R-PEP-27, a Potent Renin Inhibitor, Decreases Plasma Angiotensin II and Blood Pressure in Normal Volunteers

The hemodynamic and humoral effects of the specific human renin inhibitor R-PEP-27 were studied in six normal human subjects on low and high sodium intake diets. An intravenous infusion of R-PEP-27 (0.5 to 16 μg/min/kg body wt) reduced blood pressure in a dose-dependent fashion; the mean arterial blood pressure at the end of the infusion fell from 128 ± 4/83 ± 4 to 119 ± 3/71 ± 3 mm Hg (mean ± SEM) (P < .01) during the low sodium intake diet. R-PEP-27 had no effect on blood pressure during the high sodium intake diet. R-PEP-27 significantly reduced plasma angiotensin II and aldosterone concentrations. The temporal response to R-PEP-27 suggests that it is a shortlived although highly potent competitive inhibitor of renin; this peptide is a valuable and specific physiologic probe of the renin-angiotensin system. Am J Hypertens 1994;7:295-30

BMP type I receptor inhibition reduces heterotopic ossification

Fibrodysplasia ossificans progressiva (FOP) is a congenital disorder of progressive and widespread postnatal ossification of soft tissues1,2,3,4 and is without known effective treatments. Affected individuals harbor conserved mutations in the ACVR1 gene that are thought to cause constitutive activation of the bone morphogenetic protein (BMP) type I receptor, activin receptor-like kinase-2 (ALK2)5. Here we show that intramuscular expression in the mouse of an inducible transgene encoding constitutively active ALK2 (caALK2), resulting from a glutamine to aspartic acid change at amino acid position 207, leads to ectopic endochondral bone formation, joint fusion and functional impairment, thus phenocopying key aspects of human FOP. A selective inhibitor of BMP type I receptor kinases, LDN-193189 (ref. 6), inhibits activation of the BMP signaling effectors SMAD1, SMAD5 and SMAD8 in tissues expressing caALK2 induced by adenovirus specifying Cre (Ad.Cre). This treatment resulted in a reduction in ectopic ossification and functional impairment. In contrast to localized induction of caALK2 by Ad.Cre (which entails inflammation), global postnatal expression of caALK2 (induced without the use of Ad.Cre and thus without inflammation) does not lead to ectopic ossification. However, if in this context an inflammatory stimulus was provided with a control adenovirus, ectopic bone formation was induced. Like LDN-193189, corticosteroid inhibits ossification in Ad.Cre-injected mutant mice, suggesting caALK2 expression and an inflammatory milieu are both required for the development of ectopic ossification in this model. These results support the role of dysregulated ALK2 kinase activity in the pathogenesis of FOP and suggest that small molecule inhibition of BMP type I receptor activity may be useful in treating FOP and heterotopic ossification syndromes associated with excessive BMP signaling

Marine Ecoregion and Deepwater Horizon Oil Spill Affect Recruitment and Population Structure of a Salt Marsh Snail

Marine species with planktonic larvae often have high spatial and temporal variation in recruitment that leads to subsequent variation in the ecology of benthic adults. Using a combination of published and unpublished data, we compared the population structure of the salt marsh snail, Littoraria irrorata, between the South Atlantic Bight and the Gulf Coast of the United States to infer geographic differences in recruitment and to test the hypothesis that the Deepwater Horizon oil spill led to widespread recruitment failure of L. irrorata in Louisiana in 2010. Size-frequency distributions in both ecoregions were bimodal, with troughs in the distributions consistent with a transition from sub-adults to adults at ~13 mm in shell length as reported in the literature; however, adult snails reached larger sizes in the Gulf Coast. The ratio of sub-adults to adults was 1.5–2 times greater in the South Atlantic Bight than the Gulf Coast, consistent with higher recruitment rates in the South Atlantic Bight. Higher recruitment rates in the South Atlantic Bight could contribute to higher snail densities and reduced adult growth in this region. The ratio of sub-adults to adults in Louisiana was lower in 2011 than in previous years, and began to recover in 2012–2014, consistent with widespread recruitment failure in 2010, when large expanses of spilled oil were present in coastal waters. Our results reveal an important difference in the ecology of a key salt marsh invertebrate between the two ecoregions, and also suggest that the Deepwater Horizon oil spill may have caused widespread recruitment failure in this species and perhaps others with similar planktonic larval stages

On looking into words (and beyond): Structures, Relations, Analyses

On Looking into Words is a wide-ranging volume spanning current research into word structure and morphology, with a focus on historical linguistics and linguistic theory. The papers are offered as a tribute to Stephen R. Anderson, the Dorothy R. Diebold Professor of Linguistics at Yale, who is retiring at the end of the 2016-2017 academic year. The contributors are friends, colleagues, and former students of Professor Anderson, all important contributors to linguistics in their own right. As is typical for such volumes, the contributions span a variety of topics relating to the interests of the honorand. In this case, the central contributions that Anderson has made to so many areas of linguistics and cognitive science, drawing on synchronic and diachronic phenomena in diverse linguistic systems, are represented through the papers in the volume. The 26 papers that constitute this volume are unified by their discussion of the interplay between synchrony and diachrony, theory and empirical results, and the role of diachronic evidence in understanding the nature of language. Central concerns of the volume include morphological gaps, learnability, increases and declines in productivity, and the interaction of different components of the grammar. The papers deal with a range of linked synchronic and diachronic topics in phonology, morphology, and syntax (in particular, cliticization), and their implications for linguistic theory

On looking into words (and beyond): Structures, Relations, Analyses

On Looking into Words is a wide-ranging volume spanning current research into word structure and morphology, with a focus on historical linguistics and linguistic theory. The papers are offered as a tribute to Stephen R. Anderson, the Dorothy R. Diebold Professor of Linguistics at Yale, who is retiring at the end of the 2016-2017 academic year. The contributors are friends, colleagues, and former students of Professor Anderson, all important contributors to linguistics in their own right. As is typical for such volumes, the contributions span a variety of topics relating to the interests of the honorand. In this case, the central contributions that Anderson has made to so many areas of linguistics and cognitive science, drawing on synchronic and diachronic phenomena in diverse linguistic systems, are represented through the papers in the volume. The 26 papers that constitute this volume are unified by their discussion of the interplay between synchrony and diachrony, theory and empirical results, and the role of diachronic evidence in understanding the nature of language. Central concerns of the volume include morphological gaps, learnability, increases and declines in productivity, and the interaction of different components of the grammar. The papers deal with a range of linked synchronic and diachronic topics in phonology, morphology, and syntax (in particular, cliticization), and their implications for linguistic theory

On looking into words (and beyond): Structures, Relations, Analyses

On Looking into Words is a wide-ranging volume spanning current research into word structure and morphology, with a focus on historical linguistics and linguistic theory. The papers are offered as a tribute to Stephen R. Anderson, the Dorothy R. Diebold Professor of Linguistics at Yale, who is retiring at the end of the 2016-2017 academic year. The contributors are friends, colleagues, and former students of Professor Anderson, all important contributors to linguistics in their own right. As is typical for such volumes, the contributions span a variety of topics relating to the interests of the honorand. In this case, the central contributions that Anderson has made to so many areas of linguistics and cognitive science, drawing on synchronic and diachronic phenomena in diverse linguistic systems, are represented through the papers in the volume. The 26 papers that constitute this volume are unified by their discussion of the interplay between synchrony and diachrony, theory and empirical results, and the role of diachronic evidence in understanding the nature of language. Central concerns of the volume include morphological gaps, learnability, increases and declines in productivity, and the interaction of different components of the grammar. The papers deal with a range of linked synchronic and diachronic topics in phonology, morphology, and syntax (in particular, cliticization), and their implications for linguistic theory