Effect of relative humidity on SOA formation from isoprene/NO photooxidation: enhancement of 2-methylglyceric acid and its corresponding oligoesters under dry conditions

The effect of relative humidity (RH) on secondary organic aerosol (SOA) formation from the photooxidation of isoprene under initially high nitric oxide (NO) conditions (i.e., isoprene/NO ~3) was investigated in a dual outdoor smog chamber. Based upon particle volume concentration measurements and the detailed chemical characterization of isoprene SOA using gas chromatography/mass spectrometry (GC/MS) and ultra performance liquid chromatography/electrospray ionization high-resolution quadrupole time-of-flight mass spectrometry (UPLC/ESI-HR-Q-TOFMS), enhanced SOA formation was observed under lower RH conditions (15-40 %) compared to higher RH conditions (40-90 %). 2-methylglyceric acid (2-MG) and its corresponding oligoesters, which have been previously shown to form from further oxidation of methacryloylperoxynitrate (MPAN), were enhanced in the particle-phase under lower RH conditions. In addition, an abundant unknown SOA tracer likely derived from the further oxidation of MPAN was detected and enhanced under lower RH conditions. In contrast, the 2-methyltetrols, which are known to mainly form from the reactive uptake of isoprene epoxydiols (IEPOX) under low-NO conditions in the presence of acidified aerosol, did not substantially vary under different RH conditions; however, isoprene-derived organosulfates were found to be enhanced under high-RH conditions, indicating the likely importance of the aqueous aerosol phase in their formation. Based upon the detailed chemical characterization results, particle-phase organic esterification is tentatively proposed to explain the observed enhancements of isoprene SOA mass under lower RH conditions. Alternative mechanisms explaining the enhancement of 2-MG and its corresponding oligoesters cannot be completely ruled out. This is one of only a few chamber studies that have examined the effect of RH on isoprene SOA formation. In comparison to our recent results obtained from aromatic SOA formation, the effect of RH on isoprene SOA formation is reversed. The results of this study highlight the importance of elucidating the key reactive intermediates that lead to SOA formation, especially since RH likely affects their ability in forming SOA. Furthermore, ignoring the effects of RH may significantly affect the accuracy of both regional and global SOA models

Empowerment or Engagement? Digital Health Technologies for Mental Healthcare

We argue that while digital health technologies (e.g. artificial intelligence, smartphones, and virtual reality) present significant opportunities for improving the delivery of healthcare, key concepts that are used to evaluate and understand their impact can obscure significant ethical issues related to patient engagement and experience. Specifically, we focus on the concept of empowerment and ask whether it is adequate for addressing some significant ethical concerns that relate to digital health technologies for mental healthcare. We frame these concerns using five key ethical principles for AI ethics (i.e. autonomy, beneficence, non-maleficence, justice, and explicability), which have their roots in the bioethical literature, in order to critically evaluate the role that digital health technologies will have in the future of digital healthcare

Role of the IL-1 Pathway in Dopaminergic Neurodegeneration and Decreased Voluntary Movement

Interleukin-1 (IL-1), a proinflammatory cytokine synthesized and released by activated microglia, can cause dopaminergic neurodegeneration leading to Parkinsons disease (PD). However, it is uncertain whether IL-1 can act directly, or by exacerbating the harmful actions of other brain insults. To ascertain the role of the IL-1 pathway on dopaminergic neurodegeneration and motor skills during aging, we compared mice with impaired [caspase-1 knockout (casp1(-/-))] or overactivated IL-1 activity [IL-1 receptor antagonist knockout (IL-1ra(-/-))] to wild-type (wt) mice at young and middle age. Their motor skills were evaluated by the open-field and rotarod tests, and quantification of their dopamine neurons and activated microglia within the substantia nigra were performed by immunohistochemistry. IL-1ra(-/-) mice showed an age-related decline in motor skills, a reduced number of dopamine neurons, and an increase in activated microglia when compared to wt or casp1(-/-) mice. Casp1(-/-) mice had similar changes in motor skills and dopamine neurons, but fewer activated microglia cells than wt mice. Our results suggest that the overactivated IL-1 pathway occurring in IL-1ra(-/-) mice in the absence of inflammatory interventions (e.g., intracerebral injections performed in animal models of PD) increased activated microglia, decreased the number of dopaminergic neurons, and reduced their motor skills. Decreased IL-1 activity in casp1(-/-) mice did not yield clear protective effects when compared with wt mice. In summary, in the absence of overt brain insults, chronic activation of the IL-1 pathway may promote pathological aspects of PD per se, but its impairment does not appear to yield advantages over wt mice.Funding Agencies|John Curtin School of Medical Research, The Australian National University</p

CART Peptide Is a Potential Endogenous Antioxidant and Preferentially Localized in Mitochondria

The multifunctional neuropeptide Cocaine and Amphetamine Regulated Transcript (CART) is secreted from hypothalamus, pituitary, adrenal gland and pancreas. It also can be found in circulatory system. This feature suggests a general role for CART in different cells. In the present study, we demonstrate that CART protects mitochondrial DNA (mtDNA), cellular proteins and lipids against the oxidative action of hydrogen peroxide, a widely used oxidant. Using cis-parinaric acid as a sensitive reporting probe for peroxidation in membranes, and a lipid-soluble azo initiator of peroxyl radicals, 2,2′-Azobis(2,4-dimethylvaleronitrile) we found that CART is an antioxidant. Furthermore, we found that CART localized to mitochondria in cultured cells and mouse brain neuronal cells. More importantly, pretreatment with CART by systemic injection protects against a mouse oxidative stress model, which mimics the main features of Parkinson's disease. Given the unique molecular structure and biological features of CART, we conclude that CART is an antioxidant peptide (or antioxidant hormone). We further propose that it may have strong therapeutic properties for human diseases in which oxidative stress is strongly involved such as Parkinson's disease

Kinase inhibitors for the treatment of inflammatory and autoimmune disorders

Drugs targeting inhibition of kinases for the treatment of inflammation and autoimmune disorders have become a major focus in the pharmaceutical and biotech industry. Multiple kinases from different pathways have been the targets of interest in this endeavor. This review describes some of the recent developments in the search for inhibitors of IKK2, Syk, Lck, and JAK3 kinases. It is anticipated that some of these compounds or newer inhibitors of these kinases will be approved for the treatment of rheumatoid arthritis, psoriasis, organ transplantation, and other autoimmune diseases

Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts

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