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Modeling Alzheimer’s disease with iPSC-derived brain cells
No full textAlzheimer’s disease is a devastating neurodegenerative disorder with no cure. Countless promising therapeutics have shown efficacy in rodent Alzheimer’s disease models yet failed to benefit human patients. While hope remains that earlier intervention with existing therapeutics will improve outcomes, it is becoming increasingly clear that new approaches to understand and combat the pathophysiology of Alzheimer’s disease are needed. Human induced pluripotent stem cell (iPSC) technologies have changed the face of preclinical research and iPSC-derived cell types are being utilized to study an array of human conditions, including neurodegenerative disease. All major brain cell types can now be differentiated from iPSCs, while increasingly complex co-culture systems are being developed to facilitate neuroscience research. Many cellular functions perturbed in Alzheimer’s disease can be recapitulated using iPSC-derived cells in vitro, and co-culture platforms are beginning to yield insights into the complex interactions that occur between brain cell types during neurodegeneration. Further, iPSC-based systems and genome editing tools will be critical in understanding the roles of the numerous new genes and mutations found to modify Alzheimer’s disease risk in the past decade. While still in their relative infancy, these developing iPSC-based technologies hold considerable promise to push forward efforts to combat Alzheimer’s disease and other neurodegenerative disorders.Swiss National Science FoundationNIHCure Alzheimer’s FundRobert and Renee Belfer Family FoundationJBP Foundatio
CpG-ODN induces a dose-dependent enrichment of immunological niches in the spleen and lungs of neonatal chicks that correlates with the protective immunity against escherichia coli
No full textImmunoprotective function of oligodeoxynucleotides containing CpG motifs (CpG-ODN) has been demonstrated in neonatal chickens against common bacterial pathogens such as E.coli and Salmonella sp. Our recent study reported that CpG-ODN administration enriches immune compartments in neonatal chicks. However, a causal relationship between CpG-ODN-induced immune enrichment and protective mechanisms remains unestablished. In this study, we investigated in ovo administered CpG-ODN-mediated immune cell recruitment in the immunological niches in lymphoid (spleen) and nonlymphoid (lungs) organs using various doses of CpG-ODN and examined whether the immunological profiles have any correlation with immunoprotection against E.coli infection. Eighteen-day-old embryonated eggs were injected with either 5, 10, 25, and 50 μg of CpG-ODN or saline ( per group). On the day of hatch (72 hr after CpG-ODN treatment), we collected the spleen and lungs ( per group) and examined the recruitment of macrophages/monocytes, their expression of MHCII and CD40, and the number of CD4+ and CD8+ T-cell subsets in the immunological niches in the spleen and lungs using flow cytometry. We observed the dose-dependent recruitment of immune cells, wherein 25 μg and 50 μg of CpG-ODN induced significant enrichment of immunological niches in both the spleen and the lungs. Four days after the CpG-ODN treatment (1-day after hatch), chicks were challenged with a virulent strain of E. coli ( or cfu, subcutaneously). Clinical outcome and mortality were monitored for 8 days postchallenge. We found that both 25 μg and 50 μg of CpG-ODN provided significant protection and reduced clinical scores compared to saline controls against E. coli infection. Overall, the present study revealed that CpG-ODNs orchestrate immunological niches in neonatal chickens in a dose-dependent manner that resulted in differential protection against E. coli infection, thus supporting a cause and effect relationship between CpG-ODN-induced immune enrichment and the antibacterial immunity.Natural Sciences and Engineering Research Council of CanadaWestern Economic Diversification CanadaSaskatchewan Chicken Industry Development FundCanadian Poultry Research CouncilAlberta Livestock and Meat Agency Ltd
Prevalence of feline herpesvirus-1, feline calicivirus, Chlamydia felis, and Bordetella bronchiseptica in a population of shelter cats on Prince Edward Island.
No full textThe prevalence of the causative agents of feline upper respiratory tract disease (URTD) has been previously documented in many regions worldwide, but has yet to be reported in eastern Canada. The objectives of this study were to determine the prevalence of feline herpesvirus-1 (FHV-1), feline calicivirus (FCV), Chlamydia felis (C. felis), and Bordetella bronchiseptica (B. bronchiseptica) in a population of shelter cats with clinical signs related to URTD on Prince Edward Island, Canada; to compare the prevalence of FHV-1 and FCV as detected by polymerase chain reaction (PCR) and virus isolation (VI) in this population; and lastly, to determine whether factors, such as co-infections, time of year, concurrent feline leukemia virus (FeLV)- or feline immunodeficiency virus (FIV)-positive status, or clinical signs, were associated with prevalence of particular pathogens. Conjunctival, nasal mucosal, and oropharyngeal swabs were collected from 82 cats with clinical signs consistent with URTD. Samples were pooled in transport medium and PCR was used to detect FHV-1, FCV, and C. felis and VI was also used to detect FHV-1 and FCV. A separate swab was submitted for aerobic bacterial culture to detect B. bronchiseptica. Feline herpesvirus-1 (FHV-1) was the most prevalent in this population, followed by C. felis, B. bronchiseptica, and FCV. Of the 4 cats that were positive for B. bronchiseptica, 3 were concurrently positive for FHV-1. All positive B. bronchiseptica cultures were resistant to cefovecin. The prevalence for FHV-1 was lowest in autumn (seasons P < 0.001) and was positively associated with the presence of nasal discharge (P = 0.018) and coughing (P = 0.043).journal article2020 Julimporte
Nietzsche on honesty and the will to truth
No full textNietzsche values intellectual honesty, but is dubious about what he calls the will to truth. This is puzzling since intellectual honesty is a component of the will to truth. In this paper, I show that this puzzle tells us something important about how Nietzsche conceives of our pursuit of truth. For Nietzsche, those who pursue truth occupy unstable ground, since being honest about the ultimate reasons for that pursuit would mean that truth could no longer satisfy the important human needs it satisfies at present. We can pursue truth, or be honest about what in us is served by such a pursuit, but not both. Nietzsche aims to show that understanding and owning up to this instability is the sort of affirmation of human life to which we ought to aspire, and is the price we pay for being free from otherworldly morality
Second law analysis of CuCl2 hydrolysis reaction in the Cu–Cl thermochemical cycle of hydrogen production
No full textThis article presents an exergy study of the hydrolysis reaction in the copper-chlorine thermochemical cycle for hydrogen production. It examines the reactor performance through a detailed analysis of thermal and chemical irreversibilities in the two-phase gas-solid reacting flow. A thermodynamic analysis is developed based on the flow availability and availability transfer in the spray reaction process to determine the ireversibilities of the reaction at different operating conditions. The reactor operating temperature and steam to copper chloride molar ratio, along with changes in the reaction kinetics, are considered as the critical parameters which affect the exergy efficiency of the hydrolysis reactor. The entropy generation associated with adding extra steam into the reactor and changing the reaction temperature is evaluated to assess the effectiveness of the decomposition process and the lost availability from the hydrolysis reaction. The effects from the side reaction and unreacted CuCl2 in the simulation reveal the exergy loss and resulting value of the exergy efficiency of 2.8% compared to the stoichiometry condition with a relatively high exergy efficiency of more than 75%. Such a large difference indicates the importance of analyzing real reaction conditions to provide a more reliable insight in identifying the sources of exergy losses
