755 research outputs found
The aspartic proteinase family of three Phytophthora species
Background: Phytophthora species are oomycete plant pathogens with such major social and economic impact that genome sequences have been determined for Phytophthora infestans, P. sojae and P. ramorum. Pepsin-like aspartic proteinases (APs) are produced in a wide variety of species (from bacteria to humans) and contain conserved motifs and landmark residues. APs fulfil critical roles in infectious organisms and their host cells. Annotation of Phytophthora APs would provide invaluable information for studies into their roles in the physiology of Phytophthora species and interactions with their hosts. Results: Genomes of Phytophthora infestans, P. sojae and P. ramorum contain 11-12 genes encoding APs. Nine of the original gene models in the P. infestans database and several in P. sojae and P. ramorum (three and four, respectively) were erroneous. Gene models were corrected on the basis of EST data, consistent positioning of introns between orthologues and conservation of hallmark motifs. Phylogenetic analysis resolved the Phytophthora APs into 5 clades. Of the 12 sub-families, several contained an unconventional architecture, as they either lacked a signal peptide or a propart region. Remarkably, almost all APs are predicted to be membrane-bound. Conclusions: One of the twelve Phytophthora APs is an unprecedented fusion protein with a putative G-protein coupled receptor as the C-terminal partner. The others appear to be related to well-documented enzymes from other species, including a vacuolar enzyme that is encoded in every fungal genome sequenced to date. Unexpectedly, however, the oomycetes were found to have both active and probably-inactive forms of an AP similar to vertebrate BACE, the enzyme responsible for initiating the processing cascade that generates the Aβ peptide central to Alzheimer's Disease. The oomycetes also encode enzymes similar to plasmepsin V, a membrane-bound AP that cleaves effector proteins of the malaria parasite Plasmodium falciparum during their translocation into the host red blood cell. Since the translocation of Phytophthora effector proteins is currently a topic of intense research activity, the identification in Phytophthora of potential functional homologues of plasmepsin V would appear worthy of investigation. Indeed, elucidation of the physiological roles of the APs identified here offers areas for future study. The significant revision of gene models and detailed annotation presented here should significantly facilitate experimental design.Fil: Kay, John. Cardiff University; Reino UnidoFil: Meijer, Harold J. G.. Wageningen University; Reino UnidoFil: Ten Have, Arjen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigaciones Biológicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: van Kan, Jan A. L.. Wageningen University; Reino Unid
Mining Explainable Predictive Features for Water Quality Management
With water quality management processes, identifying and interpreting
relationships between features, such as location and weather variable tuples,
and water quality variables, such as levels of bacteria, is key to gaining
insights and identifying areas where interventions should be made. There is a
need for a search process to identify the locations and types of phenomena that
are influencing water quality and a need to explain how the quality is being
affected and which factors are most relevant. This paper addresses both of
these issues. A process is developed for collecting data for features that
represent a variety of variables over a spatial region and which are used for
training models and inference. An analysis of the performance of the features
is undertaken using the models and Shapley values. Shapley values originated in
cooperative game theory and can be used to aid in the interpretation of machine
learning results. Evaluations are performed using several machine learning
algorithms and water quality data from the Dublin Grand Canal basin
Anisotropic intrinsic lattice thermal conductivity of phosphorene from first principles
Phosphorene, the single layer counterpart of black phosphorus, is a novel
two-dimensional semiconductor with high carrier mobility and a large
fundamental direct band gap, which has attracted tremendous interest recently.
Its potential applications in nano-electronics and thermoelectrics call for a
fundamental study of the phonon transport. Here, we calculate the intrinsic
lattice thermal conductivity of phosphorene by solving the phonon Boltzmann
transport equation (BTE) based on first-principles calculations. The thermal
conductivity of phosphorene at is
(zigzag) and
(armchair), showing an obvious anisotropy along different directions. The
calculated thermal conductivity fits perfectly to the inverse relation with
temperature when the temperature is higher than Debye temperature (). In comparison to graphene, the minor contribution around
of the ZA mode is responsible for the low thermal conductivity of
phosphorene. In addition, the representative mean free path (MFP), a critical
size for phonon transport, is also obtained.Comment: 5 pages and 6 figures, Supplemental Material available as
http://www.rsc.org/suppdata/cp/c4/c4cp04858j/c4cp04858j1.pd
The Use of Transport Time Scales as Indicators of Pollution Persistence in a Macro-Tidal Setting
An understanding of water exchange processes is essential for assessing water quality management issues in coastal bays. This paper evaluates the impact of water exchange processes on pollution persistence in a macro-tidal semi-closed coastal bay through two transport time scales (TTS), namely residence time and exposure time. The numerical model was calibrated against field-measured data for various tidal conditions. Simulated current speeds and directions were shown to agree well with the field data. By considering different release scenarios of a conservative tracer by the refinement of an integrated hydrodynamic and solute transport model (the EFDC), the two TTS were used for interpreting the water exchange processes in a semi-closed system, and for describing the effects of advective and dispersive processes on the transport and fate of pollutants. The results indicate that the magnitudes of river inflows to the bay, tidal ranges, and tracer release times significantly influence the residence and exposure times. Return coefficients were shown to be variable, confirming the different effects of returning water for the different conditions that were studied. For the tested river flow magnitudes and tide conditions, the exposure times were generally higher than the residence times, but particularly so for neap tide conditions. The results, therefore, highlight the risks associated with pollutants leaving a specified domain on an outgoing tide but re-entering on subsequent incoming tides. The spatial distributions of the exposure and residence times across the model domain confirmed that for the case of Dublin Bay, river inputs have a potentially greater impact on water quality on the northern side of the bay
Inflammatory mediators and cell adhesion molecules as indicators of severity of atherosclerosis: the Rotterdam Study
Inflammatory mediators and soluble cell adhesion molecules predict
cardiovascular events. It is not clear whether they reflect the severity
of underlying atherosclerotic disease. Within the Rotterdam Study, we
investigated the associations of C-reactive protein (CRP), interleukin-6
(IL-6), soluble intercellular adhesion molecule-1, and soluble vascular
cell adhesion molecule-1 with noninvasive measures of atherosclerosis.
Levels of CRP were assessed in a random sample of 1317 participants, and
levels of IL-6 and soluble cell adhesion molecules were assessed in a
subsample of 714 participants. In multivariate analyses, logarithmically
transformed CRP (regression coefficient [beta]=-0.023, 95% CI -0.033 to
-0.012) and IL-6 (beta=-0.025, 95% CI -0.049 to -0.001) were inversely
associated with the ankle-arm index. Only CRP was associated with carotid
intima-media thickness (beta=0.018, 95% CI 0.010 to 0.027). Compared with
the lowest tertile, the odds ratio for moderate to severe carotid plaques
associated with levels of CRP in the highest tertile was 2.0 (95% CI 1.3
to 3.0). Soluble intercellular adhesion molecule-1 levels were strongly
associated with carotid plaques (odds ratio 2.5, 95% CI 1.5 to 4.4
[highest versus lowest tertile]). Soluble vascular cell adhesion
molecule-1 was not significantly associated with any of the measures of
atherosclerosis. This study indicates that CRP is associated with the
severity of atherosclerosis measured at various sites. Associations of the
other markers with atherosclerosis were less consistent
Influenza activity in Europe during eight seasons (1999–2007): an evaluation of the indicators used to measure activity and an assessment of the timing, length and course of peak activity (spread) across Europe
<p>Abstract</p> <p>Background</p> <p>The European Influenza Surveillance Scheme (EISS) has collected clinical and virological data on influenza since 1996 in an increasing number of countries. The EISS dataset was used to characterise important epidemiological features of influenza activity in Europe during eight winters (1999–2007). The following questions were addressed: 1) are the sentinel clinical reports a good measure of influenza activity? 2) how long is a typical influenza season in Europe? 3) is there a west-east and/or south-north course of peak activity ('spread') of influenza in Europe?</p> <p>Methods</p> <p>Influenza activity was measured by collecting data from sentinel general practitioners (GPs) and reports by national reference laboratories. The sentinel reports were first evaluated by comparing them to the laboratory reports and were then used to assess the timing and spread of influenza activity across Europe during eight seasons.</p> <p>Results</p> <p>We found a good match between the clinical sentinel data and laboratory reports of influenza collected by sentinel physicians (overall match of 72% for +/- 1 week difference). We also found a moderate to good match between the clinical sentinel data and laboratory reports of influenza from non-sentinel sources (overall match of 60% for +/- 1 week). There were no statistically significant differences between countries using ILI (influenza-like illness) or ARI (acute respiratory disease) as case definition. When looking at the peak-weeks of clinical activity, the average length of an influenza season in Europe was 15.6 weeks (median 15 weeks; range 12–19 weeks). Plotting the peak weeks of clinical influenza activity reported by sentinel GPs against the longitude or latitude of each country indicated that there was a west-east spread of peak activity (spread) of influenza across Europe in four winters (2001–2002, 2002–2003, 2003–2004 and 2004–2005) and a south-north spread in three winters (2001–2002, 2004–2005 and 2006–2007).</p> <p>Conclusion</p> <p>We found that: 1) the clinical data reported by sentinel physicians is a valid indicator of influenza activity; 2) the length of influenza activity across the whole of Europe was surprisingly long, ranging from 12–19 weeks; 3) in 4 out of the 8 seasons, there was a west-east spread of influenza, in 3 seasons a south-north spread; not associated with type of dominant virus in those seasons.</p
Erratum to: ‘Integrated analysis of the local and systemic changes preceding the development of post-partum cytological endometritis’
ErratumErratum to: ‘Integrated analysis of the local and systemic changes preceding the development of post-partum cytological endometritis’ -http://hdl.handle.net/11019/90
Markers of inflammation and cellular adhesion molecules in relation to insulin resistance in nondiabetic elderly: the Rotterdam study
Insulin resistance, which is highly prevalent in the elderly, is suggested
to be accompanied by an increased acute phase response. Until now, it is
unclear whether cellular adhesion molecules are involved in the clustering
of insulin resistance. In the present study, we examined the relationship
of insulin resistance (measured by postload insulin) with levels of
markers of inflammation and cellular adhesion molecules in a random sample
of 574 nondiabetic elderly men and women participating in the Rotterdam
Study. Associations were assessed by regression analysis, with ln-insulin
as the dependent variable [regression coefficient (95% confidence
interval)]. In our population, insulin was strongly and significantly (P <
0.001) associated with the markers of inflammation C-reactive protein
[1.52 (0.96-2.08)], alpha-1-antichymotrypsin [1.25 (0.82-1.69)], and IL-6
[2.60 (1.69-3.52)], adjusted for age and gender. Associations weakened, to
some extent, after additional adjustment for measures of obesity, smoking,
and cardiovascular disease. Insulin was associated with the soluble
intercellular adhesion molecule 1 [2.22 (1.29-3.16; P < 0.001)], whereas
no association with the soluble vascular cell adhesion molecule 1 was
found. The strength of the associations of insulin with C-reactive
protein, alpha-1-antichymotrypsin, IL-6, and soluble intercellular
adhesion molecule 1, as assessed by standardized regression coefficients,
was comparable with the strength of the associations of insulin with
high-density lipoprotein cholesterol, body mass index, and waist-to-hip
ratio. The results of this population-based study indicate that low-grade
inflammation and the cellular adhesion molecule soluble intercellular
adhesion molecule 1 are an integral part of insulin resistance in
nondiabetic elderly. These factors may contribute to the well-known
relationship between insulin resistance and cardiovascular disease risk
and might potentially become therapeutic targets in insulin resistant
subjects
GATA3 mRNA expression, but not mutation, associates with longer progression-free survival in ER-positive breast cancer patients treated with first-line tamoxifen for recurrent disease
In breast cancer, GATA3 mutations have been associated with a favorable prognosis and the response to neoadjuvant aromatase inhibitor treatment. Therefore, we investigated whether GATA3 mutations predict the outcome of tamoxifen treatment in the advanced setting. In a retrospective study consisting of 235 hormone-naive patients with ER-positive breast cancer who received tamoxifen as first-line treatment for recurrent disease, GATA3 mutations (in 14.0% of patients) did not significantly associate with either the overall response rate (ORR) or with the length of progression-free survival (PFS) after the start of tamoxifen therapy. Interestingly, among 148 patients for whom both mutation and mRNA expression data were available, GATA3 mutations associated with an increased expression of GATA3. However, only 23.7% of GATA3 high tumors had a mutation. Evaluation of the clinical significance of GATA3 mRNA revealed that it was associated with prolonged PFS, but not with the ORR, also in multivariate analysis. Thus, GATA3 mRNA expression, but not GATA3 mutation, is an independent predictor of prolonged PFS in ER-positive breast cancer patients who received first-line tamoxifen for recurrent disease. Besides GATA3 mutation, other mechanisms must exist that underlie increased GATA3 levels
- …