Galactose inhibition of the constitutive transport of hexoses in Saccharomyces cerevisiae

The relationship between the pathways of glucose and galactose utilization in Saccharomyces cerevisiae has been studied. Galactose (which is transported and phosphorylated by inducible systems) is a strong inhibitor of the utilization of glucose, fructose and mannose (which have the same constitutive transport and phosphorylation systems). Conversely, all these three hexoses inhibit the utilization of galactose, though with poor efficiency. These cross-inhibitions only occur in yeast adapted to galactose or in galactose-constitutive mutants. The efficiency of galactose as inhibitor is even greater than the efficiencies of each of the other three hexoses to inhibit the utilization of each other. Phosphorylation is not involved in the inhibition and transport of sugars is the affected step. The cross-inhibitions between galactose and either glucose, fructose or mannose do not implicate utilization of one hexose at the expense of the other, as it occurs in the mutual interactions between the latter three sugars. it seems that, by growing the yeast in galactose, a protein component is synthesized, or alternatively modified, that once bound to either galactose or any one of the other three hexoses (glucose, fructose or mannose), cross-interacts respectively with the constitutive or the inducible transport systems, impairing their function.This work was supported by a grant (PB87-0206) from the DGICYT, Promoción General del Conocimiento.Peer Reviewe

Healthy living the the Amsterdam region:Housing market, environmental quality, health and inequality in the metropolitan region

De centrale vraag was in hoeverre veranderde planning in de Amsterdamse regionale woningmarkt bijdraagt aan verschillen in de mate van blootstelling aan omgevingseffecten voor kopers en huurders, en in hoeverre omgevingskwaliteit en vervuiling te koppelen is aan gezondheidsuitkomsten.Het onderzoek bracht hierom unieke, grootschalige kwantitatieve datasets over woonomgeving, individuele bewoners en medische gesteldheid bij elkaar. Hierdoor kon de blootstelling aan luchtvervuiling, geluidoverlast, groenvoorzieningen en hittestress vergeleken worden, en konden de effecten van blootstelling op psychische en lichamelijke gezondheid geschat worden. Het onderzoek laat verschillen zien zijn tussen kopers en huurders in blootstelling. In de meest recente nieuwbouw is dit verschil met name groter voor particuliere huurders. Dit lijkt een gevolg van recente verstedelijking langs infrastructuur en in bevolkte gebieden (verdichting in de stad). Ondanks aanzienlijke blootstellings- en gezondheidsverschillen tussen huurders en kopers, is het verband tussen verschillen in blootstelling en gezondheidsuitkomsten echter zwak, en behoeft verder onderzoek.De uitkomsten dragen bij aan academische debatten over milieurechtvaardigheid, ruimtelijke gezondheid, en het cumulatieve karakter van ongelijkheden. Daarnaast biedt het inzicht in de opeenstapeling van verschillende dimensies van ongelijkheid en kunnen de bevindingen bijdragen aan de ontwikkeling van interventies en beleid voor een duurzame, gezondere, en rechtvaardigere ruimtelijke ordening, buurtontwikkeling en woningmarkt. Om beleid en interventies te helpen zijn samen met maatschappelijke partners vijf beleidsdilemma’s opgesteld.Het twee jaar durende onderzoek is uitgevoerd door een interdisciplinair team van geografen, planologen en medisch onderzoekers van Amsterdam Institute for Social Science Research (AISSR) en van Amsterdam UMC, onder leiding van dr. Wouter van Gent (Urban Geographies, UvA). Maatschappelijke partners zijn GGD Amsterdam, Amsterdamse Federatie Woningcorporaties, Stichting de Gezonde Stad, en de Gemeente Amsterdam. Het project is gefinancierd door Kenniscentrum Ongelijkheid

Optimization by Quantum Annealing: Lessons from hard 3-SAT cases

The Path Integral Monte Carlo simulated Quantum Annealing algorithm is applied to the optimization of a large hard instance of the Random 3-SAT Problem (N=10000). The dynamical behavior of the quantum and the classical annealing are compared, showing important qualitative differences in the way of exploring the complex energy landscape of the combinatorial optimization problem. At variance with the results obtained for the Ising spin glass and for the Traveling Salesman Problem, in the present case the linear-schedule Quantum Annealing performance is definitely worse than Classical Annealing. Nevertheless, a quantum cooling protocol based on field-cycling and able to outperform standard classical simulated annealing over short time scales is introduced.Comment: 10 pages, 6 figures, submitted to PR

Observations of the Magnetic Cataclysmic Variable VV Puppis with the Far Ultraviolet Spectroscopic Explorer

We present the first far-ultraviolet (FUV) observations of the magnetic cataclysmic variable VV Puppis, obtained with the Far Ultraviolet Spectroscopic Explorer satellite. In addition, we have obtained simultaneous ground-based optical photometric observations of VV Pup during part of the FUV observation. The shapes of the FUV and optical light curves are consistent with each other and with those of past observations at optical, extreme-ultraviolet, and X-ray wavelengths. Time-resolved FUV spectra during the portion of VV Pup's orbit when the accreting magnetic pole of the white dwarf can be seen show an increasing continuum level as the accretion spot becomes more directly visible. The most prominent features in the spectrum are the O VI 1031.9A, 1037.6A emission lines. We interpret the shape and velocity shift of these lines in the context of an origin in the accretion funnel near the white dwarf surface. A blackbody function with T > 90,000 K provides an adequate fit to the FUV spectral energy distribution of VV Pup.Comment: 18 pages, 6 figures, 1 table; to be published in the Astronomical Journa

Spitzer Space Telescope observations of magnetic cataclysmic variables: possibilities for the presence of dust in polars

We present Spitzer Space Telescope photometry of six short-period polars, EF Eri, V347 Pav, VV Pup, V834 Cen, GG Leo, and MR Ser. We have combined the Spitzer Infrared Array Camera (3.6 -8.0 microns) data with the 2MASS J, H, K_s photometry to construct the spectral energy distributions of these systems from the near- to mid-IR (1.235 - 8 microns). We find that five out of the six polars have flux densities in the mid-IR that are substantially in excess of the values expected from the stellar components alone. We have modeled the observed SEDs with a combination of contributions from the white dwarf, secondary star, and either cyclotron emission or a cool, circumbinary dust disk to fill in the long-wavelength excess. We find that a circumbinary dust disk is the most likely cause of the 8 micron excess in all cases, but we have been unable to rule out the specific (but unlikely) case of completely optically thin cyclotron emission as the source of the observed 8 micron flux density. While both model components can generate enough flux at 8 microns, neither dust nor cyclotron emission alone can match the excess above the stellar components at all wavelengths. A model combining both cyclotron and dust contributions, possibly with some accretion-generated flux in the near-IR, is probably required, but our observed SEDs are not sufficiently well-sampled to constrain such a complicated model. If the 8 micron flux density is caused by the presence of a circumbinary dust disk, then our estimates of the masses of these disks are many orders of magnitude below the mass required to affect CV evolution.Comment: 58 pages, 14 figures, ApJ accepte

The UK prevalence of hereditary haemorrhagic telangiectasia and its association with sex, socioeconomic status and region of residence: a population-based study

Background Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disorder of aberrant blood vessel development characterised by arteriovenous malformations. HHT is associated with significant morbidity due to complications including epistaxis, gastrointestinal bleeding and stroke. We explored the hypothesis that a diagnosis of HHT is associated with sex, socioeconomic status and geographical location.Methods We used The Health Improvement Network, a longitudinal, computerised general practice database covering 5% of the UK population to calculate prevalence estimates for HHT stratified by age, sex, socioeconomic status and geographical location.Results The 2010 UK point prevalence for HHT was 1.06/10 000 person years (95% CI 0.95 to 1.17) or 1 in 9400 individuals. The diagnosed prevalence of HHT was significantly higher in women compared with men (adjusted prevalence rate ratio (PRR) 1.53, 95% CI 1.24 to 1.88) and in those from the most affluent socioeconomic group compared with the least (adjusted PRR 1.74, 95% CI 1.14 to 2.64). The PRR varied between different regions of the UK, being highest in the South West and lowest in the West Midlands (adjusted PRR for former compared with latter 1.86, 95% CI 1.61 to 2.15).Conclusions HHT prevalence is more common in the UK population than previously demonstrated, though this updated figure is still likely to be an underestimate. HHT appears to be significantly under-diagnosed in men, which is likely to reflect their lower rates of consultation with primary care services. There is under-diagnosis in patients from lower socioeconomic groups and a marked variation in the prevalence of diagnosis between different geographical regions across the UK that requires further investigation

Plant-RRBS, a bisulfite and next-generation sequencing-based methylome profiling method enriching for coverage of cytosine positions

Background: Cytosine methylation in plant genomes is important for the regulation of gene transcription and transposon activity. Genome-wide methylomes are studied upon mutation of the DNA methyltransferases, adaptation to environmental stresses or during development. However, from basic biology to breeding programs, there is a need to monitor multiple samples to determine transgenerational methylation inheritance or differential cytosine methylation. Methylome data obtained by sodium hydrogen sulfite (bisulfite)-conversion and next-generation sequencing (NGS) provide genome- wide information on cytosine methylation. However, a profiling method that detects cytosine methylation state dispersed over the genome would allow high-throughput analysis of multiple plant samples with distinct epigenetic signatures. We use specific restriction endonucleases to enrich for cytosine coverage in a bisulfite and NGS-based profiling method, which was compared to whole-genome bisulfite sequencing of the same plant material. Methods: We established an effective methylome profiling method in plants, termed plant-reduced representation bisulfite sequencing (plant-RRBS), using optimized double restriction endonuclease digestion, fragment end repair, adapter ligation, followed by bisulfite conversion, PCR amplification and NGS. We report a performant laboratory protocol and a straightforward bioinformatics data analysis pipeline for plant-RRBS, applicable for any reference-sequenced plant species. Results: As a proof of concept, methylome profiling was performed using an Oryza sativa ssp. indica pure breeding line and a derived epigenetically altered line (epiline). Plant-RRBS detects methylation levels at tens of millions of cytosine positions deduced from bisulfite conversion in multiple samples. To evaluate the method, the coverage of cytosine positions, the intra-line similarity and the differential cytosine methylation levels between the pure breeding line and the epiline were determined. Plant-RRBS reproducibly covers commonly up to one fourth of the cytosine positions in the rice genome when using MspI-DpnII within a group of five biological replicates of a line. The method predominantly detects cytosine methylation in putative promoter regions and not-annotated regions in rice. Conclusions: Plant-RRBS offers high-throughput and broad, genome- dispersed methylation detection by effective read number generation obtained from reproducibly covered genome fractions using optimized endonuclease combinations, facilitating comparative analyses of multi-sample studies for cytosine methylation and transgenerational stability in experimental material and plant breeding populations

Preindustrial control simulations with HadGEM3-GC3.1 for CMIP6

Pre‐industrial control simulations with the HadGEM3‐GC3.1 climate model are presented at two resolutions. These are N216ORCA025, which has a horizontal resolution of 60km in the atmosphere and 0.25° in the ocean, and N96ORCA1, which has a horizontal resolution of 130km in the atmosphere and 1° in the ocean. The aim of this study is to document the climate variability in these simulations, make comparisons against present‐day observations (albeit under different forcing), and discuss differences arising due to resolution. In terms of interannual variability in the leading modes of climate variability the two resolutions behave generally very similarly. Notable differences are in the westward extent of El‐Niño and the pattern of Atlantic multidecadal variability, in which N216ORCA025 compares more favourably to observations, and in the Antarctic Circumpolar Current, which is far too weak in N216ORCA025. In the North Atlantic region, N216ORCA025 has a stronger and deeper AMOC, which compares well against observations, and reduced biases in temperature and salinity in the North Atlantic subpolar gyre (NA SPG). These simulations are being provided to the sixth Coupled Model Intercomparison Project (CMIP6) and provide a baseline against which further forced experiments may be assessed

Protocol for the STRONG trial: stereotactic body radiation therapy following chemotherapy for unresectable perihilar cholangiocarcinoma, a phase I feasibility study

INTRODUCTION: For patients with perihilar cholangiocarcinoma (CCA), surgery is the only treatment modality that can result in cure. Unfortunately, in the majority of these patients, the tumours are found to be unresectable at presentation due to either local invasive tumour growth or the presence of distant metastases. For patients with unresectable CCA, palliative chemotherapy is the standard treatment yielding an estimated median overall survival (OS) of 12-15.2 months. There is no evidence from randomised trials to support the use of stereotactic body radiation therapy (SBRT) for CCA. However, small and most often retrospective studies combining chemotherapy with SBRT have shown promising results with OS reaching up to 33-35 months.METHODS AND ANALYSIS: This study has been designed as a single-centre phase I feasibility trial and will investigate the addition of SBRT after standard chemotherapy in patients with unresectable perihilar CCA (T1-4 N0-1 M0). A total of six patients will be included. SBRT will be delivered in 15 fractions of 3-4.5 Gy (risk adapted). The primary objective of this study is to determine feasibility and toxicity. Secondary outcomes include local tumour control, progression-free survival (PFS), OS and quality of life. Length of follow-up will be 2 years. As an ancillary study, the personalised effects of radiotherapy will be measured in vitro, in patient-derived tumour and bile duct organoid cultures.ETHICS AND DISSEMINATION: Ethics approval for the STRONG trial has been granted by the Medical Ethics Committee of Erasmus MC Rotterdam, the Netherlands. It is estimated that all patients will be included between October 2017 and October 2018. The results of this study will be published in a peer-reviewed journal, and presented at national and international conferences.TRIAL REGISTRATION NUMBER: NCT03307538; Pre-results

Respiratory symptoms among infants at risk for asthma: association with surfactant protein A haplotypes

BACKGROUND: We examined the association between single nucleotide polymorphisms (SNPs) in loci encoding surfactant protein A (SFTPA) and risk of wheeze and persistent cough during the first year of life among a cohort of infants at risk for developing asthma. METHODS: Between September 1996 and December 1998, mothers of newborn infants were invited to participate if they had an older child with clinician-diagnosed asthma. Each mother was given a standardized questionnaire within 4 months of her infant's birth. Infant respiratory symptoms were collected during quarterly telephone interviews at 6, 9 and 12 months of age. Due to the association of SFTPA polymorphisms and race/ethnicity, analyses were restricted to 221 white infants for whom whole blood and respiratory data were available. Ordered logistic regression models were used to examine the association between respiratory symptom frequency and SFTPA haplotypes. RESULTS: The 6A allele haplotype of SFTPA1, with an estimated frequency of 6% among our study infants, was associated with an increased risk of persistent cough (OR 3.69, 95% CI 1.71, 7.98) and wheeze (OR 4.72, 95% CI 2.20, 10.11). The 6A/1A haplotype of SFTPA, found among approximately 5% of the infants, was associated with an increased risk of persistent cough (OR 3.20, 95% CI 1.39, 7.36) and wheeze (OR 3.25, 95% CI 1.43, 7.37). CONCLUSION: Polymorphisms within SFTPA loci may be associated with wheeze and persistent cough in white infants at risk for asthma. These associations require replication and exploration in other ethnic/racial groups