The Adjuvanticity of an O. volvulus-Derived rOv-ASP-1 Protein in Mice Using Sequential Vaccinations and in Non-Human Primates

Adjuvants potentiate antigen-specific protective immune responses and can be key elements promoting vaccine effectiveness. We previously reported that the Onchocerca volvulus recombinant protein rOv-ASP-1 can induce activation and maturation of naïve human DCs and therefore could be used as an innate adjuvant to promote balanced Th1 and Th2 responses to bystander vaccine antigens in mice. With a few vaccine antigens, it also promoted a Th1-biased response based on pronounced induction of Th1-associated IgG2a and IgG2b antibody responses and the upregulated production of Th1 cytokines, including IL-2, IFN-γ, TNF-α and IL-6. However, because it is a protein, the rOv-ASP-1 adjuvant may also induce anti-self-antibodies. Therefore, it was important to verify that the host responses to self will not affect the adjuvanticity of rOv-ASP-1 when it is used in subsequent vaccinations with the same or different vaccine antigens. In this study, we have established rOv-ASP-1's adjuvanticity in mice during the course of two sequential vaccinations using two vaccine model systems: the receptor-binding domain (RBD) of SARS-CoV spike protein and a commercial influenza virus hemagglutinin (HA) vaccine comprised of three virus strains. Moreover, the adjuvanticity of rOv-ASP-1 was retained with an efficacy similar to that obtained when it was used for a first vaccination, even though a high level of anti-rOv-ASP-1 antibodies was present in the sera of mice before the administration of the second vaccine. To further demonstrate its utility as an adjuvant for human use, we also immunized non-human primates (NHPs) with RBD plus rOv-ASP-1 and showed that rOv-ASP-1 could induce high titres of functional and protective anti-RBD antibody responses in NHPs. Notably, the rOv-ASP-1 adjuvant did not induce high titer antibodies against self in NHPs. Thus, the present study provided a sound scientific foundation for future strategies in the development of this novel protein adjuvant

IMOBILISASI ZEOLIT BEKAS PENYERAP LIMBAH RAFINAT DARI PRODUKSI RADIOISOTOP MOLIBDENUM-99 DENGAN POLIMER

Rafinat waste that produced by Instalation of Radioisotop Production is contained uranium. The research of uranium sorption by zeolite Alumino Silico Phosphate (ASP) and selected of best waste loading for immobilisation of saturated zeolite uranium used resin epoxy has been done. Uranium used is a simulation waste from uranyl nitrat hexahydrat which has 50 ppm in concentration. Zeolite ASP was made by mixing pure zeolite with Ammonium Dihydrogen Phosphate (ADHP). This research was done to variate the factor that influence the sorption process. Which are composition of zeolite ASP,retention time, and pH. The result of selected variable will be used for making saturated zeolite uranium will be immobilized with epoxy resin with variation of waste loading. Optimum condition of uranium sorption reached on zeolite ASP 1:1 with pH 7 and retention time for 12 minutes with uranium removal efficiency 51,1 %. Base on density, compressive strenght, and leaching rate ,the best result for polymer-waste block is on 20 % waste loading. In that condition the density for polymer waste block is 1,0538 gram/cm3 , the compreesive strenght 19,36 kN/cm3 and the leaching rate is not detected. Key word: Sorption, zeolite ASP, waste loading, epoxy resi

Crystallization and preliminary X-ray analysis of \u3ci\u3eNa\u3c/i\u3e-ASP-1, a multi-domain pathogenesis-related-1 protein from the human hookworm parasite \u3ci\u3eNecator americanus\u3c/i\u3e

Human hookworm infection is a major cause of anemia and malnutrition in the developing world. In an effort to control hookworm infection, the Human Hookworm Vaccine Initiative has identified candidate vaccine antigens from the infective larval stage (L3) of the parasite, including a family of pathogenesis-related-1 (PR-1) proteins known as the ancylostoma-secreted proteins (ASPs). The functions of the ASPs are unknown. In addition, it is unclear why some ASPs have one while others have multiple PR-1 domains. There are no known structures of a multi-domain ASP and in an effort to remedy this situation, recombinant Na-ASP-1 has been expressed, purified and crystallized. Na-ASP-1 is a 406-amino-acid multi-domain ASP from the prevalent human hookworm parasite Necator americanus. Useful X-ray data to 2.2 A ° have been collected from a crystal that belongs to the monoclinic space group P21 with unit-cell parameters a = 67.7, b = 74.27, c = 84.60 Å, β = 112.12°. An initial molecular-replacement solution has been obtained with one monomer in the asymmetric unit

Crystallization and preliminary X-ray analysis of \u3ci\u3eNa\u3c/i\u3e-ASP-1, a multi-domain pathogenesis-related-1 protein from the human hookworm parasite \u3ci\u3eNecator americanus\u3c/i\u3e

Human hookworm infection is a major cause of anemia and malnutrition in the developing world. In an effort to control hookworm infection, the Human Hookworm Vaccine Initiative has identified candidate vaccine antigens from the infective larval stage (L3) of the parasite, including a family of pathogenesis-related-1 (PR-1) proteins known as the ancylostoma-secreted proteins (ASPs). The functions of the ASPs are unknown. In addition, it is unclear why some ASPs have one while others have multiple PR-1 domains. There are no known structures of a multi-domain ASP and in an effort to remedy this situation, recombinant Na-ASP-1 has been expressed, purified and crystallized. Na-ASP-1 is a 406-amino-acid multi-domain ASP from the prevalent human hookworm parasite Necator americanus. Useful X-ray data to 2.2 A ° have been collected from a crystal that belongs to the monoclinic space group P21 with unit-cell parameters a = 67.7, b = 74.27, c = 84.60 Å, β = 112.12°. An initial molecular-replacement solution has been obtained with one monomer in the asymmetric unit

Pro-domain removal in ASP-2 and the cleavage of the amyloid precursor are influenced by pH

BACKGROUND: One of the signatures of Alzheimer's disease is the accumulation of aggregated amyloid protein, Aβ, in the brain. Aβ arises from cleavage of the Amyloid Precursor protein by β and γ secretases, which present attractive candidates for therapeutic targeting. Two β-secretase candidates, ASP-1 and ASP-2, were identified as aspartic proteases, both of which cleave the amyloid precursor at the β-site. These are produced as immature transmembrane proteins containing a pro-segment. RESULTS: ASP-2 expressed in HEK293-cells cleaved the Swedish mutant amyloid precursor at different β-sites at different pHs in vitro. Recent reports show that furin cleaves the pro-peptide of ASP-2, whereas ASP-1 undergoes auto-catalysis. We show that purified recombinant ASP-2 cleaves its own pro-peptide at ph 5 but not pH 8.5 as seen by mass spectrometry, electrophoresis and N-terminal sequencing. CONCLUSION: We suggest that ASP-2 processing as well as activity are influenced by pH, and hence the cellular localisation of the protein may have profound effects on the production of Aβ. These factors should be taken into consideration in the design of potential inhibitors for these enzymes

Extreme morning chronotypes are often familial and not exceedingly rare: the estimated prevalence of advanced sleep phase, familial advanced sleep phase, and advanced sleep-wake phase disorder in a sleep clinic population.

Study objectivesReport the first prevalence estimates of advanced sleep phase (ASP), familial advanced sleep phase (FASP), and advanced sleep-wake phase disorder (ASWPD). This can guide clinicians on the utility of screening for extreme chronotypes both for clinical decision-making and to flag prospective participants in the study of the genetics and biology of FASP.MethodsData on morning or evening sleep schedule preference (chronotype) were collected from 2422 new patients presenting to a North American sleep center over 9.8 years. FASP was determined using a severity criterion that has previously identified dominant circadian mutations in humans. All patients were personally seen and evaluated by one of the authors (C.R.J.).ResultsOur results demonstrate an ASP prevalence of 0.33%, an FASP prevalence of 0.21%, and an ASWPD prevalence of at least 0.04%. Most cases of young-onset ASP were familial.ConclusionsAmong patients presenting to a sleep clinic, conservatively 1 out of every 300 patients will have ASP, 1 out of every 475 will have FASP, and 1 out of every 2500 will have ASWPD. This supports obtaining a routine circadian history and, for those with extreme chronotypes, obtaining a family history of circadian preference. This can optimize treatment for evening sleepiness and early morning awakening and lead to additional circadian gene discovery. We hope these findings will lead to improved treatment options for a wide range of sleep and medical disorders in the future