AliasServer: a web server to handle multiple aliases used to refer to proteins

SUMMARY: AliasServer provides services that facilitate the assembly of data or datasets that make use of different identifiers for refering to the same protein. This resource relies on a database which contains, for a given organism, a non-redundant list of protein sequences associated with a set of aliases. AVAILABILITY: AliasServer is available as an interactive Web server at http://cbi.labri.fr/outils/alias/ and as a web service using a SOAP interface. The complete tool, including sources and data, is available for local installations upon request. SUPPLEMENTARY INFORMATION: Technical documentation is available at http://cbi.labri.fr/outils/alias/asdoc.pdf     

Application of actinomycetes to soil to ameliorate water repellency

AIMS: The aim of this study was to develop a novel isolation technique using a mixture of Bacillus and Streptomyces phages to selectively isolate wax-utilizing non-streptomycete actinomycetes effective in ameliorating water repellency in a problem soil. METHODS AND RESULTS: Phages added to a soil suspension reduced the dominance of Bacillus and Streptomyces isolates and significantly increased the number of non-streptomycete actinomycetes on isolation plates. Promising isolates, grown on a medium containing beeswax as sole carbon source, were selected for application to water repellent soil. Their addition significantly reduced water repellency. CONCLUSIONS: Phage application significantly increased the isolation of non-streptomycete actinomycetes. Wax-utilizing isolates were found to significantly reduce water repellency in a problem soil. SIGNIFICANCE AND IMPACT OF THE STUDY: The phage technique can be used for the routine isolation of non-streptomycete actinomycetes. Beeswax medium can be used to selectively isolate wax-utilizing micro-organisms with the potential to ameliorate water repellency in soil.     

Exposure to tobacco smoke and low birth weight: from epidemiology to metabolomics

Introduction: The exposure to tobacco smoke during pregnancy is one of the leading causes of perinatal adverse outcomes such as stillbirth, intrauterine growth restriction (IUGR), and low birth weight, but the underlying biological mechanisms are still unclear. The incidence of this phenomenon maybe largely underestimated since the evaluation is made mainly by self-assessment questionnaires rather than measuring nicotine metabolites (such as cotinine) in biological fluids. In this context metabolomics may be useful to assess the actual number of pregnant women and to highlight the pathophysiological mechanisms that lead to the abovementioned adverse outcomes.

Areas covered: The aims of this review are to analyze the literature and the application of the omics sciences, such as genomics and metabolomics concerning the negative effects of smoking during pregnancy in order to give a comprehensive picture of all the study made so far and to point out the potential of metabolomics as an investigative, predictive, and diagnostic tool.

Expert commentary: Metabolomics in recent years has proved an excellent tool to try to understand the problems in perinatal medicine. With the increase in the number of studies we are convinced that it can be a useful instrument of investigation in this field.     

Galectins control MTOR and AMPK in response to lysosomal damage to induce autophagy

The Ser/Thr protein kinase MTOR (mechanistic target of rapamycin kinase) regulates cellular metabolism and controls macroautophagy/autophagy. Autophagy has both metabolic and quality control functions, including recycling nutrients at times of starvation and removing dysfunctional intracellular organelles. Lysosomal damage is one of the strongest inducers of autophagy, and yet mechanisms of its activation in response to lysosomal membrane damage are not fully understood. Our recent study has uncovered a new signal transduction system based on cytosolic galectins that elicits autophagy by controlling master regulators of metabolism and autophagy, MTOR and AMPK, in response to lysosomal damage. Thus, intracellular galectins are not, as previously thought, passive tags recognizing damage to guide selective autophagy receptors, but control the activation state of AMPK and MTOR in response to endomembrane damage.

Abbreviations: MTOR: mechanistic target of rapamycin kinase; AMPK: AMP-activated protein kinase / Protein Kinase AMP-Activated; SLC38A9: Solute Carrier Family 38 Member 9; APEX2: engineered ascorbate peroxidase 2; RRAGA/B: Ras Related GTP Binding A or B; LAMTOR1: Late Endosomal/Lysosomal Adaptor, MAPK and MTOR Activator 1; LGALS8: Lectin, Galactoside-Binding, Soluble, 8 / Galectin 8; LGALS9: Lectin, Galactoside-Binding, Soluble, 9 / Galectin 9; TAK1: TGF-Beta Activated Kinase 1 / Mitogen-Activated Protein Kinase Kinase Kinase 7 (MAP3K7); STK11/LKB1: Serine/Threonine Kinase 11 / Liver Kinase B1; ULK1: Unc-51 Like Autophagy Activating Kinase 1.     

Cross-resistance to antibiotics of Escherichia coli adapted to benzalkonium chloride or exposed to stress-inducers

AIMS: To study the effects of adaptation and stress on the resistance to benzalkonium chloride (BC) and cross-resistance to antibiotics in Escherichia coli. METHODS AND RESULTS: Precultivation of E. coli ATCC 11775 and E. coli DSM 682 in the presence of subinhibitory concentrations of BC or stress inducers (salicylate, chenodeoxycholate and methyl viologen) resulted in higher minimum inhibitory concentration (MIC) of BC and chloramphenicol (CHL). Adaptation to growth in sixfold of the initial MIC of BC resulted in stable BC resistance and enhanced tolerance to several antibiotics and ethidium bromide (EtBr). The MIC of CHL increased more than 10-fold for both strains. Enhanced efflux of EtBr in adapted E. coli ATCC 11775 indicated that the observed resistance was due to efflux. Changes in outer membrane protein profiles were detected in the BC-adapted cells. There were no indications of lower membrane permeability to BC. CONCLUSIONS: Induction of stress response or gradual adaptation to BC or CHL results in acquired cross-tolerance between BC and antibiotics in E. coli. Enhanced efflux was one of the observed differences in adapted cells. SIGNIFICANCE AND IMPACT OF THE STUDY: Provided not taking due precautions, extensive use of disinfectants could lead to emergence of antibiotic-resistant isolates.     

Correction to: Glyconanoparticles as tools to prevent antimicrobial resistance

Glycoconjugate Journal - A Correction to this paper has been published: https://doi.org/10.1007/s10719-021-09995-7     

Erratum to

Erratum to:

Generation of antisera to purified prions in lipid rafts

Volume 4, Issue 2

April/May/June 2010

Pages 94 - 104

DOI: 10.4161/pri.4.2.12622

Robert Hnasko, Ana V. Serban, George Carlson, Stanley Prusiner and Larry H. Stanker     

Review of biomarkers to assess the effects of switching from cigarettes to modified risk tobacco products

Context: One approach to reducing the harm caused by cigarette smoking, at both individual and population level, is to develop, assess and commercialize modified risk alternatives that adult smokers can switch to. Studies to demonstrate the exposure and risk reduction potential of such products generally involve the measuring of biomarkers, of both exposure and effect, sampled in various biological matrices.

Objective: In this review, we detail the pros and cons for using several biomarkers as indicators of effects of changing from conventional cigarettes to modified risk products.

Materials and methods: English language publications between 2008 and 2017 were retrieved from PubMed using the same search criteria for each of the 25 assessed biomarkers. Nine exclusion criteria were applied to exclude non-relevant publications.

Results: A total of 8876 articles were retrieved (of which 7476 were excluded according to the exclusion criteria). The literature indicates that not all assessed biomarkers return to baseline levels following smoking cessation during the study periods but that nine had potential for use in medium to long-term studies.

Discussion and conclusion: In clinical studies, it is important to choose biomarkers that show the biological effect of cessation within the duration of the study.     

Soil C:N:P stoichiometry responds to vegetation change from grassland to woodland

Woody encroachment has been a major land cover change in dryland ecosystems during the past century. While numerous studies have demonstrated strong effects of woody encroachment on soil carbon (C), nitrogen (N), and phosphorus (P) storage, far less is known about the plasticity of soil C:N:P stoichiometry in response to woody encroachment. We assessed landscape-scale patterns of spatial heterogeneity in soil C:N:P ratios throughout a 1.2 m soil profile in a region where grassland is being replaced by a diverse assemblage of subtropical woody plants dominated by Prosopis glandulosa, an N₂-fixing tree. Woody species had leaf and fine root C:N:P ratios significantly different from grasses. Variation in soil C:N ratios in both horizontal and vertical planes was remarkably smaller than that of soil N:P and C:P ratios. Spatial patterns of soil C:N ratio throughout the profile were not strongly related to vegetation cover. In contrast, spatial patterns of soil N:P and C:P ratios displayed a strong resemblance to that of vegetation cover throughout the soil profile. Within the uppermost soil layer (0–5 cm), soil N:P and C:P ratios were higher underneath woody patches while lower within the grassland; however, this pattern was reversed in subsurface soils (15–120 cm). These results indicate a complex response of soil C:N:P stoichiometry to vegetation change, which could have important implications for understanding C, N, and P interactions and nutrient limitations in dryland ecosystems.     

Inverse problem approach to regularized regression models with application to predicting recovery after stroke

Regression modelling is a powerful statistical tool often used in biomedical and clinical research. It could be formulated as an inverse problem that measures the discrepancy between the target outcome and the data produced by representation of the modelled predictors. This approach could simultaneously perform variable selection and coefficient estimation. We focus particularly on a linear regression issue, , where is the parameter of interest and its components are the regression coefficients. The inverse problem finds an estimate for the parameter , which is mapped by the linear operator to the observed outcome data . This problem could be conveyed by finding a solution in the affine subspace . However, in the presence of collinearity, high-dimensional data and high conditioning number of the related covariance matrix, the solution may not be unique, so the introduction of prior information to reduce the subset and regularize the inverse problem is needed. Informed by Huber's robust statistics framework, we propose an optimal regularizer to the regression problem. We compare results of the proposed method and other penalized regression regularization methods: ridge, lasso, adaptive-lasso and elastic-net under different strong hypothesis such as high conditioning number of the covariance matrix and high error amplitude, on both simulated and real data from the South London Stroke Register. The proposed approach can be extended to mixed regression models. Our inverse problem framework coupled with robust statistics methodology offer new insights in statistical regression and learning. It could open a new research development for model fitting and learning.     

Drawing Shadows to Stone

Drawing Shadows to Stone: Photographing North Pacific Peoples (1897-1902). American Museum of Natural History, New York, New York, November 14, 1997- March 1, 1998.
Drawing Shadows to Stone: The Photography of the Jesup North Pacific Expedition, 1897-1902. Laurel Kendall. Barbara Mathé. and Thomas Ross Miller. with Stanley A. Freed. Ruth S. Freed. and Laila Williamson. New York: American Museum of Natural History, 1997, and Seattle: University of Washington Press, 1997. 112 pp., 97 illust.     

Tissue-based assay for ornithine decarboxylase to identify patients likely to respond to difluoromethylornithine.

In a previous publication, we showed that a clinical trial of DL-alpha-difluoromethyl ornithine (DFMO), in combination with PCV (procarbazine, CCNU, vincristine) increased survival of patients with anaplastic gliomas (WHO III) but not glioblastoma multiforme (WHO IV). We believe that treatment outcome (survival) is inversely related to tumor ornithine decarboxylase (ODC) levels. To prove this, we needed to develop an assay to quantify ODC levels in formalin-fixed tumor tissues, which would enable a retrospective study of tumor biopsy specimens from the landmark clinical trial. We developed an assay using a specific polyclonal antibody coupled to an Alexa fluorescent dye. Transgenic MHC-ODC mice with differing levels of ODC in heart muscle were used to establish the relationship between mean gray-scale intensity and enzymatic ODC activity. We found a direct relationship between mean gray-scale intensity of the ODC antibody coupled to Alexa 647 dye and enzymatic activity. Preliminary analysis of a human glioma tissue array shows that tumor-specific variations in levels of ODC can be semiquantitated. We show that mean gray-scale intensity of astrocytoma:glioblastoma is 1:6 and of anaplastic astrocytoma:glioblastoma is 1:4. We also compared the intensity of antibody to Ki67 coupled with phycoerythrin simultaneously in cells but failed to see a relationship that crossed histologies. We conclude that we can measure levels of ODC in formalin-fixed tumor tissue using an antibody to ODC coupled to Alexa 647 dye, and this will enable us to conduct a future study to correlate survival of patients with gliomas of different histologies treated with DFMO to tumor ODC levels.     

How to have an effective academic sabbatical: recommendations for what to do and what to avoid

Sabbaticals - i.e., academic sabbaticals, sabbatical leaves, sabbatical semesters - provide faculty members with a unique opportunity to engage in scholarly projects. Ranging from a year to shorter periods, these time windows - usually free of rigid day-to-day obligations - can be powerful means to reflect on past and present projects, to renew perspectives, and to receive fresh impetus for both your research and teaching. When reading the literature on sabbaticals, it is somewhat surprising that relatively small amounts of space are devoted to this important part of academic life. Here we provide practical recommendations [1-4: pre-sabbatical; 5-8: intra-sabbatical; 9-10: post-sabbatical] for making your sabbatical a satisfying endeavor.     

Application of proteomics to graft-versus-host disease: from biomarker discovery to potential clinical applications

Introduction: Graft-versus-host disease (GVHD) is a frequent and potentially life-threatening complication that occurs in many patients who undergo hematopoietic stem cell transplantation. In an effort to develop blood and tissue-based biochemical assays for GVHD diagnosis, high throughput proteomic platforms have been widely utilized for the identification and validation of disease biomarkers for both acute and chronic GVHD.

Areas covered: This article reviews biomarker research findings on acute and chronic GVHD ascertained by studying peripheral blood, urine and saliva that gives biological information on systemic or localized disease. While the primary focus of GVHD biomarker discovery has been on identification and validation of prognostic and predictive biomarkers that might allow stratification of disease risk, molecular biomarkers that might aid patient diagnosis and/or response to treatment have also been reported.

Expert commentary: Unbiased as well as targeted proteomic studies of acute and chronic GVHD have identified some distinguishing features of the two diseases especially the role of certain immune cell populations. A combination of patient risk stratification using panels of biomarkers and the application of novel targeted therapeutics should help to reduce the burden of GVHD, and hence improve the quality of life for patients following hematopoietic stem cell transplantation.     

The Arabidopsis root stele transporter NPF2.3 contributes to nitrate translocation to shoots under salt stress

In most plants, constitutes the major source of nitrogen, and its assimilation into amino acids is mainly achieved in shoots. Furthermore, recent reports have revealed that reduction of translocation from roots to shoots is involved in plant acclimation to abiotic stress. NPF2.3, a member of the NAXT (nitrate excretion transporter) sub‐group of the NRT1/PTR family (NPF) from Arabidopsis, is expressed in root pericycle cells, where it is targeted to the plasma membrane. Transport assays using NPF2.3‐enriched Lactococcus lactis membranes showed that this protein is endowed with transport activity, displaying a strong selectivity for against Cl^?. In response to salt stress, translocation to shoots is reduced, at least partly because expression of the root stele transporter gene NPF7.3 is decreased. In contrast, NPF2.3 expression was maintained under these conditions. A loss‐of‐function mutation in NPF2.3 resulted in decreased root‐to‐shoot translocation and reduced shoot content in plants grown under salt stress. Also, the mutant displayed impaired shoot biomass production when plants were grown under mild salt stress. These mutant phenotypes were dependent on the presence of Na⁺ in the external medium. Our data indicate that NPF2.3 is a constitutively expressed transporter whose contribution to translocation to the shoots is quantitatively and physiologically significant under salinity.     

Modelling the work to be done by Escherichia coli to adapt to sudden temperature upshifts

AIMS: This paper studies and models the effect of the amplitude of a sudden temperature upshift DeltaT on the adaptation period of Escherichia coli, in terms of the work to be done by the cells during the subsequent lag phase (i.e., the product of growth rate mumax and lag phase duration lambda). METHODS AND RESULTS: Experimental data are obtained from bioreactor experiments with E. coli K12 MG1655. At a predetermined time instant during the exponential growth phase, a sudden temperature upshift is applied (no other environmental changes take place). The length of the (possibly) induced lag phase and the specific growth rate after the shift are quantified with the growth model of Baranyi and Roberts (Int J Food Microbiol 23, 1994, 277). Different models to describe the evolution of the product lambda x mumax as a function of the amplitude of the temperature shift are statistically compared. CONCLUSIONS: The evolution of lambda x mumax is influenced by the amplitude of the temperature shift DeltaT and by the normal physiological temperature range. As some cut-off is observed, the linear model with translation is preferred to describe this evolution. SIGNIFICANCE AND IMPACT OF THE STUDY: This work contributes to the characterization of microbial lag phenomena, in this case for E. coli K12 MG1655, in view of accurate predictive model building.     

抗t-PA抗体水平和血栓的相关性研究

目的:研究自身免疫性疾病病人抗t-PA抗体水平和病人血栓形成之间的关系。方法:用酶联免疫吸附法(ELISA)检测原发性抗磷脂综合症和红斑狼疮患者(32例狼疮样抗凝物阳性,32例狼疮样抗凝物阴性)与40例健康对照的IgG类抗t-pA抗体的水平,用Pearson Chi-Square test的方法分析了病人体内IgG类抗t-PA抗体水平和血栓之间的相关性。结果:本试验研究的病人群体中IgG类抗t-PA抗体阳性的有13(20.3%)个,并且我们的研究表明IgG类抗t-PA抗体阳性和血栓病史显著相关(P=0.04)。结论:原发性抗磷脂综合症和红斑狼疮病人群体中有较高的IgG类抗t-PA抗体水平,它们可能和病人体内血栓的发生有关。     

Ratios of leptin to insulin and adiponectin to endothelin are sex-dependently associated with extent of coronary atherosclerosis

Objective: Noninvasive diagnostics of early stages of coronary artery disease and discrimination between various extents of vascular lesions in patients is an important clinical problem especially considering wide spread use of cholesterol lowering drugs that affect lipid and lipoprotein profiling. The main goal of our study was to evaluate applicability of new combinations of noninvasive biomarkers such as leptin to insulin and adiponectin to endothelin ratios, for detection of early stages of coronary atherosclerosis versus later stages of the disease.

Patients and methods: A number of previously validated serum biomarkers were tested in a group of 500 patients with coronary artery disease and examined for their association with severity of coronary lesion according to Gensini score determined by coronary angiography.

Results: Lowest extent of coronary lesions was associated with significant increase in apoA-I levels and with significantly increased ratios of adiponectin to endothelin and leptin to insulin. In male but not in female patients, adiponectin to endothelin ratio below 7.0 was associated with Gensini score representing early to high coronary lesions (p?=?0.02). In female but not in male patients, leptin to insulin ratio below 3.5 was associated with Gensini score representing early to high coronary lesions (p?=?0.013).

Conclusion: Leptin to insulin and adiponectin to endothelin ratios are novel derived biomarkers useful for noninvasive diagnostics of initial stages of coronary lesions in patients with coronary artery disease.