Rheology of distorted nematic liquid crystals

We use lattice Boltzmann simulations of the Beris--Edwards formulation of nematodynamics to probe the response of a nematic liquid crystal with conflicting anchoring at the boundaries under shear and Poiseuille flow. The geometry we focus on is that of the hybrid aligned nematic (HAN) cell, common in devices. In the nematic phase, backflow effects resulting from the elastic distortion in the director field render the velocity profile strongly non-Newtonian and asymmetric. As the transition to the isotropic phase is approached, these effects become progressively weaker. If the fluid is heated just above the transition point, however, another asymmetry appears, in the dynamics of shear band formation.Comment: 7 pages, 4 figures. Accepted for publication in Europhys. Let

Glycogen Synthase Kinase 3 Inactivation Drives T-bet-Mediated Downregulation of Co-receptor PD-1 to Enhance CD8(+) Cytolytic T Cell Responses.

Despite the importance of the co-receptor PD-1 in T cell immunity, the upstream signaling pathway that regulates PD-1 expression has not been defined. Glycogen synthase kinase 3 (GSK-3, isoforms α and β) is a serine-threonine kinase implicated in cellular processes. Here, we identified GSK-3 as a key upstream kinase that regulated PD-1 expression in CD8(+) T cells. GSK-3 siRNA downregulation, or inhibition by small molecules, blocked PD-1 expression, resulting in increased CD8(+) cytotoxic T lymphocyte (CTL) function. Mechanistically, GSK-3 inactivation increased Tbx21 transcription, promoting enhanced T-bet expression and subsequent suppression of Pdcd1 (encodes PD-1) transcription in CD8(+) CTLs. Injection of GSK-3 inhibitors in mice increased in vivo CD8(+) OT-I CTL function and the clearance of murine gamma-herpesvirus 68 and lymphocytic choriomeningitis clone 13 and reversed T cell exhaustion. Our findings identify GSK-3 as a regulator of PD-1 expression and demonstrate the applicability of GSK-3 inhibitors in the modulation of PD-1 in immunotherapy.C.E.R. was supported by Wellcome Trust 092627/Z/10/Z, J.A.H. by an Irvington Institute Postdoctoral Fellowship from the Cancer Research Institute (New York), and E.I.Z. by a Leukemia and Lymphoma Society Scholar Award and a grant from the NIH AI081923. We thank Dr. Graham Lord (King’s College London) for the kind gift of the Ifng CNS-12 promoter.This is the final version of the article. It first appeared from Cell Press via http://dx.doi.org/10.1016/j.immuni.2016.01.01

Glucose Oxidation to Pyruvate Is Not Essential for Brucella suis Biovar 5 Virulence in the Mouse Model

Brucella species cause brucellosis, a worldwide extended zoonosis. The brucellae are related to free-living and plant-associated alpha 2-Proteobacteria and, since they multiply within host cells, their metabolism probably reflects this adaptation. To investigate this, we used the rodent-associated Brucella suis biovar 5, which in contrast to the ruminant-associated Brucella abortus and Brucella melitensis and other B. suis biovars, is fast-growing and conserves the ancestral Entner-Doudoroff pathway (EDP) present in the plant-associated relatives. We constructed mutants in Edd (glucose-6-phosphate dehydratase; first EDP step), PpdK (pyruvate phosphate dikinase; phosphoenolpyruvate pyruvate), and Pyk (pyruvate kinase; phosphoenolpyruvate -> pyruvate). In a chemically defined medium with glucose as the only C source, the Edd mutant showed reduced growth rates and the triple Edd-PpdK-Pyk mutant did not grow. Moreover, the triple mutant was also unable to grow on ribose or xylose. Therefore, B. suis biovar 5 sugar catabolism proceeds through both the Pentose Phosphate shunt and EDP, and EDP absence and exclusive use of the shunt could explain at least in part the comparatively reduced growth rates of B. melitensis and B. abortus. The triple Edd-PpdK-Pyk mutant was not attenuated in mice. Thus, although an anabolic use is likely, this suggests that hexose/pentose catabolism to pyruvate is not essential for B. suis biovar 5 multiplication within host cells, a hypothesis consistent with the lack of classical glycolysis in all Brucella species and of EDP in B. melitensis and B. abortus. These results and those of previous works suggest that within cells, the brucellae use mostly 3 and 4 C substrates fed into anaplerotic pathways and only a limited supply of 5 and 6 C sugars, thus favoring the EDP loss observed in some species

The attitudes of European consumers toward innovation in bread; interest of the consumers toward selected quality attributes

16 pages, 7 tables, 4 figures.-- The definitive version is available at www3.interscience.wiley.comThe present survey is integrated in the European project entitled EU-FRESHBAKE. This three years project started in October 2006. It aims at developing innovative processes and innovative formulations for the Bake Off technology taking into consideration, energy demand of the process, nutrition parameters and overall quality of the bread. To help and to advise the project on the expectations of the European consumers toward innovation, a consumer survey has been carried out taking into consideration 1050 consumers from 5 countries (Belgium, Croatia, Spain, France and Poland). The global objectives are (i) to better understand the attitudes of the European innovations in bread and (ii) to understand the main determinants of it. Globally the key points that arose from the survey were the environmental concern and the concern regarding health; these two aspects seem to steer the attitudes of the consumer. Basically, two categories of consumers were observed; (i) frequent (daily) buyers with a focus on quality and pleasure and (ii) less frequent buyers (once a week) with a more pronounced interest in nutrition and energy (process). The first group was named the crust group and the second one the crumb group. The crumb family seems to be the one that is the most interested in the outcomes of the EU-FRESHBAKE project. This group is concerned by nutrition quality and would prefer a bread which has been done with a less energy demanding process. The “crust” group is schematically less interested in the nutrition, in the shelf life and in the energy demand of the process used to prepare the bread. The results from this survey should be handled with care due to the relative small size of the sample and to the fact that the average age of the sample was rather young.This study (report, paper, workshop…) has been carried out with financial support from the Commission of the European Communities, FP6, Thematic Area “Food quality and safety”, FOOD-2006-36302 EU-FRESH BAKE.Peer reviewe

p-Adic Mathematical Physics

A brief review of some selected topics in p-adic mathematical physics is presented.Comment: 36 page

Correction to: Rev1 wbdR tagged vaccines against Brucella ovis

Correction to: Rev1 wbdR tagged vaccines against Brucella ovis, Vet Res (2019) 50:95 https://doi.org/10.1186/s13567-019-0714-

WadD, a New Brucella Lipopolysaccharide Core Glycosyltransferase Identified by Genomic Search and Phenotypic Characterization

Brucellosis, an infectious disease caused by Brucella, is one of the most extended bacterial zoonosis in the world and an important cause of economic losses and human suffering. The lipopolysaccharide (LPS) of Brucella plays a major role in virulence as it impairs normal recognition by the innate immune system and delays the immune response. The LPS core is a branched structure involved in resistance to complement and polycationic peptides, and mutants in glycosyltransferases required for the synthesis of the lateral branch not linked to the O-polysaccharide (O-PS) are attenuated and have been proposed as vaccine candidates. For this reason, the complete understanding of the genes involved in the synthesis of this LPS section is of particular interest. The chemical structure of the Brucella LPS core suggests that, in addition to the already identified WadB and WadC glycosyltransferases, others could be implicated in the synthesis of this lateral branch. To clarify this point, we identified and constructed mutants in 11 ORFs encoding putative glycosyltransferases in B. abortus. Four of these ORFs, regulated by the virulence regulator MucR (involved in LPS synthesis) or the ByrR/ByrS system (implicated in the synthesis of surface components), were not required for the synthesis of a complete LPS neither for virulence or interaction with polycationic peptides and/or complement. Among the other seven ORFs, six seemed not to be required for the synthesis of the core LPS since the corresponding mutants kept the O-PS and reacted as the wild type with polyclonal sera. Interestingly, mutant in ORF BAB1_0953 (renamed wadD) lost reactivity against antibodies that recognize the core section while kept the O-PS. This suggests that WadD is a new glycosyltransferase adding one or more sugars to the core lateral branch. WadD mutants were more sensitive than the parental strain to components of the innate immune system and played a role in chronic stages of infection. These results corroborate and extend previous work indicating that the Brucella LPS core is a branched structure that constitutes a steric impairment preventing the elements of the innate immune system to fight against Brucella

SMAD4 target genes are part of a transcriptional network that integrates the response to BMP and SHH signaling during early limb bud patterning

SMAD4 regulates gene expression in response to BMP and TGFβ signal transduction, and is required for diverse morphogenetic processes, but its target genes have remained largely elusive. Here, we identify the SMAD4 target genes in mouse limb buds using an epitope-tagged Smad4 allele for ChIP-seq analysis in combination with transcription profiling. This analysis shows that SMAD4 predominantly mediates BMP signal transduction during early limb bud development. Unexpectedly, the expression of cholesterol biosynthesis enzymes is precociously downregulated and intracellular cholesterol levels are reduced in Smad4-deficient limb bud mesenchymal progenitors. Most importantly, our analysis reveals a predominant function of SMAD4 in upregulating target genes in the anterior limb bud mesenchyme. Analysis of differentially expressed genes shared between Smad4- and Shh-deficient limb buds corroborates this function of SMAD4 and also reveals the repressive effect of SMAD4 on posterior genes that are upregulated in response to SHH signaling. This analysis uncovers opposing trans-regulatory inputs from SHH- and SMAD4-mediated BMP signal transduction on anterior and posterior gene expression during the digit patterning and outgrowth in early limb buds