Mutagenesis to Orient Conjugation and Preserve Self-adjuvant Properties of Flagellin in Conjugates.

Bacterial flagellins are unique for their capacity to activate both the innate and the adaptive immune response through a Toll-like receptor 5 (TLR5) signaling cascade. Used as a carrier protein in conjugate vaccines, it is crucial to preserve their self-adjuvant properties during the conjugation step. Considering the absence of cysteine in the Salmonella enterica flagellin FliC sequence, we have investigated the impact of five mutations (A2 C, K180 C, T240 C, D251 C and S306 C) alone or in combination on TLR5 activation.

Impedimetric Characterization of NanA Structural Domains Activity on Sialoside-Containing Interfaces.

is a pathogenic bacterium that contains the surface-bound neuraminidase, . has two domains that interact with sialosides. It is hard to determine the contribution of each domain separately on catalysis or binding.

Pectin Remodeling and Involvement of AtPME3 in the Parasitic Plant-Plant Interaction, -.

is a root parasitic plant fully dependent on host plants for nutrition and development. Upon germination, the parasitic seedling develops inside the infected roots a specific organ, the haustorium, thanks to the cell wall-degrading enzymes of haustorial intrusive cells, and induces modifications in the host's cell walls. The model plant is susceptible to ; thus, mutants in cell wall metabolism, particularly those involved in pectin remodeling, like , are of interest in studying the involvement of cell wall-degrading enzymes in the establishment of plant-plant interactions.

Multivalent inhibition of the fumigatus KDNase.

is a saprophytic fungus and opportunistic pathogen often causing fatal infections in immunocompromised patients. Recently KDNAse, an exoglycosidase hydrolyzing 3-deoxy-D-galacto-D--nonulosonic acid (KDN), a rare sugar from the sialic acid family, was identified and characterized. The principal function of KDNAse is still unclear, but a study suggests a critical role in fungal cell wall morphology and virulence.

Early Detection of Cardiotoxicity Using [Cu]Cu-NODAGA-E[(cRGDyK)]2 PET Imaging in a Rat Model of Doxorubicin-Induced Heart Failure.

Doxorubicin (DOX) is a common and highly effective chemotherapeutic. However, its use is limited by cardiotoxic effects and the lack of methods to detect these at early time points. In the present study, we evaluated if [Cu]Cu-NODAGA-E[(cRGDyK)]2 positron emission tomography-computed tomography ([Cu]Cu-RGD PET/CT) could detect cardiotoxicity in a rat model of DOX-induced heart failure.

Harbour porpoises respond to recreational boats by speeding up and moving away from the boat path.

Recreational boats are common in many coastal waters, yet their effects on cetaceans and other sensitive marine species remain poorly understood. To address this knowledge gap, we used drone video footage recorded from a recreational boat to quantify how harbour porpoises () responded to the boat approaching at different speeds (10 or 20 knots). Furthermore, we used a hydrophone to record boat noise levels at full bandwidth (0.

Innovations to Improve Lung Isolation Training for Thoracic Anesthesia: A Narrative Review.

A double-lumen tube or bronchial blocker positioning using flexible bronchoscopy for lung isolation and one-lung ventilation requires specific technical competencies. Training to acquire and retain such skills remains a challenge in thoracic anesthesia. Recent technological and innovative developments in the field of simulation have opened up exciting new horizons and possibilities.

Effectiveness and family experiences of interventions promoting partnerships between families and pediatric and neonatal intensive care units: a mixed methods systematic review.

Objective: The objective of this mixed methods review was to examine the effectiveness and family experiences of interventions promoting partnerships between families and the multidisciplinary health care team in pediatric and neonatal intensive care units.

Introduction: Hospitalization of infants and children in neonatal intensive care units and pediatric intensive care units has a significant effect on their families, including increased stress, anxiety, and depression. Available evidence syntheses focused on specific family-centered care, but not on partnership, which is another aspect that may improve families' outcomes and experiences.

Anti-PD-1 therapy triggers Tfh cell-dependent IL-4 release to boost CD8 T cell responses in tumor-draining lymph nodes.

Anti-PD-1 therapy targets intratumoral CD8+ T cells to promote clinical responses in cancer patients. Recent evidence suggests an additional activity in the periphery, but the underlying mechanism is unclear. Here, we show that anti-PD-1 mAb enhances CD8+ T cell responses in tumor-draining lymph nodes by stimulating cytokine production in follicular helper T cells (Tfh).

[Ten years of nurse consultation at the pediatric emergency department].

The Nurse consultation (CI) was implemented in 2013 at the emergency department of the Lausanne Children's Hospital. It offers medical delegated care for children aged three to 18. Ten years after its implementation, this article takes stock of its progress.

[Antipsychotic prescribing in adults : what to watch out for ?].

Antipsychotics are known to produce frequent and/or potentially serious adverse effects, including neurological, cardiovascular, metabolic and endocrine effects. The side-effects of antipsychotics vary according to their affinity for different central and peripheral receptors, and individual vulnerabilities. Some of these side-effects are dose-dependent, while others are little or not ; thus, management strategies need to be adapted.

Semisynthetic Pneumococcal Glycoconjugate Nanovaccine.

Pneumococcal conjugate vaccines offer an excellent safety profile and high protection against the serotypes comprised in the vaccine. However, inclusion of protein antigens fromcombined with potent adjuvants and a suitable delivery system are expected to both extend protection to serotype strains not represented in the formulation and stimulate a broader immune response, thus more effective in young children, elderly, and immunocompromised populations. Along this line, nanoparticle (NP) delivery systems can enhance the immunogenicity of antigens by protecting them from degradation and increasing their uptake by antigen-presenting cells, as well as offering co-delivery with adjuvants.

Click-electrochemistry for the rapid labeling of virus, bacteria and cell surfaces.

Methods for direct covalent ligation of microorganism surfaces remain poorly reported, and mostly based on metabolic engineering for bacteria and cells functionalization. While effective, a faster method avoiding the bio-incorporation step would be highly complementary. Here, we used N-methylluminol (NML), a fully tyrosine-selective protein anchoring group after one-electron oxidation, to label the surface of viruses, living bacteria and cells.

Imaging of atherosclerosis with [Cu]Cu-DOTA-TATE in a translational head-to-head comparison study with [F]FDG, and Na[F]F in rabbits.

Atherosclerosis is a chronic inflammatory disease of the larger arteries that may lead to cardiovascular events. Identification of patients at highest risk of cardiovascular events is challenging, but molecular imaging using positron emission tomography (PET) may prove useful. The aim of this study was to evaluate and compare head-to-head three different PET tracers.

Tumor-intrinsic sensitivity to the pro-apoptotic effects of IFN-γ is a major determinant of CD4 CAR T-cell antitumor activity.

CD4 T cells and CD4 chimeric antigen receptor (CAR) T cells display highly variable antitumor activity in preclinical models and in patients; however, the mechanisms dictating how and when CD4 T cells promote tumor regression are incompletely understood. With the help of functional intravital imaging, we report that interferon (IFN)-γ production but not perforin-mediated cytotoxicity was the dominant mechanism for tumor elimination by anti-CD19 CD4 CAR T cells. Mechanistically, mouse or human CD4 CAR T-cell-derived IFN-γ diffused extensively to act on tumor cells at distance selectively killing tumors sensitive to cytokine-induced apoptosis, including antigen-negative variants.

[Ga]Ga-NODAGA-E[(cRGDyK)] angiogenesis PET following myocardial infarction in an experimental rat model predicts cardiac functional parameters and development of heart failure.

Background: Angiogenesis has increasingly been a target for imaging and treatment over the last decade. The integrin αβ is highly expressed in cells during angiogenesis and are therefore a promising target for imaging. In this study, we aimed to investigate the PET tracer [Ga]Ga-RGD as a marker of angiogenesis following MI and its ability to predict cardiac functional parameters.

Immunomodulation under the lens of real-time in vivo imaging.

Modulation of cells and molecules of the immune system not only represents a major opportunity to treat a variety of diseases including infections, cancer, autoimmune, and inflammatory disorders but could also help understand the intricacies of immune responses. A detailed mechanistic understanding of how a specific immune intervention may provide clinical benefit is essential for the rational design of efficient immunomodulators. Visualizing the impact of immunomodulation in real-time and in vivo has emerged as an important approach to achieve this goal.

Site-Selective Unnatural Amino Acid Incorporation at Single or Multiple Positions to Control Sugar-Protein Connectivity in Glycoconjugate Vaccine Candidates.

In cellulo site-specific unnatural amino acid incorporation based on amber stop codon reassignment is a powerful tool to modify proteins at defined positions. This technique is herein applied to the selective functionalization of the Pneumococcal surface adhesin A protein at three distinct positions. N -propargyloxycarbonyl-l-lysine residues were incorporated and their alkyne groups reacted using click-chemistry with a synthetic azido-functionalized tetrasaccharide representative of one repeat unit of the Streptococcus pneumoniae serotype 14 capsular polysaccharide.

Insomnia disorders are associated with increased cardiometabolic disturbances and death risks from cardiovascular diseases in psychiatric patients treated with weight-gain-inducing psychotropic drugs: results from a Swiss cohort.

Study Objectives: Insomnia disorders as well as cardiometabolic disorders are highly prevalent in the psychiatric population compared to the general population. We aimed to investigate their association and evolution over time in a Swiss psychiatric cohort.

Methods: Data for 2861 patients (8954 observations) were obtained from two prospective cohorts (PsyMetab and PsyClin) with metabolic parameters monitored routinely during psychotropic treatment.

Semaglutide reduces vascular inflammation investigated by PET in a rabbit model of advanced atherosclerosis.

Background And Aims: The objective of this study was to investigate the effects of semaglutide, a long acting glucagon-like peptide-1 receptor agonist, on atherosclerotic inflammation and calcification using a multimodality positron emission tomography and computed tomography (PET/CT) approach.

Methods: Atherosclerotic New Zealand White rabbits were randomized to an intervention- (n = 12) or placebo group (n = 11) receiving either semaglutide or saline-placebo. PET/CT imaging was done before and after 16-weeks of intervention.

[Gabapentinoids : misuses and addictions].

Cases of addictions and misuses on gabapentinoids are increasingly reported. But the underlying pharmacological mechanism is not completely understood. Here is an uptodate of the current knowledges on this dependence and its management.