First two unrelated cases of isolated sedoheptulokinase deficiency: A benign disorder?

We present the first two reported unrelated patients with an isolated sedoheptulokinase (SHPK) deficiency. The first patient presented with neonatal cholestasis, hypoglycemia, and anemia, while the second patient presented with congenital arthrogryposis multiplex, multiple contractures, and dysmorphisms. Both patients had elevated excretion of erythritol and sedoheptulose, and each had a homozygous nonsense mutation in SHPK. SHPK is an enzyme that phosphorylates sedoheptulose to sedoheptulose-7-phosphate, which is an important intermediate of the pentose phosphate pathway. It is questionable whether SHPK deficiency is a causal factor for the clinical phenotypes of our patients. This study illustrates the necessity of extensive functional and clinical workup for interpreting a novel variant, including nonsense variants

Threshold effects of air pollution and climate change on understory plant communities at forested sites in the eastern United States

Forest understory plant communities in the eastern United States are often diverse and are potentially sensitive to changes in climate and atmospheric inputs of nitrogen caused by air pollution. In recent years, empirical and processed-based mathematical models have been developed to investigate such changes in plant communities. In the study reported here, a robust set of understory vegetation response functions (expressed as version 2 of the Probability of Occurrence of Plant Species model for the United States [US-PROPS v2]) was developed based on observations of forest understory and grassland plant species presence/absence and associated abiotic characteristics derived from spatial datasets. Improvements to the US-PROPS model, relative to version 1, were mostly focused on inclusion of additional input data, development of custom species-level input datasets, and implementation of methods to address uncertainty. We investigated the application of US-PROPS v2 to evaluate the potential impacts of atmospheric nitrogen (N) and sulfur (S) deposition, and climate change on forest ecosystems at three forested sites located in New Hampshire, Virginia, and Tennessee in the eastern United States. Species-level N and S critical loads (CLs) were determined under ambient deposition at all three modeled sites. The lowest species-level CLs of N deposition at each site were between 2 and 11 kg N/ha/yr. Similarly, the lowest CLs of S deposition, based on the predicted soil pH response, were less than 2 kg S/ha/yr among the three sites. Critical load exceedance was found at all three model sites. The New Hampshire site included the largest percentage of species in exceedance. Simulated warming air temperature typically resulted in lower maximum occurrence probability, which contributed to lower CLs of N and S deposition. The US-PROPS v2 model, together with the PROPS-CLF model to derive CL functions, can be used to develop site-specific CLs for understory plants within broad regions of the United States. This study demonstrates that species-level CLs of N and S deposition are spatially variable according to the climate, light availability, and soil characteristics at a given location. Although the species niche models generally performed well in predicting occurrence probability, there remains uncertainty with respect to the accuracy of reported CLs. As such, the specific CLs reported here should be considered as preliminary estimates. Graphical abstrac

Prediction of plant species occurrence as affected by nitrogen deposition and climate change on a European scale

Plant species occurrence in Europe is affected by changes in nitrogen deposition and climate. Insight into potential future effects of those changes can be derived by a model approach based on field-based empirical evidence on a continental scale. In this paper, we present a newly developed empirical model PROPS, predicting the occurrence probabilities of plant species in response to a combination of climatic factors, nitrogen deposition and soil properties. Parameters included were temperature, precipitation, nitrogen deposition, soil pH and soil C/N ratio. The PROPS model was fitted to plant species occurrence data of about 800,000 European relevés with estimated values for pH and soil C/N ratio and interpolated climate and modelled N deposition data obtained from the Ensemble meteo data set and EMEP model results, respectively. The model was validated on an independent data set. The test of ten species against field data gave an average Pearson's r-value of 0.79. PROPS was applied to a grassland and a heathland site to evaluate the effect of scenarios for nitrogen deposition and climate change on the Habitat Suitability Index (HSI), being the average of the relative probabilities, compared to the maximum probability, of all target species in a habitat. Results for the period 1930–2050 showed that an initial increase and later decrease in nitrogen deposition led to a pronounced decrease in HSI, and with dropping nitrogen deposition to an increase of the HSI. The effect of climate change appeared to be limited, resulting in a slight increase in HSI

Shared as well as distinct roles of EHD proteins revealed by biochemical and functional comparisons in mammalian cells and C. elegans

BACKGROUND: The four highly homologous human EHD proteins (EHD1-4) form a distinct subfamily of the Eps15 homology domain-containing protein family and are thought to regulate endocytic recycling. Certain members of this family have been studied in different cellular contexts; however, a lack of concurrent analyses of all four proteins has impeded an appreciation of their redundant versus distinct functions. RESULTS: Here, we analyzed the four EHD proteins both in mammalian cells and in a cross-species complementation assay using a C. elegans mutant lacking the EHD ortholog RME-1. We show that all human EHD proteins rescue the vacuolated intestinal phenotype of C. elegans rme-1 mutant, are simultaneously expressed in a panel of mammalian cell lines and tissues tested, and variably homo- and hetero-oligomerize and colocalize with each other and Rab11, a recycling endosome marker. Small interfering RNA (siRNA) knock-down of EHD1, 2 and 4, and expression of dominant-negative EH domain deletion mutants showed that loss of EHD1 and 3 (and to a lesser extent EHD4) but not EHD2 function retarded transferrin exit from the endocytic recycling compartment. EH domain deletion mutants of EHD1 and 3 but not 2 or 4, induced a striking perinuclear clustering of co-transfected Rab11. Knock-down analyses indicated that EHD1 and 2 regulate the exit of cargo from the recycling endosome while EHD4, similar to that reported for EHD3 (Naslavsky et al. (2006) Mol. Biol. Cell 17, 163), regulates transport from the early endosome to the recycling endosome. CONCLUSION: Altogether, our studies suggest that concurrently expressed human EHD proteins perform shared as well as discrete functions in the endocytic recycling pathway and lay a foundation for future studies to identify and characterize the molecular pathways involved

Zijn Mars- en maanbodem geschikt voor plantenteelt?

Als ruimtereizigers in de toekomst langere tijd op de maan en op Mars willen verblijven, dan zullen ze daar voedsel moeten gaan verbouwen. Maar kan dat wel? Is plantengroei mogelijk op bodems van die hemellichamen? Om dat te onderzoeken hebben we een experiment opgezet met kunstmatige Mars- en maanbodems waarop zaden van verschillende plantensoorten te kiemen zijn gelegd en gevolgd in hun groei

The difference between rare and exceptionally rare: molecular characterization of ribose 5-phosphate isomerase deficiency

Ribose 5-phosphate isomerase (RPI) deficiency is an enzymopathy of the pentose phosphate pathway. It manifests with progressive leukoencephalopathy and peripheral neuropathy and belongs, with one sole diagnosed case, to the rarest human disorders. The single patient was found compound heterozygous for a RPI frameshift and a missense (RPI(Ala61Val)) allele. Here, we report that two patient-derived cell lines differ in RPI enzyme activity, enzyme concentration, and mRNA expression. Furthermore, we present a transgenic yeast model, which exhibits metabolite- and enzyme-activity changes that correspond to the human syndrome and show that the decrease in RPI activity in patient cells is not fully attributable to the residue exchange. Taken together, our results demonstrate that RPI deficiency is caused by the combination of a RPI null allele with an allele that encodes for a partially active enzyme which has, in addition, cell-type-dependent expression deficits. We speculate that a low probability for comparable traits accounts for the rareness of RPI deficiency

Stikstofoverschot door bijvoeren van grazers

In de Amsterdamse Waterleidingduinen wordt verruiging bestreden door het inscharen van runderen. Het bijvoeren van het vee in de winter zorgt voor een extra input van stikstof boven op de aanwezige atmosferische depositie. Het bijvoeren kan daardoor leiden tot een (verdere) overschrijding van de kritische depositie voor enkele gevoelige habitattypen zoals de grijze duinen

Herijking van de EHS voor drie verschillende provincies

Bij het aantreden in 2010 van het kabinet Rutte I is het natuurbeleid drastisch veranderd. De plannen voor de Ecologische hoofdstructuur (EHS), het natuurnetwerk van Nederland, werden versoberd. De herziening van het natuurbeleid bood echter ook kansen om na ruim twintig jaar werken aan de EHS te kijken waar verbetering mogelijk is. Provincies ontwikkelden daarom plannen voor een ‘herijkte EHS’. Vijf provincies vroegen aan Alterra om uit te zoeken in hoeverre deze herijkte EHS tot ecologische verbeteringen leidt. In dit artikel beschrijven we de aanpak van de evaluaties van de provinciale plannen voor een herijkte EHS, waarbij we de studies voor Gelderland, Overijssel en Limburg in meer detail beschrijven

Dynamic rerouting of the carbohydrate flux is key to counteracting oxidative stress

<p>Abstract</p> <p>Background</p> <p>Eukaryotic cells have evolved various response mechanisms to counteract the deleterious consequences of oxidative stress. Among these processes, metabolic alterations seem to play an important role.</p> <p>Results</p> <p>We recently discovered that yeast cells with reduced activity of the key glycolytic enzyme triosephosphate isomerase exhibit an increased resistance to the thiol-oxidizing reagent diamide. Here we show that this phenotype is conserved in <it>Caenorhabditis elegans </it>and that the underlying mechanism is based on a redirection of the metabolic flux from glycolysis to the pentose phosphate pathway, altering the redox equilibrium of the cytoplasmic NADP(H) pool. Remarkably, another key glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), is known to be inactivated in response to various oxidant treatments, and we show that this provokes a similar redirection of the metabolic flux.</p> <p>Conclusion</p> <p>The naturally occurring inactivation of GAPDH functions as a metabolic switch for rerouting the carbohydrate flux to counteract oxidative stress. As a consequence, altering the homoeostasis of cytoplasmic metabolites is a fundamental mechanism for balancing the redox state of eukaryotic cells under stress conditions.</p