15 research outputs found

    An amino acid substitution found in animals with low susceptibility to prion diseases confers a protective dominant-negative effect in prion-infected transgenic mice

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    While prion diseases have been described in numerous species, some, including those of the Canidae family, appear to show resistance or reduced susceptibility. A better understanding of the factors underlying prion susceptibility is crucial for the development of effective treatment and control measures. We recently demonstrated resistance to prion infection in mice overexpressing a mutated prion protein (PrP) carrying a specific amino acid substitution characteristic of canids. Here, we show that coexpression of this mutated PrP and wild-type mouse PrP in transgenic mice inoculated with different mouse-adapted prion strains (22 L, ME7, RML, and 301C) significantly increases survival times (by 45 to 113%). These data indicate that this amino acid substitution confers a dominant-negative effect on PrP, attenuating the conversion of PrPC to PrPSc and delaying disease onset without altering the neuropathological properties of the prion strains. Taken together, these findings have important implications for the development of new treatment approaches for prion diseases based on dominant-negative proteins

    Defective HNF4alpha-dependent gene expression as a driver of hepatocellular failure in alcoholic hepatitis

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    Alcoholic hepatitis (AH) is a life-threatening condition characterized by profound hepatocellular dysfunction for which targeted treatments are urgently needed. Identification of molecular drivers is hampered by the lack of suitable animal models. By performing RNA sequencing in livers from patients with different phenotypes of alcohol-related liver disease (ALD), we show that development of AH is characterized by defective activity of liver-enriched transcription factors (LETFs). TGFβ1 is a key upstream transcriptome regulator in AH and induces the use of HNF4α P2 promoter in hepatocytes, which results in defective metabolic and synthetic functions. Gene polymorphisms in LETFs including HNF4α are not associated with the development of AH. In contrast, epigenetic studies show that AH livers have profound changes in DNA methylation state and chromatin remodeling, affecting HNF4α-dependent gene expression. We conclude that targeting TGFβ1 and epigenetic drivers that modulate HNF4α-dependent gene expression could be beneficial to improve hepatocellular function in patients with AH

    SELNET clinical practice guidelines for bone sarcoma

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    Bone sarcoma are infrequent diseases, representing < 0.2% of all adult neoplasms. A multidisciplinary management within reference centers for sarcoma, with discussion of the diagnostic and therapeutic strategies within an expert multidisciplinary tumour board, is essential for these patients, given its heterogeneity and low frequency. This approach leads to an improvement in patient's outcome, as demonstrated in several studies. The Sarcoma European Latin-American Network (SELNET), aims to improve clinical outcome in sarcoma care, with a special focus in Latin-American countries. These Clinical Practice Guidelines (CPG) have been developed and agreed by a multidisciplinary expert group (including medical and radiation oncologist, surgical oncologist, orthopaedic surgeons, radiologist, pathologist, molecular biologist and representatives of patients advocacy groups) of the SELNET consortium, and are conceived to provide the standard approach to diagnosis, treatment and follow-up of bone sarcoma patients in the Latin-American context

    Fire regimes shape biodiversity: responses of avian guilds to burned forests in Andean temperate ecosystems of southern Chile

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    Fire regimes of forests, i.e., time interval, frequency, extent, and severity of fire events, influence structural changes in the vegetation, and thus shape the composition of avian communities. We studied the diversity of avian guilds in sites with different fire regimes (unburned, burned 2002, burned 2015, and burned 2002 and 2015), testing both the "intermediate disturbance" and "vertical vegetation structure" hypotheses, in globally threatened temperate forests in Chile. From 2016 to 2018, we quantified habitat attributes (160 plots) and estimated avian richness and density (160 point counts). The site that was burned once in 2015 showed the highest density of standing dead trees at 96.5% higher than the unburned/control site, whereas the site that burned twice showed the lowest density of live trees, lowest average diameter at breast height of trees (DBH), and smallest volume of coarse woody debris. Overall, we recorded 35 avian species with the highest richness (n = 24 species) in the site that was burned once in 2002. We found that, 16 years after a site was burned, the avian community composition became relatively similar to the unburned site. The density of most avian guilds decreased in burned sites but granivores, shrub users, and migrants showed positive responses. Understory users, foliage users, and resident species showed negative responses to burned sites. These responses were strongly related to fire-driven changes in habitat attributes, supporting both of our tested hypotheses. Given that increasing levels of disturbance from fire are anticipated, future management of temperate forest biodiversity should consider that specific species and guilds will depend on remnant habitat attributes in burned sites

    Diversity and singularity of the avifauna in the austral peat bogs of the Cape Horn Biosphere Reserve, Chile

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    Sphagnum-dominated peat bogs that are strongly embedded within the southern temperate forest matrix are increasingly being used for agriculture. Nevertheless, little is known about their biodiversity. Moreover, the remote areas of southern Chile where peat bogs are found, such as the Cape Horn Biosphere Reserve (CHBR, 54-55ºS), where birds are the most diverse and best represented group of vertebrates, have not been well-investigated. With the aim to broaden this knowledge in the CHBR, we studied the diversity of the avian assemblage in peat bogs on Navarino Island. We compared the composition of avian species between wetlands with and without peat bogs to test if Sphagnum bogs represented a singular habitat for birds in this area. Furthermore, the 37 bird species recorded in these habitats were classifed according to guild structure. The community similarity values showed that peat bogs hosted a bird composition that was different from that present in wetlands without Sphagnum, suggesting that peat bogs are a singular type of habitat for birds in the CHBR. The most frequently feeding groups recorded in these wetlands were insectivores (48.7%), followed by omnivores (23.1%). Our results showed that, in contrast to previous studies of birds in peat bogs, these environments constituted a distinct wetland habitat for feeding, reproduction and sheltering for some species in the CHBR. Thus, plans for the conservation and rational use of peat ecosystems should consider the high value of these habitats for biodiversity on a landscape scale, especially for birds of the southernmost extreme of the Americas.Las turberas esfagnosas que se encuentran fuertemente embebidas en la matriz de bosques templados australes, se utilizan de forma creciente en agricultura. Sin embargo, el conocimiento de su biodiversidad es escaso. Más aún, zonas remotas del sur de Chile donde se encuentran las turberas, como la Reserva de Biosfera Cabo de Hornos (RBCH, 54-55º S), donde las aves constituyen el grupo de vertebrados más diverso y representativo, aún han sido escasamente estudiadas. Con el objetivo de aportar en su conocimiento en la RBCH, se estudió la diversidad del ensamble de aves en turberas esfagnosas de la isla Navarino. Se exploró si su composición específca es igual al de los humedales sin turbera, probando si las turberas constituyen o no un hábitat singular para las aves. También se clasifcó a las 37 especies de aves registradas en estos hábitats de acuerdo a la estructura de gremios. Los valores de similitud taxocenótica señalaron que la composición de aquellos con turbera difrió de aquellos sin turbera, sugiriendo que este hábitat es singular para las aves. El tipo de alimentación más frecuente fue la insectivoría (48,7%), seguido por la omnivoría (23,1%). Los resultados muestran que, a diferencia de lo señalado en trabajos previos sobre aves de turberas, estos ambientes constituyen un humedal-hábitat singular para la alimentación, reproducción y refugio de algunas especies en la RBCH. De esta manera, la conservación y uso racional de turberas debe considerar el valor que tienen como hábitat para la biodiversidad a escala de paisaje, especialmente para las aves del extremo sur americano

    Social-ecological filters drive the functional diversity of beetles in homegardens of campesinos and migrants in the southern Andes

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    Abstract Homegardens are coupled social-ecological systems that act as biodiversity reservoirs while contributing to local food sovereignty. These systems are characterized by their structural complexity, while involving management practices according to gardener’s cultural origin. Social–ecological processes in homegardens may act as filters of species’ functional traits, and thus influence the species richness-functional diversity relationship of critical agroecosystem components like beetles (Coleoptera). We tested the species richness-functional diversity relationship of beetle communities and examined whether habitat structure across different levels, sociodemographic profiles, and management practices act as filters in homegardens in a Global Biodiversity Hotspot, Chile. For 100 homegardens (50 campesino and 50 migrant), we sampled beetles and habitat attributes, and surveyed gardeners’ sociodemographic profiles and management practices. We recorded 85 beetle species and found a positive relationship between species richness and functional richness that saturated when functionally similar species co-occur more often than expected by chance, indicating functional redundancy in species-rich homegardens. Gardener origin (campesino/migrant), homegarden area (m2), structural complexity (index), and pest control strategy (natural, chemical, or none) were the most influential social–ecological filters that selectively remove beetle species according to their functional traits. We discuss opportunities in homegarden management for strengthening local functional diversity and resilience under social-environmental changes
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