Effects of Substituents on Photophysical and CO-Photoreleasing Properties of 2,6-Substituted meso-Carboxy BODIPY Derivatives

Carbon monoxide (CO) is an endogenously produced signaling molecule involved in the control of a vast array of physiological processes. One of the strategies to administer therapeutic amounts of CO is the precise spatial and temporal control over its release from photoactivatable CO-releasing molecules (photoCORMs). Here we present the synthesis and photophysical and photochemical properties of a small library of meso-carboxy BODIPY derivatives bearing different substituents at positions 2 and 6. We show that the nature of substituents has a major impact on both their photophysics and the efficiency of CO photorelease. CO was found to be efficiently released from pi -extended 2,6-arylethynyl BODIPY derivatives possessing absorption spectra shifted to a more biologically desirable wavelength range. Selected photoCORMs were subjected to in vitro experiments that did not reveal any serious toxic effects, suggesting their potential for further biological research

Impact of permeate flux and gas sparging rate on membrane performance and process economics of granular anaerobic membrane bioreactors

This research investigated the impact of permeate flux and gas sparging rate on membrane permeability, dissolved and colloidal organic matter (DCOM) rejection and process economics of granular anaerobic membrane bioreactors (AnMBRs). The goal of the study was to understand how membrane fouling control strategies influence granular AnMBR economics. To this end, short- and long-term filtration tests were performed under different permeate flux and specific gas demand (SGD) conditions. The results showed that flux and SGD conditions had a direct impact on membrane fouling. At normalised fluxes (J20) of 4.4 and 8.7 L m−2 h−1 (LMH) the most favourable SGD condition was 0.5 m3 m−2 h−1, whereas at J20 of 13.0 and 16.7 LMH the most favourable SGD condition was 1.0 m3 m−2 h−1. The flux and the SGD did not have a direct impact on DCOM rejection, with values ranging between 31 and 44%. The three-dimensional excitation-emission matrix fluorescence (3DEEM) spectra showed that protein-like fluorophores were predominant in mixed liquor and permeate samples (67-79%) and were retained by the membrane (39-50%). This suggests that protein-like fluorophores could be an important foulant for these systems. The economic analysis showed that operating the membranes at moderate fluxes (J20 = 7.8 LMH) and SGD (0.5 m3 m−2 h−1) could be the most favourable alternative. Finally, a sensitivity analysis illustrated that electricity and membrane cost were the most sensitive economic parameters, which highlights the importance of reducing SGD requirements and improving membrane permeability to reduce costs of granular AnMBRs

Factors that sustain indigenous youth mentoring programs : a qualitative systematic review

Background Indigenous youth worldwide continue to experience disproportional rates of poorer mental health and well-being compared to non-Indigenous youth. Mentoring has been known to establish favorable outcomes in many areas of health but is still in its early phases of research within Indigenous contexts. This paper explores the barriers and facilitators of Indigenous youth mentoring programs to improve mental health outcomes and provides evidence for governments’ response to the United Nations Declaration on the Rights of Indigenous Peoples. Methods A systematic search for published studies was conducted on PubMed, Embase, Scopus, CINAHL, and grey literature through Trove, OpenGrey, Indigenous HealthInfoNet, and Informit Indigenous Collection. All papers included in the search were peer-reviewed and published from 2007 to 2021. The Joanna Briggs Institute approaches to critical appraisal, data extraction, data synthesis, and confidence of findings were used. Results A total of eight papers describing six mentoring programs were included in this review; six papers were from Canada, and two originated from Australia. Studies included mentor perspectives (n=4) (incorporating views of parents, carers, Aboriginal assistant teachers, Indigenous program facilitators, young adult health leaders, and community Elders), mentee perspectives (n=1), and both mentor and mentee perspectives (n=3). Programs were conducted nationally (n=3) or within specific local Indigenous communities (n=3) with varying mentor styles and program focus. Five synthesized findings were identified from the data extraction process, each consisting of four categories. These synthesized findings were: establishing cultural relevancy, facilitating environments, building relationships, facilitating community engagement, and leadership responsibilities, which were discussed in the context of extant mentoring theoretical frameworks. Conclusion Mentoring is an appropriate strategy for improving general well-being. However, more research is needed to explore program sustainability and maintaining outcomes in the long term

Primary Aldosteronism: KCNJ5 Mutations and Adrenocortical Cell Growth

Aldosterone-producing adenomas with somatic mutations in the KCNJ5 G-protein-coupled inwardly rectifying potassium channel are a cause of primary aldosteronism. These mutations drive aldosterone excess, but their role in cell growth is undefined. Our objective was to determine the role of KCNJ5 mutations in adrenal cell proliferation and apoptosis. The Ki67 proliferative index was positively correlated with adenoma diameter in aldosterone-producing adenomas with a KCNJ5 mutation (r=0.435, P=0.007), a negative correlation was noted in adenomas with no mutation detected (r=-0.548, P=0.023). Human adrenocortical cell lines were established with stable expression of cumate-inducible wild-type or mutated KCNJ5. Increased cell proliferation was induced by low-level induction of KCNJ5-T158A expression compared with control cells (P=0.009), but increased induction ablated this difference. KCNJ5-G151R displayed no apparent proliferative effect, but KCNJ5-G151E and L168R mutations each resulted in decreased cell proliferation (difference P<0.0001 from control cells, both comparisons). Under conditions tested, T158A had no effect on apoptosis, but apoptosis increased with expression of G151R (P<0.0001), G151E (P=0.008), and L168R (P<0.0001). We generated a specific KCNJ5 monoclonal antibody which was used in immunohistochemistry to demonstrate strong KCNJ5 expression in adenomas without a KCNJ5 mutation and in the zona glomerulosa adjacent to adenomas irrespective of genotype as well as in aldosterone-producing cell clusters. Double immunofluorescence staining for KCNJ5 and CYP11B2 (aldosterone synthase) showed markedly decreased KCNJ5 immunostaining in CYP11B2-positive cells compared with CYP11B2-negative cells in aldosterone-producing adenomas with a KCNJ5 mutation. Together, these findings support the concept that cell growth effects of KCNJ5 mutations are determined by the expression level of the mutated channel

Calendar year 2003 : annual site enviromental report for Tonopah Test Range, Nevada and Kauai Test Facility, Hawaii.

Tonopah Test Range (TTR) in Nevada and Kauai Test Facility (KTF) in Hawaii are government-owned, contractor-operated facilities operated by Sandia Corporation, a subsidiary of Lockheed Martin Corporation. The U.S. Department of Energy (DOE), National Nuclear Security Administration (NNSA), through the Sandia Site Office (SSO), in Albuquerque, NM, manages TTR and KTF's operations. Sandia Corporation conducts operations at TTR in support of DOE/NNSA's Weapons Ordnance Program and has operated the site since 1957. Westinghouse Government Services subcontracts to Sandia Corporation in administering most of the environmental programs at TTR. Sandia Corporation operates KTF as a rocket preparation launching and tracking facility. This Annual Site Environmental Report (ASER) summarizes data and the compliance status of the environmental protection and monitoring program at TTR and KTF through Calendar Year (CY) 2003. The compliance status of environmental regulations applicable at these sites include state and federal regulations governing air emissions, wastewater effluent, waste management, terrestrial surveillance, and Environmental Restoration (ER) cleanup activities. Sandia Corporation is responsible only for those environmental program activities related to its operations. The DOE/NNSA, Nevada Site Office (NSO) retains responsibility for the cleanup and management of ER TTR sites. Currently, there are no ER Sites at KTF. Environmental monitoring and surveillance programs are required by DOE Order 450.1, Environmental Protection Program (DOE 2003) and DOE Order 231.1 Chg 2., Environment, Safety, and Health Reporting (DOE 1996)

Rim-to-Rim Wearables at the Canyon for Health (R2R WATCH): Physiological, Cognitive, and Biological Markers of Performance Decline in an Extreme Environment

Success in extreme environments comes with a cost of subtle performance decrements that if not mitigated properly can lead to lifethreatening consequences. Identification and prediction of performance decline could alleviate deleterious consequences and enhance success in challenging and high-risk operations. The Rim-to-Rim Wearables at the Canyon for Health (R2R WATCH) project was designed to examine the cognitive, physiological, and biological markers of performance decline in the extreme environment of the Grand Canyon Rim-to-Rim (R2R) hike. The study utilized commercial off-the-shelf cognitive and physiological monitoring techniques, along with subjective self-assessments and hematologic measurements to determine subject performance and changes across the hike. The multiyear effort collected these multiple data streams in parallel on a large sample of participants hiking the R2R, leading to a rich and complex data set. This article describes the methodology and its evolution as devices and measurements were assessed after each data collection event. It also highlights a subset of the patterns of results found across the data streams. Subsequent work will draw on this data set to focus on building more sophisticated, predictive statistical models and dive deeper into specific analyses (such as the physiological and biological profiles of hikers who were left behind by their hiking partners)

Interactions between the Nse3 and Nse4 Components of the SMC5-6 Complex Identify Evolutionarily Conserved Interactions between MAGE and EID Families

The SMC5-6 protein complex is involved in the cellular response to DNA damage. It is composed of 6-8 polypeptides, of which Nse1, Nse3 and Nse4 form a tight sub-complex. MAGEG1, the mammalian ortholog of Nse3, is the founding member of the MAGE (melanoma-associated antigen) protein family and Nse4 is related to the EID (E1A-like inhibitor of differentiation) family of transcriptional repressors.Using site-directed mutagenesis, protein-protein interaction analyses and molecular modelling, we have identified a conserved hydrophobic surface on the C-terminal domain of Nse3 that interacts with Nse4 and identified residues in its N-terminal domain that are essential for interaction with Nse1. We show that these interactions are conserved in the human orthologs. Furthermore, interaction of MAGEG1, the mammalian ortholog of Nse3, with NSE4b, one of the mammalian orthologs of Nse4, results in transcriptional co-activation of the nuclear receptor, steroidogenic factor 1 (SF1). In an examination of the evolutionary conservation of the Nse3-Nse4 interactions, we find that several MAGE proteins can interact with at least one of the NSE4/EID proteins.We have found that, despite the evolutionary diversification of the MAGE family, the characteristic hydrophobic surface shared by all MAGE proteins from yeast to humans mediates its binding to NSE4/EID proteins. Our work provides new insights into the interactions, evolution and functions of the enigmatic MAGE proteins

A threefold perspective on the role of a pockmark in benthic faunal communities and biodiversity patterns

Pockmarks are circular-shaped depressions that increase seabed heterogeneity and are characterized by discontinuous fluid emissions. To understand how environmental conditions of pockmarks affect the structure of macroand meiofauna, we investigated two sites in a pockmark field in the northwestern Madagascar margin. In a comparative approach, we explored the community structure of the dominant taxa (Polychaeta, Nematoda and hyaline foraminifera) in each component (macro-, metazoan meiofauna and foraminifera, respectively). The investigated active pockmark showed approximately two times higher meiofauna abundance compared to in a site away from another pockmark field, but macrofauna showed the opposite trend, with almost half density at the pockmark site. However, at both sites, macroand meiofauna showed higher richness and abundance values in the top well-oxygenated layers of the sediment than in the underlaying ones. Polychaeta and Nematoda showed lower richness in the pockmark, opposed to hyaline foraminiferans, but lower evenness in the pockmark was found for the three groups. The detection of gas flares in the water column attests of the recent activity within the pockmark. High amount of sulfur-bearing minerals (mainly pyrite) evidences a production of dissolved free sulfides (not detected at the time of sampling) by sulfate reduction process driven by organic matter degradation and anaerobic oxidation of methane. Furthermore, recent increase in sedimentation rates in the past 70 years and organic matter inputs could have led to higher organic matter degradation rates resulting in reduced conditions and a high oxygen consumption. All this together seem to act as key factors in the determination of variation in richness, abundance and community composition of macrofauna and meiofauna. Additionally, some taxa seem to be more tolerant to these extreme conditions, such as species belonging to the Nematoda genus Desmodora and the phylum Kinorhyncha, which are highly abundant in the pockmark, and hence, may be considered as potential bioindicators of pockmark activity in this area. Further studies are required for a better assessment