Anatomical pattern of the umbilical artery (round lig. of the urinary bladder) and urogenital artery in the guinea pig (Cavia porcellus, L., 1756)

This work deals with the study of the visceral branches of the internal iliac artery in guinea pig. Twenty animals (10 males and 10 females), adults were sacrificed with ethylic ether, injected with contrasting substance into abdominal aorta and dissected through stereoscopic microscope. In results were described the origin and permeability of the umbilical artery and the origin and branching of the urogenital artery. These observations in the guinea pig were comparatively discussed with others similarly described in several mammalians including: another laboratorial rodents, cat, dog, rabbit and man.Foi realizado estudo anatômico dos ramos viscerais da a. ilíaca interna na cobaia. Foram utilizadas 20 cobaias (10 machos e 10 fêmeas), adultas, sacrificadas com éter etílico (saturação anestésica), injetadas com contraste na aorta abdominal (látex corado) e dissecadas sob lupa. Em resultados são descritas a origem e a perviedade da a. umbilical e a origem e a ramescência da a. urogenital. Estas observações na cobaia foram comparativamente discutidas com outras semelhantemente descritas em diferentes mamíferos incluindo: outros roedores de laboratório, gato, cão, coelho e Homem

Semi-analytic galaxies : I. Synthesis of environmental and star-forming regulation mechanisms

We present results from the semi-analytic model of galaxy formation SAG applied on the MULTIDARK simulation MDPL2. SAG features an updated supernova (SN) feedback scheme and a robust modelling of the environmental effects on satellite galaxies. This incorporates a gradual starvation of the hot gas halo driven by the action of ram pressure stripping (RPS), that can affect the cold gas disc, and tidal stripping (TS), which can act on all baryonic components. Galaxy orbits of orphan satellites are integrated providing adequate positions and velocities for the estimation of RPS and TS. The star formation history and stellar mass assembly of galaxies are sensitive to the redshift dependence implemented in the SN feedback model. We discuss a variant of our model that allows to reconcile the predicted star formation rate density at z ≳ 3 with the observed one, at the expense of an excess in the faint end of the stellar mass function at z= 2. The fractions of passive galaxies as a function of stellar mass, halo mass, and the halo-centric distances are consistent with observational measurements. The model also reproduces the evolution of the main sequence of star-forming central and satellite galaxies. The similarity between them is a result of the gradual starvation of the hot gas halo suffered by satellites, in which RPS plays a dominant role. RPS of the cold gas does not affect the fraction of quenched satellites but it contributes to reach the right atomic hydrogen gas content for more massive satellites (M* ≳1010M⊙).Instituto de Astrofísica de La PlataFacultad de Ciencias Astronómicas y Geofísica

Semi-analytic galaxies : I. Synthesis of environmental and star-forming regulation mechanisms

We present results from the semi-analytic model of galaxy formation SAG applied on the MULTIDARK simulation MDPL2. SAG features an updated supernova (SN) feedback scheme and a robust modelling of the environmental effects on satellite galaxies. This incorporates a gradual starvation of the hot gas halo driven by the action of ram pressure stripping (RPS), that can affect the cold gas disc, and tidal stripping (TS), which can act on all baryonic components. Galaxy orbits of orphan satellites are integrated providing adequate positions and velocities for the estimation of RPS and TS. The star formation history and stellar mass assembly of galaxies are sensitive to the redshift dependence implemented in the SN feedback model. We discuss a variant of our model that allows to reconcile the predicted star formation rate density at z ≳ 3 with the observed one, at the expense of an excess in the faint end of the stellar mass function at z= 2. The fractions of passive galaxies as a function of stellar mass, halo mass, and the halo-centric distances are consistent with observational measurements. The model also reproduces the evolution of the main sequence of star-forming central and satellite galaxies. The similarity between them is a result of the gradual starvation of the hot gas halo suffered by satellites, in which RPS plays a dominant role. RPS of the cold gas does not affect the fraction of quenched satellites but it contributes to reach the right atomic hydrogen gas content for more massive satellites (M* ≳1010M⊙).Instituto de Astrofísica de La PlataFacultad de Ciencias Astronómicas y Geofísica

Calibration of semi-analytic models of galaxy formation using particle swarm optimization

We present a fast and accurate method to select an optimal set of parameters in semi-analytic models of galaxy formation and evolution (SAMs). Our approach compares the results of a model against a set of observables applying a stochastic technique called Particle Swarm Optimization (PSO), a self-learning algorithm for localizing regions of maximum likelihood in multidimensional spaces that outperforms traditional sampling methods in terms of computational cost. We apply the PSO technique to the SAG semi-analytic model combined with merger trees extracted from a standard Lambda Cold Dark Matter N-body simulation. The calibration is performed using a combination of observed galaxy properties as constraints, including the local stellar mass function and the black hole to bulge mass relation. We test the ability of the PSO algorithm to find the best set of free parameters of the model by comparing the results with those obtained using a MCMC exploration. Both methods find the same maximum likelihood region, however, the PSO method requires one order of magnitude fewer evaluations. This new approach allows a fast estimation of the best-fitting parameter set in multidimensional spaces, providing a practical tool to test the consequences of including other astrophysical processes in SAMs.Facultad de Ciencias Astronómicas y GeofísicasInstituto de Astrofísica de La Plat

Expression of Mutant or Cytosolic PrP in Transgenic Mice and Cells Is Not Associated with Endoplasmic Reticulum Stress or Proteasome Dysfunction

The cellular pathways activated by mutant prion protein (PrP) in genetic prion diseases, ultimately leading to neuronal dysfunction and degeneration, are not known. Several mutant PrPs misfold in the early secretory pathway and reside longer in the endoplasmic reticulum (ER) possibly stimulating ER stress-related pathogenic mechanisms. To investigate whether mutant PrP induced maladaptive responses, we checked key elements of the unfolded protein response (UPR) in transgenic mice, primary neurons and transfected cells expressing two different mutant PrPs. Because ER stress favors the formation of untranslocated PrP that might aggregate in the cytosol and impair proteasome function, we also measured the activity of the ubiquitin proteasome system (UPS). Molecular, biochemical and immunohistochemical analyses found no increase in the expression of UPR-regulated genes, such as Grp78/Bip, CHOP/GADD153, or ER stress-dependent splicing of the mRNA encoding the X-box-binding protein 1. No alterations in UPS activity were detected in mutant mouse brains and primary neurons using the UbG76V-GFP reporter and a new fluorogenic peptide for monitoring proteasomal proteolytic activity in vivo. Finally, there was no loss of proteasome function in neurons in which endogenous PrP was forced to accumulate in the cytosol by inhibiting cotranslational translocation. These results indicate that neither ER stress, nor perturbation of proteasome activity plays a major pathogenic role in prion diseases

The RESET project: constructing a European tephra lattice for refined synchronisation of environmental and archaeological events during the last c. 100 ka

This paper introduces the aims and scope of the RESET project (. RESponse of humans to abrupt Environmental Transitions), a programme of research funded by the Natural Environment Research Council (UK) between 2008 and 2013; it also provides the context and rationale for papers included in a special volume of Quaternary Science Reviews that report some of the project's findings. RESET examined the chronological and correlation methods employed to establish causal links between the timing of abrupt environmental transitions (AETs) on the one hand, and of human dispersal and development on the other, with a focus on the Middle and Upper Palaeolithic periods. The period of interest is the Last Glacial cycle and the early Holocene (c. 100-8 ka), during which time a number of pronounced AETs occurred. A long-running topic of debate is the degree to which human history in Europe and the Mediterranean region during the Palaeolithic was shaped by these AETs, but this has proved difficult to assess because of poor dating control. In an attempt to move the science forward, RESET examined the potential that tephra isochrons, and in particular non-visible ash layers (cryptotephras), might offer for synchronising palaeo-records with a greater degree of finesse. New tephrostratigraphical data generated by the project augment previously-established tephra frameworks for the region, and underpin a more evolved tephra 'lattice' that links palaeo-records between Greenland, the European mainland, sub-marine sequences in the Mediterranean and North Africa. The paper also outlines the significance of other contributions to this special volume: collectively, these illustrate how the lattice was constructed, how it links with cognate tephra research in Europe and elsewhere, and how the evidence of tephra isochrons is beginning to challenge long-held views about the impacts of environmental change on humans during the Palaeolithic. © 2015 Elsevier Ltd.RESET was funded through Consortium Grants awarded by the Natural Environment Research Council, UK, to a collaborating team drawn from four institutions: Royal Holloway University of London (grant reference NE/E015905/1), the Natural History Museum, London (NE/E015913/1), Oxford University (NE/E015670/1) and the University of Southampton, including the National Oceanography Centre (NE/01531X/1). The authors also wish to record their deep gratitude to four members of the scientific community who formed a consultative advisory panel during the lifetime of the RESET project: Professor Barbara Wohlfarth (Stockholm University), Professor Jørgen Peder Steffensen (Niels Bohr Institute, Copenhagen), Dr. Martin Street (Romisch-Germanisches Zentralmuseum, Neuwied) and Professor Clive Oppenheimer (Cambridge University). They provided excellent advice at key stages of the work, which we greatly valued. We also thank Jenny Kynaston (Geography Department, Royal Holloway) for construction of several of the figures in this paper, and Debbie Barrett (Elsevier) and Colin Murray Wallace (Editor-in-Chief, QSR) for their considerable assistance in the production of this special volume.Peer Reviewe

Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups

Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease