289 research outputs found

    SIKB0102: Synchronizing Excavation Data for Preservation and Re-Use

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    Key issue in re-using data from excavations is the need to understand the meaning of the contents. Integrating studies have a hard time using old datasets, for obvious reasons like finding the right data in the first place, understanding unknown codes, and the inherent difficulty of combining data from different excavations. These problems are commonly addressed by archiving and publishing harmonized data, which enables searching through combined datasets, but at the price of losing important detail. Despite hesitation, an interchange format for digital archaeological data was needed. We played a major role in the drafting group for what would later become the 'SIKB0102' interchange standard, where we ultimately focused on: 1) keeping the original level of detail while providing a harmonized view; 2) serving archiving as well as data interchange in active projects; 3) control of versions and 4) making sure that relations, key to solving archaeological mysteries, are central. An unusually flexible interchange format was created, that can hold detailed data together with, and linked to, harmonized data. Having the harmonized data makes it easy to search and combine datasets, while having the related detailed data makes it possible to drill down to the original level of detail. Archaeological data is all about structure and location, so we took care of including the vector geo-location data in the specification as well. Combining all these aspects in one interchange format make the SIKB0102 specification stands out. In The Netherlands the archaeological research data must be provided to the national archival institute (DANS), and the KNA (quality standard for the Dutch archaeology) demands submitting the data to the national archive. Today the KNA requires to provide archaeological excavation data according the SIKB0102 specification, which is a big step forward in re-using archaeological excavation data.

    A comparison between the homocyclic aromatic metabolic pathways from plant-derived compounds by bacteria and fungi

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    Aromatic compounds derived from lignin are of great interest for renewable biotechnical applications. They can serve in many industries e.g. as biochemical building blocks for bioplastics or biofuels, or as antioxidants, flavor agents or food preservatives. In nature, lignin is degraded by microorganisms, which results in the release of homocyclic aromatic compounds. Homocyclic aromatic compounds can also be linked to polysaccharides, tannins and even found freely in plant biomass. As these compounds are often toxic to microbes already at low concentrations, they need to be degraded or converted to less toxic forms. Prior to ring cleavage, the plant- and lignin-derived aromatic compounds are converted to seven central ring-fission intermediates, i.e. catechol, protocatechuic acid, hydroxyquinol, hydroquinone, gentisic acid, gallic acid and pyrogallol through complex aromatic metabolic pathways and used as energy source in the tricarboxylic acid cycle. Over the decades, bacterial aromatic metabolism has been described in great detail. However, the studies on fungal aromatic pathways are scattered over different pathways and species, complicating a comprehensive view of fungal aromatic metabolism. In this review, we depicted the similarities and differences of the reported aromatic metabolic pathways in fungi and bacteria. Although both microorganisms share the main conversion routes, many alternative pathways are observed in fungi. Understanding the microbial aromatic metabolic pathways could lead to metabolic engineering for strain improvement and promote valorization of lignin and related aromatic compounds.Peer reviewe

    Vanillic acid and methoxyhydroquinone production from guaiacyl units and related aromatic compounds using Aspergillus niger cell factories

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    Background The aromatic compounds vanillin and vanillic acid are important fragrances used in the food, beverage, cosmetic and pharmaceutical industries. Currently, most aromatic compounds used in products are chemically synthesized, while only a small percentage is extracted from natural sources. The metabolism of vanillin and vanillic acid has been studied for decades in microorganisms and many studies have been conducted that showed that both can be produced from ferulic acid using bacteria. In contrast, the degradation of vanillin and vanillic acid by fungi is poorly studied and no genes involved in this metabolic pathway have been identified. In this study, we aimed to clarify this metabolic pathway in Aspergillus niger and identify the genes involved. Results Using whole-genome transcriptome data, four genes involved in vanillin and vanillic acid metabolism were identified. These include vanillin dehydrogenase (vdhA), vanillic acid hydroxylase (vhyA), and two genes encoding novel enzymes, which function as methoxyhydroquinone 1,2-dioxygenase (mhdA) and 4-oxo-monomethyl adipate esterase (omeA). Deletion of these genes in A. niger confirmed their role in aromatic metabolism and the enzymatic activities of these enzymes were verified. In addition, we demonstrated that mhdA and vhyA deletion mutants can be used as fungal cell factories for the accumulation of vanillic acid and methoxyhydroquinone from guaiacyl lignin units and related aromatic compounds. Conclusions This study provides new insights into the fungal aromatic metabolic pathways involved in the degradation of guaiacyl units and related aromatic compounds. The identification of the involved genes unlocks new potential for engineering aromatic compound-producing fungal cell factories.Peer reviewe

    Annual patterns in phytoplankton phenology in Antarctic coastal waters explained by environmental drivers

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    Coastal zones of Antarctica harbor rich but highly variable phytoplankton communities. The mechanisms that control the dynamics of these communities are not well defined. Here we elucidate the mechanisms that drive seasonal species succession, based on algal photophysiological characteristics and environmental factors. For this, phytoplankton community structure together with oceanographic parameters was studied over a 5‐year period (2012–2017) at Rothera Station at Ryder Bay (Western Antarctic Peninsula). Algal pigment patterns and photophysiological studies based on fluorescence analyses were combined with data from the Rothera Time‐Series program. Considerable interannual variation was observed, related to variations in wind‐mixing, ice cover and an El Niño event. Clear patterns in the succession of algal classes became manifest when combining the data collected over the five successive years. In spring, autotrophic flagellates with a high light affinity were the first to profit from increasing light and sea ice melt. These algae most likely originated from sea‐ice communities, stressing the role of sea ice as a seeding vector for the spring bloom. Diatoms became dominant towards summer in more stratified and warmer surface waters. These communities displayed significantly lower photoflexibility than spring communities. There are strong indications for mixotrophy in cryptophytes, which would explain much of their apparently random occurrence. Climate models predict continuing retreat of Antarctic sea‐ice during the course of this century. For the near‐future we predict that the marginal sea‐ice zone will still harbor significant communities of haptophytes and chlorophytes, whereas increasing temperatures will mainly be beneficial for diatoms

    Cost analysis of mydriasis strategies in cataract surgery care in the Netherlands

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    PURPOSE: To investigate the economic impact of an intracameral mydriatics and anesthesic agent (ICMA), topical mydriatics, and a mydriatic ocular insert in cataract patients. SETTING: One public hospital in the Netherlands. DESIGN: Prospective cohort study. METHODS: Resource use data were collected from a healthcare and societal perspective on the day of surgery. Other outcome parameters included pupil size, surgeon satisfaction, postoperative pain, and Catquest-9SF scores. RESULTS: Mean costs per patient were &OV0556; 506 in the ICMA group (n=122), &OV0556; 474 in the ocular insert group (n=115), and &OV0556; 451 in the topical group (n=131). The acquisition cost of ICMA was highest and resulted in longer surgical time. After correction for an imbalance in the distribution of fast and slow surgeons, mean costs in the ocular insert and topical groups were comparable (&OV0556; 450 versus &OV0556; 444). There was no difference in the use of additional mydriatics intraoperatively (P=0.521).The mean ratio of pupil size to white-to-white distance was lower in the ICMA group during all intraoperative measurements (P<0.001), but similar between the topical and ocular insert groups (P range 0.11-0.82). CONCLUSIONS: In the investigated setting in the Netherlands, ICMA was the most costly strategy. In addition, pupil size was lowest in the ICMA group, but did not result in more additional mydriasis measures intraoperatively. The ocular insert was comparable to topical mydriatics in regard to costs and pupil size. Implementation of ICMA could be considered when availability of nurses or physical space for perioperative care is limited

    Prediction of disease severity in multiple acyl-CoA dehydrogenase deficiency:a retrospective and laboratory cohort study

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    Multiple acyl-CoA dehydrogenase deficiency (MADD) is an ultra-rare inborn error of mitochondrial fatty acid oxidation (FAO) and amino acid metabolism. Individual phenotypes and treatment response can vary markedly. We aimed to identify markers that predict MADD phenotypes. We performed a retrospective nationwide cohort study; then developed an MADD-disease severity scoring system (MADD-DS3) based on signs and symptoms with weighed expert opinions; and finally correlated phenotypes and MADD-DS3 scores to FAO flux (oleate and myristate oxidation rates) and acylcarnitine profiles after palmitate loading in fibroblasts. Eighteen patients, diagnosed between 1989 and 2014, were identified. The MADD-DS3 entails enumeration of eight domain scores, which are calculated by averaging the relevant symptom scores. Lifetime MADD-DS3 scores of patients in our cohort ranged from 0 to 29. FAO flux and [U-13C]C2-, C5-, and [U-13C]C16-acylcarnitines were identified as key variables that discriminated neonatal from later onset patients (all P <.05) and strongly correlated to MADD-DS3 scores (oleate: r = −.86; myristate: r = −.91; [U-13C]C2-acylcarnitine: r = −.96; C5-acylcarnitine: r =.97; [U-13C]C16-acylcarnitine: r =.98, all P <.01). Functional studies in fibroblasts were found to differentiate between neonatal and later onset MADD-patients and were correlated to MADD-DS3 scores. Our data may improve early prediction of disease severity in order to start (preventive) and follow-up treatment appropriately. This is especially relevant in view of the inclusion of MADD in population newborn screening programs

    Cinnamic Acid and Sorbic acid Conversion Are Mediated by the Same Transcriptional Regulator in Aspergillus niger

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    Cinnamic acid is an aromatic compound commonly found in plants and functions as a central intermediate in lignin synthesis. Filamentous fungi are able to degrade cinnamic acid through multiple metabolic pathways. One of the best studied pathways is the non-oxidative decarboxylation of cinnamic acid to styrene. In Aspergillus niger, the enzymes cinnamic acid decarboxylase (CdcA, formally ferulic acid decarboxylase) and the flavin prenyltransferase (PadA) catalyze together the non-oxidative decarboxylation of cinnamic acid and sorbic acid. The corresponding genes, cdcA and padA, are clustered in the genome together with a putative transcription factor previously named sorbic acid decarboxylase regulator (SdrA). While SdrA was predicted to be involved in the regulation of the non-oxidative decarboxylation of cinnamic acid and sorbic acid, this was never functionally analyzed. In this study, A. niger deletion mutants of sdrA, cdcA, and padA were made to further investigate the role of SdrA in cinnamic acid metabolism. Phenotypic analysis revealed that cdcA, sdrA and padA are exclusively involved in the degradation of cinnamic acid and sorbic acid and not required for other related aromatic compounds. Whole genome transcriptome analysis of ΔsdrA grown on different cinnamic acid related compounds, revealed additional target genes, which were also clustered with cdcA, sdrA, and padA in the A. niger genome. Synteny analysis using 30 Aspergillus genomes demonstrated a conserved cinnamic acid decarboxylation gene cluster in most Aspergilli of the Nigri clade. Aspergilli lacking certain genes in the cluster were unable to grow on cinnamic acid, but could still grow on related aromatic compounds, confirming the specific role of these three genes for cinnamic acid metabolism of A. niger.Peer reviewe

    Brown-Vialetto-Van Laere and Fazio Londe syndrome is associated with a riboflavin transporter defect mimicking mild MADD: a new inborn error of metabolism with potential treatment

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    We report on three patients (two siblings and one unrelated) presenting in infancy with progressive muscle weakness and paralysis of the diaphragm. Metabolic studies revealed a profile of plasma acylcarnitines and urine organic acids suggestive of a mild form of the multiple acyl-CoA dehydrogenation defect (MADD, ethylmalonic/adipic acid syndrome). Subsequently, a profound flavin deficiency in spite of a normal dietary riboflavin intake was established in the plasma of all three children, suggesting a riboflavin transporter defect. Genetic analysis of these patients demonstrated mutations in the C20orf54 gene which encodes the human homolog of a rat riboflavin transporter. This gene was recently implicated in the Brown-Vialetto-Van Laere syndrome, a rare neurological disorder which may either present in infancy with neurological deterioration with hypotonia, respiratory insufficiency and early death, or later in life with deafness and progressive ponto-bulbar palsy. Supplementation of riboflavin rapidly improved the clinical symptoms as well as the biochemical abnormalities in our patients, demonstrating that high dose riboflavin is a potential treatment for the Brown-Vialetto-Van Laere syndrome as well as for the Fazio Londe syndrome which is considered to be the same disease entity without the deafnes

    CreA-mediated repression of gene expression occurs at low monosaccharide levels during fungal plant biomass conversion in a time and substrate dependent manner

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    Funding Information: The work conducted by the U.S. Department of Energy Joint Genome Institute, a DOE Office of Science User Facility, was supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231 . CK, EB was supported by a grant of the Applied and Engineering Sciences division of NWO , and the Technology Program of the Ministry of Economic Affairs 016.130.609 to RPdV. PD was supported by a grant of the Netherlands Scientific Organization NWO 824.15.023 to RPdV. The Academy of Finland grant no. 308284 to MRM is acknowledged. Publisher Copyright: © 2021 The Author(s)Carbon catabolite repression enables fungi to utilize the most favourable carbon source in the environment, and is mediated by a key regulator, CreA, in most fungi. CreA-mediated regulation has mainly been studied at high monosaccharide concentrations, an uncommon situation in most natural biotopes. In nature, many fungi rely on plant biomass as their major carbon source by producing enzymes to degrade plant cell wall polysaccharides into metabolizable sugars. To determine the role of CreA when fungi grow in more natural conditions and in particular with respect to degradation and conversion of plant cell walls, we compared transcriptomes of a creA deletion and reference strain of the ascomycete Aspergillus niger during growth on sugar beet pulp and wheat bran. Transcriptomics, extracellular sugar concentrations and growth profiling of A. niger on a variety of carbon sources, revealed that also under conditions with low concentrations of free monosaccharides, CreA has a major effect on gene expression in a strong time and substrate composition dependent manner. In addition, we compared the CreA regulon from five fungi during their growth on crude plant biomass or cellulose. It showed that CreA commonly regulated genes related to carbon metabolism, sugar transport and plant cell wall degrading enzymes across different species. We therefore conclude that CreA has a crucial role for fungi also in adapting to low sugar concentrations as occurring in their natural biotopes, which is supported by the presence of CreA orthologs in nearly all fungi.Peer reviewe

    Tissue-specific suppression of thyroid hormone signaling in various mouse models of aging

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    DNA damage contributes to the process of aging, as underscored by premature aging syndromes caused by defective DNA repair. Thyroid state changes during aging, but underlying mechanisms remain elusive. Since thyroid hormone (TH) is a key regulator of metabolism, changes in TH signaling have widespread effects. Here, we reveal a significant common transcriptomic signature in livers from hypothyroid mice, DNA repair-deficient mice with severe (Csbm/m/Xpa-/-) or intermediate (Ercc1-/Δ-7) progeria and naturally aged mice. A strong induction of TH-inactivating deiodinase D3 and decrease of TH-activating D1 activities are observed in Csbm/m/Xpa-/- livers. Similar findings are noticed in Ercc1-/Δ-7, in naturally aged animals and in wild-type mice exposed to a chronic subtoxic dose of DNAdamaging agents. In contrast, TH signaling in muscle, heart and brain appears unaltered. These data show a strong suppression of TH signaling in specific peripheral organs in premature and normal aging, probably lowering metabolism, while other tissues appear to preserve metabolism. D3-mediated TH inactivation is unexpected, given its expression mainly in fetal tissues. Our studies highlight the importance of DNA damage as the underlying mechanism of changes in thyroid state. Tissue-specific regulation of deiodinase activities, ensuring diminished TH signaling, may contribute importantly to the protective metabolic response in aging
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