bluuebunny/crossref_metadata_2025 huggingface dataset:
Reinfection withChlamydophila abortusby Uterine and Indirect Cohort Routes Reduces Fertility in Cattle Preexposed toChlamydophila
Authors: DeGraves Fred J. , Kim TeaYoun , Jee JunBae , Schlapp Tobias , Hehnen Hans-Robert , Kaltenboeck Bernhard
Published: April 2004

This study investigated the effects of controlled reinfection on fertility of cattle naturally preexposed toChlamydophila abortus. All animals had high prechallenge levels of immunoglobulin M (IgM), IgG, IgG1, and IgG2 serum antibodies against ruminantC. abortusin a chemiluminescent enzyme-linked immunosorbent assay. Twenty virgin heifers were estrus synchronized with prostaglandin F2, artificially inseminated 2 to 3 days later, and challenged immediately by intrauterine administration of 0, 104, 105, 106, or 108inclusion-forming units (IFU) ofC. abortus. Ten heifers were estrus synchronized, inseminated, and uterine challenged 2 weeks later. These animals were also indirectly exposed toC. abortusinfection (cohort challenged) by contact with their previously challenged cohorts. Pregnancy was determined by rectal palpation 42 days after insemination. All anti-C. abortusantibody isotypes increased in heifers following uterine challenge with 108IFU. A total of 11, 83, 50, 66, and 0% of heifers were pregnant after uterine challenge with 0, 104, 105, 106, and 108IFU ofC. abortus, respectively. A total of 50 and 65% of heifers were pregnant with and without cohort challenge, respectively. Uterine inoculum dose and cohort challenge (or, alternatively, a negative pregnancy outcome [infertility]) correlated highly significantly with a rise in postchallenge anti-C. abortusIgM levels over prechallenge levels. Logistic regression modeled fertility, with uterine challenge dose and cohort challenge or prechallenge IgM as predictors (P< 0.05). The models predict that the uterineC. abortusinoculum causing infertility is 8.5-fold higher for heifers without cohort exposure and 17-fold higher for heifers with high IgM levels than for heifers with cohort exposure or with low IgM levels.
Alcohol Exacerbates Murine Pulmonary Tuberculosis
Authors: Mason Carol M. , Dobard Elizabeth , Zhang Ping , Nelson Steve
Published: April 2004

Alcohol consumption has been described as a risk factor for infection withMycobacterium tuberculosis, but its contribution to tuberculosis has been difficult to isolate from other adverse socioeconomic factors. Our objective was to evaluate the impact of alcohol consumption on pulmonary infection withM. tuberculosisin a murine model. BALB/c mice were maintained on the Lieber-DeCarli liquid ethanol diet or a liquid control diet and infected intratracheally with low-doseM. tuberculosisH37Rv. Lung organism burdens, lung and lung-associated lymph node CD4+- and CD8+- lymphocyte numbers and rates of proliferation, and CD4+-lymphocyte cytokine production levels were compared between the groups. The alcohol-consuming mice had significantly higher lung organism burdens than the control mice, and the CD4+- and CD8+-lymphocyte responses to pulmonary infection withM. tuberculosiswere blunted in the alcohol group. Lymphocyte proliferation and production of gamma interferon were decreased in the CD4+lymphocytes from the alcohol-consuming mice. Additionally, lung granulomas were significantly smaller in the alcohol-consuming mice. In conclusion, murine alcohol consumption is associated with decreased control of pulmonary infection withM. tuberculosis, which is accompanied by alterations in the region-specific CD4+- and CD8+-lymphocyte responses and defective lung granuloma formation.
Complement Protein C3 Binding toMycobacterium tuberculosisIs Initiated by the Classical Pathway in Human Bronchoalveolar Lavage Fluid
Authors: Ferguson J. Scott , Weis Jeremy J. , Martin Jennifer L. , Schlesinger Larry S.
Published: April 2004

In high concentrations of fresh nonimmune human serum,Mycobacterium tuberculosisactivates the alternative pathway of complement and binds C3 protein, resulting in enhanced phagocytosis by complement receptors on human alveolar macrophages. Yet in the lung, the alternative pathway of complement is relatively inactive compared to the classical pathway. To begin to determine whether C3 opsonophagocytosis ofM. tuberculosisby alveolar macrophages can occur in the lung of the immunologically naive host, we characterized the binding of C3 toM. tuberculosisin different concentrations of fresh nonimmune human serum and concentrated human bronchoalveolar lavage fluid. Here we show that in human serum, C3 binding toM. tuberculosisis rapid, initiated by either the alternative pathway or the classical pathway, depending on the concentration of serum, and occurs by covalent linkages between the bacterial surface and the C3 cleavage products, C3b or C3bi. Human bronchoalveolar lavage fluid contains C3 protein and functional classical pathway activity that mediates the binding of C3 to the surface ofM. tuberculosis. These studies provide evidence that whenM. tuberculosisis first inhaled into the lungs of the human host, the bacterium is opsonized by C3 cleavage via classical pathway activation within the alveolus, providing a C3-dependent entry pathway into resident alveolar macrophages.
Cross-Reactivity ofSchistosoma mansoniCytosolic Superoxide Dismutase, a Protective Vaccine Candidate, with Host Superoxide Dismutase and Identification of Parasite-Specific B Epitopes
Authors: Carvalho-Queiroz Claudia , Cook Rosemary , Wang Ching C. , Correa-Oliveira Rodrigo , Bailey Nicola A. , Egilmez Nejat K. , Mathiowitz Edith , LoVerde Philip T.
Published: April 2004

Schistosoma mansoni, an intravascular parasite, has evolved a number of immune evasion mechanisms to establish itself in the host, such as antioxidant enzymes. Our laboratory has demonstrated that the highest levels of certain antioxidant enzymes are found in adult worms, which are the least susceptible to immune killing. Vaccination of mice with naked DNA constructs containing the gene encoding Cu/Zn cytosolic superoxide dismutase (SmCT-SOD) showed significant levels of protection compared to a control group, and our data demonstrate that the adult worms are a target of the immune response that confers resistance in SmCT-SOD DNA-vaccinated mice. Because SmCT-SOD shows significant identity with the human homologue, we evaluated the reactivity of anti-SmCT-SOD antibodies derived from SmCT-SOD-immunized mice and rabbits and fromS. mansoni-infected individuals to human superoxide dismutase (hSOD) and SmCT-SOD parasite-specific peptides to assess the potential for autoimmune responses from immunization with the recombinant molecule. In addition, we evaluated the ability of various SmCT-SOD adjuvant-delivered immunizations to induce cross-reactive antibodies. Both mouse and rabbit antibodies generated against SmCT-SOD recognized the denatured form of hSOD. The same antibodies did not recognize nondenatured hSOD. Sera from infected individuals with different clinical forms of schistosomiasis recognized SmCT-SOD but not hSOD. Antibodies from mice immunized with different SmCT-SOD-containing formulations of both DNA and protein were able to recognize SmCT-SOD-derived peptides but not soluble hSOD. All together, these findings serve as a basis for developing a subunit vaccine against schistosomiasis.
Essential Role for the
gtfA
Gene Encoding a Putative Glycosyltransferase in the Adherence of
Porphyromonas gingivalis
Authors: Narimatsu Masahiro , Noiri Yuichiro , Itoh Shousaku , Noguchi Nobuo , Kawahara Takashi , Ebisu Shigeyuki
Published: April 2004

Porphyromonas gingivalis
, an oral bacterium, might play a role in the pathogenesis or progression of adult periodontitis. In this study, we isolated from
P. gingivalis
a putative glycosyltransferase gene, designated
gtfA
, which had a consensus domain for glycosyltransferase in its N terminus. GtfA consisted of 248 amino acids and its predicted molecular mass was 28 kDa; however, as the molecular mass of endogenous GtfA protein was around 40 kDa, this suggested that GtfA had undergone some posttranslational modifications. To reveal the role of the
gtfA
gene in
P. gingivalis
, we established
gtfA
-deficient strains by allelic replacement. Morphologically,
gtfA
-deficient
P. gingivalis
lacked mature fimbriae.
gtfA
-deficient
P. gingivalis
also showed a very low ability for autoaggregation, and its ability to attach to epithelial cells was severely impaired. Thus, the results indicate that the
gtfA
gene is required for
P. gingivalis
autoaggregation as well as attachment to epithelial cells. These results suggest that GtfA might have an important role in the pathogenicity of
P. gingivalis
by regulating adhesion.
A Comparative Genome Analysis Identifies Distinct Sorting Pathways in Gram-Positive Bacteria
Authors: Comfort David , Clubb Robert T.
Published: April 2004

Surface proteins in gram-positive bacteria are frequently required for virulence, and many are attached to the cell wall by sortase enzymes. Bacteria frequently encode more than one sortase enzyme and an even larger number of potential sortase substrates that possess an LPXTG-type cell wall sorting signal. In order to elucidate the sorting pathways present in gram-positive bacteria, we performed a comparative analysis of 72 sequenced microbial genomes. We show that sortase enzymes can be partitioned into five distinct subfamilies based upon their primary sequences and that most of their substrates can be predicted by making a few conservative assumptions. Most bacteria encode sortases from two or more subfamilies, which are predicted to function nonredundantly in sorting proteins to the cell surface. Only ∼20% of sortase-related proteins are most closely related to the well-characterized
Staphylococcus aureus
SrtA protein, but nonetheless, these proteins are responsible for anchoring the majority of surface proteins in gram-positive bacteria. In contrast, most sortase-like proteins are predicted to play a more specialized role, with each anchoring far fewer proteins that contain unusual sequence motifs. The functional sortase-substrate linkage predictions are available online (
http://www.doe-mbi.ucla.edu/Services/Sortase/
) in a searchable database.
Comparative Study of Brain CD8+T Cells Induced by Sporozoites and Those Induced by Blood-StagePlasmodium bergheiANKA Involved in the Development of Cerebral Malaria
Authors: Bagot Sébastien , Nogueira Fatima , Collette Alexis , do Rosario Virgilio , Lemonier François , Cazenave Pierre-André , Pied Sylviane
Published: April 2004

To obtain insight into the mechanisms that contribute to the pathogenesis ofPlasmodiuminfections, we developed an improved rodent model that mimics human malaria closely by inducing cerebral malaria (CM) through sporozoite infection. We used this model to carry out a detailed study on isolated T cells recruited from the brains of mice during the development of CM. We compared several aspects of the immune response related to the experimental model ofPlasmodium bergheiANKA infection induced by sporozoites in C57BL/6 mice and those related to a blood-stage infection. Our data show that in both models, oligoclonal TCRVβ4+, TCRVβ6+, TCRVβ8.1+, and TCRVβ11+major histocompatibility complex class I-restricted CD8 T cells were present in the brains of CM+mice. These CD8+T cells display an activated phenotype, do not undergo apoptosis, secrete gamma interferon or tumor necrosis factor alpha, and are associated with the development of the neurological syndrome.
Cleavage of Complement C3b to iC3b on the Surface ofStaphylococcus aureusIs Mediated by Serum Complement Factor I
Authors: Cunnion K. M. , Hair P. S. , Buescher E. S.
Published: April 2004

Complement-mediated opsonization ofStaphylococcus aureusbearing the dominant capsule serotypes, serotypes 5 and 8, remains incompletely understood. We have previously shown that complement plays a vital role in the efficient phagocytosis of a serotype 5S. aureusstrain and that the opsonic fragments of the central complement protein C3, C3b and iC3b, were present on the bacterial surface after incubation in human serum. In the present studies, C3b and iC3b were found on several serotype 5 and 8S. aureusstrains after incubation in human serum. Using purified classical activation pathway complement proteins and the Western blot assay, we showed that when C3b was generated on theS. aureussurface no iC3b fragments were found, suggesting that other serum proteins may be required for cleaving C3b to iC3b. When C3b-coatedS. aureuswas incubated with serum factor I, a complement regulatory protein, iC3b was generated. Purified factor H, a serum protein cofactor for factor I, did not enhance factor I-mediated cleavage of C3b. These findings suggest that C3b cleavage to iC3b onS. aureusis mediated by serum factor I and does not require factor H.
Borrelia burgdorferi-Induced Expression of Matrix Metalloproteinases from Human Chondrocytes Requires Mitogen-Activated Protein Kinase and Janus Kinase/Signal Transducer and Activator of Transcription Signaling Pathways
Authors: Behera Aruna K. , Thorpe Cheleste M. , Kidder J. Michael , Smith Wendy , Hildebrand Ethan , Hu Linden T.
Published: April 2004

Elevations in matrix metalloproteinase 1 (MMP-1) and MMP-3 have been found in patients with Lyme arthritis and in in vitro models of Lyme arthritis using cartilage explants and chondrocytes. The pathways by whichB. burgdorferi, the causative agent of Lyme disease, induces the production of MMP-1 and MMP-3 have not been elucidated. We examined the role of the extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK) and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways in MMP induction byB. burgdorferi. Infection withB. burgdorferiresults in rapid phosphorylation of p38 and JNK within 15 to 30 min. Inhibition of JNK and p38 MAPK significantly reducedB. burgdorferi-induced MMP-1 and MMP-3 expression. Inhibition of ERK1/2 completely inhibited the expression of MMP-3 in human chondrocytes followingB. burgdorferiinfection but had little effect on the expression of MMP-1.B. burgdorferiinfection also induced phosphorylation and nuclear translocation of STAT-3 and STAT-6 in primary human chondrocytes. Expression of MMP-1 and MMP-3 was significantly inhibited by inhibition of JAK3 activity. Induction of MMP-1 and -3 following MAPK and JAK/STAT activation was cycloheximide sensitive, suggesting synthesis of intermediary proteins is required. Inhibition of tumor necrosis factor alpha (TNF-α) significantly reduced MMP-1 but not MMP-3 expression fromB. burgdorferi-infected cells; inhibition of interleukin-1β (IL-1β) had no effect. Treatment ofB. burgdorferi-infected cells with JAK and MAPK inhibitors significantly inhibited TNF-α induction, consistent with at least a partial role for TNF-α inB. burgdorferi-induced MMP-1 expression in chondrocytes.
The Alternative Activation Pathway and Complement Component C3 Are Critical for a Protective Immune Response againstPseudomonas aeruginosain a Murine Model of Pneumonia
Authors: Mueller-Ortiz Stacey L. , Drouin Scott M. , Wetsel Rick A.
Published: April 2004

Pseudomonas aeruginosais a leading cause of hospital-acquired pneumonia, and approximately 80% of patients with cystic fibrosis are infected with this bacterium. To investigate the overall role of complement and the complement activation pathways in the host defense againstP. aeruginosapulmonary infection, we challenged C3-, C4-, and factor B-deficient mice withP. aeruginosavia intranasal inoculation. In these studies, C3−/−mice had a higher mortality rate than C3+/+mice. Factor B−/−mice, but not C4−/−mice, infected withP. aeruginosahad a mortality rate similar to that of C3−/−mice, indicating that in this model the alternative pathway of complement activation is required for the host defense againstPseudomonasinfection. C3−/−mice had 6- to 7-fold more bacteria in the lungs and 48-fold more bacteria in the blood than did C3+/+mice at 24 h postinfection. In vitro, phagocytic cells from C3+/+or C3−/−mice exhibited a decreased ability to bind and/or ingestP. aeruginosain the presence of C3-deficient serum compared to phagocytic cells in the presence of serum with sufficient C3. C3−/−mice displayed a significant increase in neutrophils in the lungs and had higher levels of interleukin-1β (IL-1β), IL-6, IL-10, KC, and MIP-2 in the lungs at 24 h postinfection than did C3+/+mice. Collectively, these results indicate that complement activation by the alternative pathway is critical for the survival of mice infected withP. aeruginosaand that the protection provided by complement is at least in part due to C3-mediated opsonization and phagocytosis ofP. aeruginosa.
An Intravaginal Live
Candida
Challenge in Humans Leads to New Hypotheses for the Immunopathogenesis of Vulvovaginal Candidiasis
Authors: Fidel Paul L. , Barousse Melissa , Espinosa Terri , Ficarra Mercedes , Sturtevant Joy , Martin David H. , Quayle Alison J. , Dunlap Kathleen
Published: April 2004

Acute and recurrent vulvovaginal candidiasis (VVC) remains a significant problem in women of childbearing age. While clinical studies of women with recurrent VVC (RVVC) and animal models have provided important data about a limited protective role of adaptive immunity, there remains a paucity of information on the protective mechanisms or factors associated with susceptibility to infection. In the present study, an intravaginal live
Candida
challenge in healthy adult women showed a differential susceptibility to symptomatic VVC, where 3 (15%) of 19 women with no history of VVC acquired a symptomatic infection compared to 6 (55%) of 11 women with an infrequent history of VVC. Furthermore, these studies revealed that protection against infection is noninflammatory while symptomatic infection correlates with a vaginal infiltration of polymorphonuclear neutrophils (PMNs) and a high vaginal fungal burden. Thus, the presence of symptomatic infection appears more dependent on host factors than on properties of the organism. Finally, vaginal lavage fluid from women with a symptomatic infection, but not those asymptomatically colonized, promoted the chemotaxis of PMNs. These results suggest that rather than RVVC/VVC being caused by an aberrant adaptive immune response, symptoms that define infection appear to be due to an aggressive innate response by PMNs.
Interleukin-12 Therapy Reduces the Number of Immune Cells and Pathology in Lungs of Mice Infected withMycobacterium tuberculosis
Authors: Nolt Dawn , Flynn JoAnne L.
Published: April 2004

Alternate modalities for the treatment ofMycobacterium tuberculosisare needed due to the rise in numbers of immunosuppressed individuals at risk for serious disease and the increasing prevalence of multidrug-resistant isolates. Interleukin-12 (IL-12) has been shown to improve immune responses againstM. tuberculosisinfection in both humans and mice. Previous studies using high-dose IL-12 in various disease models reported a paradoxical immunosuppression. We demonstrate here that exogenous administration of IL-12 for 8 weeks after an aerosolized low dose ofM. tuberculosisresults in increased survival and decreased pulmonary bacterial loads for CD4-T-cell-deficient mice, most likely due to an early increase in gamma interferon. IL-12 treatment did not impair or enhance the ability of the wild-type mice to control infection, as measured by bacterial numbers. Two novel findings are reported here regarding exogenous IL-12 therapy forM. tuberculosisinfections: (i) IL-12 treatment resulted in decreased numbers of immune cells and reduced frequencies of lymphocytes (CD8+, CD4+, and NK cells) in the lungs of infected mice and (ii) IL-12 therapy reduced the pathology ofM. tuberculosis-infected lungs, as granulomas were smaller and less numerous. These studies support an immunoregulatory role for IL-12 in tuberculosis.
Cerebral Edema and Cerebral Hemorrhages in Interleukin-10-Deficient Mice Infected with
Plasmodium chabaudi
Authors: Sanni Latifu A. , Jarra William , Li Ching , Langhorne Jean
Published: April 2004

During a
Plasmodium chabaudi
infection in interleukin-10 (IL-10) knockout mice, there is greater parasite sequestration, more severe cerebral edema, and a high frequency of cerebral hemorrhage compared with infection of C57BL/6 mice. Anti-tumor necrosis factor alpha treatment ameliorated both cerebral edema and hemorrhages, suggesting that proinflammatory responses contributed to cerebral complications in infected IL-10
−/−
mice.
RECENT DEVELOPMENTS IN THE STUDY OF OCEAN TURBULENCE
Authors: Thorpe S.A.
Published: April 2004

▪ Abstract  This review describes the changes in the understanding of turbulence and mixing in the upper layers of the ocean, the abyssal ocean, and in continental shelf seas that have come in the past 25 years, largely through advances in instruments and methodology.
GLOBAL GLACIAL ISOSTASY AND THE SURFACE OF THE ICE-AGE EARTH: The ICE-5G (VM2) Model and GRACE
Authors: Peltier W.R.
Published: April 2004

▪ Abstract  The 100 kyr quasiperiodic variation of continental ice cover, which has been a persistent feature of climate system evolution throughout the most recent 900 kyr of Earth history, has occurred as a consequence of changes in the seasonal insolation regime forced by the influence of gravitational n-body effects in the Solar System on the geometry of Earth's orbit around the Sun. The impacts of the changing surface ice load upon both Earth's shape and gravitational field, as well as upon sea-level history, have come to be measurable using a variety of geological and geophysical techniques. These observations are invertible to obtain useful information on both the internal viscoelastic structure of the solid Earth and on the detailed spatiotemporal characteristics of glaciation history. This review focuses upon the most recent advances that have been achieved in each of these areas, advances that have proven to be central to the construction of the refined model of the global process of glacial isostatic adjustment, denoted ICE-5G (VM2). A significant test of this new global model will be provided by the global measurement of the time dependence of the gravity field of the planet that will be delivered by the GRACE satellite system that is now in space.
BIOGENIC MANGANESE OXIDES: Properties and Mechanisms of Formation
Authors: Tebo Bradley M. , Bargar John R. , Clement Brian G. , Dick Gregory J. , Murray Karen J. , Parker Dorothy , Verity Rebecca , Webb Samuel M.
Published: April 2004

▪ Abstract  Manganese(IV) oxides produced through microbial activity, i.e., biogenic Mn oxides or Mn biooxides, are believed to be the most abundant and highly reactive Mn oxide phases in the environment. They mediate redox reactions with organic and inorganic compounds and sequester a variety of metals. The major pathway for bacterial Mn(II) oxidation is enzymatic, and although bacteria that oxidize Mn(II) are phylogenetically diverse, they require a multicopper oxidase-like enzyme to oxidize Mn(II). The oxidation of Mn(II) to Mn(IV) occurs via a soluble or enzyme-complexed Mn(III) intermediate. The primary Mn(IV) biooxide formed is a phyllomanganate most similar to δ-MnO2or acid birnessite. Metal sequestration by the Mn biooxides occurs predominantly at vacant layer octahedral sites.
Rapid downregulation of adipose tissue lipoprotein lipase activity on food deprivation: evidence that TNF-α is involved
Authors: Wu Gengshu , Brouckaert Peter , Olivecrona Thomas
Published: April 2004

When food was removed from young rats in the early morning, adipose tissue tumor necrosis factor (TNF)-α activity increased 50% and lipoprotein lipase (LPL) activity decreased 70% in 6 h. There was a strong negative correlation between the TNF-α and LPL activities. Exogenous TNF-α further decreased LPL activity. Pentoxifylline, known to decrease production of TNF-α, had no effect on LPL activity in fed rats but almost abolished the rise of TNF-α and the decrease of LPL activity in rats deprived of food. The specific activity of LPL decreased from 0.92 mU/ng in fed rats to 0.35 and 0.24 mU/ng in rats deprived of food given saline or TNF-α, indicating a shift in the LPL molecules toward an inactive state. Lipopolysaccharide increased adipose tissue TNF-α and decreased LPL activity. Both of these effects were strongly impeded by pretreatment of the rats with pentoxifylline, or dexamethasone. Pretreatment of the rats with actinomycin D virtually abolished the response of LPL activity to food deprivation or exogenous TNF-α. We conclude that food deprivation, like lipopolysaccharide, signals via TNF-α to a gene whose product causes a rapid shift of newly synthesized LPL molecules toward an inactive form and thereby shuts down extraction of lipoprotein triglycerides by the adipose tissue.
Effects of short- and medium-term calorie restriction on muscle mitochondrial proton leak and reactive oxygen species production
Authors: Bevilacqua Lisa , Ramsey Jon J. , Hagopian Kevork , Weindruch Richard , Harper Mary-Ellen
Published: April 2004

Reductions in cellular oxygen consumption (V̇o2) and reactive oxygen species (ROS) production have been proposed as mechanisms underlying the anti-aging effects of calorie restriction (CR). Mitochondria are a cell's greatest “sink” for oxygen and also its primary source of ROS. The mitochondrial proton leak pathway is responsible for 20–30% of V̇o2 in resting cells. We hypothesized that CR leads to decreased proton leak with consequential decreases in V̇o2, ROS production, and cellular damage. Here, we report the effects of short-term (2-wk, 2-mo) and medium-term (6-mo) CR (40%) on rat muscle mitochondrial proton leak, ROS production, and whole animal V̇o2. Whole body V̇o2 decreased with CR at all time points, whereas mass-adjusted V̇o2 was normal until the 6-mo time point, when it was 40% lower in CR compared with control rats. At all time points, maximal leak-dependent V̇o2 was lower in CR rats compared with controls. Proton leak kinetics indicated that mechanisms of adaptation to CR were different between short- and medium-term treatments, with the former leading to decreases in protonmotive force (Δp) and state 4 V̇o2 and the latter to increases in Δp and decreases in state 4 V̇o2. Results from metabolic control analyses of oxidative phosphorylation are consistent with the idea that short- and medium-term responses are distinct. Mitochondrial H2O2 production was lower in all three CR groups compared with controls. Overall, this study details the rapid effects of short- and medium-term CR on proton leak, ROS production, and metabolic control of oxidative phosphorylation. Results indicate that a reduction in mitochondrial V̇o2 and ROS production may be a mechanism for the actions of CR.
Pancreatic β-cells communicate via intermittent release of ATP
Authors: Hellman Bo , Dansk Heléne , Grapengiesser Eva
Published: April 2004

The role of external ATP for intercellular communication was studied in glucose-stimulated pancreatic β-cells isolated from ob/ob mice. Digital image analyses with fura-2 revealed spontaneous transients of cytoplasmic Ca2+appearing in synchrony in the absence of cell contacts. After removal of slow oscillations with methoxyverapamil, addition of ATP (0.1–100 μM) resulted in prompt firing of a transient, followed by suppression of the generation and synchronization of spontaneously occurring transients. It was possible to trigger transients during the suppressive phase by raising the concentration of ATP. The dual action of ATP was mimicked by ADP or 2-methylthio-ATP but not by AMP or UTP. The number of spontaneous transients and their synchronization were reduced in the presence of the dephosphorylating agent apyrase. Additional evidence that intermittent release of ATP participates in the generation of spontaneous Ca2+transients was obtained from the suppression observed from use of antagonists of the purinoceptors [suramin (0.3–30 μM), pyridoxalphosphate-6-azophenyl-2,4-disulfonic acid (PPADS; 10–30 μM) and 2-deoxy- N-methyladenosine (MRS 2179; 0.3–30 μM)] or from counteracting β-cell release of ATP by inhibiting exocytosis with 100 nM epinephrine, 100 nM somatostatin, or lowering the temperature below 30°C. The data indicate that ATP has time-dependent actions (prompt stimulation followed by inhibition) on the generation of Ca2+transients mediated by P2Y receptors. It is proposed that β-cells both receive a neural ATP signal with coordinating effects on their Ca2+oscillations and propagate this message to adjacent cells via intermittent release of ATP combined with gap junction coupling.
Role of acidosis-induced increases in calcium on PTH secretion in acute metabolic and respiratory acidosis in the dog
Authors: López Ignacio , Aguilera-Tejero Escolástico , Estepa José Carlos , Rodríguez Mariano , Felsenfeld Arnold J.
Published: April 2004

Recently, we showed that both acute metabolic acidosis and respiratory acidosis stimulate parathyroid hormone (PTH) secretion in the dog. To evaluate the specific effect of acidosis, ionized calcium (iCa) was clamped at a normal value. Because iCa values normally increase during acute acidosis, we now have studied the PTH response to acute metabolic and respiratory acidosis in dogs in which the iCa concentration was allowed to increase (nonclamped) compared with dogs with a normal iCa concentration (clamped). Five groups of dogs were studied: control, metabolic (clamped and nonclamped), and respiratory (clamped and nonclamped) acidosis. Metabolic (HCl infusion) and respiratory (hypoventilation) acidosis was progressively induced during 60 min. In the two clamped groups, iCa was maintained at a normal value with an EDTA infusion. Both metabolic and respiratory acidosis increased ( P < 0.05) iCa values in nonclamped groups. In metabolic acidosis, the increase in iCa was progressive and greater ( P < 0.05) than in respiratory acidosis, in which iCa increased by 0.04 mM and then remained constant despite further pH reductions. The increase in PTH values was greater ( P < 0.05) in clamped than in nonclamped groups (metabolic and respiratory acidosis). In the nonclamped metabolic acidosis group, PTH values first increased and then decreased from peak values when iCa increased by >0.1 mM. In the nonclamped respiratory acidosis group, PTH values exceeded ( P < 0.05) baseline values only after iCa values stopped increasing at a pH of 7.30. For the same increase in iCa in the nonclamped groups, PTH values increased more in metabolic acidosis. In conclusion, 1) both metabolic acidosis and respiratory acidosis stimulate PTH secretion; 2) the physiological increase in the iCa concentration during the induction of metabolic and respiratory acidosis reduces the magnitude of the PTH increase; 3) in metabolic acidosis, the increase in the iCa concentration can be of sufficient magnitude to reverse the increase in PTH values; and 4) for the same degree of acidosis-induced hypercalcemia, the increase in PTH values is greater in metabolic than in respiratory acidosis.
Metabolomic analysis of adrenal lipids during hypoxia in the neonatal rat: implications in steroidogenesis
Authors: Bruder Eric D. , Lee Ping C. , Raff Hershel
Published: April 2004

The nursing rat pup exposed to hypoxia from birth exhibits ACTH-independent increases in corticosterone and renin/ANG II-independent increases in aldosterone. These increases are accompanied by significant elevation of plasma lipid concentrations in the hypoxic neonates. The purpose of the present study was to compare changes in the concentrations of specific fatty acid metabolites and lipid classes in serum and adrenal tissue from normoxic and hypoxic rat pups. We hypothesized that lipid alterations resulting from hypoxia may partly explain increases in steroidogenesis. Rats were exposed to normoxia or hypoxia from birth, and pooled serum and adrenal tissue from 7-day-old pups were subjected to metabolomic analyses. Hypoxia resulted in specific and significant changes in a number of fatty acid metabolites in both serum and the adrenal. Hypoxia increased the concentrations of oleic (18:1 n-9), eicosapentaenoic (EPA; 20:5 n-3), and arachidonic (20:4 n-6) acids in the triacylglyceride fraction of serum and decreased oleic and EPA concentrations in the cholesterol ester fraction. In the adrenal, hypoxia caused an increase in several n-6 fatty acids in the triacylglyceride fraction, including linoleic (18:2 n-6) and arachidonic acid. There was also an increase in the concentration of α-linolenic acid (18:3 n-3) in the triacylglyceride fraction of the hypoxic adrenal, along with an increase in linoleic acid concentration in the diacylglyceride fraction. We propose that specific changes in lipid metabolism in the adrenal, as a result of hypoxia, may partly explain the increased steroidogenesis previously observed. The mechanism responsible may involve alterations in cellular signaling and/or mitochondrial function. These cellular changes may be a mechanism by which the neonate can increase circulating adrenal steroids necessary for survival, therefore bypassing a relative insensitivity to normal stimuli.
The Role of the Nation State in International Environmental Policy
Authors: Trittin Jürgen
Published: April 2004

In this article, the German Minister for the Environment, Nature Conservation and Nuclear Safety analyzes the role of the nation state in international environmental policy. With reference to the European Union, he argues that independent national environmental policy no longer exists inside the Union. Brussels now has greater influence on environmental legislation than any nation state in Europe—a development that the minister expressly welcomes. He argues that it has proven highly useful for Union members to speak with one voice at global environmental conferences and to present a united front just like one strong nation state. On the other hand, the communitarization within Europe does not prevent members from becoming front-runners in environmental policy. The minister further calls for changes at the global level to ensure that global environmental institutions and environmental law are given much greater weight. The historic task of nation states today is to introduce global environmental legislation that is more powerful than any nation state or any transnational corporation. The German government therefore strongly favors transforming UNEP into a world environment organization that can stand up to the WTO, the FAO and transnational corporations.
Functional significance of variation in trophic morphology within feeding microhabitat-differentiated cichlid species in Lake Malawi
Authors: Kassam Daud , Adams Dean , Yamaoka Kosaku
Published: April 2004

Shape variation in trophic morphology between species in two trophic guilds (zooplankton and epilithic algal feeders) was investigated using landmark-based geometric morphometrics. Three disarticulated bone elements from the head region were examined; the neurocranium, the premaxilla and lower jaw. From separate analyses of each bone element, significant shape variation was identified between species in each trophic guild. The deformation grids generated revealed that, for the zooplankton feeders, Ctenopharynx pictus has a longer neurocranium, a longer and ventrally directed vomer, a larger orbit, a shorter ascending arm, a shorter maxillad spine, and a more compressed articular bone relative to Copadichromis borleyi. In algal feeders, Labeotropheus fuelleborni has a shorter neurocranium, a smaller orbit, a ventrally directed vomer, a longer ascending arm, a shorter dentigerous arm, increased height of the articular process, and a more elongated dentary than Petrotilapia genalutea. Observed anatomical differences are discussed in terms of function, specifically with respect to the feeding microhabitat differentiation between species in each trophic guild. These differences enable us to appreciate the role that trophic morphology plays in enhancing ecological segregation, leading to coexistence of the species.
Socio-Demographic Effects on Cultural Biases
Authors: Grendstad Gunnar , Sundback Susan
Published: April 2004

Grid-group theory claims that patterns of social relations only, and not socio-demographic characteristics, can account for biases, of which the theory prescribes four: hierarchy, egalitarianism, individualism and fatalism. Survey analysts conventionally employ respondents’ socio-demographic correlates when accounting for values. We take the value survey strategy and apply it to grid-group theory’s four biases. Employing a 1999 survey administered in Iceland, Norway, Denmark, Sweden and Finland ( n= 4,832), we combine two goals in this article. We test how sex, age, education and income can account for biases. By extension, we test grid-group theory’s claim of no such effect. The results show that biases are influenced by socio-demographics in ways unaccounted for by the theory. The four correlates explain on average 9 per cent of the variation in the biases. Education is the only correlate that has a negative and significant effect across all biases in all countries. Women adhere to egalitarianism, whereas men adhere to individualism. Age is a consistent positive correlate of hierarchy, whereas income is a consistent negative correlate of fatalism. Grid-group theory will not be impaired if it can be shown how robust socio-demographic correlates interact with patterns of social relations.
Lower Educated Workers and Part-Time Work
Authors: Wielers Rudi , van der Meer Peter
Published: April 2004

The thesis of the article is that strong growth in the number of part-time jobs in The Netherlands between 1973 and 1991 negatively affected the labour market participation of men, especially lower educated men. The thesis consists of a behavioural component, which explains why lower educated men are not attracted and do not gain access to part-time jobs, and an institutional component, which explains why the labour market position of lower educated men in The Netherlands deteriorated relatively rapidly during the period 1973-91. The thesis is underpinned by an empirical analysis of labour market participation of lower educated male workers in part-time and full-time jobs. Competing theses, such as upgrading of the job structure, displacement by better educated workers and sector shift from manufacturing to services, are tested empirically, but prove to be less convincing explanations for the deteriorated labour market position of lower educated men than the explanation of the growth of part-time jobs.
Positive Youth Development in the United States: Research Findings on Evaluations of Positive Youth Development Programs
Authors: Catalano Richard F. , Berglund M. Lisa , Ryan Jean A. M. , Lonczak Heather S. , Hawkins J. David
Published: April 2004

This article summarizes a much lengthier one that appeared in Prevention and Treatment. The earlier article grew out of a project initiated by the Department of Health and Human Services Office of the Assistant Secretary for Planning and Evaluation. The Positive Youth Development Evaluation project described why policy makers, practitioners, and prevention scientists advocated a shift in approach for how youth issues are addressed in this country. The Positive Youth Development Evaluation project sought to define how youth development programs have been defined in the literature and then to locate, through a structured search, strong evaluations of these programs and summarize the outcomes of these evaluations. In the current article, we explain why prevention has shifted from a single problem focus to a focus on factors that affect both positive and problem youth development, describe what is meant by positive youth development, and summarize what we know about the effectiveness of positive youth development programs.
Harnessing Hope through NGO Activism
Authors: Courville Sasha , Piper Nicola
Published: April 2004

This article explores the relationship between hope and agency in the contexts of migrant rights activism and alternative trading relationships created through social and environmental certification systems. Using interviews with key respondents from nongovernmental organizations (NGOs), hope is assigned a positive role in the complex process of social change, providing that common goals can be agreed upon and achieved along the way. Two main layers of analysis emerge in this article. The first explores the relationship between hope and agency, with a particular focus on power, both enabling and coercive. Powerful groups can hijack hope, but also hope can be used to mobilize various marginalized groups to find a collective voice, eventually leading to empowerment. The power relations among groups determine how competing collective hopes play out in action. A second layer to the relationship between hope and action is the way in which hope effects social change. Through conceptualizing hope within the context of the change process, we address the relationship between hope, agency, and time. An important ingredient linking hope, agency, and time in a sustainable manner is the notion of empowerment.
Controlling Street-Level Police Discretion
Authors: Mastrofski Stephen D.
Published: April 2004

The Committee to Review Research on Police Policyand Practices’ Fairness and Effectiveness in Policing:The Evidenceprovides a review of research on thecauses of street-level police behavior, but the reportoffers little insight into how to control that discretioneffectively. This is not due to deficiencies in the reportbut rather to limitations of the available research. Thisarticle discusses four problems with that research:underdeveloped theory, weak research designs,insufficient generalizability of findings, and inattention to thekinds of police discretion that really matter to policymakers, practitioners, and the public. The article givesspecial attention to the last problem and makesrecommendations for improving the quality of research tobetter inform choices about how to control policestreetlevel discretion.
Lawful Policing
Authors: Skogan Wesley G. , Meares Tracey L.
Published: April 2004

Police compliance with the law is one of the most important aspects of a democratic society. Americans expect the police to enforce laws to promote safety and to reduce crime, victimization, and fear, but no one believes that the police should have unlimited power to do so. We expect police to enforce laws fairly according to law and rules that circumscribe their enforcement powers. The existence of these rules justify the claim that police are a rule-bound institution engaged in the pursuit of justice and the protection of individual liberties, as well as the battle against crime. This article reviews research on the extent to which police follow laws and rules, especially constitutional criminal procedure rules, addressing seizures, searches, interrogations, and deadly force. Also reviewed is research pertaining to police adherence to rules governing excessive force, corruption, and racial profiling.
Inception Rates of Deliberate Self-Harm among Adolescents in West London
Authors: Bhugra Dinesh , Thompson Neil , Singh Jayshree , Fellow-Smith Elizabeth
Published: April 2004

Background: Studies have suggested that inception rates of deliberate self-harm among different ethnic group adolescents are broadly similar.

Aims: We set out to study the rates of adolescent self-harm over a calendar year in Ealing - part of West London.

Methods: All cases of deliberate self-harm presenting to the A&E department and paediatrics were identified and socio-cultural factors studied. Ethnicity was obtained using self-ascription.

Results: A total of 76 cases were identified over one year. Using the at risk population as denominator, no differences in inception rates were noted according to ethnicity. Overdoses were the commonest method used for deliberate self-harm.

Conclusions: The similarities between the Asian and white adolescents suggest that some common aetiological factors may be at play. The risk factors may be related to gender rather than ethnicity in this age group.
‘Never to go forth of the limits’ Space and melancholy in Robert Burton’s library project
Authors: Barczyk-Barakonska Liliana
Published: April 2004

This article is a study of early seventeenth-century melancholy in the context of a library project introduced by Robert Burton in his Anatomy of Melancholy (1621). Modelled on the great libraries of the times, Burton’s library is designed to function as the only space free of melancholy and as such is to be structured on the principle of isolation.

Discussing the interrelations between the Burtonian vision of the melancholy reader and his concepts of space, the article explores the terms of isolation Burton establishes in order to construct the library. The article is also an analysis of the problem ofborder transgression, which is constitutive for the notion of melancholy. Finally, the article presents issues involving the moulding of the brand new man Burton envisions: a man free of melancholy and inhabiting the supposedly isolated space of the library.
Is There A Melancholic Gaze? From Visual Distemper to Visionary Fancy
Authors: Crignon-de Oliveira Claire
Published: April 2004

The aim of this paper is to show the ambivalence of the idea of melancholy in seventeenth-century England from the specific perspective of the melancholic gaze. If the perturbation of the senses and of visual perception may be seen by physicians as a pathological condition, this can also lead the melancholic to develop visionary powers, which can be understood as a remedy against melancholic distemper, as Robert Burton shows in his Anatomy of Melancholy.
Cultural Memory on Film Soundtracks
Authors: Hillman Roger
Published: April 2004

This article addresses issues of cultural memory arising from the use of classical music on film soundtracks. The phenomenon is considered in three forms: (1) historical layering, as in Jane Campion’s Portrait of a Lady and Kieslowski’s Three Colours: Blue ; (2) memory and nostalgia, especially in Benigni’s Life is Beautiful , and in the possibilities available to classical music in European compared with US films; (3) musical memory in a given culture, from It Happened Here (Brownlow/ Mollo) through to various directors of the New German Cinema. The reception histories of the ‘Deutschlandlied’ and of Beethoven’s Ninth Symphony are enriched by consideration of their frequent use in West German films of the 1970s, as part of a quest for national identity. Alongside the established critical tool of scopic regimes, the article pleads for attention to acoustic regimes as a neglected aspect of cultural studies.
Contradictions of Democracy in a Workers’ Cooperative
Authors: Varman Rahul , Chakrabarti Manali
Published: April 2004

Organizational democracy has become a key issue in current change-management programmes, such as restructuring, total quality management and Enterprise Resource Planning, and there has been a persistent quest for a post-Fordist model in recent times. The article emphasizes the need to study democratic processes per se, given that democracy faces significant odds vis-a-vis the larger context, even in those organizations that have been expressly initiated for democratic functioning. The contradictions with the context inevitably manifest themselves inside the organization as well. The present study makes a case for understanding organizational democracy as an evolving reality, based on participant observation of democratic functioning within a workers’ cooperative over seven years.