Stimulation of renin secretion by nitric oxide is mediated by phosphodiesterase 3

This study aimed to characterize the cellular pathways along which nitric oxide (NO) stimulates renin secretion from the kidney. Using the isolated perfused rat kidney model we found that renin secretion stimulated 4- to 8-fold by low perfusion pressure (40 mmHg), by macula densa inhibition (100 μmol/liter of bumetanide), and by adenylate cyclase activation (3 nmol/liter of isoproterenol) was markedly attenuated by the NO synthase inhibitor nitro-l-arginine methyl ester (l-Name) (1 mM) and that the inhibition by l-Name was compensated by the NO-donor sodium nitroprusside (SNP) (10 μmol/liter). Similarly, inhibition of cAMP degradation by blockade of phosphodiesterase 1 (PDE-1) (20 μmol/liter of 8-methoxymethyl-1-methyl-3-(2-methylpropyl)xanthine) or of PDE-4 (20 μmol/liter of rolipram) caused a 3- to 4-fold stimulation of renin secretion that was attenuated by l-Name and that was even overcompensated by sodium nitroprusside. Inhibition of PDE-3 by 20 μmol/liter of milrinone or by 200 nmol/liter of trequinsin caused a 5- to 6-fold stimulation of renin secretion that was slightly enhanced by NO synthase inhibition and moderately attenuated by NO donation. Because PDE-3 is a cGMP-inhibited cAMP-PDE the role of endogenous cGMP for the effects of NO was examined by the use of the specific guanylate cyclase inhibitor 1-H-(1,2,4)oxodiazolo(4,3a)quinoxalin-1-one (20 μmol). In the presence of 1H-[1,2,4]oxodiazolo[4,3-a]quinoxalin-1-one the effect of NO on renin secretion was abolished, whereas PDE-3 inhibitors exerted their normal effects. These findings suggest that PDE-3 plays a major role for the cAMP control of renin secretion. Our findings are compatible with the idea that the stimulatory effects of endogenous and exogenous NO on renin secretion are mediated by a cGMP-induced inhibition of cAMP degradation.

(Re)discovering the Gaulcross Hoard

Acknowledgements We would like to thank Charles and Helen Gray for permitting access to the land and for support in the excavation of the hoard. Thanks also to Bruce Mann and the Aberdeenshire Council Archaeology Service for advice and supporting the radiocarbon dating. Fraser Hunter and Tanja Romankiewicz assisted during a very cold excavation. Fraser and Alice Blackwell kindly read and commented on drafts of this paper. The fieldwork was funded through a donation to the University of Aberdeen’s Development Trust and undertaken as part of the Northern Picts project, in association with the Tarbat Discovery Centre.

Vaginal progesterone prophylaxis for preterm birth (the OPPTIMUM study) : a multicentre, randomised, double-blind trial

Acknowledgments We thank the members of the Trial Steering and Data Monitoring Committee and all the people who helped in the conduct of the study (including the OPPTIMUM collaborative group and other clinicians listed in the appendix). We are grateful to Paul Piette (Besins Healthcare Corporate, Brussels, Belgium) and Besins Healthcare for their kind donation of active and placebo drug for use in the study, and to staff of the pharmacy and research and development departments of the participating hospitals. We are also grateful to the many people who helped in this study but who we have been unable to name, and in particular all the women (and their babies) who participated in OPPTIMUM. OPPTIMUM was funded by the Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute of Health Research (NIHR) partnership, award number G0700452, revised to 09/800/27. The EME Programme is funded by the MRC and NIHR, with contributions from the Chief Scientist Office in Scotland and National Institute for Social Care and Research in Wales. The views expressed in this publication are those of the author(s) and not necessarily those of the MRC, National Health Service, NIHR, or the Department of Health. The funder had no involvement in data collection, analysis or interpretation, and no role in the writing of this manuscript or the decision to submit for publication.

ApoNifH functions in iron–molybdenum cofactor synthesis and apodinitrogenase maturation

NifH (dinitrogenase reductase) has three important roles in the nitrogenase enzyme system. In addition to its role as the obligate electron donor to dinitrogenase, NifH is required for the iron–molybdenum cofactor (FeMo-co) synthesis and apodinitrogenase maturation. We have investigated the requirement of the Fe–S cluster of NifH for these processes by preparing apoNifH. The 4Fe–4S cluster of NifH was removed by chelation of the cluster with α, α′-bipyridyl. The resulting apoNifH was tested in in vitro FeMo-co synthesis and apodinitrogenase maturation reactions and was found to function in both these processes. Thus, the presence of a redox active 4Fe–4S cluster in NifH is not required for its function in FeMo-co synthesis and in apodinitrogenase maturation. This, in turn, implies that the role of NifH in these processes is not one of electron transfer or of iron or sulfur donation.

GPGPU implementation of growing neural gas: application to 3D scene reconstruction

Self-organising neural models have the ability to provide a good representation of the input space. In particular the Growing Neural Gas (GNG) is a suitable model because of its flexibility, rapid adaptation and excellent quality of representation. However, this type of learning is time-consuming, especially for high-dimensional input data. Since real applications often work under time constraints, it is necessary to adapt the learning process in order to complete it in a predefined time. This paper proposes a Graphics Processing Unit (GPU) parallel implementation of the GNG with Compute Unified Device Architecture (CUDA). In contrast to existing algorithms, the proposed GPU implementation allows the acceleration of the learning process keeping a good quality of representation. Comparative experiments using iterative, parallel and hybrid implementations are carried out to demonstrate the effectiveness of CUDA implementation. The results show that GNG learning with the proposed implementation achieves a speed-up of 6× compared with the single-threaded CPU implementation. GPU implementation has also been applied to a real application with time constraints: acceleration of 3D scene reconstruction for egomotion, in order to validate the proposal.

Donación voluntaria de sangre de cordón umbilical en el Hospital Universitario Virgen de la Arrixaca (2010-2011). Situación actual e influencia de las variables obstétrico-fetales

Objetivos: A principios de 2010 el Hospital Universitario Virgen de la Arrixaca puso en marcha, en el servicio de partos, el protocolo de donación voluntaria de sangre de cordón umbilical (SCU). Desde la reflexión y la autoevaluación, planteamos un análisis de nuestra situación actual a través del estudio de la influencia de las variables obstétrico-fetales en la calidad de las muestras. Métodos: Con este fin hemos planteado un trabajo de tipo observacional, descriptivo, retrospectivo y de corte transversal desde mayo de 2010 a noviembre de 2011, con el objetivo de aumentar la calidad de las unidades de SCU y optar por una gestión eficiente que haga sostenible el proyecto. Resultados: Se obtuvieron 123 donaciones potenciales de sangre de cordón y del análisis multivariable de las mismas obtuvimos una correlación positiva significativa entre el número de leucocitos, las semanas de gestación y el parto vaginal. El peso inicial de la unidad se incrementó significativamente a mayor peso del recién nacido y paridad de la donante. Conclusiones: Como conclusiones del estudio nos planteamos esbozar posibles factores predictivos que permitan seleccionar las muestras de mayor calidad y sean complemento de los actuales estándares elaborados por el Banco Público de Málaga. En este sentido nuestros resultados sugieren que en los partos con más semanas de gestación, paridad de la gestante y peso del recién nacido, así como en los partos vaginales, encontramos mayores posibilidades de obtener muestras de alta calidad.

Phosphorylated α-synuclein-immunoreactive retinal neuronal elements in Parkinson's disease subjects

Visual symptoms are relatively common in Parkinson's disease (PD) and optical coherence tomography has indicated possible retinal thinning. Accumulation of aggregated α-synuclein is thought to be a central pathogenic event in the PD brain but there have not as yet been reports of retinal synucleinopathy. Retinal wholemounts were prepared from subjects with a primary clinicopathological diagnosis of PD (N = 9), dementia with Lewy bodies (DLB; N = 3), Alzheimer's disease (N = 3), progressive supranuclear palsy (N = 2) as well as elderly normal control subjects (N = 4). These were immunohistochemically stained with an antibody against α-synuclein phosphorylated at serine 129, which is a specific molecular marker of synucleinopathy. Phosphorylated α-synuclein-immunoreactive (p-syn IR) nerve fibers were present in 7/9 PD subjects and in 1/3 DLB subjects; these were sparsely distributed and superficially located near or at the inner retinal surface. The fibers were either long and straight or branching, often with multiple en-passant varicosities along their length. The straight fibers most often had an orientation that was radial with respect to the optic disk. Together, these features are suggestive of either retinopetal/centrifugal fibers or of ganglion cell axons. In one PD subject there were sparse p-syn IR neuronal cell bodies with dendritic morphology suggestive of G19 retinal ganglion cells or intrinsically photosensitive ganglion cells. There were no stained nerve fibers or other specific staining in any of the non-PD or non-DLB subjects. It is possible that at least some of the observed visual function impairments in PD subjects might be due to α-synucleinopathy.

Letter from Francis Dana to Samuel Langdon, 1780 January 19

This one-page letter from Harvard alumnus Francis Dana (1743-1811; Harvard AB 1762), in Bilbao, Spain, to Harvard President Samuel Langdon concerns the donation of a Spanish book by Dana to the College Library.

Letter from Robert Bell to Edward Wigglesworth, 1781 June 16

This brief letter from Robert Bell in Boston, Massachusetts, to Professor Edward Wigglesworth concerns the donation of books to the College Library.

College Book 3, 1636-1779

This volume was begun by Thomas Danforth, most likely around 1687, and contains transcriptions of donation records, property inventories, College laws, Overseers and Corporation minutes, and other official documents dating from 1636 onwards. By copying these documents into one volume, Danforth brought together a chronicle of Harvard's early history. Some of its content duplicates that of College Book 1, and other entries were copied from sources which no longer exist, including College Book 2, which was destroyed by fire in 1764. Danforth, who served as College Treasurer from 1650 to 1668, as Steward from 1668 to 1682, and again as Treasurer from 1682 to 1683, is believed to have created this volume as a precautionary measure during the great upheaval surrounding the 1684 annulment of the Royal Charter of the Massachusetts Colony and consequent dissolution of the Harvard Corporation. Some scholars believe he created College Book 3 in fear that the College's original records, from which it was largely derived and copied, might be destroyed.

Diary and commonplace book of Peres Fobes, 1759-1760

The diary and commonplace book of Perez Fobes is written on unlined pages in a notebook with a sewn binding at the top of the pages; only the edge of the original leather softcover remain. The volume holds handwritten entries added irregularly from August 23, 1759 until December 1760 while Fobes was a student at Harvard College. The topics range from the irreverent, to the mundane, to the theological and scientific. The notebook serves to chronicle both his daily activities, such as books he read, lectures he attended, and travel, as well as a place to note humorous sayings, transcribe book passages, or ponder religious ideas such as original sin. In the volume, Fobes devotes considerable space to the subject of astronomy, and drew a picture of the "The Solar System Serundum Coper[nici] with the Or[bit] of 5 Remarkable Comets." At the back of the book, on unattached pages is a short personal dictionary for the letters A-K kept by Fobes.

Student notebook of Jonathan Trumbull, 1724-1725

The bound notebook contains academic texts copied by Harvard student Jonathan Trumbull in 1724 and 1725. The volume includes transcriptions of Harvard Instructor Judah Monis' Hebrew Grammar, Tutor William Brattle's Compendium of Logic, and Fellow Charles Morton's Natural Logic.

Letter from Oliver Wendell to John Thornton Kirkland, 1817

One letter offering Harvard President Kirkland a donation of 100 dollars to acquire a "handsome Christening Cup or Baptismal Basin" for the new College Church, which held services in University Hall.

Memorandum Concerning the Holyoke Bowl, 1904 June 14

One-page typed document reflecting the donation of the Holyoke Caudle Cup by Charlotte A. Hedge in 1903. Provenance information is also included. There is a handwritten note at the bottom of the page regarding the cup’s inclusion in an exhibition catalog published by the Boston Museum of Fine Arts.

Inventory of Silver Plate, Belonging to Harvard College, and in the Keeping of the President, 1886 December 8

Black and white composition book sent to the Harvard College Library containing a typed "copy of notes made in the spring of 1886" by John H. Buck. Includes historical information, and physical descriptions and valuations of the Great Salt, the Stoughton Cup, the Browne Cup, and the christening basin acquired with the donation of Oliver Wendell, as well as notes on other gifts of silver.