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Nano-Assembled Polyphosphazene Delivery System Enables Effective Intranasal Immunization with Nipah Virus Subunit Vaccine.
ACS Appl Bio Mater
June 2024
Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, Maryland 20850, United States.
The ultimate vaccine against infections caused by Nipah virus should be capable of providing protection at the respiratory tract─the most probable port of entry for this pathogen. Intranasally delivered vaccines, which target nasal-associated lymphoid tissue and induce both systemic and mucosal immunity, are attractive candidates for enabling effective vaccination against this lethal disease. Herein, the water-soluble polyphosphazene delivery vehicle assembles into nanoscale supramolecular constructs with the soluble extracellular portion of the Hendra virus attachment glycoprotein─a promising subunit vaccine antigen against both Nipah and Hendra viruses.
View Article and Find Full Text PDFExcluding Digenic Inheritance of and Variants in Mabry Syndrome (OMIM 239300) Patient: Phenotypic Spectrum Associated with Gene Variants in Hyperphosphatasia with Mental Retardation Syndrome-3 (HPMRS3).
Genes (Basel)
January 2023
Yale Pediatrics (Endocrinology), Yale University School of Medicine, New Haven, CT 06521, USA.
Unlabelled: We present a case report of a child with features of hyperphosphatasia with neurologic deficit (HPMRS) or Mabry syndrome (MIM 239300) with variants of unknown significance in two post-GPI attachments to proteins genes, and , that underlie HPMRS 3 and 4.
Background: In addition to HPMRS 3 and 4, disruption of four phosphatidylinositol glycan (PIG) biosynthesis genes, , , and , result in HPMRS 1, 2, 5 and 6, respectively.
Methods: Targeted exome panel sequencing identified homozygous variants of unknown significance (VUS) in c:284A>G and c:259G>A.
Structural insights into human acid-sensing ion channel 1a inhibition by snake toxin mambalgin1.
Elife
September 2020
Tsinghua-Peking Joint Center for Life Sciences, Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Department of Chemistry, Tsinghua University, Beijing, China.
Acid-sensing ion channels (ASICs) are proton-gated cation channels that are involved in diverse neuronal processes including pain sensing. The peptide toxin Mambalgin1 (Mamba1) from black mamba snake venom can reversibly inhibit the conductance of ASICs, causing an analgesic effect. However, the detailed mechanism by which Mamba1 inhibits ASIC1s, especially how Mamba1 binding to the extracellular domain affects the conformational changes of the transmembrane domain of ASICs remains elusive.
View Article and Find Full Text PDFDegradation versus Inhibition: Development of Proteolysis-Targeting Chimeras for Overcoming Statin-Induced Compensatory Upregulation of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase.
J Med Chem
May 2020
MOE Key Laboratory of Protein Sciences, School of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, P.R. China.
3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) is an eight-pass transmembrane protein in the endoplasmic reticulum (ER) and a classical drug target to treat dyslipidemia. Statins including the well-known atorvastatin (Lipitor; Pfizer) have been widely used for the prevention and treatment of cardiovascular disease for decades. However, statins can elicit a compensatory upregulation of HMGCR protein and cause adverse effects including skeletal muscle damage.
View Article and Find Full Text PDFA post glycosylphosphatidylinositol (GPI) attachment to proteins, type 2 (PGAP2) variant identified in Mabry syndrome index cases: Molecular genetics of the prototypical inherited GPI disorder.
Eur J Med Genet
April 2020
Department of Pediatrics, College of Medicine, University of Kentucky, United States.
We report that recessive inheritance of a post-GPI attachment to proteins 2 (PGAP2) gene variant results in the hyperphosphatasia with neurologic deficit (HPMRS) phenotype described by Mabry et al., in 1970. HPMRS, or Mabry syndrome, is now known to be one of 21 inherited glycosylphosphatidylinositol (GPI) deficiencies (IGDs), or GPI biosynthesis defects (GPIBDs).
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