The role of T cell subsets and cytokines in the regulation of intracellular bacterial infection

Cellular immune responses are a critical part of the host's defense against intracellular bacterial infections. Immunity to Brucella abortus crucially depends on antigen-specific T cell-mediated activation of macrophages, which are the major effectors of cell-mediated killing of this organism. T lymphocytes that proliferate in response to B. abortus were characterized for phenotype and cytokine activity. Human, murine, and bovine T lymphocytes exhibited a type 1 cytokine profile, suggesting an analogous immune response in these different hosts. In vivo protection afforded by a particular cell type is dependent on the antigen presented and the mechanism of antigen presentation. Studies using MHC class I and class II knockout mice infected with B. abortus have demonstrated that protective immunity to brucellosis is especially dependent on CD8+ T cells. To target MHC class I presentation we transfected ex vivo a murine macrophage cell line with B. abortus genes and adoptively transferred them to BALB/c mice. These transgenic macrophage clones induced partial protection in mice against experimental brucellosis. Knowing the cells required for protection, vaccines can be designed to activate the protective T cell subset. Lastly, as a new strategy for priming a specific class I-restricted T cell response in vivo, we used genetic immunization by particle bombardment-mediated gene transfer

Optimal heat release shaping in a reactivity controlled compression ignition (RCCI) engine

[EN] The present paper addresses the optimal heat release (HR) law in a single cylinder engine operated under reactivity controlled compression ignition (RCCI) combustion mode to minimise the indicated specific fuel consumption (ISFC) subject to different constraints including pressure related limits (maximum cylinder pressure and maximum cylinder pressure gradient). With this aim, a 0-dimensional (0D) engine combustion model has been identified with experimental data. Then, the optimal control problem of minimising the ISFC of the engine at different operating conditions of the engine operating map has been stated and analytically solved. To evaluate the method viability a data-driven model is developed to obtain the control actions (gasoline fraction) leading to the calculated optimal HR, more precisely to the optimal ratio between premixed and diffusive combustion. The experimental results obtained with such controls and the differences with the optimal HR are finally explained and discussed.This work was supported by Ministerio de Economía y Competitividad through Project TRA2016-78717-R.Guardiola, C.; Plá Moreno, B.; García Martínez, A.; Boronat-Colomer, V. (2017). Optimal heat release shaping in a reactivity controlled compression ignition (RCCI) engine. Control Theory and Technology. 15(2):117-128. https://doi.org/10.1007/s11768-017-6155-5S117128152F. Payri, J. M. Luján, C. Guardiola, et al. A challenging future for the IC engine: New technologies and the control role. Oil & Gas Science and Technology–Revue D IFP Energies Nouvelles, 2015, 70(1): 15–30.H. Yanagihara, Y. Sato, J. Minuta. A simultaneous reduction in NOx and soot in diesel engines under a new combustion system (Uniform Bulky Combustion System–UNIBUS). Proceedings of the 17th international Vienna Motor Symposium, Vienna, 1996: 303–314.D. A. Splitter, M. L. Wissink, T. L. Hendricks, et al. Comparison of RCCI, HCCI, and CDC operation from low to full load. THIESEL 2012 conference on thermo-and fluid dynamic processes in direct injection engines. Valencia, 2012.J. Benajes, J. V. Pastor, A. García, et al. The potential of RCCI concept to meet EURO VI NOx limitation and ultra-low soot emissions in a heavy-duty engine over the whole engine map. Fuel, 2015, 159(1): 952–961.J. Benajes, A. García, J. Monsalve-Serrano, et al. An assessment of the dual-mode reactivity controlled compression ignition/conventional diesel combustion capabilities in a EURO VI medium-duty diesel engine fueled with an intermediate ethanol-gasoline blend and biodiesel. Energy Conversion and Management, 2016, 123(1): 381–391.S. Molina, A. García, J. M. Pastor, et al. Operating range extension of RCCI combustion concept from low to full load in a heavy-duty engine. Applied Energy, 2015, 143: 211–227.D. A. Splitter, R. D. Reitz. 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Critical thinking for 21st-century education: A cyber-tooth curriculum?

It is often assumed that the advent of digital technologies requires fundamental change to the curriculum and to the teaching and learning approaches used in schools around the world to educate this generation of “digital natives” or the “net generation”. This article analyses the concepts of 21st-century skills and critical thinking, to understand how these aspects of learning might contribute to a 21st-century education. The author argues that, although both critical thinking and 21st-century skills are indeed necessary in a curriculum for a 21st-century education, they are not sufficient, even in combination. The role of knowledge and an understanding of differing cultural perspectives and values indicate that education should also fit local contexts in a global world and meet the specific needs of students in diverse cultures. It should also fit the particular technical and historical demands of the 21st century in relation to digital skills

Complete Genome Sequence of Mycoplasma suis and Insights into Its Biology and Adaption to an Erythrocyte Niche

Mycoplasma suis, the causative agent of porcine infectious anemia, has never been cultured in vitro and mechanisms by which it causes disease are poorly understood. Thus, the objective herein was to use whole genome sequencing and analysis of M. suis to define pathogenicity mechanisms and biochemical pathways. M. suis was harvested from the blood of an experimentally infected pig. Following DNA extraction and construction of a paired end library, whole-genome sequencing was performed using GS-FLX (454) and Titanium chemistry. Reads on paired-end constructs were assembled using GS De Novo Assembler and gaps closed by primer walking; assembly was validated by PFGE. Glimmer and Manatee Annotation Engine were used to predict and annotate protein-coding sequences (CDS). The M. suis genome consists of a single, 742,431 bp chromosome with low G+C content of 31.1%. A total of 844 CDS, 3 single copies, unlinked rRNA genes and 32 tRNAs were identified. Gene homologies and GC skew graph show that M. suis has a typical Mollicutes oriC. The predicted metabolic pathway is concise, showing evidence of adaptation to blood environment. M. suis is a glycolytic species, obtaining energy through sugars fermentation and ATP-synthase. The pentose-phosphate pathway, metabolism of cofactors and vitamins, pyruvate dehydrogenase and NAD+ kinase are missing. Thus, ribose, NADH, NADPH and coenzyme A are possibly essential for its growth. M. suis can generate purines from hypoxanthine, which is secreted by RBCs, and cytidine nucleotides from uracil. Toxins orthologs were not identified. We suggest that M. suis may cause disease by scavenging and competing for host' nutrients, leading to decreased life-span of RBCs. In summary, genome analysis shows that M. suis is dependent on host cell metabolism and this characteristic is likely to be linked to its pathogenicity. The prediction of essential nutrients will aid the development of in vitro cultivation systems

Advances in structure elucidation of small molecules using mass spectrometry

The structural elucidation of small molecules using mass spectrometry plays an important role in modern life sciences and bioanalytical approaches. This review covers different soft and hard ionization techniques and figures of merit for modern mass spectrometers, such as mass resolving power, mass accuracy, isotopic abundance accuracy, accurate mass multiple-stage MS(n) capability, as well as hybrid mass spectrometric and orthogonal chromatographic approaches. The latter part discusses mass spectral data handling strategies, which includes background and noise subtraction, adduct formation and detection, charge state determination, accurate mass measurements, elemental composition determinations, and complex data-dependent setups with ion maps and ion trees. The importance of mass spectral library search algorithms for tandem mass spectra and multiple-stage MS(n) mass spectra as well as mass spectral tree libraries that combine multiple-stage mass spectra are outlined. The successive chapter discusses mass spectral fragmentation pathways, biotransformation reactions and drug metabolism studies, the mass spectral simulation and generation of in silico mass spectra, expert systems for mass spectral interpretation, and the use of computational chemistry to explain gas-phase phenomena. A single chapter discusses data handling for hyphenated approaches including mass spectral deconvolution for clean mass spectra, cheminformatics approaches and structure retention relationships, and retention index predictions for gas and liquid chromatography. The last section reviews the current state of electronic data sharing of mass spectra and discusses the importance of software development for the advancement of structure elucidation of small molecules