bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Comparative Genome Analysis Identifies Distinct Sorting Pathways in Gram-Positive Bacteria
Authors: Comfort David , Clubb Robert T. 
Published: April 2004

ABSTRACT

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

ABSTRACTTo 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

ABSTRACTComplement-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

ABSTRACTElevations 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

ABSTRACTPseudomonas 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

ABSTRACT

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

ABSTRACTAlternate 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

ABSTRACT

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.
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

Abstract
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.
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.
Italian Psychiatry in an International Context: Ugo Cerletti and the Case of Electroshock
Authors: Passione Roberta 
Published: April 2004

Taking as its starting point the Italian psychiatric context between the end of the nineteenth century and the first years of the twentieth century, this essay analyses Italian psychiatry’s steps towards a new theoretical and therapeutical framework. Focusing on Ugo Cerletti’s work on the electric shock, this paper shows how this Italian psychiatric renewal occurred at the same time as a process of internationalization of psychiatric knowledge, practice and problems. Moving from Europe to America, the author describes Cerletti’s position towards the wide spread of a merely empirical and technical use of electric shock, and reconstructs an international debate on the divorce of electric shock from research.
Indoor and Outdoor Mycoflora in the Different Districts of the City of Istanbul (Turkey)
Authors: Çolakoğlu Günay 
Published: April 2004

In this study, the mycoflora in indoor and outdoor air in the six different districts of the city of Istanbul were investigated at two monthly intervals from November 15, 2001 to September 15, 2002. The aim of the study was to find out the densities of airborne fungal spores that can cause an allergic response on inhalation and/or asthma. A total of 504 samples were observed by using the Petri Plate Gravitational Method; fungi were isolated from these samples and 2198 colonies were counted. Identification of these showed 18 genera, 40 species and 6 colonies of indeterminate spores from the indoor air samples and 19 genera, 32 species and 12 colonies of indeterminate spores from the outdoor air. The identification of the fungi was made according to their microscopic, macromorphological properties and through references. The dominant genera were the same in both indoor and outdoor air. Penicillium was found in greatest abundance followed by Aspergillus, Cladosporium, Alternaria, Rhizopus and Fusarium. There were some differences between the environments as Cladosporiumand Alternaria were found more often in the outdoor air. Overall the results showed that in all districts there was a high density of the fungi Penicillium and Aspergillus in the indoor air while in the outdoor air, Cladosporium and Alternaria densities were high. There were also differences in the distribution of other fungal genera between the indoor and outdoor air samples.
In situ Damage Quantification in Bolts
Authors: Barke D. W. , Chiu W. K. , Fernando S. 
Published: April 2004

Transient stress waves have been used to quantify the extent of damage in cylindrical structures. In the present study, this technique is extended to the in situ quantification of damage in a bolt. Piezoelectric wafers were bonded to either end of two bolts, one of which was loaded in tension in a steel block. Both bolts were incrementally damaged by sawing a cut, to observe the changes in a stress wave which had traversed the bolts in the presence of increasing damage. A clear relationship between the extent of damage in the bolt and the attenuation of the stress wave was observed. Tension in the bolt did not affect this relationship, illustrating the in situ applicability of the technique. In a second set of experiments, bolts were subjected to conditions in which stress corrosion cracking would occur, whilst stress waves were excited in each bolt, to illustrate the ability of the method to detect a naturally occurring form of damage. It was found that the attenuation of a stress wave which had traversed the bolt was proportional to the extent of stress corrosion damage, measured by the residual strength. It is concluded that the technique is capable of detecting in situ damage in structural grades of fasteners.
The Web of Transformative Education
Authors: Markos Laura 
Published: April 2004

A new, occasional feature in the Journal, this article introduces a number of organizations and online resources of potential interest to JTE readers, drawing on scholarly and lay organizations, the various disciplines and communities of practice participating in the transformative education dialogue, individual and institutional membership organizations, and a variety of orientations and geographical bases. Organizations wishing to be considered for feature in future issues of JTE are invited to write to journal@isote.org. Organizations and Web sites included in this issue are: ADEA Working Group on Non-Formal Education (http://www.adeanet.org/wgnfe); ASPBAE Asian South Pacific Bureau of Adult Education (http://www.aspbae.org); The Center for Contemplative Mind in Society (http://www.contemplativemind.org); Instituto Paulo Freire (http://www.paulofreire.org); International Longevity Center (http://www.ilcusa.org); Max Planck Institute for Human Development (http://www.mpibberlin.mpg.deen/sitemap/index.htm); MIDMAC Midlife Research, The John D. and Catherine T. MacArthur Foundation Research Network on Successful Midlife Development (http://midmac.med.harvard.edu./midmac.html); Positive Aging (http://positiveaging.net); and Second Journey (http://www.secondjourney.org).
Genotype/phenotype correlation of the G85E mutation in a large cohort of cystic fibrosis patients
Authors: Decaestecker K. , Decaestecker E. , Castellani C. , Jaspers M. , Cuppens H. , De Boeck K. 
Published: April 2004

In this European study, the phenotype in 68 patients, homozygous or compound heterozygous for the G85E mutation, was investigated.Each index case was compared with two cystic fibrosis (CF) patients from the same clinic, matched for age and sex: one with pancreatic sufficiency (PS) and one with pancreatic insufficiency (PI).When comparing 31 G85E/F508del and F508del/F508del patients, there were no differences in median age at diagnosis, mean sweat chloride value, most recent weight for height, most recent forced expiratory volume in one second % predicted, prevalence of chronicPseudomonas aeruginosacolonisation and typical CF complications. However, PI was less frequent in the G85E/F508del group. Comparison of 55 G85E patients (with second mutation known and not classified as mild) with PS controls (n=44) showed that the G85E patients had a significantly higher sweat chloride, more often failure to thrive at diagnosis, higher prevalence of PI, worse current weight for height, higher prevalence of chronicP. aeruginosacolonisation and liver cirrhosis. Pulse-chase experiments revealed that G85E cystic fibrosis transmembrane conductance regulator failed to mature on a M470 as well as on a V470 background. Therefore, G85E is a class II mutation.Although there is variability in its clinical presentation, G85E mutation results in a severe phenotype.
Impact of sputum bacteria on airway inflammation and health status in clinical stable COPD
Authors: Banerjee D. , Khair O.A. , Honeybourne D. 
Published: April 2004

Chronic obstructive pulmonary disease (COPD) is characterised by sputum production, bacterial colonisation, neutrophilic bronchial airway inflammation and poor health status. The aim of this study was to determine the impact of sputum potentially pathogenic microorganisms (PPMs) on bronchial airway inflammation, health status and plasma fibrinogen levels in subjects with moderate-to-severe COPD during the clinical stable state.Sputum total cell and neutrophil counts, supernatant interleukin‐8, leukotriene B4, tumour necrosis factor‐α and neutrophil elastase levels, neutrophil chemotaxis and plasma fibrinogen levels were estimated. Health status was determined using the St George's Respiratory Questionnaire and the 36‐item Short-Form Health Survey questionnaire.Twenty-seven (40%) subjects had PPMs and 40 (60%) non‐PPMs in their sputum. Both groups were of similar age, body mass index, smoking history and lung function. The PPMs group showed significantly higher levels of interleukin‐8, leukotriene B4, tumour necrosis factor‐α, neutrophil elastase and increased neutrophil chemotaxis. They also exhibited worse health status and raised plasma fibrinogen levels compared to the non‐PPMs group.In conclusion, subjects with clinically stable moderate-to-severe chronic obstructive pulmonary disease who had potentially pathogenic microorganisms in their sputum demonstrated an exaggerated airway inflammatory response, poorer health status and increased plasma fibrinogen levels than those who had nonpotentially pathogenic microorganisms.