microRNAs (miRNAs) are important post-transcriptional regulators that activate silencing mechanisms by annealing to mRNA transcripts. While plant miRNAs match their targets with nearly-full complementarity leading to mRNA cleavage, miRNAs in most animals require only a short sequence called 'seed' to inhibit target translation. Recent findings showed that miRNAs in cnidarians, early-branching metazoans, act similarly to plant miRNAs, by exhibiting full complementarity and target cleavage; however, it remained unknown if seed-based regulation was possible in cnidarians.
View Article and Find Full Text PDFStem cells are the foundation for cell therapy due to their ability to self-renew, differentiate into other cell types, and persist throughout the life of an organism. Stem cell isolation and transplantation have not yet been established in Hexacorallia, a cnidarian subclass containing stony corals and sea anemones. Here, we demonstrate that candidate stem cells in the hexacorallian Nematostella vectensis can be transplanted into adult animals.
View Article and Find Full Text PDFMultiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS), with a putative autoimmune origin and complex pathogenesis. Modification of the natural history of MS by reducing relapses and slowing disability accumulation was first attained in the 1990 s with the development of the first-generation disease-modifying therapies. Glatiramer acetate (GA), a copolymer of L-alanine, L-lysine, L-glutamic acid, and L-tyrosine, was discovered due to its ability to suppress the animal model of MS, experimental autoimmune encephalomyelitis.
View Article and Find Full Text PDFNat Cardiovasc Res
September 2024
Myocardial injury may ultimately lead to adverse ventricular remodeling and development of heart failure (HF), which is a major cause of morbidity and mortality worldwide. Given the slow pace and substantial costs of developing new therapeutics, drug repurposing is an attractive alternative. Studies of many organs, including the heart, highlight the importance of the immune system in modulating injury and repair outcomes.
View Article and Find Full Text PDFThe ability of an animal to effectively capture prey and defend against predators is pivotal for survival. Venom is often a mixture of many components including toxin proteins that shape predator-prey interactions. Here, we used the sea anemone to test the impact of toxin genotypes on predator-prey interactions.
View Article and Find Full Text PDFIsr J Health Policy Res
September 2023
Ion channels of the DEG/ENaC family share a similar structure but serve strikingly diverse biological functions, such as Na reabsorption, mechanosensing, proton-sensing, chemosensing and cell-cell communication via neuropeptides. This functional diversity raises the question of the ancient function of DEG/ENaCs. Using an extensive phylogenetic analysis across many different animal groups, we found a surprising diversity of DEG/ENaCs already in Cnidaria (corals, sea anemones, hydroids and jellyfish).
View Article and Find Full Text PDFAmong the medically most important snakes in the world, the species belonging to the genus have been attributed to the highest number of human envenomings, deaths and disabilities. Given their significant clinical relevance, the venoms of Russell's vipers ( and ) have been the primary focus of research. In contrast, the composition, activity, ecology and evolution of venom of its congener, the Palestine viper (), have remained largely understudied.
View Article and Find Full Text PDFData analysis has increasingly relied on machine learning in recent years. Since machines implement mathematical algorithms without knowing the physical nature of the problem, they may be accurate but lack the flexibility to move across different domains. This manuscript presents a machine-educating approach where a machine is equipped with a physical model, universal building blocks, and an unlabeled dataset from which it derives its decision criteria.
View Article and Find Full Text PDFWhile the biogenesis of microRNAs (miRNAs) in both animals and plants depends on the RNase III Dicer, its partner proteins are considered distinct for each kingdom. Nevertheless, recent discovery of homologs of Hyponastic Leaves1 (HYL1), a 'plant-specific' Dicer partner, in the metazoan phylum Cnidaria, challenges the view that miRNAs evolved convergently in animals and plants. Here, we show that the HYL1 homolog Hyl1-like a (Hyl1La) is crucial for development and miRNA biogenesis in the cnidarian model .
View Article and Find Full Text PDFAxonal and neuronal pathologies are a central constituent of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), induced by the myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide. In this study, we investigated neurodegenerative manifestations in chronic MOG 35-55 induced EAE and the effect of glatiramer acetate (GA) treatment on these manifestations. We report that the neuronal loss seen in this model is not attributed to apoptotic neuronal cell death.
View Article and Find Full Text PDFAnimals evolved a broad repertoire of innate immune sensors and downstream effector cascades for defense against RNA viruses. Yet, this system varies greatly among different bilaterian animals, masking its ancestral state. In this study, we aimed to characterize the antiviral immune response of the cnidarian Nematostella vectensis and decipher the function of the retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) known to detect viral double-stranded RNA (dsRNA) in bilaterians but activate different antiviral pathways in vertebrates and nematodes.
View Article and Find Full Text PDFIntroduction: The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) delivered in a group format could facilitate the implementation of evidence-based psychological treatments.
Objective: This study compared the efficacy of group UP and diagnosis-specific cognitive behavioral therapy (dCBT) for anxiety and depression in outpatient mental health services.
Methods: In this pragmatic, multi-center, single-blinded, non-inferiority, randomized controlled trial (RCT), we assigned 291 patients with major depressive disorder, social anxiety disorder, panic disorder, or agoraphobia to 14 weekly sessions in mixed-diagnosis UP or single-diagnosis dCBT groups.
In multiple sclerosis (MS), astrocytes respond to the inflammatory stimulation with an early robust process of morphological, transcriptional, biochemical, and functional remodeling. Recent studies utilizing novel technologies in samples from MS patients, and in an animal model of MS, experimental autoimmune encephalomyelitis (EAE), exposed the detrimental and the beneficial, in part contradictory, functions of this heterogeneous cell population. In this review, we summarize the various roles of astrocytes in recruiting immune cells to lesion sites, engendering the inflammatory loop, and inflicting tissue damage.
View Article and Find Full Text PDFB cells have essential functions in multiple sclerosis and in its mouse model, experimental autoimmune encephalomyelitis, both as drivers and suppressors of the disease. The suppressive effects are driven by a regulatory B cell (Breg) population that functions, primarily but not exclusively, via the production of IL-10. However, the mechanisms modulating IL-10-producing Breg abundance are poorly understood.
View Article and Find Full Text PDFMicroRNAs (miRNAs) base-pair to messenger RNA targets and guide Argonaute proteins to mediate their silencing. This target regulation is considered crucial for animal physiology and development. However, this notion is based exclusively on studies in bilaterians, which comprise almost all lab model animals.
View Article and Find Full Text PDFBackground: Experimental autoimmune encephalomyelitis (EAE) induced by the myelin oligodendrocyte glycoprotein (MOG) peptide 35-55, is a widely used multiple sclerosis (MS) model. Unlike the spontaneous occurrence of MS, in EAE, external immunization with the MOG peptide (200-300 µg/mouse), emulsified in adjuvant enriched with Mycobacterium Tuberculosis (MT) H37Ra (100-500 µg mouse), and pertussis toxin (PTx, 200-500 ng/mouse) injections, are applied, which heavily boosts the immune system.
New Method: A detailed and systematic titration of the MOG 35-55 EAE induction protocol in C57BL/6 mice reveals the minimal doses of the MOG 35-55 peptide, MT H37Ra, and PTx, required for disease manifestation.
Background: In cnidarians, antagonistic interactions with predators and prey are mediated by their venom, whose synthesis may be metabolically expensive. The potentially high cost of venom production has been hypothesized to drive population-specific variation in venom expression due to differences in abiotic conditions. However, the effects of environmental factors on venom production have been rarely demonstrated in animals.
View Article and Find Full Text PDFTo identify the mechanisms relevant for the therapeutic effect of glatiramer acetate (GA), we studied T- and B- regulatory cells as well as GM-CSF expression in mice recovered from experimental autoimmune encephalomyelitis (EAE). Selective depletion of Tregs reduced but did not eliminate the ability of GA to ameliorate EAE, indicating a role for additional immune-subsets. The prevalence of Bregs in the periphery and the CNS of EAE-mice increased following GA-treatment.
View Article and Find Full Text PDFDrosha and Dicer are RNase III family members of classes II and III, respectively, which play a major role in the maturation of micro-RNAs. The two proteins share similar domain arrangement and overall fold despite no apparent sequence homology. The overall structural and catalytic reaction similarity of both proteins, on the one hand, and differences in the substrate and its binding mechanisms, on the other, suggest that both proteins also share dynamic similarities and dissimilarities.
View Article and Find Full Text PDFMultiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) which carries a significant burden of morbidity and mortality. Herein we examine the effects of acute treatment with tuftsin-phosphorylcholine (TPC), a novel immune-modulating helminth derived compound, on a murine model of MS. Experimental autoimmune encephalomyelitis (EAE) mice received acute treatment with TPC showed an improved clinical score and significantly less signs of inflammation and demyelination in CNS tissue compared with vehicle treated EAE mice.
View Article and Find Full Text PDFEfficient and safe detection of Bacillus anthracis spores (BAS) is a challenging task especially in bio-terror scenarios where the agent is concealed. We provide a proof-of-concept for the identification of concealed BAS inside mail envelopes using short-wave infrared hyperspectral imaging (SWIR-HSI). The spores and two other benign materials are identified according to their typical absorption spectrum.
View Article and Find Full Text PDFGlatiramer acetate (GA, Copaxone®, Copolymer1, Cop 1) is an approved drug for the treatment of relapsing-remitting multiple sclerosis (RRMS). Its efficacy in reducing the frequency of exacerbations and its safety profile establish it as a first-line therapy for MS. Evidence from the animal model experimental autoimmune encephalomyelitis (EAE) and from MS patients indicate that GA affects various levels of the innate and the adaptive immune response, inducing deviation from the pro-inflammatory to the anti-inflammatory pathways.
View Article and Find Full Text PDF