Insights into the evolution of sialic acid catabolism among bacteria

<p>Abstract</p> <p>Background</p> <p>Sialic acids comprise a family of nine-carbon amino sugars that are prevalent in mucus rich environments. Sialic acids from the human host are used by a number of pathogens as an energy source. Here we explore the evolution of the genes involved in the catabolism of sialic acid.</p> <p>Results</p> <p>The cluster of genes encoding the enzymes <it>N</it>-acetylneuraminate lyase (NanA), epimerase (NanE), and kinase (NanK), necessary for the catabolism of sialic acid (the Nan cluster), are confined 46 bacterial species, 42 of which colonize mammals, 33 as pathogens and 9 as gut commensals. We found a putative sialic acid transporter associated with the Nan cluster in most species. We reconstructed the phylogenetic history of the NanA, NanE, and NanK proteins from the 46 species and compared them to the species tree based on 16S rRNA. Within the NanA phylogeny, Gram-negative and Gram-positive bacteria do not form distinct clades. NanA from <it>Yersinia </it>and <it>Vibrio </it>species was most closely related to the NanA clade from eukaryotes. To examine this further, we reconstructed the phylogeny of all NanA homologues in the databases. In this analysis of 83 NanA sequences, Bacteroidetes, a human commensal group formed a distinct clade with Verrucomicrobia, and branched with the Eukaryotes and the <it>Yersinia/Vibrio </it>clades. We speculate that pathogens such as <it>V. cholerae </it>may have acquired NanA from a commensal aiding their colonization of the human gut. Both the NanE and NanK phylogenies more closely represented the species tree but numerous incidences of incongruence are noted. We confirmed the predicted function of the sialic acid catabolism cluster in members the major intestinal pathogens <it>Salmonella enterica, Vibrio cholerae, V. vulnificus, Yersinia enterocolitica </it>and <it>Y. pestis</it>.</p> <p>Conclusion</p> <p>The Nan cluster among bacteria is confined to human pathogens and commensals conferring them the ability to utilize a ubiquitous carbon source in mucus rich surfaces of the human body. The Nan region shows a mosaic evolution with NanA from <it>Bacteroidetes, Vibrio </it>and <it>Yersinia </it>branching closely together with NanA from eukaryotes.</p

Excision Dynamics of Vibrio Pathogenicity Island-2 from Vibrio Cholerae: Role of a Recombination Directionality Factor VefA

Vibrio Pathogenicity Island-2 (VPI-2) is a 57 kb region present in choleragenic V. cholerae isolates that is required for growth on sialic acid as a sole carbon source. V. cholerae non-O1/O139 pathogenic strains also contain VPI-2, which in addition to sialic acid catabolism genes also encodes a type 3 secretion system in these strains. VPI-2 integrates into chromosome 1 at a tRNA-serine site and encodes an integrase intV2 (VC1758) that belongs to the tyrosine recombinase family. ntV2 is required for VPI-2 excision from chromosome 1, which occurs at very low levels, and formation of a non-replicative circular intermediate

Use of a tyrosine kinase inhibitor as neoadjuvant therapy for non-small cell lung cancer: A case report

We report here a 66-year-old woman diagnosed with bronchioloalveolar carcinoma of the right lung cT4N2M0. The patient was from the Philippines, had never smoked, and tested positive for an EGFR mutation. She received gefitinib as neoadjuvant therapy for two months and displayed a partial response. The tumour was resected by performing a right pneumonectomy. The residual viable tumour accounted for less than 10%. Adjuvant chemotherapy with carboplatin-taxol was administered for four cycles. Fifteen months post-surgery, two brain metastases were found. Gefitinib was prescribed, and one month later complete radiological response was assessed. The patient remains asymptomatic and without visible disease four months later. Controlled randomised trials are needed to clarify the role of these target therapies in the neoadjuvant settin

Plant residue chemical quality modulates the soil microbial response related to decomposition and soil organic carbon and nitrogen stabilization in a rainfed Mediterranean agroecosystem

Soils play a major role in the global carbon cycle and are crucial to the management of climate change. Changes in plant cover derived from different agricultural practices induce variations in the quality of plant residue inputs and in the soil microbial community structure and activity, which may enhance the storage and protection of organic carbon (OC) and nitrogen (N) within aggregates. The aim of this study was to assess how differences in the chemical composition of plant residues in combination with tillage management practices affect the local microbial community activity and structure, and subsequent soil aggregation and OC and N dynamics in an organic, rainfed almond (Prunus dulcis Mill.) orchard. In the laboratory, three types of plant residue (shoots, roots, and the combination of both) coming from different species belonging to each agricultural practice (reduced tillage, reduced tillage plus green manure, reduced tillage plus organic manure, and no-tillage) were mixed with their respective soils and the CO2 released was measured over 243 days at 60% WHC and 28 °C. Water-stable aggregates (including microaggregates within macroaggregates), enzymatic activities related to carbon (dehydrogenase and ß-glucosidase) and N (urease) cycling, and the microbial biomass and community structure through phospholipid fatty acid analysis, were measured at the end of the incubation period. Our results indicate that the chemical composition of plant residues controls the microbial community response, mediating decomposition and the incorporation of OC and N in stable aggregates. Therefore, the incorporation of labile and N-rich plant residues into the soil by reduced tillage is recommended since mixing roots and shoots from green manure increased the formation of free micro-aggregates and improved OC and N stabilization in our semiarid agroecosystem. © 2021 Elsevier LtdThis research was supported with funds from the Fundaci?n S?neca of the Murcia Region (projects 08757/PI/08, EMISEMUR 19350/PI/14 and DECADE 20917/PI/18). Parts of this research were performed within the framework of the project IMPASEC AGL2011-25069 funded by the Spanish Ministerio de Econom?a y Competitividad. Mar?a Almagro was supported by the Juan de la Cierva Program (Grant IJCI-2015-23500) and Antonio Ruiz-Navarro by the Fundaci?n General from the Spanish Research Council (CSIC, ConFuturo Progamme). We thank members of the Soil and Water Conservation Group - Eloisa Garc?a, Inmaculada Montoya, and Mar?a Jos? Espinosa - for helping us with the field and laboratory work, and Gonzalo Barber? for his useful advice with statistical analyses. We also thanks Gonzalo Herv?s, from the Instituto de Ganader?a de Monta?a of the Spanish Research Council, for performing the fiber fraction analysis. We are also grateful to Claire Chenu and two anonymous reviewers for their constructive and insightful comments on earlier versions of the manuscript

Does aquatic exercise improve commonly reported predisposing risk factors to falls within the elderly? A systematic review

Background According to the World Health Organization, the elderly are at the highest risk of injury or death from a fall. Age-related changes in strength, balance and flexibility are degenerative factors that may increase the risk of falling, and an aquatic training may offer a favourable environment to improve these modifiable risk factors. Methods A systematic review was conducted to assess the potential preventative role of aquatic exercise for reducing the risk of falls in the elderly by improving predisposing risk factors. Electronic databases and reference lists of pertinent articles published between 2005 and 2018 were searched. Randomized controlled trials (RCTs) that directly or indirectly addressed the effect of aquatic exercise for the prevention of falls in healthy participants were included within the synthesis. Studies were included if they were reported between January 2005 and May 2018 within a population aged between 60 and 90 years old that were without exercise-effecting comorbidities. Data related to participant demographics, study design, methodology, interventions and outcomes was extracted by one reviewer. Methodological quality assessment was independently performed by two reviewers using the PEDro (Physiotherapy Evidence Database) scale. Results Fourteen trials met the inclusion criteria. Exercise intervention duration and frequency varied from 2 to 24 weeks, from 2 to 3 times per week, from 40 to 90 min per session. Fall rate was not reported in any of the studies analysed. However, aquatic exercise improved key predisposing physical fitness components that are modifiable and internal risk factors for falling. Conclusions There is limited, low-quality evidence to support the use of aquatic exercise for improving physiological components that are risk factors for falling. Although the evidence is limited, and many interventions are not well described, these results should be considered by health and exercise professionals when making evidence-based, clinical decisions regarding training programmes to reduce the risk of falling

Telepathology Networking in VISN-12 of the Veterans Health Administration

The Veterans Integrated Service Network (VISN)-12, headquartered in Chicago, has implemented a telepathology network between the eight VISN-12 hospital laboratories and Loyola University Medical School linked by an economical, high-speed wide-area network (WAN). Implementation of the WAN has reduced monthly telecommunications costs in VISN-12 by approximately 67%. In addition to telepathology, the WAN enables real-time teleradiology (general, computer tomography, and ultrasound), telefluoroscopy, telenuclear medicine imaging, telepsychiatry, and other forms of teleconsultation. Current applications of telepathology in VISN-12 include: primary diagnosis and consultation in surgical pathology, interpretation of serum protein electrophoresis and immunofixation gels, provision of support for consolidated microbiology laboratories, review of problematic peripheral blood smears, and distance learning. We have learned a variety of lessons from telepathology. The enthusiasm and technical skill of providers are essential for success. As well, frequent communication and rapid technical support are necessary. Finally, in a supportive environment, telepathology is a tool that can help bring together clinical laboratories with shared missions and goals.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63151/1/153056200750040200.pd

Discovering markers of healthy aging:a prospective study in a Danish male birth cohort

There is a pressing need to identify markers of cognitive and neural decline in healthy late-midlife participants. We explored the relationship between cross-sectional structural brain-imaging derived phenotypes (IDPs) and cognitive ability, demographic, health and lifestyle factors (non-IDPs). Participants were recruited from the 1953 Danish Male Birth Cohort (N=193). Applying an extreme group design, members were selected in 2 groups based on cognitive change between IQ at age ~20y (IQ-20) and age ~57y (IQ-57). Subjects showing the highest (n=95) and lowest (n=98) change were selected (at age ~57) for assessments on multiple IDPs and non-IDPs. We investigated the relationship between 453 IDPs and 70 non-IDPs through pairwise correlation and multivariate canonical correlation analysis (CCA) models. Significant pairwise associations included positive associations between IQ-20 and gray-matter volume of the temporal pole. CCA identified a richer pattern - a single "positive-negative" mode of population co-variation coupling individual cross-subject variations in IDPs to an extensive range of non-IDP measures (r = 0.75, Pcorrected < 0.01). Specifically, this mode linked higher cognitive performance, positive early-life social factors, and mental health to a larger brain volume of several brain structures, overall volume, and microstructural properties of some white matter tracts. Interestingly, both statistical models identified IQ-20 and gray-matter volume of the temporal pole as important contributors to the inter-individual variation observed. The converging patterns provide novel insight into the importance of early adulthood intelligence as a significant marker of late-midlife neural decline and motivates additional study

Long-term effectiveness of sustainable land management practices to control runoff, soil erosion, and nutrient loss and the role of rainfall intensity in Mediterranean rainfed agroecosystems

Mediterranean environments are especially susceptible to soil erosion and to inappropriate soil management, leading to accelerated soil loss. Sustainable Land Management (SLM) practices (such as reduced tillage, no-tillage, cover crops, etc.,) have the potential to reduce soil, organic carbon (OC), and nutrient losses by erosion. However, the effectivity of these practices is site-dependent and varies under different rainfall conditions. The objective of this paper was to evaluate the effects of SLM practices in two rainfed systems (a wheat field and an almond orchard) representative of a large area of the driest Mediterranean regions - on runoff, soil erosion, particle size distribution, and OC and nutrient (N and P) contents in sediments. The influence of the rainfall characteristics on the effectiveness of the SLM practices was also evaluated. The SLM implemented were: reduced tillage (RT) in the wheat field and almond orchard and reduced tillage combined with green manure (RTG) in the almond orchard; these were compared to conventional tillage, the usual practice in the area. Open erosion plots were set up to monitor the effects of SLM on soil carbon and nutrients and on soil erosion after each rainfall event over six years (2010 2016). The results show that the SLM practices evaluated resulted in increased organic carbon (OC) and nutrients (N and P) contents in the soil, and reduced runoff, erosion, and mobilization of organic carbon and nutrients in sediments. Reductions in runoff of 30% and 65% and decreases in erosion of 65 and 85% were found in the wheat field and almond orchards, respectively. In addition, the total OC, N, and P losses in the wheat field were reduced by 56%, 45%, and 64%, respectively, while in the almond field the OC, N, and P losses were reduced by 90% under RT and by 85% under RTG. The beneficial effect of the SLM practices on soil erosion was observed within 18 months of their implementation and continued throughout the six years of the study. Furthermore, the effectiveness of tillage reduction with respect to erosion control and carbon and nutrients mobilization was highest during the most intense rainfall events, which are responsible for the highest erosion rates in Mediterranean areas. Our results support the key role of SLM practices under semiarid conditions as useful tools for climate change mitigation and adaptation, given the expected increase in high-intensity rainfall events in semiarid areas. © 2019 The AuthorsThis study site has been funded by several national (CYCIT AGL201125069//CICYT AGL2010-20941//CGL2013-42009-R//CGL2014-55-405-R), Regional (Séneca Foundation: 08757/PI/08//19350/PI/14), and European Commission H2020 (F6 DG RTD 037046 and Grant 728003, DIVERFARMING projects). Joris de Vente acknowledges support from a Ramón y Cajal research grant (RYC-2012-10375) and María Almagro was supported by the Juan de la Cierva Program (IJCI-2015-23500)

Modelling the distribution of white matter hyperintensities due to ageing on MRI images using Bayesian inference

White matter hyperintensities (WMH), also known as white matter lesions, are localised white matter areas that appear hyperintense on MRI scans. WMH commonly occur in the ageing population, and are often associated with several factors such as cognitive disorders, cardiovascular risk factors, cerebrovascular and neurodegenerative diseases. Despite the fact that some links between lesion location and parametric factors such as age have already been established, the relationship between voxel-wise spatial distribution of lesions and these factors is not yet well understood. Hence, it would be of clinical importance to model the distribution of lesions at the population-level and quantitatively analyse the effect of various factors on the lesion distribution model. In this work we compare various methods, including our proposed method, to generate voxel-wise distributions of WMH within a population with respect to various factors. Our proposed Bayesian spline method models the spatio-temporal distribution of WMH with respect to a parametric factor of interest, in this case age, within a population. Our probabilistic model takes as input the lesion segmentation binary maps of subjects belonging to various age groups and provides a population-level parametric lesion probability map as output. We used a spline representation to ensure a degree of smoothness in space and the dimension associated with the parameter, and formulated our model using a Bayesian framework. We tested our algorithm output on simulated data and compared our results with those obtained using various existing methods with different levels of algorithmic and computational complexity. We then compared the better performing methods on a real dataset, consisting of 1000 subjects of the UK Biobank, divided in two groups based on hypertension diagnosis. Finally, we applied our method on a clinical dataset of patients with vascular disease. On simulated dataset, the results from our algorithm showed a mean square error (MSE) value of , which was lower than the MSE value reported in the literature, with the advantage of being robust and computationally efficient. In the UK Biobank data, we found that the lesion probabilities are higher for the hypertension group compared to the non-hypertension group and further verified this finding using a statistical t-test. Finally, when applying our method on patients with vascular disease, we observed that the overall probability of lesions is significantly higher in later age groups, which is in line with the current literature