Crystal Structure of the PAC1R Extracellular Domain Unifies a Consensus Fold for Hormone Recognition by Class B G-Protein Coupled Receptors

Pituitary adenylate cyclase activating polypeptide (PACAP) is a member of the PACAP/glucagon family of peptide hormones, which controls many physiological functions in the immune, nervous, endocrine, and muscular systems. It activates adenylate cyclase by binding to its receptor, PAC1R, a member of class B G-protein coupled receptors (GPCR). Crystal structures of a number of Class B GPCR extracellular domains (ECD) bound to their respective peptide hormones have revealed a consensus mechanism of hormone binding. However, the mechanism of how PACAP binds to its receptor remains controversial as an NMR structure of the PAC1R ECD/PACAP complex reveals a different topology of the ECD and a distinct mode of ligand recognition. Here we report a 1.9 Å crystal structure of the PAC1R ECD, which adopts the same fold as commonly observed for other members of Class B GPCR. Binding studies and cell-based assays with alanine-scanned peptides and mutated receptor support a model that PAC1R uses the same conserved fold of Class B GPCR ECD for PACAP binding, thus unifying the consensus mechanism of hormone binding for this family of receptors

Long-term trends in submicron particle concentrations in a metropolitan area of the northeastern United States

Significant changes in emission sources have occurred in the northeastern United States over the past decade, due in part to the implementation of emissions standards, the introduction and addition of abatement technologies for road transport, changes in fuel sulfur content for road and non-road transport, as well as economic impacts of a major recession and differential fuel prices. These changes in emission scenarios likely affected the concentrations of airborne submicron particles. This study investigated the characteristics of 11–500 nm particle number concentrations and their size spectra in Rochester, NY during the past 15 years (2002 to 2016). The modal structure, diurnal, weekly and monthly patterns of particle number concentrations are analyzed. Long-term trends are quantified using seasonal-trend decomposition procedures based on “Loess”, Mann-Kendall regression with Theil-Sen slope and piecewise regression. Particle concentrations underwent significant (p < 0.05) downward trends. An annual decrease of −323 particles/cm3/y (−4.6%/y) was estimated for the total particle number concentration using Theil-Sen analysis. The trends were driven mainly by the decrease in particles in the 11–50 nm range (−181 particles/cm3/y; −4.7%/y). Slope changes were investigated annually and seasonally. Piecewise regression found different slopes for different portions of the overall period with the strongest declines between 2005 and 2011/2013, followed by small upward trends between 2013 and 2016 for most size bins, possibly representing increased vehicular traffic after the recovery from the 2008 recession

Significant genetic differentiation among populations of Anomalocardia brasiliana (Gmelin, 1791): A bivalve with planktonic larval dispersion

Four Brazilian populations of Anomalocardia brasiliana were tested for mutual genetic homogeneity, using data from 123 sequences of the mtDNA cytochrome oxidase c subunit I gene. A total of 36 haplotypes were identified, those shared being H3 (Canela Island, Prainha and Acupe) and both H5 and H9 (Prainha and Acupe). Haplotype diversity values were high, except for the Camurupim population, whereas nucleotide values were low in all the populations, except for that of Acupe. Only the Prainha population showed a deviation from neutrality and the SSD test did not reject the demographic expansion hypothesis. Fst values showed that the Prainha and Acupe populations represent a single stock, whereas in both the Canela Island and Camurupim stocks, population structures are different and independent. The observed structure at Canela Island may be due to the geographic distance between this population and the remainder. The Camurupim population does not share any haplotype with the remaining populations in northeastern Brazil. The apparent isolation could be due to the rocky barrier located facing the mouth of the Mamanguape River. The results highlight the importance of wide-scale studies to identify and conserve local genetic diversity, especially where migration is restricted