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PubMed2004

Improved DOSY NMR data processing by data enhancement and combination of multivariate curve resolution with non-linear least square fitting.

The quality of DOSY NMR data can be improved by careful pre-processing techniques. Baseline drift, peak shift, and phase shift commonly exist in real-world DOSY NMR data. These phenomena seriously hinder the data analysis and should be removed as much as possible. In this paper, a series of preprocessing operations are proposed so that the subsequent multivariate curve resolution can yield optimal results. First, the baseline is corrected according to a method by Golotvin and Williams. Next, frequency and phase shift are removed by a new combination of reference deconvolution (FIDDLE), and a method presented by Witjes et al. that can correct several spectra simultaneously. The corrected data are analysed by the combination of multivariate curve resolution with non-linear least square regression (MCR-NLR). The MCR-NLR method turns out to be more robust and leads to better resolution of the pure components than classic MCR.

Journal Article↗
PubMed2004

Non-photochemical quenching kinetics during the dark to light transition in relation to the formation of antheraxanthin and zeaxanthin.

Nonlinear regression analysis (NLR) is applied to quantify the dynamic response of non-photochemical fluorescence quenching (NPQ) of Trifolium repens cv. Regal upon dark to light transition. Commonly, only steady-state levels of NPQ are evaluated, ignoring transient kinetics. Experimental NPQ kinetics are fitted best with a sum of two functions: a sigmoidal Hill function plus a transient logarithmic normal function. It is shown that not only steady-state level of NPQ, but also the speed at which steady state is reached, increased with light intensity. The question is raised which biological processes cause the induction of the components of NPQ kinetics. The NPQ kinetics are found to resemble the kinetics of antheraxanthin and zeaxanthin formation during a dark to light transition. Furthermore, both molecules are known to induce NPQ. The hypothesis is put forward that a transient phase of NPQ (0-2 min after transition) is dependent upon concentrations of antheraxanthin, whereas the saturating phase corresponds with the production of zeaxanthin. A mathematical model, based on the presented hypothesis, predicts the effect of increasing light intensity on concentrations of antheraxanthin and zeaxanthin which correspond with experimental results. Implications of the hypothesis are discussed as well as the role of NLR in evaluating chlorophyll a fluorescence kinetics.

Adaptation, Ocular↗
PubMed2006

Sensing of bacteria: NOD a lonely job.

Recognition of bacteria by the vertebrate innate immune system relies on detection of invariant molecules by specialized receptors. The view is emerging that activation of both Toll-like receptors (TLRs) and Nod-like receptors (NLRs) by different bacterial agonists is important in order to mount an inflammatory response in the host. Priming of cells with peptidoglycan and products that are sensed by cytosolic-localized members of the NLR family have a synergistic effect on TLR signalling and vice versa. Currently, the underlying molecular mechanisms of this cross-talk between NLR and TLR signalling are beginning to emerge. These reveal that the two sensing-systems are non-redundant in bacterial recognition and that their cross-talk plays an important role in immunological homeostasis.

Animals↗
PubMed2006

Capture-recapture estimation of underreporting of legionellosis cases to the National Legionellosis Register: Italy 2002.

The objective of this study was to evaluate the degree of underreporting to the Italian National Legionellosis Register (NLR). For the year 2002, all cases of Legionellosis notified to the NLR were compared with cases recorded in the hospital discharge record (HDR) database. The number of unreported cases and the total number of cases in the population were estimated using the capture-recapture method with two independent data sources. Seventeen out of 21 Italian regions participated in the study. Overall, underreporting was estimated to be 21.4% and was found to be significantly greater in the Centre-South (28.2%) than in the North (20.0%). However, even after taking into account the higher degree of underreporting, a significantly lower incidence of the disease is registered in central-southern Italy. The hypothesis, which needs to be verified, is that, in addition to underreporting, under-diagnosis of legionellosis is more widespread in this geographical area.

Epidemiologic Methods↗
PubMed1991

Control of methionine biosynthesis in Escherichia coli K12: a closer study with analogue-resistant mutants.

Control of methionine biosynthesis in Escherichia coli K12 was reinvestigated by using methionine-analogue-resistant mutants. Norleucine (NL) and alpha-methylmethionine (MM) were found to inhibit methionine biosynthesis directly whereas ethionine (Et) competitively inhibited methionine utilization. Adenosylation of Et to generate S-adenosylethionine (AdoEt) by cell-free enzyme from E. coli K12 was demonstrated. Tolerance of increasing concentrations of NL by E. coli K12 mutants is expressed serially as phenotypes NLR, NLREtR, NLRMMR and finally NLREtRMMR. All spontaneous NLR mutants had a metK mutation, whereas NTG-induced mutants had mutations in both the metK and metJ genes. The kinetics of methionine adenosylation by the E. coli K12 cell-free enzyme were found to be similar to those reported for the yeast enzyme, showing the typical lag phase at low methionine concentration and disappearance of this phase when AdoMet was included in the incubation mixture. NL extended the lag phase, and lowered the rate of subsequent methionine adenosylation, but did not affect the shortening of the lag phase of adenosylation by AdoMet.

Adenosine↗
PubMed2025

The Annotated Blueprint: Integrated Functional Genomic Resources for a model Tetraploid Wheat Triticum turgidum cv. Kronos.

Triticum turgidum cv. Kronos is a tetraploid wheat cultivar that underpins one of the richest community platforms for functional genomics. Over the past decade, about 3,000 exome- and promoter-capture datasets, linked to mutagenized seed stocks, and transcriptomic and phenotypic resources have accumulated, yet the absence of a reference genome has constrained their impact. Here, we present a chromosome-scale reference genome of Kronos with high-confidence annotations, including manual curation of over 1,000 disease resistance (NLR) genes. This reference revealed previously hidden NLR diversity and clarified their genomic organization at chromosomal ends. Re-analysis of exome- and promoter-capture datasets enabled high-resolution mutation discovery in genes and regulatory regions that were previously inaccessible, uncovering the full standing variation present in Kronos mutant lines. We further re-curated transcriptomic and small RNA datasets, generating improved, genome-wide maps of microRNAs and phasiRNAs important for wheat development. Collectively, these resources elevate Kronos to reference quality and establish it as a versatile platform for functional and translational wheat research.

Journal Article↗
PubMed2006

A comparison of multivariable regression models to analyse cost data.

RATIONALE, AIMS AND OBJECTIVES: Analysis of cost data is important in providing reliable information to aid budgeting decisions. Certain features of cost data, such as its typically highly skewed distribution and the need to estimate arithmetic mean costs in order to allow inferences to be made on total costs, make it difficult to analyse. Multivariable regression analysis is useful for estimating the influence of explanatory variables on cost in order to predict costs of future patients and allows for the control of variables which influence cost but whose distributions differ between comparison groups. This is especially important in the case of observational studies, where there may be no control over the balance of characteristics between the comparison groups. METHOD: This paper compares the appropriateness of various multivariable models of cost data by examining regression diagnostics, using as an example data collected on costs incurred in the treatment of inflammatory bowel disease. The models compared are normal and bootstrapped multiple linear regression, median regression, gamma model with the log link and normal linear regression (NLR) of log costs. RESULTS: Gamma modelling with the log link was found to be the most suitable model. CONCLUSIONS: Bootstrapping was found to make very little difference to conclusions from the NLR model.

Health Care Costs↗
PubMed2006

Serum lipoprotein(a) level and clinical coronary stenosis progression in patients with myocardial infarction: re-revascularization rate is high in patients with high-Lp(a).

BACKGROUND: High serum lipoprotein(a) (Lp(a)) levels are associated with coronary artery disease. METHODS AND RESULTS: The serum Lp(a) levels of 130 patients with acute myocardial infarction (AMI) who underwent direct percutaneous coronary intervention were investigated. On the basis of Lp(a) level at 1 month after the onset of AMI, the patients were classified into 2 groups (high-Lp(a) (> or =30 mg/dl) and low-Lp(a) (< 30 mg/dl)) for evaluation of the clinical coronary stenosis progression (CCSP) rate. CCSP is defined as either target lesion revascularization (TLR) or new lesion revascularization (NLR). The CCSP rate was significantly higher in the high-Lp(a) group than in the low-Lp(a) group (65.8% vs 29.3%, p<0.01). In patients who had coronary stents in the acute phase (n=79), the CCSP and NLR rates were significantly higher in the high-Lp(a) group than in the low-Lp(a) group (45.0% vs 20.3%, p<0.05; 35.0% vs 6.8%, p<0.01), but there was no significant difference in TLR rate between the 2 groups (10.0% vs 13.6%, p=0.858). CONCLUSIONS: High serum Lp(a) level is a significant risk factor for CCSP, but does not influence restenosis after stenting.

Adult↗
PubMed2006

Comparison between 100-g glucose tolerance test and two other screening tests for gestational diabetes: combined fasting glucose with risk factors and 50-g glucose tolerance test.

CONTEXT AND OBJECTIVE: Lack of consensus about which screening tests to use for gestational diabetes mellitus (GDM) and difficulties in performing the gold-standard diagnostic test, the 100-g glucose tolerance test (100-g GTT), justify comparison with alternatives. The aim was to compare this with two other screening tests: combined fasting glucose with risk factors (FG + RF) and 50-g GTT. DESIGN AND SETTING: Prospective longitudinal cohort study in the Hospital School of Universidade Federal de Mato Grosso do Sul. METHODS: The three tests were performed independently on 341 pregnant women. Sensitivity (S), specificity (Sp), positive (PPV) and negative (NPV) predictive values, positive (PLR) and negative (NLR) likelihood ratios, and false-positive (FP) and false-negative (FR) rates obtained with FG + RF and 50-g GTT were compared with values from 100-g GTT. The average one-hour post-intake glucose levels (1hPG) with 50-g and 100-g were compared. Students t test was used in the statistical analysis. RESULTS: FG + RF led more pregnant women (53.9%) to diagnostic confirmation than did 50-g GTT (14.4%). The tests were equivalent for S (86.4 and 76.9%), PPV (98.7 and 98.9%), NLR (0.3 and 0.27) and FR (15.4 and 23.1%). Average 1hPG values were similar: 50-g GTT = 106.8 mg/dl and 100-g GTT = 107.5 mg/dl. CONCLUSION: Diagnostic efficiency with simplicity, practicality and low cost make FG + RF more appropriate for screening for GDM. The equivalence of 1hPG allows a new, cheaper and less uncomfortable protocol to be proposed for screening and diagnosing GDM.

Adult↗
PubMed2006

Nucleotide-binding oligomerization domain-like receptors: intracellular pattern recognition molecules for pathogen detection and host defense.

The nucleotide binding oligomerization domain-like receptor (NLR) family of pattern recognition molecules is involved in a diverse array of processes required for host immune responses against invading pathogens. Unlike TLRs that mediate extracellular recognition of microbes, several NLRs sense pathogens in the cytosol and upon activation induce host defense signaling pathways. Although TLRs and NLRs differ in their mode of pathogen recognition and function, they share similar domains for microbial sensing and cooperate to elicit immune responses against the pathogen. Genetic variation in several NLR genes is associated with the development of inflammatory disorders or increased susceptibility to microbial infection. Further understanding of NLRs should provide critical insight into the mechanisms of host defense and the pathogenesis of inflammatory diseases.

Adaptor Proteins, Signal Transducing↗
PubMed2003

A membrane assisted hybrid bioreactor for the post treatment of an anaerobic effluent from a fish canning factory.

An innovative membrane assisted hybrid bioreactor was used to treat a mixture of two streams produced in a fish canning factory: a highly loaded stream that had previously been treated in an anaerobic contact reactor, and a second stream with a relatively low COD and N concentration. Experiments were carried out during two experimental stages: an aerobic stage, which is focused in the study on the aerobic oxidation of ammonia and COD and a nitrification-denitrification stage in which the study was mainly focused on the removal of nitrogen. Results of the aerobic period pointed out that it was feasible to achieve ammonia and COD removals of around 99% at OLR of 6.5 kg COD/m3 x d and NLR of 1.8 kg N-NH4+/m3 x d. Specific nitrifying activities of up to 0.78 g N-NH4+/g protein x d and 0.25 g N-NH4+/g VSS x d, were recorded for the attached and suspended biomass, respectively. Around 50-60% of the nitrifying capacity of the reactor was a result of the nitrifying capacity of the biofilm. During the nitrification-denitrification stage 76% of nitrogen removal was attained at an NLR of 0.8 kg N-NH4+/m3 x d. The biofilm nitrifying activity was not affected by the operating conditions of the system, as a result of the preferential consumption of COD by suspended biomass in the reactor. Thus, the combination of a hybrid system, with both suspended and attached biomass, and an ultrafiltration membrane module might be an alternative for treating wastewaters in compact biological systems. The intrinsic characteristics of the system made it feasible to operate at high OLR without problems related with the settling properties of the sludge or the drop in the nitrogen conversion. There were no solids in the effluent as a result of the use of the membrane filtration module.

Bacteria, Anaerobic↗
PubMed2006

TLRs, NLRs and RLRs: a trinity of pathogen sensors that co-operate in innate immunity.

Significant advances in our understanding of innate immunity have been made following the identification of three families of pathogen sensors: Toll-like receptors (TLRs), NOD-like receptors (NLRs) and RIG-I-like receptors (RLRs). Members of the TLR family recognize bacteria, viruses, fungi and protozoa; NLRs with known functions detect bacteria, and RLRs are anti-viral. It is likely that interplay between these families ensures the efficient co-ordination of innate immune responses, through either synergistic or co-operative signalling. Important interactions occur between TLRs and certain NLRs for inducing the pro-inflammatory cytokine interleukin (IL)-1beta. TLRs induce pro-IL-1beta production and prime NLR-containing multi-protein complexes, termed "inflammasomes", to respond to bacterial products and products of damaged cells. This results in caspase-1 activation and the subsequent processing of pro-IL-1beta to its active form. In this article, we hypothesize that during the first phase of the host response to infection, an important interplay occurs between these families, providing a substantial combinatorial repertoire in innate immunity.

Adaptor Proteins, Signal Transducing↗
PubMed2026

Blood-based proteomic profiling reveals context-dependent changes in BCL2-associated signaling during taxane therapy in breast cancer patients.

The quality of life for many cancer survivors is compromised due to severe, long-lasting side effects of chemotherapy. As part of a pilot, prospective, non-interventional study to examine the side effects of chemotherapy in breast cancer patients, we examined the change in protein expression in blood collected from patients before and after treatment with taxanes for 12&#x2009;weeks. Protein expression was measured with reverse phase proteomic arrays (RPPA), which revealed divergent changes in apoptosis, senescence, and calcium signaling-related proteins depending on treatment setting (neoadjuvant vs. adjuvant). The largest change identified was BCL2 (B-cell lymphoma 2), a founding member of the BCL2 family of proteins that regulate apoptosis. Other proteins regulated by BCL2, including RB1 (retinoblastoma protein 1) and NLRP3 (NLR family pyrin domain containing 3) changed significantly over the course of treatment. These differences are consistent with intracellular calcium signaling dysregulation and activation of stress-response pathways that overlap with senescent-associated secretory phenotype (SASP)-like signaling, which has been implicated in cancer recurrence. To contextualize these observations, we generated Kaplan-Meier survival curves using publicly available proteomics data from The Cancer Proteome Atlas (TCPA). This work aims to demonstrate how blood-based proteomics can serve as a non-invasive method to monitor systemic physiological shifts during cancer therapy, offering a framework for generating hypotheses about chemotherapy timing and long-term outcomes.

Humans↗
PubMed2006

Real-life applications of the MULVADO software package for processing DOSY NMR data.

MULVADO is a newly developed software package for DOSY NMR data processing, based on multivariate curve resolution (MCR), one of the principal multivariate methods for processing DOSY data. This paper will evaluate this software package by using real-life data of materials used in the printing industry: two data sets from the same ink sample but of different quality. Also a sample of an organic photoconductor and a toner sample are analysed. Compared with the routine DOSY output from monoexponential fitting, one of the single channel algorithms in the commercial Bruker software, MULVADO provides several advantages. The key advantage of MCR is that it overcomes the fluctuation problem (non-consistent diffusion coefficient of the same component). The combination of non-linear regression (NLR) and MCR can yield more accurate resolution of a complex mixture. In addition, the data pre-processing techniques in MULVADO minimise the negative effects of experimental artefacts on the results of the data. In this paper, the challenges for analysing polymer samples and other more complex samples will also be discussed.

Magnetic Resonance Spectroscopy↗
PubMed1988

Granulocyte progenitors (CFU-D) in neutrophilic leukemoid reaction are hyporesponsive to macrophage-induced inhibition.

The responsiveness of marrow granulocyte progenitors (CFU-D) to macrophage-derived stimulatory and inhibitory factors has been studied using diffusion chamber technique in 12 patients with neutrophilic leukemoid reaction (with granulocyte count in the range between 10-40 G/l) and ten healthy subjects. CFU-D from patients with neutrophilic leukemoid reaction (NLR) revealed a normal reactivity to colony-stimulating activity, whereas they were hyporesponsive to macrophage-derived indomethacin-sensitive inhibition. This altered response was correlated both with the concentration of granulocyte progenitors in the S phase and with blood neutrophilic leukocytosis. In patients with higher granulocyte count and increased concentration of CFU-D during active DNA synthesis a more pronounced hyporesponsiveness of granulocyte progenitors to macrophage-induced inhibition has been found.

Animals↗
PubMed2002

Latex allergy.

The prevalence of IgE mediated natural latex rubber allergy is estimated to be < 1% in the general population, < 17% in medical personnel and approximately 0% in children with spina bifida. We review the definition, diagnosis, prevention, and treatment of NLR allergy.

Diagnosis, Differential↗
PubMed1979

Brain stem afferents to visual cortical areas 17, 18 and 19 in the cat, demonstrated by horseradish peroxidase.

The origins of brain stem projections to the cytoarchitectonically different areas 17, 18 and 19 of the cat's visual cortex were studied following small horseradish peroxidase (HRP) injections. Labelled cells were counted in a dopaminergic nucleus (nucleus linearis rostralis (NLR)), other catecholaminergic nuclei (locus coeruleus, parabrachialis nuclei and nucleus subcoeruleus) and serotonergic nuclei (nucleus raphe dorsalis (NRD) and nucleus centralis superior (NCS)). Area 18 receives afferents from more locus coeruleus cells than either of areas 17 or 19. The number of labelled cells in the catecholaminergic nuclei far exceeds that in the serotonergic nuclei.

Afferent Pathways↗
PubMed2006

Crystal structure of the Nod1 caspase activation and recruitment domain.

Nod-like receptors (NLRs), Nod1 and Nod2 are cytosolic detectors of pathogen-associated molecular patterns (PAMPs). Nod1 is a three-domain protein, consisting of a caspase activation and recruitment domain (CARD), a nucleotide-binding oligomerization domain (NOD), and a leucine-rich repeat domain (LRR). The binding of PAMPs to the LRR results in the activation of signaling through homophilic CARD-CARD interactions. Several CARD structures have been determined, including a recent NMR structure of Nod1 CARD. In contrast to the reported NMR structure, the crystal structure reported here is a dimer, where the sixth helix is swapped between two monomers. While the overall structure is very similar to the known CARD structures, this is the first report of a homodimeric CARD structure. The ability of the CARD to exist in monomeric and dimeric forms suggests another level of regulation in the activation of NLR proteins.

Binding Sites↗