32 research outputs found

    Restriction of essential amino acids dictates the systemic metabolic response to dietary protein dilution

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    Dietary protein dilution, where protein is reduced and replaced by other nutrient sources without caloric restriction, promotes metabolic health via the hepatokine Fgf21. Here, the authors show that essential amino acids threonine and tryptophan are necessary and sufficient to induce these effects

    Recommendations from the European Working Group for Value Assessment and Funding Processes in Rare Diseases (ORPH-VAL)

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    International audienceAbstractRare diseases are an important public health issue with high unmet need. The introduction of the EU Regulation on orphan medicinal products (OMP) has been successful in stimulating investment in the research and development of OMPs. Despite this advancement, patients do not have universal access to these new medicines. There are many factors that affect OMP uptake, but one of the most important is the difficulty of making pricing and reimbursement (P&R) decisions in rare diseases. Until now, there has been little consensus on the most appropriate assessment criteria, perspective or appraisal process. This paper proposes nine principles to help improve the consistency of OMP P&R assessment in Europe and ensure that value assessment, pricing and funding processes reflect the specificities of rare diseases and contribute to both the sustainability of healthcare systems and the sustainability of innovation in this field. These recommendations are the output of the European Working Group for Value Assessment and Funding Processes in Rare Diseases (ORPH-VAL), a collaboration between rare disease experts, patient representatives, academics, health technology assessment (HTA) practitioners, politicians and industry representatives. ORPH-VAL reached its recommendations through careful consideration of existing OMP P&R literature and through a wide consultation with expert stakeholders, including payers, regulators and patients. The principles cover four areas: OMP decision criteria, OMP decision process, OMP sustainable funding systems and European co-ordination. This paper also presents a guide to the core elements of value relevant to OMPs that should be consistently considered in all OMP appraisals. The principles outlined in this paper may be helpful in drawing together an emerging consensus on this topic and identifying areas where consistency in payer approach could be achievable and beneficial. All stakeholders have an obligation to work together to ensure that the promise of OMP’s is realised

    Comparison of Microbial Communities in the Sediments and Water Columns of Frozen Cryoconite Holes in the McMurdo Dry Valleys, Antarctica

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    Although cryoconite holes, sediment-filled melt holes on glacier surfaces, appear small and homogenous, their microbial inhabitants may be spatially partitioned. This partitioning could be particularly important for maintaining biodiversity in holes that remain isolated for many years, such as in Antarctica. We hypothesized that cryoconite holes with greater species richness and biomass should exhibit greater partitioning between the sediments and water, promoting greater biodiversity through spatial niche partitioning. We tested this hypothesis by sampling frozen cryoconite holes along a gradient of biomass and biodiversity in the Taylor Valley, Antarctica, where ice-lidded cryoconite holes are a ubiquitous feature of glaciers. We extracted DNA and chlorophyll a from the sediments and water of these samples to describe biodiversity and quantify proxies for biomass. Contrary to our expectation, we found that cryoconite holes with greater richness and biomass showed less partitioning of phylotypes by the sediments versus the water, perhaps indicating that the probability of sediment microbes being mixed into the water is higher from richer sediments. Another explanation may be that organisms from the water were compressed by freezing down to the sediment layer, leaving primarily relic DNA of dead cells to be detected higher in the frozen water. Further evidence of this explanation is that the dominant sequences unique to water closely matched organisms that do not live in cryoconite holes or the Dry Valleys (e.g., vertebrates); so this cryptic biodiversity could represent unknown microbial animals or DNA from atmospheric deposition of dead biomass in the otherwise low-biomass water. Although we cannot rule out spatial niche partitioning occurring at finer scales or in melted cryoconite holes, we found no evidence of partitioning between the sediments and water in frozen holes. Future work should include more sampling of cryoconite holes at a finer spatial scale, and characterizing the communities of the sediments and water when cryoconite holes are melted and active

    A Naganishia in high places: functioning populations or dormant cells from the atmosphere?

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    Here, we review the current state of knowledge concerning high-elevation members of the extremophilic Cryptococcus albidus clade (now classified as the genus Naganishia). These fungi dominate eukaryotic microbial communities across the highest elevation, soil-like material (tephra) on volcanoes such as Llullaillaco, Socompa, and Saírecabur in the Atacama region of Chile, Argentina, and Bolivia. Recent studies indicate that Naganishia species are among the most resistant organisms to UV radiation, and a strain of N. friedmannii from Volcán Llullaillaco is the first organism that is known to grow during the extreme, diurnal freeze-thaw cycles that occur on a continuous basis at elevations above 6000 m.a.s.l. in the Atacama region. These and other extremophilic traits discussed in this review may serve a dual purpose of allowing Naganishia species to survive long-distance transport through the atmosphere and to survive the extreme conditions found at high elevations. Current evidence indicates that there are frequent dispersal events between high-elevation volcanoes of Atacama region and the Dry Valleys of Antarctica via “Rossby Wave” merging of the polar and sub-tropical jet streams. This dispersal hypothesis needs further verification, as does the hypothesis that Naganishia species are flexible “opportunitrophs” that can grow during rare periods of water (from melting snow) and nutrient availability (from Aeolian inputs) in one of the most extreme terrestrial habitats on Earth

    Microbial Species–Area Relationships in Antarctic Cryoconite Holes Depend on Productivity

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    The island species–area relationship (ISAR) is a positive association between the number of species and the area of an isolated, island-like habitat. ISARs are ubiquitous across domains of life, yet the processes generating ISARs remain poorly understood, particularly for microbes. Larger and more productive islands are hypothesized to have more species because they support larger populations of each species and thus reduce the probability of stochastic extinctions in small population sizes. Here, we disentangled the effects of “island” size and productivity on the ISAR of Antarctic cryoconite holes. We compared the species richness of bacteria and microbial eukaryotes on two glaciers that differ in their productivity across varying hole sizes. We found that cryoconite holes on the more productive Canada Glacier gained more species with increasing hole area than holes on the less productive Taylor Glacier. Within each glacier, neither productivity nor community evenness explained additional variation in the ISAR. Our results are, therefore, consistent with productivity shaping microbial ISARs at broad scales. More comparisons of microbial ISARs across environments with limited confounding factors, such as cryoconite holes, and experimental manipulations within these systems will further contribute to our understanding of the processes shaping microbial biogeography

    Microbial Biogeochemistry and Phosphorus Limitation in Cryoconite Holes on Glaciers Across the Taylor Valley, Mcmurdo Dry Valleys, Antarctica

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    Cryoconite holes host active microbial communities despite their extreme physical conditions. In the McMurdo Dry Valleys of Antarctica, these perennially cold, mini-ecosystems form ice lids that can persist for many years thereby isolating the cryoconite from nutrient and carbon inputs. Despite much recent work on cryoconite holes in Antarctica, little is known about nutrient dynamics and limitations in these ice-enclosed ecosystems. We used multiple biogeochemical approaches, including stable isotope signatures (δ15N and δ13C), nutrients concentrations (C, N, P), and enzyme activities, to evaluate what nutrients are likely limiting to biological activity in cryoconite hole sediments on Taylor, Canada, and Commonwealth glaciers in Taylor Valley, one of the McMurdo Dry Valleys. Nutrient concentrations (C, N, and P) varied in accordance with previous studies showing that the most inland of the three glaciers (Taylor Glacier) is the most oligotrophic. C-to-N ratios of Canada and Commonwealth cryoconite- hole sediments were close to the global mean for biologically-active sediments and soils, whereas Taylor Glacier cryoconite deviated from the global mean and were similar to the high C:N ratios seen in Taylor Valley soils. C and N stable isotope signatures on Commonwealth and Canada glaciers are congruent with values for efficient C and N fixation by nostocalean cyanobacteria, combined with higher levels of denitrification on Canada Glacier. In contrast, stable isotope signatures on the more oligotrophic Taylor Glacier are reflective of atmospheric deposition of N and C, or N inputs from nearby soils. Enzyme stoichiometric approaches further support extreme nutrient limitation on Taylor Glacier and indicate that P is the ultimate limiting nutrient across all three glaciers. Extremely high DIN-to-phosphate ratios also indicate P limitation across all three glaciers with Commonwealth Glacier being less severely P-limited than the other two glaciers. At a broader scale, this work provides a comprehensive framework for understanding how biogeochemical cycling of C, N and P vary across nutrient and climatic gradients in the cryobiosphere, and point towards the need for experimental work to test the relative controls of climate, microbes, and nutrients on biogeochemistry of cryoconite holes and other ecosystems of the cryosphere
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