We are living in an era of environmental change with undeniable parallels with past mass extinctions. To improve our understanding of planetary health and resilience, we must expand our research beyond traditional lab models. Forecasting the future of biological diversity relies on extrapolation of past trends, which necessitates the study of a wider range of biological systems.
View Article and Find Full Text PDFUpon stimulation of membrane receptors, nicotinic acid adenine dinucleotide phosphate (NAADP) is formed as second messenger within seconds and evokes Ca signaling in many different cell types. Here, to directly stimulate NAADP signaling, MASTER-NAADP, a Membrane permeAble, STabilized, bio-rEversibly pRotected precursor of NAADP is synthesized and release of its active NAADP mimetic, benzoic acid C-nucleoside, 2'-phospho-3'F-adenosine-diphosphate, by esterase digestion is confirmed. In the presence of NAADP receptor HN1L/JPT2 (hematological and neurological expressed 1-like protein, HN1L, also known as Jupiter microtubule-associated homolog 2, JPT2), this active NAADP mimetic releases Ca and increases the open probability of type 1 ryanodine receptor.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Cell Res
December 2024
Ca signalling is pivotal in T cell activation, an essential process in adaptive immune responses. Key to this activation are Ca microdomains, which are transient increases in cytosolic Ca concentration occurring within narrow regions between the endoplasmic reticulum (ER) and the plasma membrane (PM), lasting a few tens of milliseconds. Adhesion Dependent Ca Microdomains (ADCM) rely on store-operated Ca entry (SOCE) via the ORAI/STIM system.
View Article and Find Full Text PDFMany animals share a lifelong capacity to adapt their growth rates and body sizes to changing environmental food supplies. However, the cellular and molecular basis underlying this plasticity remains only poorly understood. We therefore studied how the sea anemones Nematostella vectensis and Aiptasia (Exaiptasia pallida) respond to feeding and starvation.
View Article and Find Full Text PDFUnderstanding the evolution of coral endosymbiosis requires a predictive framework that integrates life-history theory and ecology with cell biology. The time has come to bridge disciplines and use a model systems approach to achieve this aim.
View Article and Find Full Text PDFCD39 is the major enzyme controlling the levels of extracellular adenosine triphosphate (ATP) via the stepwise hydrolysis of ATP to adenosine diphosphate (ADP) and adenosine monophosphate (AMP). As extracellular ATP is a strong promoter of inflammation, monoclonal antibodies (mAbs) blocking CD39 are utilized therapeutically in the field of immune-oncology. Though anti-CD39 mAbs are highly specific for their target, they lack deep penetration into the dense tissue of solid tumors, due to their large size.
View Article and Find Full Text PDFFront Endocrinol (Lausanne)
February 2024
Introduction: During thermogenesis, adipose tissue (AT) becomes more active and enhances oxidative metabolism. The promotion of this process in white AT (WAT) is called "browning" and, together with the brown AT (BAT) activation, is considered as a promising approach to counteract obesity and metabolic diseases. Transient receptor potential cation channel, subfamily M, member 2 (TRPM2), is an ion channel that allows extracellular Ca influx into the cytosol, and is gated by adenosine diphosphate ribose (ADPR), produced from NAD degradation.
View Article and Find Full Text PDFTRPM2 is a Ca permeable, non-selective cation channel in the plasma membrane that is involved in the innate immune response regulating, for example, chemotaxis in neutrophils and cytokine secretion in monocytes and macrophages. The intracellular adenine nucleotides ADP-ribose (ADPR) and 2'-deoxy-ADPR (2dADPR) activate the channel, in combination with their co-agonist Ca. Interestingly, activation of human TRPM2 (hsTRPM2) by 2dADPR is much more effective than activation by ADPR.
View Article and Find Full Text PDFCa microdomains play a key role in intracellular signaling processes. For instance, they mediate the activation of T cells and, thus, the initial adaptive immune system. They are, however, also of utmost importance for activation of other cells, and a detailed understanding of the dynamics of these spatially localized Ca signals is crucial for a better understanding of the underlying signaling processes.
View Article and Find Full Text PDFBundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz
December 2023
Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz
December 2023
October 2019 saw the launch of iMED DENT, the first model study program in dentistry in Germany. The launch was preceded by a development process lasting several years in which European locations, among others, with innovative dental study programs were initially visited. The central reform objective of the model study program was then defined: the development, implementation, and ongoing optimization of an interdisciplinary curriculum with a scientific focus that integrates theoretical and practical dental content.
View Article and Find Full Text PDFCellular Ca signaling is highly organized in time and space. Locally restricted and short-lived regions of Ca increase, called Ca microdomains, constitute building blocks that are differentially arranged to create cellular Ca signatures controlling physiological responses. Here, we focus on Ca microdomains occurring in restricted cytosolic spaces between the plasma membrane and the endoplasmic reticulum, called endoplasmic reticulum-plasma membrane junctions.
View Article and Find Full Text PDFPhotosymbiotic cnidarians generally seek bright environments so that their symbionts can be photosynthetically active. However, excess light may result in a breakdown of symbiosis due to the accumulation of photodamage in symbionts causing symbiont loss (bleaching). It is currently unknown if photosymbiotic cnidarians sense light only to regulate spawning time and to facilitate predation, or whether they also use their light-sensing capacities to protect their symbionts from photodamage.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
October 2023
The planula larvae of the sea anemone Aiptasia have so far not been reported to complete their life cycle by undergoing metamorphosis into adult forms. This has been a major obstacle in their use as a model for coral-dinoflagellate endosymbiosis. Here, we show that Aiptasia larvae actively feed on crustacean nauplii, displaying a preference for live prey.
View Article and Find Full Text PDFSymbiotic interactions occur in all domains of life, providing organisms with resources to adapt to new habitats. A prime example is the endosymbiosis between corals and photosynthetic dinoflagellates. Eukaryotic dinoflagellate symbionts reside inside coral cells and transfer essential nutrients to their hosts, driving the productivity of the most biodiverse marine ecosystem.
View Article and Find Full Text PDFOmnivorous animals, including mice and humans, tend to prefer energy-dense nutrients rich in fat over plant-based diets, especially for short periods of time, but the health consequences of this short-term consumption of energy-dense nutrients are unclear. Here, we show that short-term reiterative switching to 'feast diets', mimicking our social eating behavior, breaches the potential buffering effect of the intestinal microbiota and reorganizes the immunological architecture of mucosa-associated lymphoid tissues. The first dietary switch was sufficient to induce transient mucosal immune depression and suppress systemic immunity, leading to higher susceptibility to Salmonella enterica serovar Typhimurium and Listeria monocytogenes infections.
View Article and Find Full Text PDFTo survive in the nutrient-poor waters of the tropics, reef-building corals rely on intracellular, photosynthetic dinoflagellate symbionts. Photosynthates produced by the symbiont are translocated to the host, and this enables corals to form the structural foundation of the most biodiverse of all marine ecosystems. Although the regulation of nutrient exchange between partners is critical for ecosystem stability and health, the mechanisms governing how nutrients are sensed, transferred, and integrated into host cell processes are largely unknown.
View Article and Find Full Text PDFNative Community Development Financial Institutions (NCDFIs) fill credit supply gaps and promote financial inclusion in Native communities. To mitigate lending risks and aid clients, NCDFIs often rely on unconventional lending practices such as providing clients with free financial counseling. Drawing on uniquely detailed consumer loan-level data of one prominent NCDFI, we empirically model the hazard of a loan turning into bad debt.
View Article and Find Full Text PDFDuring an immune response, T cells migrate from blood vessel walls into inflamed tissues by migrating across the endothelium and through extracellular matrix (ECM). Integrins facilitate T cell binding to endothelial cells and ECM proteins. Here, we report that Ca microdomains observed in the absence of T cell receptor (TCR)/CD3 stimulation are initial signaling events triggered by adhesion to ECM proteins that increase the sensitivity of primary murine T cells to activation.
View Article and Find Full Text PDFCa signaling is one of the essential signaling systems for T lymphocyte activation, the latter being an essential step in the pathogenesis of autoimmune diseases such as multiple sclerosis (MS). Store-operated Ca entry (SOCE) ensures long lasting Ca signaling and is of utmost importance for major downstream T lymphocyte activation steps, e.g.
View Article and Find Full Text PDFNicotinamide adenine dinucleotide (NAD) and its 2'-phosphorylated cousin NADP are precursors for the enzymatic formation of the Ca-mobilizing second messengers adenosine diphosphoribose (ADPR), 2'-deoxy-ADPR, cyclic ADPR, and nicotinic acid adenine dinucleotide phosphate (NAADP). The enzymes involved are either NAD glycohydrolases CD38 or sterile alpha toll/interleukin receptor motif containing-1 (SARM1), or (dual) NADPH oxidases (NOX/DUOX). Enzymatic function(s) are reviewed and physiological role(s) in selected cell systems are discussed.
View Article and Find Full Text PDFDuring metastasis, cancer cells invade, intravasate, enter the circulation, extravasate, and colonize target organs. Here, we examined the role of interleukin (IL)-22 in metastasis. Immune cell-derived IL-22 acts on epithelial tissues, promoting regeneration and healing upon tissue damage, but it is also associated with malignancy.
View Article and Find Full Text PDFBoosting NAD levels are considered a promising means to promote healthy aging and ameliorate dysfunctional metabolism. The expression of CD38, the major NAD-consuming enzyme, is downregulated during thermogenesis in both brown and white adipose tissues (BAT and WAT). Moreover, BAT activation and WAT "browning" were enhanced in mice.
View Article and Find Full Text PDFHandb Exp Pharmacol
April 2023
Nicotinic acid adenine dinucleotide phosphate (NAADP) is the most potent Ca mobilizing second messenger known to date. Major steps elucidating metabolism and Ca mobilizing activity of NAADP are reviewed, with emphasis on a novel redox cycle between the inactive reduced form, NAADPH, and the active oxidized form, NAADP. Oxidation from NAADPH to NAADP is catalyzed in cell free system by (dual) NADPH oxidases NOX5, DUOX1, and DUOX2, whereas reduction from NAADP to NAADPH is catalyzed by glucose 6-phosphate dehydrogenase.
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