bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin-7 (IL-7) Treatment Accelerates Neutrophil Recruitment through γδ T-Cell IL-17 Production in a Murine Model of Sepsis
Authors: Kasten Kevin R. , Prakash Priya S. , Unsinger Jacqueline , Goetzman Holly S. , England Lisa G. , Cave Cindy M. , Seitz Aaron P. , Mazuski Cristina N. , Zhou Tony T. , Morre Michel , Hotchkiss Richard S. , Hildeman David A. , Caldwell Charles C. 
Published: September 2010

ABSTRACTThe sepsis syndrome represents an improper immune response to infection and is associated with unacceptably high rates of mortality and morbidity. The interactions between T cells and the innate immune system while combating sepsis are poorly understood. In this report, we observed that treatment with the potent, antiapoptotic cytokine interleukin-7 (IL-7) accelerated neutrophil recruitment and improved bacterial clearance. We first determined that T cells were necessary for the previously observed IL-7-mediated enhanced survival. Next, IL-7 increased Bcl-2 expression in T cells isolated from septic mice as early as 3 h following treatment. This treatment resulted in increased gamma interferon (IFN-γ) and IP-10 production within the septic peritoneum together with local and systemic increases of IL-17 in IL-7-treated mice. We further demonstrate that the increase in IL-17 was largely due to increased recruitment and production by γδ T cells, which express CXCR3. Consistent with increased IL-17 production, IL-7 treatment increased CXCL1/KC production, neutrophil recruitment, and bacterial clearance. Significantly, end-organ tissue injury was not significantly different between vehicle- and IL-7-treated mice. Collectively, these data illustrate that IL-7 can mediate the cross talk between Th1 and Th17 lymphocytes during sepsis such that neutrophil recruitment and bacterial clearance is improved while early tissue injury is not increased. All together, these observations may underlay novel potential therapeutic targets to improve the host immune response to sepsis.
Multiple Antigen Peptide Vaccines againstPlasmodium falciparumMalaria
Authors: Mahajan Babita , Berzofsky Jay A. , Boykins Robert A. , Majam Victoria , Zheng Hong , Chattopadhyay Rana , de la Vega Patricia , Moch J. Kathleen , Haynes J. David , Belyakov Igor M. , Nakhasi Hira L. , Kumar Sanjai 
Published: September 2010

ABSTRACTThe multiple antigen peptide (MAP) approach is an effective method to chemically synthesize and deliver multiple T-cell and B-cell epitopes as the constituents of a single immunogen. Here we report on the design, chemical synthesis, and immunogenicity of threePlasmodium falciparumMAP vaccines that incorporated antigenic epitopes from the sporozoite, liver, and blood stages of the life cycle. Antibody and cellular responses were determined in three inbred (C57BL/6, BALB/c, and A/J) strains, one congenic (HLA-A2 on the C57BL/6 background) strain, and one outbred strain (CD1) of mice. All three MAPs were immunogenic and induced both antibody and cellular responses, albeit in a somewhat genetically restricted manner. Antibodies against MAP-1, MAP-2, and MAP-3 had an antiparasite effect that was also dependent on the mouse major histocompatibility complex background. Anti-MAP-1 (CSP-based) antibodies blocked the invasion of HepG2 liver cells byP.falciparumsporozoites (highest, 95.16% in HLA-A2 C57BL/6; lowest, 11.21% in BALB/c). Furthermore, antibodies generated following immunizations with the MAP-2 (PfCSP, PfLSA-1, PfMSP-142, and PfMSP-3b) and MAP-3 (PfRAP-1, PfRAP-2, PfSERA, and PfMSP-142) vaccines were able to reduce the growth of blood stage parasites in erythrocyte cultures to various degrees. Thus, MAP-based vaccines remain a viable option to induce effective antibody and cellular responses. These results warrant further development and preclinical and clinical testing of the next generation of candidate MAP vaccines that are based on the conserved protective epitopes fromPlasmodiumantigens that are widely recognized by populations of divergent HLA types from around the world.
The Two Variants of the
Streptococcus pneumoniae
Pilus 1 RrgA Adhesin Retain the Same Function and Elicit Cross-Protection
In Vivo
Authors: Moschioni Monica , Emolo Carla , Biagini Massimiliano , Maccari Silvia , Pansegrau Werner , Donati Claudio , Hilleringmann Markus , Ferlenghi Ilaria , Ruggiero Paolo , Sinisi Antonia , Pizza Mariagrazia , Norais Nathalie , Barocchi Michèle A. , Masignani Vega 
Published: September 2010

ABSTRACT

Thirty percent of
Streptococcus pneumoniae
isolates contain pilus islet 1, coding for a pilus composed of the backbone subunit RrgB and two ancillary proteins, RrgA and RrgC. RrgA is the major determinant of
in vitro
adhesion associated with pilus 1, is protective
in vivo
in mouse models, and exists in two variants (clades I and II). Mapping of the sequence variability onto the RrgA structure predicted from X-ray data showed that the diversity was restricted to the “head” of the protein, which contains the putative binding domains, whereas the elongated “stalk” was mostly conserved. To investigate whether this variability could influence the adhesive capacity of RrgA and to map the regions important for binding, two full-length protein variants and three recombinant RrgA portions were tested for adhesion to lung epithelial cells and to purified extracellular matrix (ECM) components. The two RrgA variants displayed similar binding abilities, whereas none of the recombinant fragments adhered at levels comparable to those of the full-length protein, suggesting that proper folding and structural arrangement are crucial to retain protein functionality. Furthermore, the two RrgA variants were shown to be cross-reactive
in vitro
and cross-protective
in vivo
in a murine model of passive immunization. Taken together, these data indicate that the region implicated in adhesion and the functional epitopes responsible for the protective ability of RrgA may be conserved and that the considerable level of variation found within the “head” domain of RrgA may have been generated by immunologic pressure without impairing the functional integrity of the pilus.
Mannheimia haemolyticaand Its Leukotoxin Cause Neutrophil Extracellular Trap Formation by Bovine Neutrophils
Authors: Aulik Nicole A. , Hellenbrand Katrina M. , Klos Heather , Czuprynski Charles J. 
Published: September 2010

ABSTRACTMannheimia haemolyticais an important member of the bovine respiratory disease complex, which is characterized by abundant neutrophil infiltration into the alveoli and fibrin deposition. Recently several authors have reported that human neutrophils release neutrophil extracellular traps (NETs), which are protein-studded DNA matrices capable of trapping and killing pathogens. Here, we demonstrate that the leukotoxin (LKT) ofM. haemolyticacauses NET formation by bovine neutrophils in a CD18-dependent manner. Using an unacylated, noncytotoxic pro-LKT produced by an ΔlktCmutant ofM. haemolytica, we show that binding of unacylated pro-LKT stimulates NET formation despite a lack of cytotoxicity. Inhibition of LKT binding to the CD18 chain of lymphocyte function-associated antigen 1 (LFA-1) on bovine neutrophils reduced NET formation in response to LKT orM. haemolyticacells. Further investigation revealed that NETs formed in response toM. haemolyticaare capable of trapping and killing a portion of the bacterial cells. NET formation was confirmed by confocal microscopy and by scanning and transmission electron microscopy. Prior exposure of bovine neutrophils to LKT enhanced subsequent trapping and killing ofM. haemolyticacells in bovine NETs. Understanding NET formation in response toM. haemolyticaand its LKT provides a new perspective on how neutrophils contribute to the pathogenesis of bovine respiratory disease.
Transport of ammonium in aquifers: retardation and degradation
Authors: Erskine A. D. 
Published: September 2010

In the assessment of the risks to groundwater posed by most landfills, the production and transport of ammonium is the key factor. Although a long list of toxic and dangerous substances can appear in the leachate from a landfill, the chemical component with the greatest impact both on the ecology and on groundwater abstractions is usually ammonium. It is therefore vital that information on the behaviour of ammonium in groundwater is compiled in order to reduce the uncertainties associated with predictions of groundwater impact.
The transport of ammonium is attenuated by two main processes: cation exchange and oxidation (often biologically enhanced). The effect of these can probably be approximated by a combination of linear retardation and exponential degradation. In principle, comparison of the breakthrough curves of ammonium and chloride at monitoring points should allow quantification of the contributions of these two processes in terms of retardation factors and decay rates.
Three case studies at different scales are compared. The results indicate that retardation factors are not higher than 3, and that degradation does contribute to reduction in concentration. While only three studies have been examined, the results seem to contrast with the typical assumptions made in risk assessments.
Interpretation of pumping tests in the Sherwood Sandstone Group, Sellafield, Cumbria, UK
Authors: STREETLY M. , CHAKRABARTY C. , MCLEOD R. 
Published: September 2010

In 1995 as part of the process to assess the suitability of a site near Sellafield, Cumbria, for a deep geological repository for solid intermediate level and some solid low level radioactive waste, United Kingdom Nirex Limited (Nirex) commissioned a series of long duration pumping tests in the various stratigraphic horizons at the site. Two of the pumping tests were conducted in vertically adjacent sections of the lower Sherwood Sandstone Group (SSG) whilst pressures were monitored at discrete intervals in surrounding monitoring boreholes. Responses were observed in over twenty monitoring zones at various levels around the pumped sections during both tests.
In order to arrive at an understanding of the hydraulic system in the SSG, a systematic methodology was adopted to analyse the data sets from the pumping tests. Preliminary analysis of the data from each responding zone used the standard 2D radial flow analytical approach. This indicated that, whilst responses conformed broadly to this model, there were important deviations. Three different analytical modifications were adopted to assess the significance of these deviations; a partial penetration model, a bounded aquifer model and a generalized radial flow model. The use of the different models allowed a conceptual model of flow processes occurring in the SSG to be developed.
Hydrogeological characterization of the onshore Quaternary sediments at Sellafield using the concept of domains
Authors: McMillan A. A. , Heathcote J. A. , Klinck B. A. , Shepley M. G. , Jackson C. P. , Degnan P. J. 
Published: September 2010

As part of an assessment of the performance of a potential deep repository for intermediate- and some low-level radioactive wastes at Sellafield, numerical models of the regional scale groundwater flow were built. Quaternary sediments play an important role in the flow because they control recharge to the deeper groundwater system. This paper outlines research carried out under the Nirex Quaternary Characterization programme at Sellafield and shows how lithological and structural characterization of the sediments has enabled the development of Quaternary Hydrogeological Domains which have been used in the regional groundwater models.
The Quaternary sediments in the Sellafield area are very varied and result from more than one ice advance. Sediments include glaciogenic diamictons, coarse glaciofluvial gravels probably deposited as sandar and silts of probable glaciolacustrine origin. These sediments are locally glacitectonically deformed. Recent alluvial, marine and lacustrine sediments are also present. The lateral extent of many of the sediment bodies is expected to be small, and therefore their complete characterization by the traditional approach of interpolating between measurements in boreholes and at outcrop is likely to be difficult, without an impracticably large number of boreholes.
Thus the hydrogeology was characterized on the basis of the geology, supported by a relatively small number of boreholes and hydraulic measurements. Quaternary Geological Domains defined by distinctive landform-sediment associations and structural characteristics were mapped. Distinctive vertical profiles of sediments were identified from subsurface data (e.g. borehole data). This enabled the Geological Domains to be refined to Hydrogeological Domains.
The overall performance of the system can be confirmed by reference to detailed field scale measurements in specific areas. The behaviour varies between providing little impediment to recharge to, or discharge from, the underlying strata of the Sherwood Sandstone Group over most of the area, but with local areas where recharge or discharge is considerably impeded. Locally, the Quaternary deposits contribute a significant part of the transmissivity of the regional aquifer.
The hydraulic characteristics of individual sediment types are known from laboratory data and limited field data. These data have been integrated and upscaled using analytic calculations based on the lithological profiles recognized in the Hydrogeological Domains. This has enabled the derivation of effective properties, which were used in the regional-scale flow models. The resulting parameter values are consistent with those independently derived from regional aquifer modelling.
Landslide susceptibility in the Río Aguas catchment, SE Spain
Authors: Griffiths J.S. , Mather A.E. , Hart A.B. 
Published: September 2010

The definitions of hazard and risk in natural hazard studies are well established in the scientific literature. However, many examples of ‘landslide hazard assessment’ only identify the susceptibility of slopes to failure and make no statement on the frequency of occurrence that would be necessary for a complete hazard evaluation. In a research programme undertaken in SE Spain the issue of landslide susceptibility in a semi-arid, neotectonic environment was examined, with some attempt to evaluate the hazard. This work involved establishing the occurrence of landsliding within the 550 km
2
Río Aguas catchment through remote sensing interpretation and field mapping. These data were compiled in an inventory containing the records of nearly 250 landslides that was analysed to establish the nature and extent of landslide susceptible situations. Within the catchment anticipated combinations of geological materials proved to be susceptible to failure, and relationships between landslide volume and travel angle were examined in relation to standard models. The highest incidence of contemporary landsliding appeared to be related to the proximity of a major river capture site, a geomorphological event that had been dated at 100 000
BP
. This produced localized rapid incision, a ten fold increase in sediment removal and the creation of oversteepened slopes that were only recently degrading to their long-term angle of stability. In addition to contemporary landslides, field mapping identified anomalous geological structures that proved to be degraded erosional remnants of ancient landslides. Relating these remnants to the river terrace sequence in the region provided some control on the relative ages of these ancient or ‘fossil’ landslides. It was concluded that any assessment of landslide risk in the study area would need to take into account not only geological materials and the contemporary geomorphological environment but also the geomorphological history of the region.
Hyaluronan Deficiency in Tumor Stroma Impairs Macrophage Trafficking and Tumor Neovascularization
Authors: Kobayashi Nobutaka , Miyoshi Seiji , Mikami Takahide , Koyama Hiroshi , Kitazawa Masato , Takeoka Michiko , Sano Kenji , Amano Jun , Isogai Zenzo , Niida Shumpei , Oguri Kayoko , Okayama Minoru , McDonald John A. , Kimata Koji , Taniguchi Shun'ichiro , Itano Naoki 
Published: September 2010

Abstract
Despite the importance of stromal cells in tumor progression, our overall understanding of the molecular signals that regulate the complex cellular interactions within tumor stroma is limited. Here, we provide multiple lines of evidence that tumor-associated macrophages (TAM) preferentially traffic to stromal areas formed within tumors in a manner dependent on a hyaluronan (HA)–rich tumor microenvironment. To address the role of stroma-derived HA in macrophage recruitment, we disrupted the HA synthase 2 (Has2) gene in stromal fibroblasts using conditional gene targeting. The Has2 null fibroblasts showed severe impairment in recruiting macrophages when inoculated with tumor cells into nude mice, which shows the contribution of stroma-derived HA in intratumoral macrophage mobilization. Furthermore, a deficiency in stromal HA attenuated tumor angiogenesis and lymphangiogenesis concomitantly with impaired macrophage recruitment. Taken together, our results suggest that stromal HA serves as a microenvironmental signal for the recruitment of TAMs, which are key regulatory cells involved in tumor neovascularization. Cancer Res; 70(18); 7073–83. ©2010 AACR.
Quantitative Imaging of Lymphatic Function with Liposomal Indocyanine Green
Authors: Proulx Steven T. , Luciani Paola , Derzsi Stefanie , Rinderknecht Matthias , Mumprecht Viviane , Leroux Jean-Christophe , Detmar Michael 
Published: September 2010

Abstract
Lymphatic vessels play a major role in cancer progression and in postsurgical lymphedema, and several new therapeutic approaches targeting lymphatics are currently being developed. Thus, there is a critical need for quantitative imaging methods to measure lymphatic flow. Indocyanine green (ICG) has been used for optical imaging of the lymphatic system, but it is unstable in solution and may rapidly enter venous capillaries after local injection. We developed a novel liposomal formulation of ICG (LP-ICG), resulting in vastly improved stability in solution and an increased fluorescence signal with a shift toward longer wavelength absorption and emission. When injected intradermally to mice, LP-ICG was specifically taken up by lymphatic vessels and allowed improved visualization of deep lymph nodes. In a genetic mouse model of lymphatic dysfunction, injection of LP-ICG showed no enhancement of draining lymph nodes and slower clearance from the injection site. In mice bearing B16 luciferase-expressing melanomas expressing vascular endothelial growth factor-C (VEGF-C), sequential near-IR imaging of intradermally injected LP-ICG enabled quantification of lymphatic flow. Increased flow through draining lymph nodes was observed in mice bearing VEGF-C–expressing tumors without metastases, whereas a decreased flow pattern was seen in mice with a higher lymph node tumor burden. This new method will likely facilitate quantitative studies of lymphatic function in preclinical investigations and may also have potential for imaging of lymphedema or improved sentinel lymph detection in cancer. Cancer Res; 70(18); 7053–62. ©2010 AACR.
Antibody-Dependent Natural Killer Cell–Mediated Cytotoxicity Engendered by a Kinase-Inactive Human HER2 Adenovirus-Based Vaccination Mediates Resistance to Breast Tumors
Authors: Triulzi Chiara , Vertuani Simona , Curcio Claudia , Antognoli Agnese , Seibt Josef , Akusjärvi Göran , Wei Wei-Zen , Cavallo Federica , Kiessling Rolf 
Published: September 2010

AbstractCancer vaccines may have applications in the therapy and prevention of mammary carcinoma. To investigate such applications, we constructed a recombinant adenoviral vaccine expressing a kinase-inactive mutant form of human HER2 and introduced this into BALB/c wild-type (WT) or HER2 transgenic mice. Here, we report contributions by antibody responses and natural killer (NK) cells in tumor protection in this model. One i.p. vaccination protected WT mice from the HER2-expressing mouse carcinoma D2F2/E2. Half of the HER2 transgenic mice were protected fully and long term after preventive vaccination. Tumor growth in mice that eventually developed neoplastic lesions was delayed. Protection in WT and HER2 transgenic mice was associated with high or low levels of IgG2a antibodies, respectively, whereas CTLs were observed in WT but not in HER2 transgenic mice. Depleting CD4+ or CD8+ cells in vaccinated WT mice had limited effects, suggesting that protection was largely independent of CD4+ or CD8+ T cells. In contrast, antibody-mediated tumor rejection seemed to contribute significantly based on a loss of protection in mice deficient for Fc-γ RI/III or B cells. Further, a role for antibody-dependent cellular cytotoxicity (ADCC) mediated by NK cells was indicated by evidence that vaccine protection could be abolished by in vivo depletion of NK cells. Lastly, NK cells and immune sera purified from WT or HER2 transgenic mice exhibited efficient ADCC of HER2-expressing tumor cells in vitro. Our findings define a critical requirement for NK cells in vaccine-induced protection against HER2-expressing tumors. Cancer Res; 70(19); 7431–41. ©2010 AACR.
IFNγ Markedly Cooperates with Intratumoral Dendritic Cell Vaccine in Dog Tumor Models
Authors: Mito Kai , Sugiura Kikuya , Ueda Kana , Hori Takako , Akazawa Takashi , Yamate Jyoji , Nakagawa Hiroshi , Hatoya Shingo , Inaba Muneo , Inoue Norimitsu , Ikehara Susumu , Inaba Toshio 
Published: September 2010

AbstractDendritic cell (DC)–based immunotherapy can trigger effective immune responses against cancer in human patients. Although accompanied by little toxicity, further improvements are needed to optimize immune responses for fully satisfactory clinical outcomes. IFNγ, a potent inducer of T helper type 1 immune responses, is considered an important tool to realize improvements. In this study, we sought to clarify the effect of IFNγ on the maturation and activation of DCs and the clinical outcome of DC-based cancer therapy in dogs. In vitro experiments indicated that IFNγ significantly enhanced the expression of immune stimulatory molecules and interleukin-12 by DCs derived from canine monocytes. IFNγ also significantly strengthened DC-mediated growth suppression against tumor cell lines. DC inoculation with concomitant delivery of IFNγ into primary or recurrent tumors elicited significant clinical responses, including four complete responses and two partial responses against malignant tumors, also eliciting partial responses against benign but actively growing tumors. Together, our results indicate that combining IFNγ and DCs could induce strong immune responses against tumors, significantly improving clinical outcomes. The present study of dogs bearing common types of cancer in humans offers a unique line of support for the development of human cancer therapies. Cancer Res; 70(18); 7093–101. ©2010 AACR.