LocateP: Genome-scale subcellular-location predictor for bacterial proteins

Contains fulltext : 69477.pdf ( ) (Open Access)BACKGROUND: In the past decades, various protein subcellular-location (SCL) predictors have been developed. Most of these predictors, like TMHMM 2.0, SignalP 3.0, PrediSi and Phobius, aim at the identification of one or a few SCLs, whereas others such as CELLO and Psortb.v.2.0 aim at a broader classification. Although these tools and pipelines can achieve a high precision in the accurate prediction of signal peptides and transmembrane helices, they have a much lower accuracy when other sequence characteristics are concerned. For instance, it proved notoriously difficult to identify the fate of proteins carrying a putative type I signal peptidase (SPIase) cleavage site, as many of those proteins are retained in the cell membrane as N-terminally anchored membrane proteins. Moreover, most of the SCL classifiers are based on the classification of the Swiss-Prot database and consequently inherited the inconsistency of that SCL classification. As accurate and detailed SCL prediction on a genome scale is highly desired by experimental researchers, we decided to construct a new SCL prediction pipeline: LocateP. RESULTS: LocateP combines many of the existing high-precision SCL identifiers with our own newly developed identifiers for specific SCLs. The LocateP pipeline was designed such that it mimics protein targeting and secretion processes. It distinguishes 7 different SCLs within Gram-positive bacteria: intracellular, multi-transmembrane, N-terminally membrane anchored, C-terminally membrane anchored, lipid-anchored, LPxTG-type cell-wall anchored, and secreted/released proteins. Moreover, it distinguishes pathways for Sec- or Tat-dependent secretion and alternative secretion of bacteriocin-like proteins. The pipeline was tested on data sets extracted from literature, including experimental proteomics studies. The tests showed that LocateP performs as well as, or even slightly better than other SCL predictors for some locations and outperforms current tools especially where the N-terminally anchored and the SPIase-cleaved secreted proteins are concerned. Overall, the accuracy of LocateP was always higher than 90%. LocateP was then used to predict the SCLs of all proteins encoded by completed Gram-positive bacterial genomes. The results are stored in the database LocateP-DB http://www.cmbi.ru.nl/locatep-db1. CONCLUSION: LocateP is by far the most accurate and detailed protein SCL predictor for Gram-positive bacteria currently available

Trait mindfulness scores are related to trajectories of depressive symptoms during pregnancy

Background Exploring possible protective factors against antenatal depression is important since antenatal depression is common and affects both mother and child. The person characteristic trait mindfulness may be such a protective factor. Because of the high variability in depressive symptoms over time, we aimed to assess the association between trait mindfulness and trajectories of depressive symptoms during pregnancy. Methods A subsample of 762 women participating in the HAPPY study completed the Three Facet Mindfulness Questionnaire-Short Form at 22 weeks of pregnancy. Possible different trajectories of Edinburgh Postnatal Depression Scale (EPDS) scores, assessed at each pregnancy trimester, were explored with growth mixture modeling. Results Three EPDS trajectories (classes) were identified: low stable symptom scores (N = 607, 79.7%), decreasing symptom scores (N = 74, 9.7%) and increasing symptom scores (N = 81, 10.6%). Compared to belonging to the low stable class (reference), women with higher scores on the trait mindfulness facets ‘acting with awareness’ and ‘non-judging’ were less likely to belong to the decreasing class (OR = 0.81, 95% CI [0.73, 0.90] and OR = 0.77, 95% CI [0.70, 0.84]) and increasing class (OR = 0.88, 95% CI [0.80, 0.97] and OR = 0.72, 95% CI [0.65, 0.79]). Women with higher scores on ‘non-reacting’ were less likely to belong to the increasing class (OR = 0.89, 95% CI [0.82, 0.97]), but not the decreasing class (OR = 0.96, 95% CI [0.87, 1.04]). All analyses were adjusted for confounders. Conclusions Characteristics of trait mindfulness predicted low stable levels of depressive symptoms throughout pregnancy. Mindfulness-based programs may be beneficial for pregnant women as a strategy to alleviate depression risks

Reversal of typical multidrug resistance by cyclosporin and its non-immunosuppressive analogue SDZ PSC 833 in Chinese hamster ovary cells expressing the mdr1 phenotype

Summary The new non-immunosuppressive cyclosporin derivative SDZ PSC 833 (PSC) is a potent agent used to overcome typical multidrug resistance (MDR) associated with overexpression of themdr1 gene encoding for a P-170 glycoprotein. In the present study, the efficacy of PSC as compared with cyclosporin was determined in Chinese hamster ovary cell lines exhibiting different levels of resistance to colchicine (0, 0.1, 0.2 and 10 μg/ml, respectively). Low concentrations of PSC (8.2nm) increased the cytotoxicity of colchicine in cell lines expressing low levels of drug resistance. The concentration resulting in 50% cell survival (LC50 value) found for colchicine alone or in combination with PSC in the CHO-A3 cell line that was resistant to 100 ng colchicine/ml decreased from >500 to 200 ng/ml at 8.2nm PSC and to 500 ng/ml for colchicine alone to 500 ng/ml for colchicine used in combination with 8.2nm PSC and to <100 ng/ml for colchicine combined with 82 or 820nm PSC. At a concentration of 82nm PSC, the maximal effect in MDR reversal was observed in the cell lines exhibiting moderate resistance. In the highly resistant cell line, PSC (820nm) also reversed colchicine resistance. In drug-accumulation experiments, we obtained a 4-fold increase in intracellular doxorubicin accumulation using 820nm PSC. A comparison of PSC with cyclosporin revealed that a cyclosporin concentration 20-fold that of PSC was required to obtain the same sensitising effect. On the basis of these data, it may be concluded that PSC is a most promising chemosensitiser

High-Level Heat Resistance of Spores of Bacillus amyloliquefaciens and Bacillus licheniformis Results from the Presence of a spoVA Operon in a Tn1546 Transposon

Bacterial endospore formers can produce spores that are resistant to many food processing conditions, including heat. Some spores may survive heating processes aimed at production of commercially sterile foods. Recently, it was shown that a spoVA operon, designated spoVA(2mob), present on a Tn1546 transposon in Bacillus subtilis, leads to profoundly increased wet heat resistance of B. subtilis spores. Such Tn1546 transposon elements including the spoVA(2mob) operon were also found in several strains of Bacillus amyloliquefaciens and Bacillus licheniformis, and these strains were shown to produce spores with significantly higher resistances to wet heat than their counterparts lacking this transposon. In this study, the locations and compositions of Tn1546 transposons encompassing the spoVA(2mob) operons in B. amyloliquefaciens and B. licheniformis were analyzed. Introduction of these spoVA(2mob) operons into B. subtilis 168 (producing spores that are not highly heat resistant) rendered mutant 168 strains that produced high-level heat resistant spores, demonstrating that these elements in B. amyloliquefaciens and B. licheniformis are responsible for high level heat resistance of spores. Assessment of growth of the nine strains of each species between 5.2°C and 57.7°C showed some differences between strains, especially at lower temperatures, but all strains were able to grow at 57.7°C. Strains of B. amyloliquefaciens and B. licheniformis that contain the Tn1546 elements (and produce high-level heat resistant spores) grew at temperatures similar to those of their Tn1546-negative counterparts that produce low-level heat resistant spores. The findings presented in this study allow for detection of B. amyloliquefaciens and B. licheniformis strains that produce highly heat resistant spores in the food chain

Online mindfulness-based intervention for women with pregnancy distress:Design of a randomized controlled trial

Background:  Psychological distress during pregnancy is common: up to 20% of the childbearing women experience symptoms of depression and anxiety. Apart from the adverse effects on the woman herself, pregnancy distress can negatively affect pregnancy outcomes, infant health, postpartum mother-child interaction and child development. Therefore, the development of interventions that reduce pregnancy distress is very important. Mindfulness-based interventions (MBIs) show promising positive effects on pregnancy distress, but there is a need for randomized controlled trials with sufficient power. Trials on online MBIs, which are readily accessible and not expensive, also show positive effects on stress reduction in non-pregnant populations. Moreover, specific working mechanisms of MBIs remain unclear. The aim of the current study is to test the effectiveness of an online MBI in pregnant women with pregnancy distress, as well as exploring potential working mechanisms. Methods:  The current study is a randomized controlled trial with repeated measures. Consenting women with elevated levels of pregnancy distress will be randomized into an intervention group (MBI) or control group (care as usual) around 12 weeks of pregnancy, with an intended sample size of 103 women in each group. The primary outcome, pregnancy distress, will be assessed via questionnaires at baseline, halfway through the intervention and post intervention in both intervention and control group, and after 8 weeks follow-up in the intervention group. Secondary outcomes are mindfulness skills, rumination and self-compassion, which are also seen as potential working mechanisms, and will be assessed via questionnaires before intervention, halfway through the intervention, post intervention and after 8 weeks follow-up in the intervention group. Tertiary outcome variables are obstetric data and will be collected from the obstetric records for both intervention and control group. Analyses will be based on the intention-to-treat principle. Multilevel regression models for repeated measures (mixed models) will be used to evaluate changes in primary and secondary outcome variables. Tertiary outcomes will be compared between groups using independent t-tests and Chi Square analyses. Discussion:  The trial is expected to increase knowledge about the effectiveness of online MBIs during pregnancy in women with pregnancy distress and to evaluate potential working mechanisms.

Measuring Mitochondrial Oxygen Tension during Red Blood Cell Transfusion in Chronic Anemia Patients:A Pilot Study

In light of the associated risks, the question has been raised whether the decision to give a blood transfusion should solely be based on the hemoglobin level. As mitochondria are the final destination of oxygen transport, mitochondrial parameters are suggested to be of added value. The aims of this pilot study were to investigate the effect of a red blood cell transfusion on mitochondrial oxygenation as measured by the COMET device in chronic anemia patients and to explore the clinical usability of the COMET monitor in blood transfusion treatments, especially the feasibility of performing measurements in an outpatient setting. To correct the effect of volume load on mitochondrial oxygenation, a red blood cell transfusion and a saline infusion were given in random order. In total, 21 patients were included, and this resulted in 31 observations. If patients participated twice, the order of infusion was reversed. In both the measurements wherein a blood transfusion was given first and wherein 500 mL of 0.9% saline was given first, the median mitochondrial oxygen tension decreased after red blood cell transfusion. The results of this study have strengthened the need for further research into the effect of blood transfusion tissue oxygenation and the potential role of mitochondrial parameters herein.</p

A preliminary study of telemedicine for patients with hepatic glycogen storage disease and their healthcare providers:from bedside to home site monitoring

BackgroundThe purpose of this project was to develop a telemedicine platform that supports home site monitoring and integrates biochemical, physiological, and dietary parameters for individual patients with hepatic glycogen storage disease (GSD). Methods and resultsThe GSD communication platform (GCP) was designed with input from software developers, GSD patients, researchers, and healthcare providers. In phase 1, prototyping and software design of the GCP has occurred. The GCP was composed of a GSD App for patients and a GSD clinical dashboard for healthcare providers. In phase 2, the GCP was tested by retrospective patient data entry. The following software functionalities were included (a) dietary registration and prescription module, (b) emergency protocol module, and (c) data import functions for continuous glucose monitor devices and activity wearables. In phase 3, the GSD App was implemented in a pilot study of eight patients with GSD Ia (n=3), GSD IIIa (n=1), and GSD IX (n=4). Usability was measured by the system usability scale (SUS). The mean SUS score was 64/100 [range: 38-93]. ConclusionsThis report describes the design, development, and validation process of a telemedicine platform for patients with hepatic GSD. The GCP can facilitate home site monitoring and data exchange between patients with hepatic GSD and healthcare providers under varying circumstances. In the future, the GCP may support cross-border healthcare, second opinion processes and clinical trials, and could possibly also be adapted for other diseases for which a medical diet is the cornerstone

COVID-19-associated immune thrombocytopenia

Thrombocytopenia is a risk factor for increased morbidity and mortality in patients with the new severe acute respiratory syndrome corona virus, SARS-CoV-2 infection (COVID-19 infection).1 Thrombocytopenia in COVID-19 patients may be caused by disseminated intravascular coagulation (DIC), sepsis or drug-induced. Recently a single case report suggested immune thrombocytopenia (ITP) may be associated with COVID-19 infection.2 ITP is a rare autoimmune disease characterized by a platelet count < 100x109/L, leading to an increased bleeding risk.3 Several risk factors have been described for ITP including environmental (e.g. infection, malignancy and drugs) and genetic predisposition.4 We report here the first case series of three patients with ITP associated with COVID-19 infection

Tyrosine phosphorylation profiling in FGF-2 stimulated human embryonic stem cells

10.1371/journal.pone.0017538PLoS ONE63