series of properties that must be satisfied by the face pairing graph of a closed minimal ℙ2-irreducible triangulation. In addition we present constraints upon the combinatorial structure of such a triangulation that can be deduced from its face pairing graph. These results are then applied to the enumeration of closed minimal ℙ2-irreducible 3-manifold triangulations, leading to a significant improvement in the performance of the enumeration algorithm. Results are offered for both orientable and non-orientable triangulations.
Synaptic Physiology in the Cochlear Nucleus Angularis of the Chick
Authors: MacLeod Katrina M. , Carr Catherine E.
Published: December 2004

Nucleus angularis (NA), one of the two cochlear nuclei in birds, is important for processing sound intensity for localization and most likely has role in sound recognition and other auditory tasks. Because the synaptic properties of auditory nerve inputs to the cochlear nuclei are fundamental to the transformation of auditory information, we studied the properties of these synapses onto NA neurons using whole cell patch-clamp recordings from auditory brain stem slices from embryonic chickens (E16–E20). We measured spontaneous excitatory postsynaptic currents (EPSCs), and evoked EPSCs and excitatory postsynaptic potentials (EPSPs) by using extracellular stimulation of the auditory nerve. These excitatory EPSCs were mediated by AMPA and N-methyl-d-aspartate (NMDA) receptors. The spontaneous EPSCs mediated by AMPA receptors had submillisecond decay kinetics (556 μs at E19), comparable with those of other auditory brain stem areas. The spontaneous EPSCs increased in amplitude and became faster with developmental age. Evoked EPSC and EPSP amplitudes were graded with stimulus intensity. The average amplitude of the EPSC evoked by minimal stimulation was twice as large as the average spontaneous EPSC amplitude (∼110 vs. ∼55 pA), suggesting that single fibers make multiple contacts onto each postsynaptic NA neuron. Because of their small size, minimal EPSPs were subthreshold, and we estimate at least three to five inputs were required to reach threshold. In contrast to the fast EPSCs, EPSPs in NA had a decay time constant of ∼12.5 ms, which was heavily influenced by the membrane time constant. Thus NA neurons spatially and temporally integrate auditory information arriving from multiple auditory nerve afferents.
Brain Responses to Ambient Temperature Fluctuations in Fish: Reduction of Blood Volume and Initiation of a Whole-Body Stress Response
Authors: van den Burg Erwin H. , Peeters Ronald R. , Verhoye Marleen , Meek Johannes , Flik Gert , Van der Linden Annemie
Published: December 2004

Spatial and temporal ambient temperature variations directly influence cellular biochemistry and thus the physiology of ectotherms. However, many aquatic ectothermic species maintain coordinated sensorimotor function during large acute body-temperature changes, which points to a compensatory mechanism within the neural system. Here we used high-resolution functional magnetic resonance imaging to study brain responses to a drop of 10°C of ambient water temperature in common carp. We observed a strong drainage of blood out of the brain as of 90 s after the onset of the temperature drop, which would be expected to reduce entry of cold blood arriving from the gills so that the change in brain temperature would be slower. Although oxygen content in the brain thus decreased, we still found specific activation in the preoptic area (involved in temperature detection and stress responses), the pituitary pars distalis (stress response), and inactivation of the anterior part of the midbrain tegmentum and the pituitary pars intermedia. We propose that the blood drainage from the brain slows down the cooling of the brain during an acute temperature drop. This could help to maintain proper brain functioning including sensorimotor activity, initiation of the stress response, and the subsequent behavioral responses.
Calcium Absorption Across Epithelia
Authors: Hoenderop Joost G. J. , Nilius Bernd , Bindels René J. M.
Published: December 2004

Ca2+is an essential ion in all organisms, where it plays a crucial role in processes ranging from the formation and maintenance of the skeleton to the temporal and spatial regulation of neuronal function. The Ca2+balance is maintained by the concerted action of three organ systems, including the gastrointestinal tract, bone, and kidney. An adult ingests on average 1 g Ca2+daily from which 0.35 g is absorbed in the small intestine by a mechanism that is controlled primarily by the calciotropic hormones. To maintain the Ca2+balance, the kidney must excrete the same amount of Ca2+that the small intestine absorbs. This is accomplished by a combination of filtration of Ca2+across the glomeruli and subsequent reabsorption of the filtered Ca2+along the renal tubules. Bone turnover is a continuous process involving both resorption of existing bone and deposition of new bone. The above-mentioned Ca2+fluxes are stimulated by the synergistic actions of active vitamin D (1,25-dihydroxyvitamin D3) and parathyroid hormone. Until recently, the mechanism by which Ca2+enter the absorptive epithelia was unknown. A major breakthrough in completing the molecular details of these pathways was the identification of the epithelial Ca2+channel family consisting of two members: TRPV5 and TRPV6. Functional analysis indicated that these Ca2+channels constitute the rate-limiting step in Ca2+-transporting epithelia. They form the prime target for hormonal control of the active Ca2+flux from the intestinal lumen or urine space to the blood compartment. This review describes the characteristics of epithelial Ca2+transport in general and highlights in particular the distinctive features and the physiological relevance of the new epithelial Ca2+channels accumulating in a comprehensive model for epithelial Ca2+absorption.
Physiology and Pathophysiology of the Calcium Store in the Endoplasmic Reticulum of Neurons
Authors: Verkhratsky Alexei
Published: December 2004

The endoplasmic reticulum (ER) is the largest single intracellular organelle, which is present in all types of nerve cells. The ER is an interconnected, internally continuous system of tubules and cisterns, which extends from the nuclear envelope to axons and presynaptic terminals, as well as to dendrites and dendritic spines. Ca2+release channels and Ca2+pumps residing in the ER membrane provide for its excitability. Regulated ER Ca2+release controls many neuronal functions, from plasmalemmal excitability to synaptic plasticity. Enzymatic cascades dependent on the Ca2+concentration in the ER lumen integrate rapid Ca2+signaling with long-lasting adaptive responses through modifications in protein synthesis and processing. Disruptions of ER Ca2+homeostasis are critically involved in various forms of neuropathology.
Ion Transport Pathology in the Mechanism of Sickle Cell Dehydration
Authors: Lew Virgilio L. , Bookchin Robert M.
Published: December 2004

Polymers of deoxyhemoglobin S deform sickle cell anemia red blood cells into sickle shapes, leading to the formation of dense, dehydrated red blood cells with a markedly shortened life-span. Nearly four decades of intense research in many laboratories has led to a mechanistic understanding of the complex events leading from sickling-induced permeabilization of the red cell membrane to small cations, to the generation of the heterogeneity of age and hydration condition of circulating sickle cells. This review follows chronologically the major experimental findings and the evolution of guiding ideas for research in this field. Predictions derived from mathematical models of red cell and reticulocyte homeostasis led to the formulation of an alternative to prevailing gradualist views: a multitrack dehydration model based on interactive influences between the red cell anion exchanger and two K+transporters, the Gardos channel (hSK4, hIK1) and the K-Cl cotransporter (KCC), with differential effects dependent on red cell age and variability of KCC expression among reticulocytes. The experimental tests of the model predictions and the amply supportive results are discussed. The review concludes with a brief survey of the therapeutic strategies aimed at preventing sickle cell dehydration and with an analysis of the main open questions in the field.
Failing States and Cumulative Causation in the World System
Authors: Wade Robert Hunter
Published: December 2004

This article takes a world-system perspective on the phenomenon of actual or potential “failing states.” While recognizing the role of “domestic” causes (including corruption and cronyism), it emphasizes factors such as widening world income inequality, the location decisions of multinational corporations, North–South terms of trade, technology non-diffusion, and the strategies of the dominant states and the global economic multilateral organizations. At the end, it considers some implications for development strategy that follow from the central development imperative of shifting the balance of economic activity away from the activities that Malthus wrote about and toward those that Schumpeter wrote about.
Identity, embodied culture and physical exercise
Authors: Strandbu Åse
Published: December 2004

The article has two closely connected aims. The first is to illuminate some embodied aspects of identity that might contribute to the understanding of the underrepresentation of girls with immigrant parents in sports clubs. The second, and most important aim, is to discuss some recent identity theories. Roughly speaking two approaches dominate studies of, and public debates on, the lives and identities of young girls with immigrant parents; hybridity and Creole identity perspectives on the one hand, and power perspectives addressing control and restrictions by parents and persons from power elites on the other. Advantages and problems with these perspectives are discussed in the light of stories about physical exercise told by girls with immigrant parents. Even though they provide some important insights, the two perspectives are criticized for lacking a grip of the non-reflexive parts of identities. The article concludes by suggesting that practice perspectives could contribute to a more complete understanding of the lives and identities of young minority girls.
Exclusion in the Liberal State
Authors: Joppke Christian
Published: December 2004

Recent literature on the ‘exclusions’ of the modern nation-state has missed a major transformation in the legitimate mode of excluding, from group to individual-based. This transformation is explored in a discussion of universalistic trends in contemporary Western states’ immigration and citizenship policies. Conflicting with the notion of a ‘nation-state’ owned by a particular ethnic group or nation, these trends are better captured in terms of a ‘liberal state’ that has self-limited its sovereign prerogatives by constitutional principles of equality and individual rights.
Satellite Cell‐Derived Exosomes: A Novel Approach to Alleviate Skeletal Muscle Atrophy and Fibrosis
Authors: Liu Hongwen , Yuan Shiguo , Liu Gaofeng , Li Junhua , Zheng Kai , Zhang Zhiwei , Zheng Sheng , Yin Li , Li Yikai
Published: February 2024

Skeletal muscle atrophy coincides with extensive fibrous tissue hyperplasia in muscle‐atrophied patients, and fibrous tissue plays a vital role in skeletal muscle function and hinders muscle fiber regeneration. However, effective drugs to manage skeletal muscle atrophy and fibrosis remain elusive. This study isolated and characterized exosomes derived from skeletal muscle satellite cells (MuSC‐Exo). The study investigated their effects on denervated skeletal muscle atrophy and fibrosis in Sprague Dawley (SD) rats via intramuscular injection. MuSC‐Exo demonstrated the potential to alleviate skeletal muscle atrophy and fibrosis. The underlying mechanism using single‐cell RNA sequencing data and functional analysis are analyzed. Mechanistic studies reveal close associations between fibroblasts and myoblasts, with the transforming growth factor β1 (TGF‐β1)‐Smad3‐Pax7 axis governing fibroblast activation in atrophic skeletal muscle. MuSC‐Exo intervention inhibited the TGF‐β1/Smad3 pathway and improved muscle atrophy and fibrosis. In conclusion, MuSC‐Exo‐based therapy may represent a novel strategy to alleviate skeletal muscle atrophy and reduce excessive fibrotic tissue by targeting Pax7 through the TGF‐β1/Smad3 pathway.
Wide‐Bandgap Polymers with a C(sp3)─F Polyfluoride Backbone Enable High‐Efficient Ternary Organic Solar Cells
Authors: He Zhilong , Zhang Yi , Lin Yi , Li Siyuan , Zhang Shimin , Xue Zhongyuan , Hao Zhe , Tang Zheng , Zhong Hongliang
Published: February 2024

Fluorination strategy is demonstrated to be a successful approach for optimizing the electron distribution and morphology of organic photovoltaic materials. The previous works focus on introducing only a few C(sp2)─F bonds into conjugated backbone or C(sp3)─F bonds into sidechains. Herein, a new strategy by introducing C(sp3)─F polyfluoride unit into the backbone is proposed, wherein the fluorine atoms are not involved into the conjugation but can promote the intermolecular interaction between backbones. Two wide‐bandgap fluoropolymers are prepared and employed as the third component for ternary organic solar cells. As expected, even if there are six fluorine atoms in a single repeat unit, the relevant fluoropolymers possess complementary absorption and aligned energy levels. More importantly, the polyfluoride backbone affords adequate non‐covalent interactions, consequently enhancing the polymer aggregation and packing order, which is verified by a fibril‐like morphology in the blend film with the host polymer PM6 and only 10 wt.% fluoropolymer. In addition, the decreased surface energy caused by polyfluoride unit is beneficial for the improvement of domain purity and the formation of nanoscale phase separation between donor and acceptor materials. As a result, the fluoropolymer‐assisted ternary device displays a higher efficiency of 18.74% compared with the binary device (17.39%).
Optimizing Color Saturation in Colloidal Photonic Crystals by Control of Absorber Amount and Distribution
Authors: Bittner Carina , Bleyer Gudrun , Nees Nico , Carneiro Miguel , Pflug Lukas , Stingl Michael , Vogel Nicolas
Published: February 2024

Nanostructured materials that mimic structural coloration in nature can be synthetically created by colloidal self‐assembly. To maximize optical effects, the natural world integrates melanin as a broadband absorber to remove incoherently scattered light. Polydopamine (PDA) is used as a synthetic analog of natural melanin to systematically investigate the influence of absorber quantity and distribution on color saturation in colloidal photonic crystals. The absorbing PDA is integrated into two distinct ways: homogenous colloidal crystals are produced from core–shell particles with incrementally increasing polydopamine shells, and heterogeneous colloidal crystals are formed by co‐assembly of varying ratios of polystyrene (PS) and absorbing PS@PDA particles. The chromaticity is quantified by converting the measured spectra to reconstructed colors in the L*a*b* color sphere to identify structures with optimal color saturation. Simulations based on the discrete dipole approximation (DDA) indicate that a homogeneous absorber distribution is most efficient in creating saturated structural coloration. Experiments, however, demonstrate that the heterogeneous absorber incorporation outperforms the homogeneous strategies, as it allows for a more precise adjustment of the absorber content in the required concentration range. These results underline the importance of incorporating absorbers and indicate efficient ways in which colloidal photonic crystals with saturated structural colors can be prepared.
An Intelligent Driving Monitoring System Utilizing Pedal Motion Sensor Integrated with Triboelectric‐Electromagnetic Hybrid Generator and Machine Learning
Authors: Lu Xiaohui , Leng Baichuan , Li Hengyu , Lv Xinzhan , Zhang Xiaosong , Qu Ting , Li Shaosong , Wang Yingting , Wen Jianming , Zhang Bangcheng , Cheng Tinghai
Published: February 2024

Driver's driving behavior and driving style have a crucial impact on traffic safety, capacity, and efficiency, so it is of great significance to monitor the driver's driving behavior and recognize their driving style. In this work, an intelligent driving monitoring system based on a triboelectric nanogenerator and electromagnetic generator is designed. The system consists of a self‐powered pedal motion sensor (SPMS) and an intelligent data processing unit (IDPU), which can monitor driving behavior and recognize driving style. SPMS is used for driving behavior monitoring, which mainly consists of a six‐phase triboelectric nanogenerator (S‐TENG) and a free‐rotating disk electromagnetic generator (FD‐EMG). S‐TENG can recognize information such as pedal movement direction, movement amplitude, and movement speed, and FD‐EMG can realize the function of a self‐powered driver's driving behavior warning. The IDPU includes a numerical calculation system for driving style characteristic variables and a driving style classifier. It can recognize the driving style based on the driving data collected by SPMS. The driving style classifier design is based on a combination of simulated driving experiments and machine learning techniques, and its accuracy is verified through experiments. This work has important potential applications in the field of traffic safety and intelligent driving.