bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of Human Cellular Immune Responses to NovelMycobacterium tuberculosisAntigens Encoded by Genomic Regions Absent inMycobacterium bovisBCG
Authors: Al-Attiyah R. , Mustafa A. S. 
Published: June 2008

ABSTRACTComparative genomics has identified several regions of differences (RDs) between the infectiousMycobacterium tuberculosisand the vaccine strains ofMycobacterium bovisBCG. We aimed to evaluate the cellular immune responses induced by antigens encoded by genes predicted in 11 RDs. Synthetic peptides covering the sequences of RD1, RD4 to RD7, RD9 to RD13, and RD15 were tested for antigen-induced proliferation and secretion of Th1 cytokine, gamma interferon (IFN-γ), by peripheral blood mononuclear cells (PBMC) obtained from culture-proven pulmonary tuberculosis (TB) patients andM. bovisBCG-vaccinated healthy subjects. Among the peptide pools, RD1 induced the best responses in both donor groups and in both assays. In addition, testing of TB patients' PBMC for secretion of proinflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin 6 [IL-6], IL-8, and IL-1β), Th1 cytokines (IFN-γ, IL-2, and TNF-β), and Th2 cytokines (IL-4, IL-5, and IL-10) showed differential effects of RD peptides in the secretion of IFN-γ and IL-10, with high IFN-γ/IL-10 ratios (32 to 5.0) in response to RD1, RD5, RD7, RD9, and RD10 and low IFN-γ/IL-10 ratios (<1.0) in response to RD12, RD13, and RD15. Peptide-mixing experiments with PBMC from healthy subjects showed that secretion of large quantities of IL-10 in response to RD12 and RD13 correlated with inhibition of Th1 responses induced by RD1 peptides. In conclusion, our results suggest thatM. tuberculosisRDs can be divided into two major groups—one group that activates PBMC to preferentially secrete IFN-γ and another group that activates preferential secretion of IL-10—and that these two groups of RDs may have roles in protection against and pathogenesis of TB, respectively.
Global Gene Expression as a Function of the Iron Status of the Bacterial Cell: Influence of Differentially Expressed Genes in the Virulence of the Human Pathogen
Vibrio vulnificus
Authors: Alice Alejandro F. , Naka Hiroaki , Crosa Jorge H. 
Published: June 2008

ABSTRACT

Vibrio vulnificus
multiplies rapidly in host tissues under iron-overloaded conditions. To understand the effects of iron in the physiology of this pathogen, we performed a genome-wide transcriptional analysis of
V. vulnificus
growing at three different iron concentrations, i.e., iron-limiting [Trypticase soy broth with 1.5% NaCl (TSBS) plus ethylenediamine-di-(
o
-hydroxyphenylacetic) acid (EDDA)], low-iron (1 μg Fe/ml; TSBS), and iron-rich (38 μg Fe/ml; TSBS plus ferric ammonium citrate) concentrations. A few genes were upregulated under the last two conditions, while several genes were expressed differentially under only one of them. A gene upregulated under both conditions encodes the outer membrane porin, OmpH, while others are related to the biosynthesis of amino sugars. An
ompH
mutant showed sensitivity to sodium dodecyl sulfate (SDS) and polymyxin B and also had a reduced competitive index compared with the wild type in the iron-overloaded mice. Under iron-limiting conditions, two of the TonB systems involved in vulnibactin transport were induced. These genes were essential for virulence in the iron-overloaded mice inoculated subcutaneously, underscoring the importance of active iron transport in infection, even under the high-iron conditions of this animal model. Furthermore, we demonstrated that a RyhB homologue is also essential for virulence in the iron-overloaded mouse. This novel information on the role of genes induced under iron limitation in the iron-overloaded mouse model and the finding of new genes with putative roles in virulence that are expressed only under iron-rich conditions shed light on the many strategies used by this pathogen to multiply rapidly in the susceptible host.
Comparison of the Susceptibilities of C57BL/6 and A/J Mouse Strains toStreptococcus suisSerotype 2 Infection
Authors: Domínguez-Punaro María de la Cruz , Segura Mariela , Radzioch Danuta , Rivest Serge , Gottschalk Marcelo 
Published: June 2008

ABSTRACTStreptococcus suisis an important swine and human pathogen. Assessment of susceptibility toS. suisusing animal models has been limited to monitoring mortality rates. We recently developed a hematogenous model ofS. suisinfection in adult CD1 outbred mice to study the in vivo development of an early septic shock-like syndrome that leads to death and a late phase that clearly induces central nervous system damage, including meningitis. In the present study, we compared the severities of septic shock-like syndrome caused byS. suisbetween adult C57BL/6J (B6) and A/J inbred mice. Clinical parameters, proinflammatory mediators, and bacterial clearance were measured to dissect potential immune factors associated with genetic susceptibility toS. suisinfection. Results showed that A/J mice were significantly more susceptible than B6 mice toS. suisinfection, especially during the acute septic phase of infection (100% of A/J and 16% of B6 mice died before 24 h postinfection). The greater susceptibility of A/J mice was associated with an exaggerated inflammatory response, as indicated by their higher production of tumor necrosis factor alpha, interleukin-12p40/p70 (IL-12p40/p70), gamma interferon, and IL-1β, but not with different bacterial loads in the blood. In addition, IL-10 was shown to be responsible, at least in part, for the higher survival in B6 mice. Our findings demonstrate that A/J mice are very susceptible toS. suisinfection and provide evidence that the balance between pro- and anti-inflammatory mediators is crucial for host survival during the septic phase.
Essential Role of the Response Regulator Rrp2 in the Infectious Cycle of
Borrelia burgdorferi
Authors: Boardman Bethany K. , He Ming , Ouyang Zhiming , Xu Haijun , Pang Xiujuan , Yang X. Frank 
Published: June 2008

ABSTRACT

Alteration of surface lipoprotein profiles is a key strategy that the Lyme disease pathogen,
Borrelia burgdorferi
, has evolved to be maintained within its enzootic cycle between arthropods and mammals. Accumulated evidence indicates that the central regulatory pathway controlling differential gene expression by
B. burgdorferi
is the RpoN-RpoS pathway (the σ
54
-σ
S
sigma factor cascade). It was previously shown that activation of the RpoN-RpoS pathway is controlled by Rrp2, a two-component response regulator and σ
54
-dependent transcriptional activator. The role of Rrp2 in the infectious cycle of
B. burgdorferi
has not been determined heretofore. In this report, we demonstrate that an
rrp2
mutant defective in activating σ
54
-dependent transcription was unable to establish infection in mice, but the
rrp2
mutant was capable of surviving within ticks during and after tick feeding. Because the
rrp2
mutant was defective in the production of OspC, an outer surface lipoprotein essential for mammalian host infection, we further examined whether the loss of infectivity of the
rrp2
mutant was solely due to the inability to produce OspC. While transformation with a shuttle vector carrying
ospC
under the control of a constitutive
flaB
promoter restored infection to an
ospC
mutant in immunodeficient SCID mice, it could not rescue the avirulent phenotype of the
rrp2
mutant. These data indicate that, in addition to controlling OspC, Rrp2 controls another factor(s) essential for
B. burgdorferi
to establish infection in mammals. Furthermore, microarray analyses revealed that 125 and 19 genes were positively and negatively regulated, respectively, by Rrp2, which provides a foundation for future identification of additional Rrp2-dependent virulence determinants in
B. burgdorferi
.
The Resistance of BALB/cJ Mice toYersinia pestisMaps to the Major Histocompatibility Complex of Chromosome 17
Authors: Turner Joshua K. , McAllister Milton M. , Xu John L. , Tapping Richard I. 
Published: June 2008

ABSTRACTYersinia pestis, the causative agent of plague, has been well studied at the molecular and genetic levels, but little is known about the role that host genes play in combating this highly lethal pathogen. We challenged several inbred strains of mice withY. pestisand found that BALB/cJ mice are highly resistant compared to susceptible strains such as C57BL/6J. This resistance was observed only in BALB/cJ mice and not in other BALB/c substrains. Compared to C57BL/6J mice, the BALB/cJ strain exhibited reduced bacterial burden in the spleen and liver early after infection as well as lower levels of serum interleukin-6. These differences were evident 24 h postinfection and became more pronounced with time. Although a significant influx of neutrophils in the spleen and liver was exhibited in both strains, occlusive fibrinous thrombi resulting in necrosis of the surrounding tissue was observed only in C57BL/6J mice. In an effort to identify the gene(s) responsible for resistance, we measured total splenic bacteria in 95 F2mice 48 h postinfection and performed quantitative trait locus mapping using 58 microsatellite markers spaced throughout the genome. This analysis revealed a single nonrecessive plague resistance locus, designatedprl1(plagueresistancelocus1), which coincides with the major histocompatibility complex of chromosome 17. A second screen of 95 backcrossed mice verified that this locus confers resistance toY. pestisearly in infection. Finally, eighth generation backcrossed mice harboringprl1were found to maintain resistance in the susceptible C57BL/6J background. These results identify a novel genetic locus in BALB/cJ mice that confers resistance toY. pestis.
Diverse Myeloid and Lymphoid Cell Subpopulations Produce Gamma Interferon during Early Innate Immune Responses toFrancisella tularensisLive Vaccine Strain
Authors: De Pascalis Roberto , Taylor Betsy C. , Elkins Karen L. 
Published: June 2008

ABSTRACTFrancisella tularensis, a small gram-negative intracellular bacterium responsible for causing tularemia, is highly pathogenic and classified as a category A agent of bioterrorism. As for other intracellular pathogens, successful protective immune responses toFrancisella tularensisrequire rapid and efficient induction of gamma interferon (IFN-γ) production. Studies using intracellular bacteria such asListeria monocytogenesas well asFrancisellasuggest that natural killer (NK) and T cells are important sources of IFN-γ. However, comprehensive characterization of specific sources of IFN-γ produced duringFrancisellainfection in vivo remains incomplete, and depletion of NK cells before infection of mice with theF. tularensislive vaccine strain (LVS) has little impact on the course or outcome of infection. In this study, we determined the cell subpopulations that respond quickly to intradermalF. tularensisLVS infection of mice by producing IFN-γ within hours to a few days. Splenic and liver lymphocytes were obtained from LVS-infected mice and analyzed for IFN-γ mRNA by reverse transcription-PCR, for intracellular cytokine expression by multiparameter flow cytometry, and for ex vivo production of IFN-γ protein by enzyme-linked immunosorbent assay. Cells producing IFN-γ were readily detectable by day 3 after infection, and numbers progressively increased through days 5 to 7. Importantly, the cell types responsible for IFN-γ production were much more varied than expected: these included not only NK cells and T cells, which might be predicted, but also other cells, including dendritic cells (DCs), “NK DCs,” NK T cells, and neutrophils. Most importantly, since RAG-1 knockout mice appeared to exhibit a frequency of IFN-γ-producing cells comparable to that of intact wild-type mice, early IFN-γ production by innate immune cells does not depend on the presence of T or B cells.
Tick-Borne Transmission of Two Genetically DistinctAnaplasma marginaleStrains following Superinfection of the Mammalian Reservoir Host
Authors: Leverich Christina K. , Palmer Guy H. , Knowles Donald P. , Brayton Kelly A. 
Published: June 2008

ABSTRACTStrain superinfection affects the dynamics of epidemiological spread of pathogens through a host population. Superinfection has recently been shown to occur for two genetically distinct strains of the tick-borne pathogenAnaplasma marginalethat encode distinctly different surface protein variants. Superinfected animals could serve as a reservoir for onward transmission of both strains if the tick vector is capable of acquiring and transmitting both strains. Whether competition among strains during development within the tick vector, which requires sequential invasion and replication events, limits colonization and subsequent transmission to a single strain is unknown. We tested this possibility by acquisition feedingDermacentor andersoniticks on a reservoir host superinfected with the genetically distinct St. Maries and EMΦ strains. Although the St. Maries strain consistently maintained higher bacteremia levels in the mammalian host and the EMΦ strain had an early advantage in colonization of the tick salivary glands, individual ticks were coinfected, and there was successful transmission of both strains. These results indicate that a genetically distinctA. marginalestrain capable of superinfecting the mammalian host can subsequently be cotransmitted and become established within the host population despite the presence of an existing established strain.
THE INTELLECTUAL CAPITAL DIMENSIONS OF DUCATI'S TURNAROUND: EXPLORING KNOWLEDGE ASSETS GROUNDING A CHANGE MANAGEMENT PROGRAM
Authors: SCHIUMA GIOVANNI , LERRO ANTONIO , SANITATE DAMIANO 
Published: June 2008

Despite the growing awareness of the importance of researching core strategic resources and capabilities for supporting organisational change, the work that has been done to the date has rarely examined and taken into account the relevance of Intellectual Capital (IC) for the success of a company's strategic turnaround program. Moreover, little attention has been given on what encompasses IC and how it can be conceptualised and interpreted in a change management perspective.Through an extensive review of the literature on IC and along with a case study of the Ducati Motor Holding — one of the leading world brands in the sportive motorcycles manufacturing — this paper aims to bridge this gap first of all by identifying which are the key-knowledge assets involved in a turnaround program, and then focusing on the impact IC has on turnaround actions.Findings highlight important implications both for theory and practice, and reveal interesting relationships that suggest further effort should be placed on the development of a knowledge base-view of company's turnaround and on the analysis of the dynamics that links knowledge assets and successful change management programs.
Anton, a special-purpose machine for molecular dynamics simulation
Authors: Shaw David E. , Deneroff Martin M. , Dror Ron O. , Kuskin Jeffrey S. , Larson Richard H. , Salmon John K. , Young Cliff , Batson Brannon , Bowers Kevin J. , Chao Jack C. , Eastwood Michael P. , Gagliardo Joseph , Grossman J. P. , Ho C. Richard , Ierardi Douglas J. , Kolossváry István , Klepeis John L. , Layman Timothy , McLeavey Christine , Moraes Mark A. , Mueller Rolf , Priest Edward C. , Shan Yibing , Spengler Jochen , Theobald Michael , Towles Brian , Wang Stanley C. 
Published: June 2008

The ability to perform long, accurate molecular dynamics (MD) simulations involving proteins and other biological macro-molecules could in principle provide answers to some of the most important currently outstanding questions in the fields of biology, chemistry, and medicine. A wide range of biologically interesting phenomena, however, occur over timescales on the order of a millisecond---several orders of magnitude beyond the duration of the longest current MD simulations.
We describe a massively parallel machine called Anton, which should be capable of executing millisecond-scale classical MD simulations of such biomolecular systems. The machine, which is scheduled for completion by the end of 2008, is based on 512 identical MD-specific ASICs that interact in a tightly coupled manner using a specialized highspeed communication network. Anton has been designed to use both novel parallel algorithms and special-purpose logic to dramatically accelerate those calculations that dominate the time required for a typical MD simulation. The remainder of the simulation algorithm is executed by a programmable portion of each chip that achieves a substantial degree of parallelism while preserving the flexibility necessary to accommodate anticipated advances in physical models and simulation methods.
Spectrally Resolved Energy Dissipation Rate and Momentum Flux of Breaking Waves
Authors: Gemmrich Johannes R. , Banner Michael L. , Garrett Chris 
Published: June 2008

Abstract
Video observations of the ocean surface taken from aboard the Research Platform FLIP reveal the distribution of the along-crest length and propagation velocity of breaking wave crests that generate visible whitecaps. The key quantity assessed is Λ(c)dc, the average length of breaking crests per unit area propagating with speeds in the range (c, c + dc). Independent of the wave field development, Λ(c) is found to peak at intermediate wave scales and to drop off sharply at larger and smaller scales. In developing seas breakers occur at a wide range of scales corresponding to phase speeds from about 0.1 cp to cp, where cp is the phase speed of the waves at the spectral peak. However, in developed seas, breaking is hardly observed at scales corresponding to phase speeds greater than 0.5 cp. The phase speed of the most frequent breakers shifts from 0.4 cp to 0.2 cp as the wave field develops. The occurrence of breakers at a particular scale as well as the rate of surface turnover are well correlated with the wave saturation. The fourth and fifth moments of Λ(c) are used to estimate breaking-wave-supported momentum fluxes, energy dissipation rate, and the fraction of momentum flux supported by air-entraining breaking waves. No indication of a Kolmogorov-type wave energy cascade was found; that is, there is no evidence that the wave energy dissipation is dominated by small-scale waves. The proportionality factor b linking breaking crest distributions to the energy dissipation rate is found to be (7 ± 3) × 10−5, much smaller than previous estimates.
A Model for Air–Sea Interaction Bulk Coefficient over a Warm Mature Sea under Strong Wind
Authors: Kihara Naoto , Hirakuchi Hiromaru 
Published: June 2008

Abstract
A boundary layer model for evaluating sensible and latent heat fluxes over a mature sea accounting for sea spray effects at wind speeds of up to 28 m s−1 is presented. Heat exchange across the ocean surface controls the development of tropical cyclones, and Emanuel’s theory suggests that the ratio of the exchange coefficient of total enthalpy to the drag coefficient should be greater than 0.75 to maintain the intensity of tropical cyclones. However, traditional bulk algorithms predict a monotonic decrease in this ratio with increasing wind speed, giving a value of less than 0.5 under tropical cyclone conditions. The present model describes a decrease in the ratio with increasing wind speed under weak to moderate winds (&lt;20 m s−1), and a plateau at approximately 0.7 under strong winds (&gt;20 m s−1).
On the Crucial Role of Basin Geometry in Double-Gyre Models of the Kuroshio Extension
Authors: Pierini Stefano 
Published: June 2008

AbstractThe decadal chaotic relaxation oscillation obtained in a recent double-gyre model study of the Kuroshio Extension intrinsic low-frequency variability was found to compare surprisingly well with the real variability of the jet as revealed by altimeter data, despite the high degree of idealization of the model. In this note it is shown that elements of realism in the basin geometry, present in that study and absent in previous double-gyre models applied to the Kuroshio Extension, play a crucial role in shaping the low-frequency variability of the jet, and can explain the good performance of the model. A series of numerical experiments with different basin geometries of increasing degrees of simplicity are analyzed. If the schematic western boundary representing the coastline south of Japan is removed, the strong decadal variability completely disappears and only a very weak periodic oscillation about an elongated state of the jet is found. If the large zonal width of the basin (representing correctly the extension of the North Pacific Ocean) is reduced by a half, then the total meridional Sverdrup transport is reduced by the same factor, and so is the intensity of the Kuroshio and Oyashio western boundary currents: as a result, the modeled Kuroshio Extension is totally unrealistic in shape and is steady. If both simplifications are introduced the resulting jet is, again, totally unrealistic, yielding a weak periodic bimodal cycle. On the basis of these results, two main conclusions are drawn: (i) the introduction of appropriate geometrical elements of realism in double-gyre model studies of the Kuroshio Extension is essential, and (ii) the Kuroshio Extension intrinsic low-frequency variability would be dramatically different if the southwestern coastline of Japan were more meridionally oriented.
Failure to develop multiple sclerosis in patients with neurologic symptoms without objective evidence
Authors: Boster A , Caon C , Perumal J , Hreha S , Zabad R , Zak I , Tselis A , Lisak R , Khan O 
Published: June 2008

Background Many patients referred to multiple sclerosis (MS) centers with symptoms suggestive of MS are found to have normal neurologic examinations, normal or non-specific brain magnetic resonance imaging (MRI) scan findings, and normal cerebrospinal fluid (CSF). Persistent symptoms often lead to multiple consultations and repeated diagnostic investigations. We performed a study to evaluate the diagnostic utility of repeated evaluations in patients with normal initial assessments and persistent neurologic symptoms. Methods 143 patients were evaluated initially and 109 returned for a second evaluation after a mean interval of 4.4 years. Results All 143 patients had normal initial examinations, brain MRI scans, screening blood tests, and CSF studies. Spinal cord imaging was normal in all patients tested (cervical cord, n = 126; 88.1%; thoracic cord, n = 58; 40.6%). Evoked potential studies were abnormal in a small percentage of patients: visual evoked potentials, VEP (8.1%), somatosensory evoked potentials, SSEP (4.9%), and brainstem auditory evoked potentials, BAEP (2.8%). All follow-up patients ( n = 109) had normal examinations and MRI scans. Repeat CSF studies ( n = 35; 32.1%) and spinal cord imaging (cervical cord n = 57; 52.3%; thoracic cord n = 32; 29.4%) were normal in all follow-up patients tested. No patients at initial presentation or at follow-up fulfilled diagnostic criteria for MS. Conclusions Patients and clinicians may be reassured that persistent neurologic symptoms in the absence of objective clinical evidence do not lead to the development of MS. Costly serial investigations should be carefully considered, particularly in the presence of normal neurologic examination at follow-up.