CD40 blockade hampers IgG class-switch while enhancing Granzyme B production by transitional B cells.

CD40-CD40L interaction is crucial for the interplay between B and T cells and determines B cell fate. Here, we investigated the effects of CD40-CD40L inhibition on B cell subsets and cytokine production using the non-depleting monoclonal anti-CD40 antibody CFZ534. CFZ534 had no impact on B cell viability but inhibited TLR9-agonistic (CpG-ODN) CD40L- as well as CD40L-mediated proliferation.

In vivo synergistic enhancement of MIF-mediated inflammation in acute lung injury by the plant ortholog Arabidopsis MDL1.

Recent research has uncovered Arabidopsis thaliana proteins that are similar to the human inflammatory cytokine MIF. Plant MIF/D-dopachrome tautomerase (D-DT)-like proteins (MDLs) can interact with human MIF, yet the significance of these findings in living organisms has not been investigated. Given MIF's key role in acute respiratory distress syndrome promoting pulmonary inflammation, pathology, and leukocyte infiltration, here we set out to investigate the interplay between MIF and MDL1, one of three A.

An atypical atherogenic chemokine that promotes advanced atherosclerosis and hepatic lipogenesis.

Atherosclerosis is the underlying cause of myocardial infarction and ischemic stroke. It is a lipid-triggered and cytokine/chemokine-driven arterial inflammatory condition. We identify D-dopachrome tautomerase/macrophage migration-inhibitory factor-2 (MIF-2), a paralog of the cytokine MIF, as an atypical chemokine promoting both atherosclerosis and hepatic lipid accumulation.

Prevalence estimates for COVID-19-related health behaviors based on the cheating detection triangular model.

Background: Survey studies in medical and health sciences predominantly apply a conventional direct questioning (DQ) format to gather private and highly personal information. If the topic under investigation is sensitive or even stigmatizing, such as COVID-19-related health behaviors and adherence to non-pharmaceutical interventions in general, DQ surveys can lead to nonresponse and untruthful answers due to the influence of social desirability bias (SDB). These effects seriously threaten the validity of the results obtained, potentially leading to distorted prevalence estimates for behaviors for which the prevalence in the population is unknown.

Engineering an inducible leukemia-associated fusion protein enables large-scale ex vivo production of functional human phagocytes.

Ex vivo expansion of human CD34+ hematopoietic stem and progenitor cells remains a challenge due to rapid differentiation after detachment from the bone marrow niche. In this study, we assessed the capacity of an inducible fusion protein to enable sustained ex vivo proliferation of hematopoietic precursors and their capacity to differentiate into functional phagocytes. We fused the coding sequences of an FK506-Binding Protein 12 (FKBP12)-derived destabilization domain (DD) to the myeloid/lymphoid lineage leukemia/eleven nineteen leukemia (MLL-ENL) fusion gene to generate the fusion protein DD-MLL-ENL and retrovirally expressed the protein switch in human CD34+ progenitors.

Plant MDL proteins synergize with the cytokine MIF at CXCR2 and CXCR4 receptors in human cells.

Mammalian macrophage migration inhibitory factor (MIF) and its paralog, D-dopachrome tautomerase, are multifunctional inflammatory cytokines. Plants have orthologous MIF and D-dopachrome tautomerase-like (MDL) proteins that mimic some of the effects of MIF on immune cells in vitro. We explored the structural and functional similarities between the three MDLs and MIF.

Linking brain activity across scales with simultaneous opto- and electrophysiology.

The brain enables adaptive behavior via the dynamic coordination of diverse neuronal signals across spatial and temporal scales: from fast action potential patterns in microcircuits to slower patterns of distributed activity in brain-wide networks. Understanding principles of multiscale dynamics requires simultaneous monitoring of signals in multiple, distributed network nodes. Combining optical and electrical recordings of brain activity is promising for collecting data across multiple scales and can reveal aspects of coordinated dynamics invisible to standard, single-modality approaches.

Heterocomplexes between the atypical chemokine MIF and the CXC-motif chemokine CXCL4L1 regulate inflammation and thrombus formation.

To fulfil its orchestration of immune cell trafficking, a network of chemokines and receptors developed that capitalizes on specificity, redundancy, and functional selectivity. The discovery of heteromeric interactions in the chemokine interactome has expanded the complexity within this network. Moreover, some inflammatory mediators, not structurally linked to classical chemokines, bind to chemokine receptors and behave as atypical chemokines (ACKs).

More than random responding: Empirical evidence for the validity of the (Extended) Crosswise Model.

The Randomized Response Technique (Warner, Journal of the American Statistical Association, 60, 63-69, 1965) has been developed to control for socially desirable responses in surveys on sensitive attributes. The Crosswise Model (CWM; Yu et al., Metrika, 67, 251-263, 2008) and its extension, the Extended Crosswise Model (ECWM; Heck et al.

Nothing but the truth? Effects of faking on the validity of the crosswise model.

In self-reports, socially desirable responding threatens the validity of prevalence estimates for sensitive personal attitudes and behaviors. Indirect questioning techniques such as the crosswise model attempt to control for the influence of social desirability bias. The crosswise model has repeatedly been found to provide more valid prevalence estimates than direct questions.

A database and deep learning toolbox for noise-optimized, generalized spike inference from calcium imaging.

Inference of action potentials ('spikes') from neuronal calcium signals is complicated by the scarcity of simultaneous measurements of action potentials and calcium signals ('ground truth'). In this study, we compiled a large, diverse ground truth database from publicly available and newly performed recordings in zebrafish and mice covering a broad range of calcium indicators, cell types and signal-to-noise ratios, comprising a total of more than 35 recording hours from 298 neurons. We developed an algorithm for spike inference (termed CASCADE) that is based on supervised deep networks, takes advantage of the ground truth database, infers absolute spike rates and outperforms existing model-based algorithms.

Controlled growth of ordered monolayers of N-heterocyclic carbenes on silicon.

N-Heterocyclic carbenes (NHCs) are promising modifiers and anchors for surface functionalization and offer some advantages over thiol-based systems. Because of their strong binding affinity and high electron donation, NHCs can dramatically change the properties of the surfaces to which they are bonded. Highly ordered NHC monolayers have so far been limited to metal surfaces.

Functional analysis of information rates conveyed by rat whisker-related trigeminal nuclei neurons.

The rat whisker system connects the tactile environment with the somatosensory thalamocortical system using only two synaptic stages. Encoding properties of the first stage, the primary afferents with somas in the trigeminal ganglion (TG), has been well studied, whereas much less is known from the second stage, the brainstem trigeminal nuclei (TN). The TN are a computational hub giving rise to parallel ascending tactile pathways and receiving feedback from many brain sites.

Macrophage Migration Inhibitory Factor (MIF) Plasma Concentration in Critically Ill COVID-19 Patients: A Prospective Observational Study.

Mortality in critically ill coronavirus disease 2019 (COVID-19) patients is high and pharmacological treatment strategies remain limited. Early-stage predictive biomarkers are needed to identify patients with a high risk of severe clinical courses and to stratify treatment strategies. Macrophage migration inhibitory factor (MIF) was previously described as a potential predictor for the outcome of critically ill patients and for acute respiratory distress syndrome (ARDS), a hallmark of severe COVID-19 disease.

Do they really wash their hands? Prevalence estimates for personal hygiene behaviour during the COVID-19 pandemic based on indirect questions.

Background: During the COVID-19 pandemic, billions of people have to change their behaviours to slow down the spreading of the virus. Protective measures include self-isolation, social (physical) distancing and compliance with personal hygiene rules, particularly regular and thorough hand washing. Prevalence estimates for the compliance with the COVID-19 measures are often based on direct self-reports.

Controlling social desirability bias: An experimental investigation of the extended crosswise model.

Indirect questioning techniques such as the crosswise model aim to control for socially desirable responding in surveys on sensitive personal attributes. Recently, the extended crosswise model has been proposed as an improvement over the original crosswise model. It offers all of the advantages of the original crosswise model while also enabling the detection of systematic response biases.

Designed CXCR4 mimic acts as a soluble chemokine receptor that blocks atherogenic inflammation by agonist-specific targeting.

Targeting a specific chemokine/receptor axis in atherosclerosis remains challenging. Soluble receptor-based strategies are not established for chemokine receptors due to their discontinuous architecture. Macrophage migration-inhibitory factor (MIF) is an atypical chemokine that promotes atherosclerosis through CXC-motif chemokine receptor-4 (CXCR4).

Can detailed instructions and comprehension checks increase the validity of crosswise model estimates?

The crosswise model is an indirect questioning technique designed to control for socially desirable responding. Although the technique has delivered promising results in terms of improved validity in survey studies of sensitive issues, recent studies have indicated that the crosswise model may sometimes produce false positives. Hence, we investigated whether an insufficient understanding of the crosswise model instructions might be responsible for these false positives and whether ensuring a deeper understanding of the model and surveying more highly educated respondents reduces the problem of false positives.

On the validity of non-randomized response techniques: an experimental comparison of the crosswise model and the triangular model.

Non-randomized response techniques (NRRTs) such as the crosswise model and the triangular model (CWM and TRM; Yu et al. Metrika, 67, 251-263, 2008) have been developed to control for socially desirable responding in surveys on sensitive personal attributes. We present the first study to directly compare the validity of the CWM and TRM and contrast their performance with a conventional direct questioning (DQ) approach.

Studying the Pro-Migratory Effects of MIF.

Macrophage migration inhibitory factor (MIF) is an upstream regulator of innate immunity and dysregulated MIF is a key mediator of acute and chronic inflammatory processes, autoimmune and cardiovascular diseases, as well as cancer. MIF is a pleiotropic cytokine with chemokine-like functions that has been designated as an atypical chemokine (ACK). It orchestrates leukocyte recruitment and migration into inflamed tissues through non-cognate interactions with the classical chemokine receptors CXCR2 and CXCR4, pathways that are further facilitated by MIF's cognate receptor CD74.

Detecting nonadherence without loss in efficiency: A simple extension of the crosswise model.

In surveys concerning sensitive behavior or attitudes, respondents often do not answer truthfully, because of social desirability bias. To elicit more honest responding, the randomized-response (RR) technique aims at increasing perceived and actual anonymity by prompting respondents to answer with a randomly modified and thus uninformative response. In the crosswise model, as a particularly promising variant of the RR, this is achieved by adding a second, nonsensitive question and by prompting respondents to answer both questions jointly.

On the comprehensibility and perceived privacy protection of indirect questioning techniques.

On surveys that assess sensitive personal attributes, indirect questioning aims at increasing respondents' willingness to answer truthfully by protecting confidentiality. However, the assumption that subjects understand questioning procedures fully and trust them to protect their privacy is rarely tested. In a scenario-based design, we compared four indirect questioning procedures in terms of their comprehensibility and perceived privacy protection.

A Strong Validation of the Crosswise Model Using Experimentally-Induced Cheating Behavior.

We constructed an online cheating paradigm that could be used to validate the Crosswise Model ( Yu, Tian, & Tang, 2008 ), a promising indirect questioning technique designed to control for socially desirable responding on sensitive questions. Participants qualified for a reward only if they could identify the target words from three anagrams, one of which was virtually unsolvable as shown on a pretest. Of the 664 participants, 15.