Thymoquinone Inhibits the CXCL12-Induced Chemotaxis of Multiple Myeloma Cells and Increases Their Susceptibility to Fas-Mediated Apoptosis

In multiple myeloma (MM), malignant plasma cells reside in the bone marrow, where they accumulate in close contact with stromal cells. The mechanisms responsible for the chemotaxis of malignant plasma cells are still poorly understood. Thus, we investigated the mechanisms involved in the chemotaxis of MDN and XG2 MM cell lines. Both cell lines strongly expressed CCR9, CXCR3 and CXCR4 chemokine receptors but only migrated toward CXCL12. Activation of CXCR4 by CXCL12 resulted in the association of CXCR4 with CD45 and activation of PLCβ3, AKT, RhoA, IκBα and ERK1/2. Using siRNA-silencing techniques, we showed CD45/CXCR4 association is essential for CXCL12-induced migration of MM cells. Thymoquinone (TQ), the major active component of the medicinal herb Nigella sativa Linn, has been described as a chemopreventive and chemotherapeutic compound. TQ treatment strongly inhibited CXCL12-mediated chemotaxis in MM cell lines as well as primary cells isolated from MM patients, but not normal PBMCs. Moreover, TQ significantly down-regulated CXCR4 expression and CXCL12-mediated CXCR4/CD45 association in MM cells. Finally, TQ also induced the relocalization of cytoplasmic Fas/CD95 to the membrane of MM cells and increased CD95-mediated apoptosis by 80%. In conclusion, we demonstrate the potent anti-myeloma activity of TQ, providing a rationale for further clinical evaluation

A quantitative assessment of primary and secondary immune responses in cattle using a B cell ELISPOT assay

The aim of the study was to build a comprehensive picture of the appearance in the blood stream of Ag-specific plasma cells and memory B cells in the bovine model. For this purpose, we have developed a method allowing the detection and quantification of both cell types within individual calves immunised with ovalbumin. During the primary response, we detected a burst of ovalbumin-specific plasma cells at days 6 and 7 post-immunisation, which was followed by the production of specific Ab, whereas a gradual increase of memory B cells was only detected from day 15. As expected, a boost immunisation performed 7 weeks later induced a quicker and stronger secondary response. Indeed, a burst of plasma cells was detected in the blood at days 3 and 4, which was followed by a strong increase in Ab titres. Furthermore, a burst of memory B cells, and not a gradual increase, was detected at days 5 and 6 post-boost immunisation. Importantly, we showed a strong correlation between the anti-ovalbumin-specific IgG titres detected 5 months after secondary immunisation and the plasma cell numbers detected in the blood at the peak response after secondary immunisation. The detection and quantification of plasma cells following an immunisation/vaccination strategy could constitute a very effective means for predicting the magnitude and longevity of an Ab response

Detectors and cryostat design for the SuMIRe Prime Focus Spectrograph (PFS)

We describe the conceptual design of the camera cryostats, detectors, and detector readout electronics for the SuMIRe Prime Focus Spectrograph (PFS) being developed for the Subaru telescope. The SuMIRe PFS will consist of four identical spectrographs, each receiving 600 fibers from a 2400 fiber robotic positioner at the prime focus. Each spectrograph will have three channels covering wavelength ranges 3800 {\AA} - 6700 {\AA}, 6500 {\AA} - 10000 {\AA}, and 9700 {\AA} - 13000 {\AA}, with the dispersed light being imaged in each channel by a f/1.10 vacuum Schmidt camera. In the blue and red channels a pair of Hamamatsu 2K x 4K edge-buttable CCDs with 15 um pixels are used to form a 4K x 4K array. For the IR channel, the new Teledyne 4K x 4K, 15 um pixel, mercury-cadmium-telluride sensor with substrate removed for short-wavelength response and a 1.7 um cutoff will be used. Identical detector geometry and a nearly identical optical design allow for a common cryostat design with the only notable difference being the need for a cold radiation shield in the IR camera to mitigate thermal background. This paper describes the details of the cryostat design and cooling scheme, relevant thermal considerations and analysis, and discusses the detectors and detector readout electronics

Prognostic significance of vascular and valvular calcifications in low- and high-gradient aortic stenosis

International audienceAims In low-gradient aortic stenosis (LGAS), the high valvulo-arterial impedance observed despite low valvular gradient suggests a high vascular load. Thoracic aortic calcifications (TACs) and valvular aortic calcifications (VACs) are, respectively, surrogates of aortic load and aortic valvular gradient. The aim of this study was to compare the respective contributions of TAC and VAC on 3-year cardiovascular (CV) mortality following TAVI in LGAS vs. high-gradient aortic stenosis (HGAS) patients. Methods and results A total of 1396 consecutive patients were included. TAC and VAC were measured on the pre-TAVI CT-scan. About 435 (31.2%) patients had LGAS and 961 (68.8%) HGAS. LGAS patients were more prone to have diabetes, coronary artery disease (CAD), atrial fibrillation (AF), and lower left ventricular ejection fraction (LVEF), P<0.05 for all. During the 3 years after TAVI, 245(17.8%) patients experienced CV mortality, 92(21.6%) in LGAS and 153(16.2%) in HGAS patients, P=0.018. Multivariate analysis adjusted for age, gender, diabetes, AF, CAD, LVEF, renal function, vascular access, and aortic regurgitation showed that TAC but not VAC was associated with CV mortality in LGAS, hazard ratio (HR) 1.085 confidence interval (CI) (1.019–1.156), P=0.011, and HR 0.713 CI (0.439–1.8), P=0.235; the opposite was observed in HGAS patients with VAC but not TAC being associated with CV mortality, HR 1.342 CI (1.034–1.742), P=0.027, and HR 1.015 CI (0.955–1.079), P=0.626. Conclusion TAC plays a major prognostic role in LGAS while VAC remains the key in HGAS patients. This confirms that LGAS is a complex vascular and valvular disease

Identification of a Newly Conserved SLA-II Epitope in a Structural Protein of Swine Influenza Virus

Despite the role of pigs as a source of new Influenza A Virus viruses (IAV) potentially capable of initiating human pandemics, immune responses to swine influenza virus (SwIV) in pigs are not fully understood. Several SwIV epitopes presented by swine MHC (SLA) class I have been identified using different approaches either in outbred pigs or in Babraham large white inbred pigs, which are 85% identical by genome wide SNP analysis. On the other hand, some class II SLA epitopes were recently described in outbred pigs. In this work, Babraham large white inbred pigs were selected to identify SLA II epitopes from SwIV H1N1. PBMCs were screened for recognition of overlapping peptides covering the NP and M1 proteins from heterologous IAV H1N1 in IFNγ ELISPOT. A novel SLA class II restricted epitope was identified in NP from swine H1N1. This conserved novel epitope could be the base for further vaccine approaches against H1N1 in pigs.info:eu-repo/semantics/publishedVersio

Hubris, humility and humanity: expanding evidence approaches for improving and sustaining community health programmes

Community-based approaches are a critical foundation for many health outcomes, including reproductive, maternal, newborn and child health (RMNCH). Evidence is a vital part of strengthening that foundation, but largely focuses on the technical content of what must be done, rather than on how disparate community actors continuously interpret, implement and adapt interventions in dynamic and varied community health systems. We argue that efforts to strengthen evidence for community programmes must guard against the hubris of relying on a single approach or hierarchy of evidence for the range of research questions that arise when sustaining community programmes at scale. Moving forward we need a broader evidence agenda that better addresses the implementation realities influencing the scale and sustainability of community programmes and the partnerships underpinning them if future gains in community RMNCH are to be realised. This will require humility in understanding communities as social systems, the complexity of the interventions they engage with and the heterogeneity of evidence needs that address the implementation challenges faced. It also entails building common ground across epistemological word views to strengthen the robustness of implementation research by improving the use of conceptual frameworks, addressing uncertainty and fostering collaboration. Given the complexity of scaling up and sustaining community RMNCH, ensuring that evidence translates into action will require the ongoing brokering of relationships to support the human creativity, scepticism and scaffolding that together build layers of evidence, critical thinking and collaborative learning to effect change

Technical Note: The Forensic Anthropology Society of Europe (FASE) Map of Identified Osteological Collections

Identified (documented) osteological collections represent an important resource in the development of forensic anthropology standards and methods as well as a precious tool for learning and training of practitioners. Even though the number of papers presenting identified collections worldwide increases, many of the collections have still not been divulged to the scientific community in sufficient detail to ascertain their exact number. The Forensic Anthropology Society of Europe (FASE) therefore developed a tool that goes beyond sporadic publications: the FASE Map of Identified Osteological Collections, which is freely accessible and continuously updated and revised. The online map is available at http://forensicanthropology.eu/osteological-collections/. The map of skeletal collections was created in 2017 and currently displays information on 153 identified osteological collections (43 of them categorized as contemporary) located in 41 different countries. This article offers a short analysis of the type, geographical location and content of the collections included in the map. The aim of this article and the map as such is to provide a useful resource to facilitate research planning and teaching in forensic anthropology and related disciplines.info:eu-repo/semantics/publishedVersio

Immune responses in pigs vaccinated with adjuvanted and non-adjuvanted A(H1N1)pdm/09 influenza vaccines used in human immunization programmes.

Following the emergence and global spread of a novel H1N1 influenza virus in 2009, two A(H1N1)pdm/09 influenza vaccines produced from the A/California/07/09 H1N1 strain were selected and used for the national immunisation programme in the United Kingdom: an adjuvanted split virion vaccine and a non-adjuvanted whole virion vaccine. In this study, we assessed the immune responses generated in inbred large white pigs (Babraham line) following vaccination with these vaccines and after challenge with A(H1N1)pdm/09 virus three months post-vaccination. Both vaccines elicited strong antibody responses, which included high levels of influenza-specific IgG1 and haemagglutination inhibition titres to H1 virus. Immunisation with the adjuvanted split vaccine induced significantly higher interferon gamma production, increased frequency of interferon gamma-producing cells and proliferation of CD4(-)CD8(+) (cytotoxic) and CD4(+)CD8(+) (helper) T cells, after in vitro re-stimulation. Despite significant differences in the magnitude and breadth of immune responses in the two vaccinated and mock treated groups, similar quantities of viral RNA were detected from the nasal cavity in all pigs after live virus challenge. The present study provides support for the use of the pig as a valid experimental model for influenza infections in humans, including the assessment of protective efficacy of therapeutic interventions