Glacier retreat and the value of ecosystem services associated with water resources in the Paron basin-Huascaran National Park (Cordillera Blanca), 2009-2018

[Español] Los glaciares tropicales son indicadores sensibles del cambio climático. La pérdida del volumen de los glaciares tropicales en la cuenca Parón (Cordillera Blanca, Perú) es una muestra de esto a nivel global y se espera que tales cambios afecten a los servicios ecosistémicos que son únicos e insustituibles. Este estudio estimó el valor económico de los servicios ecosistémicos asociados con el recurso hídrico impactados por el retroceso glaciar en la cuenca de Parón-Parque Nacional Huascarán (Cordillera Blanca, Perú) entre los años 2009 y 2018. La metodología inició cartografiando los glaciares de 2009 a 2018 usando imágenes satelitales de alta resolución tomadas en temporada seca. Luego, se reconstruyeron las superficies 3D de los mismos usando la herramienta GLABTOP permitiendo calcular el volumen. Con los datos obtenidos se calculó el valor del servicio ecosistémico del turismo y recreación, y provisión de flujo hídrico. Los resultados indican que los glaciares de la cuenca Parón se han reducción de ~1.82% del área glaciar y en una tasa de deglaciación máxima de 0.08 (km2/año). Los resultados de la reconstrucción 3D muestran un 1.8% más de espesores entre los 40 y 60 m, con una pérdida de hielo de 1.02 km3, a una tasa máxima de 0.14 km3/año. Los valores monetarios presentes de los servicios de 2009 a 2018 se estimaron en $52 029.34 para el servicio de turismo y recreación y de$3 213 258.21 para el servicio de provisión de flujo hídricos, calculados a 8% de tasa de descuento. Por lo tanto, se recomienda que se debe incrementar la inversión en programas sobre la red hídrica de la cuenca de Parón, como mayores servicios, usos poblacionales o industriales.[English] Tropical glaciers are sensitive indicators of climate change. The loss of the volume of tropical glaciers in the Paron basin (Cordillera Blanca, Peru), is an example of this at a global level and these changes are expected to affect ecosystem services that are unique and irreplaceable. This study estimated the economic value of ecosystem services associated with water resources impacted by glacial retreat in the Paron basin - Huascaran National Park (Cordillera Blanca, Peru) between the years 2009 and 2018. The methodology started by mapping glaciers from 2009 to 2018 using high-resolution satellite images taken during the dry season. Then, the 3D surfaces of the glaciers were reconstructed using the GLABTOP tool to calculate the volume. With the data obtained, the value of the Tourism and Recreation ecosystem service, provision of Water Flow, was calculated. The results indicate that the glaciers of the Paron basin have been reduced by ~1.82% of the glacial area and at a maximum deglaciation rate of 0.08 (km2/year). The results of the 3D reconstruction show 1.8% more thickness between 40 and 60 m with an ice loss of 1.02 km3, at a maximum rate of 0.14 km3/year. The present monetary values of the services from 2009 to 2018 were estimated at $52 029.34 for the tourism and recreation service and$3 213 258.21 for the water flow provision service, calculated at 8% discount rate. Therefore, it is recommended that investment in programs on the Paron watershed water network, such as increased services, population or industrial use, should be increased

Retroceso glaciar y el valor de los servicios ecosistémicos asociados con el recurso hídrico en la cuenca Parón-Parque Nacional Huascarán (Cordillera Blanca), 2009-2018

[Español] Los glaciares tropicales son indicadores sensibles del cambio climático. La pérdida del volumen de los glaciares tropicales en la cuenca Parón (Cordillera Blanca, Perú) es una muestra de esto a nivel global y se espera que tales cambios afecten a los servicios ecosistémicos que son únicos e insustituibles. Este estudio estimó el valor económico de los servicios ecosistémicos asociados con el recurso hídrico impactados por el retroceso glaciar en la cuenca de Parón-Parque Nacional Huascarán (Cordillera Blanca, Perú) entre los años 2009 y 2018. La metodología inició cartografiando los glaciares de 2009 a 2018 usando imágenes satelitales de alta resolución tomadas en temporada seca. Luego, se reconstruyeron las superficies 3D de los mismos usando la herramienta GLABTOP permitiendo calcular el volumen. Con los datos obtenidos se calculó el valor del servicio ecosistémico del turismo y recreación, y provisión de flujo hídrico. Los resultados indican que los glaciares de la cuenca Parón se han reducción de ~1.82% del área glaciar y en una tasa de deglaciación máxima de 0.08 (km2/año). Los resultados de la reconstrucción 3D muestran un 1.8% más de espesores entre los 40 y 60 m, con una pérdida de hielo de 1.02 km3, a una tasa máxima de 0.14 km3/año. Los valores monetarios presentes de los servicios de 2009 a 2018 se estimaron en $52 029.34 para el servicio de turismo y recreación y de$3 213 258.21 para el servicio de provisión de flujo hídricos, calculados a 8% de tasa de descuento. Por lo tanto, se recomienda que se debe incrementar la inversión en programas sobre la red hídrica de la cuenca de Parón, como mayores servicios, usos poblacionales o industriales.[English] Tropical glaciers are sensitive indicators of climate change. The loss of the volume of tropical glaciers in the Paron basin (Cordillera Blanca, Peru), is an example of this at a global level and these changes are expected to affect ecosystem services that are unique and irreplaceable. This study estimated the economic value of ecosystem services associated with water resources impacted by glacial retreat in the Paron basin - Huascaran National Park (Cordillera Blanca, Peru) between the years 2009 and 2018. The methodology started by mapping glaciers from 2009 to 2018 using high-resolution satellite images taken during the dry season. Then, the 3D surfaces of the glaciers were reconstructed using the GLABTOP tool to calculate the volume. With the data obtained, the value of the Tourism and Recreation ecosystem service, provision of Water Flow, was calculated. The results indicate that the glaciers of the Paron basin have been reduced by ~1.82% of the glacial area and at a maximum deglaciation rate of 0.08 (km2/year). The results of the 3D reconstruction show 1.8% more thickness between 40 and 60 m with an ice loss of 1.02 km3, at a maximum rate of 0.14 km3/year. The present monetary values of the services from 2009 to 2018 were estimated at $52 029.34 for the tourism and recreation service and$3 213 258.21 for the water flow provision service, calculated at 8% discount rate. Therefore, it is recommended that investment in programs on the Paron watershed water network, such as increased services, population or industrial use, should be increased

Discovery of Diverse Small Molecule Chemotypes with Cell-Based PKD1 Inhibitory Activity

Protein kinase D (PKD) is a novel family of serine/threonine kinases regulated by diacylglycerol, which is involved in multiple cellular processes and various pathological conditions. The limited number of cell-active, selective inhibitors has historically restricted biochemical and pharmacological studies of PKD. We now markedly expand the PKD1 inhibitory chemotype inventory with eleven additional novel small molecule PKD1 inhibitors derived from our high throughput screening campaigns. The in vitro IC50s for these eleven compounds ranged in potency from 0.4 to 6.1 µM with all of the evaluated compounds being competitive with ATP. Three of the inhibitors (CID 1893668, (1Z)-1-(3-ethyl-5-methoxy-1,3-benzothiazol-2-ylidene)propan-2-one; CID 2011756, 5-(3-chlorophenyl)-N-[4-(morpholin-4-ylmethyl)phenyl]furan-2-carboxamide; CID 5389142, (6Z)-6-[4-(3-aminopropylamino)-6-methyl-1H-pyrimidin-2-ylidene]cyclohexa-2,4-dien-1-one) inhibited phorbol ester-induced endogenous PKD1 activation in LNCaP prostate cancer cells in a concentration-dependent manner. The specificity of these compounds for PKD1 inhibitory activity was supported by kinase assay counter screens as well as by bioinformatics searches. Moreover, computational analyses of these novel cell-active PKD1 inhibitors indicated that they were structurally distinct from the previously described cell-active PKD1 inhibitors while computational docking of the new cell-active compounds in a highly conserved ATP-binding cleft suggests opportunities for structural modification. In summary, we have discovered novel PKD1 inhibitors with in vitro and cell-based inhibitory activity, thus successfully expanding the structural diversity of small molecule inhibitors available for this important pharmacological target

Amphipathic DNA polymers exhibit antiviral activity against systemic Murine Cytomegalovirus infection

<p>Abstract</p> <p>Background</p> <p>Phosphorothioated oligonucleotides (PS-ONs) have a sequence-independent, broad spectrum antiviral activity as amphipathic polymers (APs) and exhibit potent in vitro antiviral activity against a broad spectrum of herpesviruses: HSV-1, HSV-2, HCMV, VZV, EBV, and HHV-6A/B, and in vivo activity in a murine microbiocide model of genital HSV-2 infection. The activity of these agents against animal cytomegalovirus (CMV) infections in vitro and in vivo was therefore investigated.</p> <p>Results</p> <p>In vitro, a 40 mer degenerate AP (REP 9) inhibited both murine CMV (MCMV) and guinea pig CMV (GPCMV) with an IC₅₀of 0.045 μM and 0.16 μM, respectively, and a 40 mer poly C AP (REP 9C) inhibited MCMV with an IC₅₀of 0.05 μM. Addition of REP 9 to plaque assays during the first two hours of infection inhibited 78% of plaque formation whereas addition of REP 9 after 10 hours of infection did not significantly reduce the number of plaques, indicating that REP 9 antiviral activity against MCMV occurs at early times after infection. In a murine model of CMV infection, systemic treatment for 5 days significantly reduced virus replication in the spleens and livers of infected mice compared to saline-treated control mice. REP 9 and REP 9C were administered intraperitoneally for 5 consecutive days at 10 mg/kg, starting 2 days prior to MCMV infection. Splenomegaly was observed in infected mice treated with REP 9 but not in control mice or in REP 9 treated, uninfected mice, consistent with mild CpG-like activity. When REP 9C (which lacks CpG motifs) was compared to REP 9, it exhibited comparable antiviral activity as REP 9 but was not associated with splenomegaly. This suggests that the direct antiviral activity of APs is the predominant therapeutic mechanism <it>in vivo</it>. Moreover, REP 9C, which is acid stable, was effective when administered orally in combination with known permeation enhancers.</p> <p>Conclusion</p> <p>These studies indicate that APs exhibit potent, well tolerated antiviral activity against CMV infection in vivo and represent a new class of broad spectrum anti-herpetic agents.</p

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Development of a Low Bias Method for Characterizing Viral Populations Using Next Generation Sequencing Technology

Background: With an estimated 38 million people worldwide currently infected with human immunodeficiency virus (HIV), and an additional 4.1 million people becoming infected each year, it is important to understand how this virus mutates and develops resistance in order to design successful therapies. Methodology/Principal Findings: We report a novel experimental method for amplifying full-length HIV genomes without the use of sequence-specific primers for high throughput DNA sequencing, followed by assembly of full length viral genome sequences from the resulting large dataset. Illumina was chosen for sequencing due to its ability to provide greater coverage of the HIV genome compared to prior methods, allowing for more comprehensive characterization of the heterogeneity present in the HIV samples analyzed. Our novel amplification method in combination with Illumina sequencing was used to analyze two HIV populations: a homogenous HIV population based on the canonical NL4-3 strain and a heterogeneous viral population obtained from a HIV patient's infected T cells. In addition, the resulting sequence was analyzed using a new computational approach to obtain a consensus sequence and several metrics of diversity. Significance: This study demonstrates how a lower bias amplification method in combination with next generation DNA sequencing provides in-depth, complete coverage of the HIV genome, enabling a stronger characterization of the quasispecies present in a clinically relevant HIV population as well as future study of how HIV mutates in response to a selective pressure

The Missing Part of Seed Dispersal Networks: Structure and Robustness of Bat-Fruit Interactions

Mutualistic networks are crucial to the maintenance of ecosystem services. Unfortunately, what we know about seed dispersal networks is based only on bird-fruit interactions. Therefore, we aimed at filling part of this gap by investigating bat-fruit networks. It is known from population studies that: (i) some bat species depend more on fruits than others, and (ii) that some specialized frugivorous bats prefer particular plant genera. We tested whether those preferences affected the structure and robustness of the whole network and the functional roles of species. Nine bat-fruit datasets from the literature were analyzed and all networks showed lower complementary specialization (H2' = 0.37±0.10, mean ± SD) and similar nestedness (NODF = 0.56±0.12) than pollination networks. All networks were modular (M = 0.32±0.07), and had on average four cohesive subgroups (modules) of tightly connected bats and plants. The composition of those modules followed the genus-genus associations observed at population level (Artibeus-Ficus, Carollia-Piper, and Sturnira-Solanum), although a few of those plant genera were dispersed also by other bats. Bat-fruit networks showed high robustness to simulated cumulative removals of both bats (R = 0.55±0.10) and plants (R = 0.68±0.09). Primary frugivores interacted with a larger proportion of the plants available and also occupied more central positions; furthermore, their extinction caused larger changes in network structure. We conclude that bat-fruit networks are highly cohesive and robust mutualistic systems, in which redundancy is high within modules, although modules are complementary to each other. Dietary specialization seems to be an important structuring factor that affects the topology, the guild structure and functional roles in bat-fruit networks