Hemolytic–uremic syndrome (HUS) is a group of blood disorders characterized by low red blood cells, acute kidney injury, and low platelets. Initial symptoms typically include bloody diarrhea, fever, vomiting, and weakness. Kidney problems and low platelets then occur as the diarrhea progresses. Children are more commonly affected, but most children recover without permanent damage to their health, although some children may have serious and sometimes life-threatening complications. Adults, especially the elderly, may present a more complicated presentation. Complications may include neurological problems and heart failure.
Anthrax toxin is a three-protein exotoxin secreted by virulent strains of the bacterium, Bacillus anthracis—the causative agent of anthrax. The toxin was first discovered by Harry Smith in 1954. Anthrax toxin is composed of a cell-binding protein, known as protective antigen (PA), and two enzyme components, called edema factor (EF) and lethal factor (LF). These three protein components act together to impart their physiological effects. Assembled complexes containing the toxin components are endocytosed. In the endosome, the enzymatic components of the toxin translocate into the cytoplasm of a target cell. Once in the cytosol, the enzymatic components of the toxin disrupts various immune cell functions, namely cellular signaling and cell migration. The toxin may even induce cell lysis, as is observed for macrophage cells. Anthrax toxin allows the bacteria to evade the immune system, proliferate, and ultimately kill the host animal. Research on anthrax toxin also provides insight into the generation of macromolecular assemblies, and on protein translocation, pore formation, endocytosis, and other biochemical processes.
CX3C motif chemokine receptor 1 (CX3CR1), also known as the fractalkine receptor or G-protein coupled receptor 13 (GPR13), is a transmembrane protein of the G protein-coupled receptor 1 (GPCR1) family and the only known member of the CX3C chemokine receptor subfamily.
α-N-acetylgalactosaminidase is a glycoside hydrolase from bacteria and animals, also known as nagalase.
ADGRV1, also known as G protein-coupled receptor 98 (GPR98) or Very Large G-protein coupled receptor 1 (VLGR1), is a protein that in humans is encoded by the GPR98 gene. Several alternatively spliced transcripts have been described.
Anthrax toxin receptor 1 is a protein that in humans is encoded by the ANTXR1 gene. Its molecular weight is predicted as about 63kDa.
NLRP1 encodes NACHT, LRR, FIIND, CARD domain and PYD domains-containing protein 1 in humans. NLRP1 was the first protein shown to form an inflammasome. NLRP1 is expressed by a variety of cell types, which are predominantly epithelial or hematopoietic. The expression is also seen within glandular epithelial structures including the lining of the small intestine, stomach, airway epithelia and in hairless or glabrous skin. NLRP1 polymorphisms are associated with skin extra-intestinal manifestations in CD. Its highest expression was detected in human skin, in psoriasis and in vitiligo. Polymorphisms of NLRP1 were found in lupus erythematosus and diabetes type 1. Variants of mouse NLRP1 were found to be activated upon N-terminal cleavage by the protease in anthrax lethal factor.
Ceroid-lipofuscinosis neuronal protein 6 is a protein that in humans is encoded by the CLN6 gene.
Glomulin is a protein that in humans is encoded by the GLMN gene.
Ceroid-lipofuscinosis neuronal protein 5 is a protein that in humans is encoded by the CLN5 gene.
C-type lectin domain family 1 member B is a protein that in humans is encoded by the CLEC1B gene.
Cytokine receptor-like factor 1 is a protein that in humans is encoded by the CRLF1 gene.
The lymphatic endothelium refers to a specialized subset of endothelial cells located in the sinus systems of draining lymph nodes. Specifically, these endothelial cells line the branched sinus systems formed by afferent lymphatic vessels, forming a single-cell layer which functions in a variety of critical physiological processes. These lymphatic endothelial cells contribute directly to immune function and response modulation, provide transport selectivity, and demonstrate orchestration of bidirectional signaling cascades. Additionally, lymphatic endothelial cells may be implicated in downstream immune cell development as well as lymphatic organogenesis. Until recently, lymphatic endothelial cells have not been characterized to their optimal potential. This system is very important in the function of continuous removal of interstitial fluid and proteins, while also having a significant function of entry for leukocytes and tumor cells. This leads to further research that is being developed on the relationship between lymphatic endothelium and metastasis of tumor cells . The lymphatic capillaries are described to be blind ended vessels, and they are made up of a single non-fenestrated layer of endothelial cells; The lymph capillaries function to aid in the uptake of fluids, macromolecules, and cells. Although they are generally similar to blood capillaries, the lymph capillaries have distinct structural differences. Lymph capillaries consist of a more wide and irregular lumen, and the endothelium in lymph capillaries is much thinner as well. Their origin has been speculated to vary based on them being dependent on specific tissue environments, and powered by organ-specific signals.(L. Gutierrez-Miranda, K. Yaniv, 2020). A lymph capillary endothelial cell is distinct from other endothelial cells in that collagen fibers are directly attached to its plasma membrane.
Juvenile hyaline fibromatosis is a very rare, autosomal recessive disease due to mutations in capillary morphogenesis protein-2. It occurs from early childhood to adulthood, and presents as slow-growing, pearly white or skin-colored dermal or subcutaneous papules or nodules on the face, scalp, and back, which may be confused clinically with neurofibromatosis. The World Health Organization in 2020 reclassified the papules and nodules that occur in juvenile hyaline fibromatosis as one of the specific benign types of tumors in the category of fibroblastic and myofibroblastic tumors.
Infantile myofibromatosis (IMF) is a rare tumor found in 1 in 150,000 to 1 in 400,000 live births. It is nonetheless the most common tumor derived from fibrous connective tissue that occurs primarily in infants and young children. IMF tumors are benign in the sense that they do not metastasize to distant tissues although when occurring in the viscera, i.e. internal organs, carry guarded to poor prognoses and can be life-threatening, particularly in newborns and young infants. The condition was first described by Arthur Purdy Stout as congenital generalized fibromatosis – in which he coined the word fibromatosis – in 1954.
Infantile systemic hyalinosis is an allelic autosomal-recessive condition characterized by multiple skin nodules, hyaline deposition, gingival hypertrophy, osteolytic bone lesions and joint contractures.
Diffuse infantile fibromatosis is a rare condition affecting infants during the first three years of life. This condition is a multicentric infiltration of muscle fibers with fibroblasts resembling those seen in aponeurotic fibromas, presenting as lesions and tumors confined usually to the muscles of the arms, neck, and shoulder area Diffuse infantile fibromatosis is characterized by fast growing benign tumors. This disorder is known to be caused by mutations in germline variants, PDGFRB and NOTCH3, which may be generationally-inherited through autosomal dominant and recessive traits. Although diffuse infantile fibromatosis is classified as benign, it can still lead to life-threatening complications and damage other organs.
Intraflagellar transport protein 74 homolog (IFT74), also known as coiled-coil domain-containing protein 2 (CCDC2) and capillary morphogenesis gene 1 protein (CMG1), is a protein that in humans is encoded by the IFT74 gene.
Espin, also known as autosomal recessive deafness type 36 protein or ectoplasmic specialization protein, is a protein that in humans is encoded by the ESPN gene. Espin is a microfilament binding protein.
Françoise Gisou van der Goot is a Swiss-Dutch cell biologist. She is a professor and the Vice President for Responsible Transformation at EPFL.
