Tissue Localization and Extracellular Matrix Degradation by PI, PII and PIII Snake Venom Metalloproteinases: Clues on the Mechanisms of Venom-Induced Hemorrhage

20 páginas, 4 figuras, 3 tablas y 7 tablas en material suplementario.Snake venom hemorrhagic metalloproteinases (SVMPs) of the PI, PII and PIII classes were compared in terms of tissue localization and their ability to hydrolyze basement membrane components in vivo, as well as by a proteomics analysis of exudates collected in tissue injected with these enzymes. Immunohistochemical analyses of co-localization of these SVMPs with type IV collagen revealed that PII and PIII enzymes co-localized with type IV collagen in capillaries, arterioles and post-capillary venules to a higher extent than PI SVMP, which showed a more widespread distribution in the tissue. The patterns of hydrolysis by these three SVMPs of laminin, type VI collagen and nidogen in vivo greatly differ, whereas the three enzymes showed a similar pattern of degradation of type IV collagen, supporting the concept that hydrolysis of this component is critical for the destabilization of microvessel structure leading to hemorrhage. Proteomic analysis of wound exudate revealed similarities and differences between the action of the three SVMPs. Higher extent of proteolysis was observed for the PI enzyme regarding several extracellular matrix components and fibrinogen, whereas exudates from mice injected with PII and PIII SVMPs had higher amounts of some intracellular proteins. Our results provide novel clues for understanding the mechanisms by which SVMPs induce damage to the microvasculature and generate hemorrhage.This work was performed in partial fulfillment of the requirements for the PhD degree for Cristina Herrera at Universidad de Costa Rica.Peer reviewe

Comment on 'Geoengineering with seagrasses: Is credit due where credit is given?'

Over the past decade scientists around the world have sought to estimate the capacity of seagrass meadows to sequester carbon, and thereby understand their role in climate change mitigation. The number of studies reporting on seagrass carbon accumulation rates is still limited, but growing scientific evidence supports the hypothesis that seagrasses have been efficiently locking away CO2 for decades to millennia (e.g. Macreadie et al 2014, Mateo et al 1997, Serrano et al 2012). Johannessen and Macdonald (2016), however, challenge the role of seagrasses as carbon traps, claiming that gains in carbon storage by seagrasses may be \u27illusionary\u27 and that \u27their contribution to the global burial of carbon has not yet been established\u27. The authors warn that misunderstandings of how sediments receive, process and store carbon have led to an overestimation of carbon burial by seagrasses. Here we would like to clarify some of the questions raised by Johannessen and Macdonald (2016), with the aim to promote discussion within the scientific community about the evidence for carbon sequestration by seagrasses with a view to awarding carbon credits

Climate change and anthropogenic intervention impact on the hydrologic anomalies in a semi-arid area : lower Zab river basin, Iraq

Climate change impact, drought phenomena and anthropogenic stress are of increasing apprehension for water resource managers and strategists, particularly in arid regions. The current study proposes a generic methodology to evaluate the potential impact of such changes at a basin scale. The Lower Zab River Basin located in the north of Iraq has been selected for illustration purposes. The method has been developed through evaluating changes during normal hydrological years to separate the effects of climate change and estimate the hydrologic abnormalities utilising Indicators of Hydrologic Alteration. The meteorological parameters were perturbed by applying adequate delta perturbation climatic scenarios. Thereafter, a calibrated rainfall-runoff model was used for streamflow simulations. Findings proved that climate change has a more extensive impact on the hydrological characteristics of the streamflow than anthropogenic intervention (i.e. the construction of a large dam in the catchment). The isolated baseflow is more sensitive to the precipitation variations than to the variations of the potential evapotranspiration. The current hydrological anomalies are expected to continue. This comprehensive basin study demonstrates how climate change impact, anthropogenic intervention as well as hydro-climatic drought and hydrological anomalies can be evaluated with a new methodology

Magnetic resonance imaging brain atrophy assessment in primary age-related tauopathy (PART)

Alzheimer disease (AD) is a neurodegenerative disorder characterized pathologically by the accumulation of amyloid-beta (Aβ) plaques and tau neurofibrillary tangles (NFTs). Recently, primary age-related tauopathy (PART) has been described as a new anatomopathological disorder where NFTs are the main feature in the absence of neuritic plaques. However, since PART has mainly been studied in post-mortem patient brains, not much is known about the clinical or neuroimaging characteristics of PART. Here, we studied the clinical brain imaging characteristics of PART focusing on neuroanatomical vulnerability by applying a previously validated multiregion visual atrophy scale. We analysed 26 cases with confirmed PART with paired clinical magnetic resonance imaging (MRI) acquisitions. In this selected cohort we found that upon correcting for the effect of age, there is increased atrophy in the medial temporal region with increasing Braak staging (r = 0.3937, p = 0.0466). Upon controlling for Braak staging effect, predominantly two regions, anterior temporal (r = 0.3638, p = 0.0677) and medial temporal (r = 0.3836, p = 0.053), show a trend for increased atrophy with increasing age. Moreover, anterior temporal lobe atrophy was associated with decreased semantic memory/language (r = - 0.5823, p = 0.0056; and r = - 0.6371, p = 0.0019, respectively), as was medial temporal lobe atrophy (r = - 0.4445, p = 0.0435). Overall, these findings support that PART is associated with medial temporal lobe atrophy and predominantly affects semantic memory/language. These findings highlight that other factors associated with aging and beyond NFTs could be involved in PART pathophysiology.NACC database is funded by NIA/NIH Grant U01 AG016976. NACC data are contributed by the NIA-funded ADCs: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, MD), P30 AG062428–01 (PI James Leverenz, MD) P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P50 AG047266 (PI Todd Golde, MD, PhD), P30 AG010133 (PI Andrew Saykin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P30 AG062421–01 (PI Bradley Hyman, MD, PhD), P30 AG062422–01 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Thomas Wisniewski, MD), P30 AG013854 (PI Robert Vassar, PhD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG010161 (PI David Bennett, MD), P50 AG047366 (PI Victor Henderson, MD, MS), P30 AG010129 (PI Charles DeCarli, MD), P50 AG016573 (PI Frank LaFerla, PhD), P30 AG062429–01(PI James Brewer, MD, PhD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG053760 (PI Henry Paulson, MD, PhD), P30 AG010124 (PI John Trojanowski, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005142 (PI Helena Chui, MD), P30 AG012300 (PI Roger Rosenberg, MD), P30 AG049638 (PI Suzanne Craft, PhD), P50 AG005136 (PI Thomas Grabowski, MD), P30 AG062715–01 (PI Sanjay Asthana, MD, FRCP), P50 AG005681 (PI John Morris, MD), P50 AG047270 (PI Stephen Strittmatter, MD, PhD). NIH grants to JFC (R01AG054008, R01NS095252, R01AG062348, RF1AG060961), the Tau Consortium, and Alzheimer’s Association (NIRG- 469 15-363188

Adaptation strategy to mitigate the impact of climate change on water resources in arid and semi-arid regions : a case study

Climate change and drought phenomena impacts have become a growing concern for water resources engineers and policy makers, mainly in arid and semi-arid areas. This study aims to contribute to the development of a decision support tool to prepare water resources managers and planners for climate change adaptation. The Hydrologiska Byråns Vattenbalansavdelning (The Water Balance Department of the Hydrological Bureau) hydrologic model was used to define the boundary conditions for the reservoir capacity yield model comprising daily reservoir inflow from a representative example watershed with the size of 14,924 km2 into a reservoir with the capacity of 6.80 Gm3. The reservoir capacity yield model was used to simulate variability in climate change-induced differences in reservoir capacity needs and performance (operational probability of failure, resilience, and vulnerability). Owing to the future precipitation reduction and potential evapotranspiration increase during the worst case scenario (−40% precipitation and +30% potential evapotranspiration), substantial reductions in streamflow of between −56% and −58% are anticipated for the dry and wet seasons, respectively. Furthermore, model simulations recommend that as a result of future climatic conditions, the reservoir operational probability of failure would generally increase due to declined reservoir inflow. The study developed preparedness plans to combat the consequences of climate change and drought

Spatial patterns and temporal variability of drought in Western Iran

An analysis of drought in western Iran from 1966 to 2000 is presented using monthly precipitation data observed at 140 gauges uniformly distributed over the area. Drought conditions have been assessed by means of the Standardized Precipitation Index (SPI). To study the long-term drought variability the principal component analysis was applied to the SPI field computed on 12-month time scale. The analysis shows that applying an orthogonal rotation to the first two principal component patterns, two distinct sub-regions having different climatic variability may be identified. Results have been compared to those obtained for the largescale using re-analysis data suggesting a satisfactory agreement. Furthermore, the extension of the large-scale analysis to a longer period (1948–2007) shows that the spatial patterns and the associated time variability of drought are subjected to noticeable changes. Finally, the relationship between hydrological droughts in the two sub-regions and El Niño Southern Oscillation events has been investigated finding that there is not clear evidence for a link between the two phenomen

The glutathione biosynthetic pathway of Plasmodium is essential for mosquito transmission

1Infection of red blood cells (RBC) subjects the malaria parasite to oxidative stress. Therefore, efficient antioxidant and redox systems are required to prevent damage by reactive oxygen species. Plasmodium spp. have thioredoxin and glutathione (GSH) systems that are thought to play a major role as antioxidants during blood stage infection. In this report, we analyzed a critical component of the GSH biosynthesis pathway using reverse genetics. Plasmodium berghei parasites lacking expression of gamma-glutamylcysteine synthetase (γ-GCS), the rate limiting enzyme in de novo synthesis of GSH, were generated through targeted gene disruption thus demonstrating, quite unexpectedly, that γ-GCS is not essential for blood stage development. Despite a significant reduction in GSH levels, blood stage forms of pbggcs− parasites showed only a defect in growth as compared to wild type. In contrast, a dramatic effect on development of the parasites in the mosquito was observed. Infection of mosquitoes with pbggcs− parasites resulted in reduced numbers of stunted oocysts that did not produce sporozoites. These results have important implications for the design of drugs aiming at interfering with the GSH redox-system in blood stages and demonstrate that de novo synthesis of GSH is pivotal for development of Plasmodium in the mosquito

Education can improve the negative perception of a threatened long-lived scavenging bird, the Andean condor

Human-wildlife conflicts currently represent one of the main conservation problems for wildlife species around the world. Vultures have serious conservation concerns, many of which are related to people's adverse perception about them due to the belief that they prey on livestock. Our aim was to assess local perception and the factors influencing people's perception of the largest scavenging bird in South America, the Andean condor. For this, we interviewed 112 people from Valle Fértil, San Juan province, a rural area of central west Argentina. Overall, people in the area mostly have an elementary education, and their most important activity is livestock rearing. The results showed that, in general, most people perceive the Andean condor as an injurious species and, in fact, some people recognize that they still kill condors. We identified two major factors that affect this perception, the education level of villagers and their relationship with livestock ranching. Our study suggests that conservation of condors and other similar scavengers depends on education programs designed to change the negative perception people have about them. Such programs should be particularly focused on ranchers since they are the ones who have the worst perception of these scavengers. We suggest that highlighting the central ecological role of scavengers and recovering their cultural value would be fundamental to reverse their persecution and their negative perception by people.Fil: Cailly Arnulphi, Verónica Beatríz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Centro de Investigaciones de la Geosfera y Biosfera. Universidad Nacional de San Juan. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones de la Geosfera y Biosfera; ArgentinaFil: Lambertucci, Sergio Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; ArgentinaFil: Borghi, Carlos Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Centro de Investigaciones de la Geosfera y Biosfera. Universidad Nacional de San Juan. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones de la Geosfera y Biosfera; Argentin