TAB2 controls a TAK1-independent cell death checkpoint at the level of TNFR1 complex II in the TNF pathway.

Tumor necrosis factor (TNF) signaling determines the cell's fate by promoting either survival or cell death via apoptosis, necroptosis or pyroptosis. Excessive or chronic cell death by TNF was shown to drive inflammatory pathologies, highlighting the importance of the mechanisms that normally block TNF cytotoxicity. This study investigates the role of TAB2, an adaptor protein traditionally linked to TAK1 activation in the TNF pathway.

Collective quench dynamics of active photonic lattices in synthetic dimensions.

Photonic emulators have enabled the study of many solid-state and quantum optics phenomena, such as Anderson localization, topological insulators and non-Hermitian dynamics. Current photonic emulators are generally limited to bosonic behaviour with local interactions, but the use of synthetic dimensions offers a pathway to overcome this constraint. Here we investigate the flow of liquid light in modulated fast-gain ring lasers, and we establish a platform for emulating quench dynamics within a synthetic photonic lattice with equal densities across the reciprocal space.

Primidone: a clinically promising candidate for the treatment of psoriasis.

Using clinically relevant animal models, we have recently demonstrated that the anticonvulsant primidone (Liskantin), approved by the FDA for the treatment of various forms of epilepsy, can effectively block RIPK1 enzymatic activity, which mediates cell death, and consequently prevent RIPK1 cytotoxicity and associated inflammatory responses. Based on these findings, we now reveal both a preventive and, more importantly, a therapeutic effect of primidone in the imiquimod (IMQ)-induced psoriasis-like inflammation model. Notably, the protective effect of IMQ in this necroinflammatory disease is directly correlated with inhibition of the activated state of RIPK1 (as monitored by auto-phosphorylation on Ser166/T169), a critical marker that had been missing in the highly contradictory studies that have previously been published.

RIPK1 is dispensable for cell death regulation in β-cells during hyperglycemia.

Objective: Receptor-interacting protein kinase 1 (RIPK1) orchestrates the decision between cell survival and cell death in response to tumor necrosis factor (TNF) and other cytokines. Whereas the scaffolding function of RIPK1 is crucial to prevent TNF-induced apoptosis and necroptosis, its kinase activity is required for necroptosis and partially for apoptosis. Although TNF is a proinflammatory cytokine associated with β-cell loss in diabetes, the mechanism by which TNF induces β-cell demise remains unclear.

Low-Loss Buried InGaAs/InP Integrated Waveguides in the Long-Wave Infrared.

In this work, we present a photonic integrated platform based on buried InGaAs waveguides with InP cladding that operates over a large mid-infrared (mid-IR) spectral range. Thanks to wet-etch fabrication patterning and Fe doping, low propagation losses below 1.2 dB/cm (0.

The autophagy protein RUBCNL/PACER represses RIPK1 kinase-dependent apoptosis and necroptosis.

Mesenchymal stem cells (MSCs) are used in cell therapy; nonetheless, their application is limited by their poor survival after transplantation in a proinflammatory microenvironment. Macroautophagy/autophagy activation in MSCs constitutes a stress adaptation pathway, promoting cellular homeostasis. Our proteomics data indicate that RUBCNL/PACER (RUN and cysteine rich domain containing beclin 1 interacting protein like), a positive regulator of autophagy, is also involved in cell death.

Tumor endothelial cell autophagy is a key vascular-immune checkpoint in melanoma.

Tumor endothelial cells (TECs) actively repress inflammatory responses and maintain an immune-excluded tumor phenotype. However, the molecular mechanisms that sustain TEC-mediated immunosuppression remain largely elusive. Here, we show that autophagy ablation in TECs boosts antitumor immunity by supporting infiltration and effector function of T-cells, thereby restricting melanoma growth.

NINJ1 is activated by cell swelling to regulate plasma membrane permeabilization during regulated necrosis.

Plasma membrane permeabilization (PMP) is a defining feature of regulated necrosis. It allows the extracellular release of damage-associated molecular patterns (DAMPs) that trigger sterile inflammation. The pore forming molecules MLKL and GSDMs drive PMP in necroptosis and pyroptosis, respectively, but the process of PMP remains unclear in many other forms of regulated necrosis.

Quantum walk comb in a fast gain laser.

Synthetic lattices in photonics enable the exploration of light states in new dimensions, transcending phenomena common only to physical space. We propose and demonstrate a quantum walk comb in synthetic frequency space formed by externally modulating a ring-shaped semiconductor laser with ultrafast recovery times. The initially ballistic quantum walk does not dissipate into low supermode states of the synthetic lattice; instead, the state stabilizes in a broad frequency comb, unlocking the full potential of the synthetic frequency lattice.

Position: A study protocol for the prevention of fall injuries in french special forces selection courses using a body-centered intervention.

Introduction: The Military Physical and Sports Training program was developed by the French Army in order to train, optimize, and maintain individual readiness. Although the health benefits of sport practice do not need to be demonstrated, such activities can cause acute musculoskeletal injuries that need to be addressed. The prevalence of lower limb injury is rather high in the French military population and, in particular, ranges from 15 to 45% during Special Forces selection courses.

Cell death checkpoints in the TNF pathway.

Tumor necrosis factor (TNF) plays a central role in orchestrating mammalian inflammatory responses. It promotes inflammation either directly by inducing inflammatory gene expression or indirectly by triggering cell death. TNF-mediated cell death-driven inflammation can be beneficial during infection by providing cell-extrinsic signals that help to mount proper immune responses.

Apoptotic cell death in disease-Current understanding of the NCCD 2023.

Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions.

From PERK to RIPK1: Design, synthesis and evaluation of novel potent and selective necroptosis inhibitors.

Receptor-Interacting serine/threonine-Protein Kinase 1 (RIPK1) emerged as an important driver of inflammation and, consequently, inflammatory pathologies. The enzymatic activity of RIPK1 is known to indirectly promote inflammation by triggering cell death, in the form of apoptosis, necroptosis and pyroptosis. Small molecule Receptor-Interacting serine/threonine-Protein Kinase 1 inhibitors have therefore recently entered clinical trials for the treatment of a subset of inflammatory pathologies.

LC3-independent autophagy is vital to prevent TNF cytotoxicity.

The (macro)autophagy field is facing a paradigm shift after the recent discovery that cytosolic cargoes can still be selectively targeted to phagophores (the precursors to autophagosomes) even in the absence of LC3 or other Atg8-protein family members. Several studies have indeed reported on the existence of an unconventional selective autophagic pathway that involves the formation of an autophagosome around the cargo through the direct selective autophagy receptor-mediated recruitment of RB1CC1/FIP200, thereby bypassing the requirement of LC3. In an article recently published in , we demonstrate the physiological importance of this unconventional autophagic pathway in the context of TNF (tumor necrosis factor) signaling.

Inhibition of RIPK1 kinase does not affect diabetes development: β-Cells survive RIPK1 activation.

Objectives: Type 1 diabetes (T1D) is caused by progressive immune-mediated loss of insulin-producing β-cells. Inflammation is detrimental to β-cell function and survival, moreover, both apoptosis and necrosis have been implicated as mechanisms of β-cell loss in T1D. The receptor interacting serine/threonine protein kinase 1 (RIPK1) promotes inflammation by serving as a scaffold for NF-κB and MAPK activation, or by acting as a kinase that triggers apoptosis or necroptosis.

Frequency chirped Fourier-Transform spectroscopy.

Fast (sub-second) spectroscopy with high spectral resolution is of vital importance for revealing quantum chemistry kinetics of complex chemical and biological reactions. Fourier transform (FT) spectrometers can achieve high spectral resolution and operate at hundreds of ms time scales in rapid-scan mode. However, the linear translation of a scanning mirror imposes stringent time-resolution limitations to these systems, which makes simultaneous high spectral and temporal resolution very difficult.

RIPK1 kinase-dependent inflammation and cell death contribute to the pathogenesis of COPD.

Background: Receptor-interacting protein kinase 1 (RIPK1) is a key mediator of regulated cell death (including apoptosis and necroptosis) and inflammation, both drivers of COPD pathogenesis. We aimed to define the contribution of RIPK1 kinase-dependent cell death and inflammation in the pathogenesis of COPD.

Methods: We assessed expression in single-cell RNA sequencing (RNA-seq) data from human and mouse lungs, and validated RIPK1 levels in lung tissue of COPD patients immunohistochemistry.

Phosphorylation of RIPK1 serine 25 mediates IKK dependent control of extrinsic cell death in T cells.

The Inhibitor of Kappa B Kinase (IKK) complex is a critical regulator of NF-κB activation. More recently, IKK has also been shown to repress RIPK1 dependent extrinsic cell death pathways by directly phosphorylating RIPK1 at serine 25. In T cells, IKK expression is essential for normal development in the thymus, by promoting survival of thymocytes independently of NF-κB activation.

ATG9A prevents TNF cytotoxicity by an unconventional lysosomal targeting pathway.

Cell death induced by tumor necrosis factor (TNF) can be beneficial during infection by helping to mount proper immune responses. However, TNF-induced death can also drive a variety of inflammatory pathologies. Protectives brakes, or cell-death checkpoints, normally repress TNF cytotoxicity to protect the organism from its potential detrimental consequences.

Effects of Native Whey Protein and Carbohydrate Supplement on Physical Performance and Plasma Markers of Muscle Damage and Inflammation during a Simulated Rugby Sevens Tournament: A Double-Blind, Randomized, Placebo-Controlled, Crossover Study.

The importance of optimized recovery during a sport competition is undisputed. The objective of this study was to determine the effects of recovery drinks comprising either carbohydrate only, or a mix of native whey proteins and carbohydrate to maintain physical performance and minimize muscle damage during a simulated rugby sevens (rugby 7s) tournament. Twelve well-trained male rugby players participated in three simulated rugby 7s tournament days with a week's interval in between.

Death by TNF: a road to inflammation.

Tumour necrosis factor (TNF) is a central cytokine in inflammatory reactions, and biologics that neutralize TNF are among the most successful drugs for the treatment of chronic inflammatory and autoimmune pathologies. In recent years, it became clear that TNF drives inflammatory responses not only directly by inducing inflammatory gene expression but also indirectly by inducing cell death, instigating inflammatory immune reactions and disease development. Hence, inhibitors of cell death are being considered as a new therapy for TNF-dependent inflammatory diseases.

Synchronization of frequency combs by optical injection.

Optical frequency combs based on semiconductor lasers are a promising technology for monolithic integration of dual-comb spectrometers. However, the stabilization of offset frequency f remains a challenging feat due the lack of octave-spanning spectra. In a dual-comb configuration, the uncorrelated jitter of the offset frequencies leads to a non-periodic signal resulting in broadened beatnotes with a limited signal-to-noise ratio (SNR).

A20 controls RANK-dependent osteoclast formation and bone physiology.

The anti-inflammatory protein A20 serves as a critical brake on NF-κB signaling and NF-κB-dependent inflammation. In humans, polymorphisms in or near the TNFAIP3/A20 gene have been associated with several inflammatory disorders, including rheumatoid arthritis (RA), and experimental studies in mice have demonstrated that myeloid-specific A20 deficiency causes the development of a severe polyarthritis resembling human RA. Myeloid A20 deficiency also promotes osteoclastogenesis in mice, suggesting a role for A20 in the regulation of osteoclast differentiation and bone formation.

Endocytic membrane repair by ESCRT-III controls antigen export to the cytosol during antigen cross-presentation.

Despite its crucial role in initiation of cytotoxic immune responses, the molecular pathways underlying antigen cross-presentation remain incompletely understood. The mechanism of antigen exit from endocytic compartments into the cytosol is a long-standing matter of controversy, confronting two main models: transfer through specific channels/transporters or rupture of endocytic membranes and leakage of luminal content. By monitoring the occurrence of intracellular damage in conventional dendritic cells (cDCs), we show that cross-presenting cDC1s display more frequent endomembrane injuries and increased recruitment of endosomal sorting complex required for transport (ESCRT)-III, the main repair system for intracellular membranes, relative to cDC2s.

Real-time monitoring of aqueous Hg reduction dynamics by magnetite/iron metal composite powders synthesized hydrothermally.

An iron-based powder material composed of zerovalent iron (8 wt.%) and magnetite (92 wt.%), has been synthesized hydrothermally at 200 °C from zero-valent iron.