Tuft cells in the intestine, immunity and beyond.

Tuft cells have gained substantial attention over the past 10 years due to numerous reports linking them with type 2 immunity and microorganism-sensing capacity in many mucosal tissues. This heightened interest is fuelled by their unique ability to produce an array of biological effector molecules, including IL-25, allergy-related eicosanoids, and the neurotransmitter acetylcholine, enabling downstream responses in diverse cell types. Operating through G protein-coupled receptor-mediated signalling pathways reminiscent of type II taste cells in oral taste buds, tuft cells emerge as chemosensory sentinels that integrate luminal conditions, eliciting appropriate responses in immune, epithelial and neuronal populations.

Catalytic, Enantioselective Cycloaddition of Pyrrole-2methides with Aldehydes toward a Synthesis of 2,3-Dihydro-1-pyrrolizin-3-ols.

An organocatalytic, highly enantioselective [6 + 2]-cycloaddition of 2-methide-2-pyrroles with aryl acetaldehydes represents a novel and straightforward route toward densely substituted 2,3-dihydro-1-pyrrolizin-3-ols, which were generated with good yields and high enantio- and diastereoselectivity. This one-step process involves a BINOL-phosphoric acid catalyzed reaction of 1-pyrrole-2-carbinols with aryl acetaldehydes via the corresponding hydrogen-bonded, chiral 2-methide-2-pyrroles.

Amplification of autoimmune organ damage by NKp46-activated ILC1s.

In systemic lupus erythematosus, loss of immune tolerance, autoantibody production and immune complex deposition are required but not sufficient for organ damage. How inflammatory signals are initiated and amplified in the setting of autoimmunity remains elusive. Here we set out to dissect layers and hierarchies of autoimmune kidney inflammation to identify tissue-specific cellular hubs that amplify autoinflammatory responses.

Recruited atypical Ly6G macrophages license alveolar regeneration after lung injury.

The lung is constantly exposed to airborne pathogens and particles that can cause alveolar damage. Hence, appropriate repair responses are essential for gas exchange and life. Here, we deciphered the spatiotemporal trajectory and function of an atypical population of macrophages after lung injury.

Parsimonious Random-Forest-Based Land-Use Regression Model Using Particulate Matter Sensors in Berlin, Germany.

Machine learning (ML) methods are widely used in particulate matter prediction modelling, especially through use of air quality sensor data. Despite their advantages, these methods' black-box nature obscures the understanding of how a prediction has been made. Major issues with these types of models include the data quality and computational intensity.

Sustained innate interferon is an essential inducer of tertiary lymphoid structures.

Tertiary lymphoid structures (TLS) resemble follicles of secondary lymphoid organs and develop in nonlymphoid tissues during inflammation and cancer. Which cell types and signals drive the development of TLS is largely unknown. To investigate early events of TLS development in the lungs, we repeatedly instilled p(I:C) plus ovalbumin (Ova) intranasally.

Atrophy links lower novelty-related locus coeruleus connectivity to cognitive decline in preclinical AD.

Introduction: Animal research has shown that tau pathology in the locus coeruleus (LC) is associated with reduced norepinephrine signaling, lower projection density to the medial temporal lobe (MTL), atrophy, and cognitive impairment. We investigated the contribution of LC-MTL functional connectivity (FC) on cortical atrophy across Braak stage regions and its impact on cognition.

Methods: We analyzed functional magnetic resonance imaging and amyloid beta (Aβ) positron emission tomography data from 128 cognitively normal participants, associating novelty-related FC with longitudinal atrophy and cognition with and without Aβ moderation.

General, Modular Access toward Immobilized Chiral Phosphoric Acid Catalysts and Their Application in Flow Chemistry.

Chiral phosphoric acids (CPAs) are among the most frequently used organocatalysts, with an ever-increasing number of applications. However, these catalysts are only obtained in a multistep synthesis and are poorly recyclable, which significantly deteriorates their environmental and economic performance. We herein report a conceptually different, general strategy for the direct immobilization of CPAs on a broad scope of solid supports including silica, polystyrene, and aluminum oxide.

The Doppler Perfusion Index of the Liver and the Underlying Duplex Sonography of Visceral Vessels-A Systematic and Comprehensive Evaluation of Reproducibility.

Prior to the curative resection of colorectal carcinoma (CRC) or pancreatic ductal adenocarcinoma (PDAC), the exclusion of hepatic metastasis using cross-sectional imaging is mandatory. The Doppler perfusion index (DPI) of the liver is a promising method for detecting occult liver metastases, but the underlying visceral duplex sonography is critically viewed in terms of its reproducibility. The aim of this study was to investigate systematically the reproducibility of the measured variables, the calculated blood flow, and the DPI.

Tuft cell IL-17RB restrains IL-25 bioavailability and reveals context-dependent ILC2 hypoproliferation.

The tuft cell-ILC2 circuit orchestrates rapid type 2 responses upon detecting microbe-derived succinate and luminal helminths. Our findings delineate key mechanistic steps, involving IP3R2 engagement and Ca flux, governing IL-25 production by tuft cells triggered by succinate detection. While IL-17RB plays a pivotal intrinsic role in ILC2 activation, it exerts a regulatory function in tuft cells.

Organocatalytic enantioselective oxa-Piancatelli rearrangement.

The first highly enantioselective oxa-Piancatelli rearrangement has been developed. This process which is catalyzed by a chiral BINOL-derived phosphoric acid rearranges a wide range of furylcarbinols into densely substituted γ-hydroxy cyclopentenones in high yield with excellent diastereo- and enantioselectivities (up to 99 : 1 er). This reaction exhibits a high functional group tolerance and was applied to complex bioactive molecules as well.

Inter-System Variability of Eight Different Handheld Ultrasound (HHUS) Devices-A Prospective Comparison of B-Scan Quality and Clinical Significance in Intensive Care.

Background: the use of handheld ultrasonography (HHUS) devices is well established in prehospital emergency diagnostics, as well as in intensive care settings. This is based on several studies in which HHUS devices were compared to conventional high-end ultrasonography (HEUS) devices. Nonetheless, there is limited evidence regarding potential variations in B-scan quality among HHUS devices from various manufacturers, and regarding whether any such differences hold clinical significance in intensive care medicine settings.

Prospective Comparison of Handheld Ultrasound Devices from Different Manufacturers with Respect to B-Scan Quality and Clinical Significance for Various Abdominal Sonography Questions.

Background: Handheld ultrasound (HHUS) devices have chiefly been deployed in emergency medicine, where they are considered a valid tool. The data situation is less clear in the case of internal questions in abdominal sonography. In our study, we investigate whether HHUS devices from different manufacturers differ in their B-scan quality, and whether any differences are relevant for the significance of an internal ultrasound examination.

Differences in the B-mode imaging quality of ultrasound devices in the mid-price segment.

Aims: A meaningful sonographic examination is decisively dependent on the B-scan quality of the ultrasound device. When selecting a suitable ultrasound device, B-scan quality should be an important purchase criterion. Although there is no generally accepted method to measure B-scan quality, we tried to evaluate comparable sonography devices from different manufacturers regarding B-scan quality.

Microbial energy metabolism fuels an intestinal macrophage niche in solitary isolated lymphoid tissues through purinergic signaling.

Maintaining macrophage (MΦ) heterogeneity is critical to ensure intestinal tissue homeostasis and host defense. The gut microbiota and host factors are thought to synergistically guide intestinal MΦ development, although the exact nature, regulation, and location of such collaboration remain unclear. Here, we report that microbial biochemical energy metabolism promotes colony-stimulating factor 2 (CSF2) production by group 3 innate lymphoid cells (ILC3s) within solitary isolated lymphoid tissues (SILTs) in a cell-extrinsic, NLRP3/P2X7R-dependent fashion in the steady state.

Intrinsic TGF-β signaling attenuates proximal tubule mitochondrial injury and inflammation in chronic kidney disease.

Excessive TGF-β signaling and mitochondrial dysfunction fuel chronic kidney disease (CKD) progression. However, inhibiting TGF-β failed to impede CKD in humans. The proximal tubule (PT), the most vulnerable renal segment, is packed with giant mitochondria and injured PT is pivotal in CKD progression.

Antibody diversity in IVIG: Therapeutic opportunities for novel immunotherapeutic drugs.

Significant progress has been made in the elucidation of human antibody repertoires. Furthermore, non-canonical functions of antibodies have been identified that reach beyond classical functions linked to protection from pathogens. Polyclonal immunoglobulin preparations such as IVIG and SCIG represent the IgG repertoire of the donor population and will likely remain the cornerstone of antibody replacement therapy in immunodeficiencies.

Brønsted Acid Catalyzed Asymmetric Synthesis of cis-Tetrahydrocannabinoids.

We report herein the catalytic asymmetric cyclization of 1-aryl terpenols to afford enantiomerically highly enriched Δ -cis-tetrahydrocannabinoid scaffolds in a single step. As powerful chiral catalysts strongly acidic imidodiphosphorimidates (IDPis) have been identified which furnish the products with good yields and excellent enantioselectivity. Upon MOM-deprotection some naturally occurring cannabimimetica such as (-)-cis-Δ -tetrahydrocannabinol and (-)-perrottetinene as well as some unnatural analogues were made accessible along a merely 3-step biomimetic sequence (MOM=methoxymethyl).

Priorities for research on neuromodulatory subcortical systems in Alzheimer's disease: Position paper from the NSS PIA of ISTAART.

The neuromodulatory subcortical system (NSS) nuclei are critical hubs for survival, hedonic tone, and homeostasis. Tau-associated NSS degeneration occurs early in Alzheimer's disease (AD) pathogenesis, long before the emergence of pathognomonic memory dysfunction and cortical lesions. Accumulating evidence supports the role of NSS dysfunction and degeneration in the behavioral and neuropsychiatric manifestations featured early in AD.

Enantioselective 1,6-Addition of β-Ketoester Enolates to Generated -Quinone Methides Enabled by Cooperative Palladium and Brønsted Acid Catalysis.

We report herein an asymmetric cooperative process for the enantioselective 1,6-addition of β-ketoesters to generated -quinone methides with chiral Pd-aqua complexes as mixed Brønsted acid-base catalysts. Excellent yields, outstanding enantiocontrol, and good diastereoselectivity across a broad substrate range are highlights of this transformation. The utility of this reaction is further demonstrated by a facile scale up and subsequent complexity-increasing modifications.