Non-sentential responses to requests for information.

When faced with requests for information ("Where did you go last night?"), why do speakers make non-sentential replies ("The movies") rather than full sentence replies ("I went to the movies")? We examine the role that pragmatic factors (politeness and formality) and memory factors (the speaker's ability to retrieve the answer to the question) play in determining whether speakers generate a non-sentential reply. Participants answered a series of questions about their lives. Pragmatic factors affected the participants' responses.

Expression and Purification of scFv-P18F3, a Bi-Modular Fusion Protein (BMFP) Targeting Human CD20.

P18F3-based bi-modular fusion proteins (BMFPs), designed to re-direct pre-existing anti-Epstein-Barr virus (EBV) endogenous polyclonal antibodies towards defined target cells, demonstrated efficient biological activity in a mouse tumor model and could potentially represent a universal and versatile platform to develop novel therapeutics against a broad range of diseases. This protocol provides step-by-step instructions for expressing scFv-P18F3, a BMFP targeting human CD20, in (SHuffle), and for purifying soluble proteins using a two-step process, namely immobilized metal affinity chromatography (IMAC) followed by size exclusion chromatography. This protocol can also be used for expression and purification of other BMFPs with alternative binding specificities.

Selective STING stimulation in dendritic cells primes antitumor T cell responses.

T cells that recognize tumor antigens are crucial for mounting antitumor immune responses. Induction of antitumor T cells in immunogenic tumors depends on STING, the intracellular innate immune receptor for cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) and related cyclic dinucleotides (CDNs). However, the optimal way to leverage STING activation in nonimmunogenic tumors is still unclear.

Meningeal macrophages protect against viral neuroinfection.

The surface of the central nervous system (CNS) is protected by the meninges, which contain a dense network of meningeal macrophages (MMs). Here, we examined the role of tissue-resident MM in viral infection. MHC-II MM were abundant neonatally, whereas MHC-II MM appeared over time.

BMFPs, a versatile therapeutic tool for redirecting a preexisting Epstein-Barr virus antibody response toward defined target cells.

Industrial production of therapeutic monoclonal antibodies is mostly performed in eukaryotic-based systems, allowing posttranslational modifications mandatory for their functional activity. The resulting elevated product cost limits therapy access to some patients. To address this limitation, we conceptualized a novel immunotherapeutic approach to redirect a preexisting polyclonal antibody response against Epstein-Barr virus (EBV) toward defined target cells.

Anti-interleukin 5 therapies failure criteria in severe asthma: a Delphi-consensus study.

Background: Current practices for assessing response to anti-interleukin 5/R treatment in severe asthma patients are heterogeneous. The objective of this study was to achieve an expert consensus defining failure criteria for anti-interleukin 5/R treatment in severe asthma patients.

Methods: Experts were invited to a 5-round Delphi exercise if they were pulmonologists managing ⩾30 patients at a nationally recognized severe asthma expert centre.

Natural killer cells and dendritic epidermal γδ T cells orchestrate type 1 conventional DC spatiotemporal repositioning toward CD8 T cells.

Successful immune responses rely on a regulated delivery of the right signals to the right cells at the right time. Here we show that natural killer (NK) and dendritic epidermal γδ T cells (DETCs) use similar mechanisms to spatiotemporally orchestrate conventional type 1 dendritic cell (cDC1) functions in the spleen, skin, and its draining lymph nodes (dLNs). Upon MCMV infection in the spleen, cDC1 clusterize with activated NK cells in marginal zones.

Type 1 conventional dendritic cells and interferons are required for spontaneous CD4 and CD8 T-cell protective responses to breast cancer.

Objectives: To better understand how immune responses may be harnessed against breast cancer, we investigated which immune cell types and signalling pathways are required for spontaneous control of a mouse model of mammary adenocarcinoma.

Methods: The NOP23 mammary adenocarcinoma cell line expressing epitopes derived from the ovalbumin model antigen is spontaneously controlled when orthotopically engrafted in syngeneic C57BL/6 mice. We combined this breast cancer model with antibody-mediated depletion of lymphocytes and with mutant mice affected in interferon (IFN) or type 1 conventional dendritic cell (cDC1) responses.

New Drug Repositioning Candidates for T-ALL Identified Human/Murine Gene Signature Comparison.

T-cell Acute Lymphoblastic Leukemia (T-ALL) is an aggressive subtype of leukemia for which important progress in treatment efficiency have been made in the past decades to reach a cure rate of 75%-80% nowadays. It is nevertheless mandatory to find new targets and active molecules for innovative therapeutic strategies as relapse is associated with a very dismal outcome. We designed an experimental workflow to highlight the conserved core pathways associated with leukemogenesis by confronting the gene expression profiles (GEPs) of human T-ALL cases to the GEP of a murine T-ALL representative model, generated by the conditional deletion of the tumor suppressor gene in T cell precursors (tPTEN-/-).

Prioritising outcomes for evaluating eosinophil-guided corticosteroid therapy among patients with acute COPD exacerbations requiring hospitalisation: a Delphi consensus study.

Objectives: Presently, those outcomes that should be prioritised for chronic obstructive pulmonary disease (COPD) exacerbation studies remain unclear. In order to coordinate multicentre studies on eosinophilia-driven corticosteroid therapy for patients hospitalised for acute exacerbation of COPD (AECOPD), we aimed to find consensus among experts in the domain regarding the prioritisation of outcomes.

Design: A modified Delphi study was proposed to recognised COPD experts.

Antagonistic Actions of FPA and IBM2 Regulate Transcript Processing from Genes Containing Heterochromatin.

Repressive epigenetic marks, such as DNA and histone methylation, are sometimes located within introns. In Arabidopsis (), INCREASE IN BONSAI METHYLATION2 (IBM2), an RNA-binding protein containing a bromo-adjacent homology domain, is required to process functional transcript isoforms of genes carrying intronic heterochromatin. In a genetic screen for suppressors of the mutation, we identified FPA, an RNA-binding protein that promotes use of proximal polyadenylation sites in genes targeted by IBM2, including encoding an essential H3K9 histone demethylase and the disease resistance gene Both IBM2 and FPA are involved in the processing of their common mRNA targets: Transcription of IBM2 target genes is restored when is mutated in and impaired in transgenic plants overexpressing By contrast, transposons targeted by IBM2 and localized outside introns are not under this antagonistic control.

A neurodevelopmental TUBB2B β-tubulin mutation impairs Bim1 (yeast EB1)-dependent spindle positioning.

Malformations of the human cerebral cortex can be caused by mutations in tubulins that associate to compose microtubules. Cerebral cortical folding relies on neuronal migration and on progenitor proliferation partly dictated by microtubule-dependent mitotic spindle positioning. A single amino acid change, F265L, in the conserved TUBB2B β-tubulin gene has been identified in patients with abnormal cortex formation.

An Arabidopsis Natural Epiallele Maintained by a Feed-Forward Silencing Loop between Histone and DNA.

The extent of epigenetic variation is currently well documented, but the number of natural epialleles described so far remains very limited. Determining the relevance of epigenetic changes for natural variation is an important question of research that we investigate by isolating natural epialleles segregating in Arabidopsis recombinant populations. We previously described a genetic incompatibility among Arabidopsis strains based on the silencing of a gene involved in fitness.

Integrating bioinformatic resources to predict transcription factors interacting with cis-sequences conserved in co-regulated genes.

Background: Using motif detection programs it is fairly straightforward to identify conserved cis-sequences in promoters of co-regulated genes. In contrast, the identification of the transcription factors (TFs) interacting with these cis-sequences is much more elaborate. To facilitate this, we explore the possibility of using several bioinformatic and experimental approaches for TF identification.

A non-canonical plant microRNA target site.

Plant microRNAs (miRNAs) typically form near-perfect duplexes with their targets and mediate mRNA cleavage. Here, we describe an unconventional miRNA target of miR398 in Arabidopsis, an mRNA encoding the blue copper-binding protein (BCBP). BCBP mRNA carries an miR398 complementary site in its 5'-untranslated region (UTR) with a bulge of six nucleotides opposite to the 5' region of the miRNA.

[Spontaneous streptococcal arthritis of the pubic symphysis].

Septic arthritis of the pubic symphysis is uncommon, and usually occurs in patients with predisposing conditions (female incontinence surgery, sports). Staphylococcus aureus and Pseudomonas aeruginosa are the main bacteria responsible of these infections. Streptococcal infections of the pubic symphysis are uncommon.

Very preterm birth: who has access to antenatal corticosteroid therapy?

We describe the administration of antenatal corticosteroid therapy (ACT) for liveborn very preterm neonates in a population-based study. A total of 790 very preterm neonates (between 24 and 31 full weeks of gestation) were included in this regionally defined population of very preterm neonates in France. The main outcome measure was non-access to ACT.

[Charcot's disease of the lumbosacral joint in spinal cord injury: a case report].

Objective: Comment on spinal damage in Charcot's disease.

Observation: We report on a paraplegic patient with T9 spinal cord injury who developed destructive arthropathy of the lumbosacral joint.

Discussion: Charcot's disease occurs sporadically during the progression of certain chronic neurological diseases.

[Quality of life and scales measuring].

Scope: To present a review of the concept and the measurement of quality of life.

Current Situation And Salient Points: The concept of quality of life was developed in the seventies aiming to complete the medical evaluation. It appeared with improvement of disease prognosis, medical evaluation and the development of patient autonomy of patients.

Effects of tumor necrosis factor antagonist treatment on hepatitis C-related immunological abnormalities.

Background: Chronic hepatitis C infection is frequently associated with a mixed cryoglobulinaemia and circulating auto-antibodies, especially anti-smooth muscle cells (SMA) and anti-liver/kidney/microsome type 1 (LKM-1) anti-tissue antibodies. Treatments with TNF antagonists favour the emergence of auto-antibodies, and particularly anti-dsDNA antibodies.

Objective: To determine the impact of TNF antagonists on hepatitis C-related immune abnormalities.

[Asymptomatic blunt vertebral artery injury after cervical spine nonpenetrating trauma].

Objective: To show the possibility of vertebral injury after cervical spine trauma.

Method: We observed 2 cases of asymptomatic thrombosis of the vertebral artery after cervical fracture.

Discussion: Thrombosis of the vertebral artery is acute in 20% of cases of cervical trauma.

[Acute low back pain induced by calcifying nucleopathy].

Introduction: The nucleopathy calcifying of the inter vertebral disk is mostly asymptomatic.

Case Record: We report a cave miming a spondylodiscit.

Discussion: Although idiopatic in most case, it is necessary to look for a calcifying metabolic disease.

Leuconostoc osteomyelitis.

Leuconostoc spp. is a variety of streptococcus that can cause disease in humans, most notably those with HIV infection or other causes of immunodepression. We report the case of a patient who had Leuconostoc osteomyelitis in an area of lymphedema.