Staphylococcal Enterotoxins

Staphylococcus aureus (S. aureus) is a Gram positive bacterium that is carried by about one third of the general population and is responsible for common and serious diseases. These diseases include food poisoning and toxic shock syndrome, which are caused by exotoxins produced by S. aureus. Of the more than 20 Staphylococcal enterotoxins, SEA and SEB are the best characterized and are also regarded as superantigens because of their ability to bind to class II MHC molecules on antigen presenting cells and stimulate large populations of T cells that share variable regions on the β chain of the T cell receptor. The result of this massive T cell activation is a cytokine bolus leading to an acute toxic shock. These proteins are highly resistant to denaturation, which allows them to remain intact in contaminated food and trigger disease outbreaks. A recognized problem is the emergence of multi-drug resistant strains of S. aureus and these are a concern in the clinical setting as they are a common cause of antibiotic-associated diarrhea in hospitalized patients. In this review, we provide an overview of the current understanding of these proteins

The impact of age on vascular smooth muscle function in humans

Aim: Advanced age is associated with vascular endothelial dysfunction, characterized by reductions in the endothelium-dependent vasodilation of the conduit and resistance arteries, in part, from decreased nitric oxide bioavailability. Although vascular smooth muscle function (SMF), assessed by responsiveness to an exogenous nitric oxide donor, is typically reported to be intact, many of these studies are limited by a small sample size. Therefore, the purpose of this meta-analysis is to systematically review and determine whether vascular SMF is different between older versus young healthy individuals. Design: We conducted a systematic search of MEDLINE, Cochrane and Scopus, since their inceptions until January 2014, for articles evaluating SMF in the brachial artery and/or resistance arteries (BASMF and RASMF, respectively), as assessed by the endothelium-independent vasodilator response to exogenous nitric oxide donors in older (≥60 years) and young (<30 years) groups of healthy individuals. Meta-analyses were performed to compare the mean difference in BASMF and the standardized mean difference in RASMF between older and young groups. Subgroup analyses were performed to identify sources of heterogeneity. Results: Fifteen studies assessing BASMF and 20 studies assessing RASMF were included, comprising 550 older and 516 young healthy individuals. After data pooling, BASMF and RASMF were lower in older compared with the young groups (mean difference = −1.89%, P = 0.04; standardized mean difference = −0.46, P = 0.0008, respectively). Significant heterogeneity was observed in the BASMF (I2 = 74%, P < 0.00001) and the RASMF (I2 = 57%, P = 0.0008) meta-analyses. Subgroup analyses revealed that studies with (predominantly) men showed similar SMF responses between the older and the young groups. Conclusion: On the basis of the current published studies, vascular SMF is reduced in conduit and resistance arteries of otherwise healthy older individuals, particularly in women

Systematic Review to Inform a World Health Organization (WHO) Clinical Practice Guideline: Benefits and Harms of Structured and Standardized Education or Advice for Chronic Primary low back pain in Adults

PURPOSE: Evaluate benefits and harms of education/advice for chronic primary low back pain (CPLBP) in adults to inform a World Health Organization (WHO) standard clinical guideline. METHODS: Electronic databases were searched for randomized controlled trials (RCTs) assessing education/advice compared with placebo/sham, usual care, or no intervention (including comparison interventions where the attributable effect of education/advice could be isolated). We conducted meta-analyses and graded the certainty of evidence. RESULTS: We screened 2514 citations and 86 full text RCTs and included 15 RCTs. Most outcomes were assessed 3 to 6 months post-intervention. Compared with no intervention, education/advice improved pain (10 RCTs, MD = -1.1, 95% CI -1.63 to -0.56), function (10 RCTs, SMD = -0.51, 95% CI -0.89 to -0.12), physical health-related quality of life (HRQoL) (2 RCTs, MD = 24.27, 95% CI 12.93 to 35.61), fear avoidance (5 RCTs, SMD = -1.4, 95% CI -2.51 to -0.29), depression (1 RCT; MD = 2.10, 95% CI 1.05 to 3.15), and self-efficacy (1 RCT; MD = 4.4, 95% CI 2.77 to 6.03). Education/advice conferred less benefit than sham Kinesio taping for improving fear avoidance regarding physical activity (1 RCT, MD = 5.41, 95% CI 0.28 to 10.54). Compared with usual care, education/advice improved pain (1 RCT, MD = -2.10, 95% CI -3.13 to -1.07) and function (1 RCT, MD = -7.80, 95% CI -14.28 to -1.32). There was little or no difference between education/advice and comparisons for other outcomes. For all outcomes, the certainty of evidence was very low. CONCLUSION: Education/advice in adults with CPLBP was associated with improvements in pain, function, HRQoL, and psychological outcomes, but with very low certainty

Supply chain knowledge management:a literature review

This paper aims to contribute to the debate on the role of knowledge management in supply chain management by reviewing the published literature. A total of 58 selected referred journal articles were systematically analyzed. This review identifies various theoretical and methodological characteristics of the way in which knowledge management applications are proposed in the supply chain context. The review shows that little evidence exists of the positive relation between the use of IT solutions and firms’ performance. Some issues remain unexplored such as the problem of knowledge obsolescence in supply chain management. A deeper understanding of the knowledge accumulation process could give new insights. The paper concludes with some future directions for theory construction and empirical research

Identification of a Phosphorylation-Dependent Nuclear Localization Motif in Interferon Regulatory Factor 2 Binding Protein 2

Background - Interferon regulatory factor 2 binding protein 2 (IRF2BP2) is a muscle-enriched transcription factor required to activate vascular endothelial growth factor-A (VEGFA) expression in muscle. IRF2BP2 is found in the nucleus of cardiac and skeletal muscle cells. During the process of skeletal muscle differentiation, some IRF2BP2 becomes relocated to the cytoplasm, although the functional significance of this relocation and the mechanisms that control nucleocytoplasmic localization of IRF2BP2 are not yet known. // Methodology/Principal Findings - Here, by fusing IRF2BP2 to green fluorescent protein and testing a series of deletion and site-directed mutagenesis constructs, we mapped the nuclear localization signal (NLS) to an evolutionarily conserved sequence 354ARKRKPSP361 in IRF2BP2. This sequence corresponds to a classical nuclear localization motif bearing positively charged arginine and lysine residues. Substitution of arginine and lysine with negatively charged aspartic acid residues blocked nuclear localization. However, these residues were not sufficient because nuclear targeting of IRF2BP2 also required phosphorylation of serine 360 (S360). Many large-scale phosphopeptide proteomic studies had reported previously that serine 360 of IRF2BP2 is phosphorylated in numerous human cell types. Alanine substitution at this site abolished IRF2BP2 nuclear localization in C2C12 myoblasts and CV1 cells. In contrast, substituting serine 360 with aspartic acid forced nuclear retention and prevented cytoplasmic redistribution in differentiated C2C12 muscle cells. As for the effects of these mutations on VEGFA promoter activity, the S360A mutation interfered with VEGFA activation, as expected. Surprisingly, the S360D mutation also interfered with VEGFA activation, suggesting that this mutation, while enforcing nuclear entry, may disrupt an essential activation function of IRF2BP2. // Conclusions/Significance - Nuclear localization of IRF2BP2 depends on phosphorylation near a conserved NLS. Changes in phosphorylation status likely control nucleocytoplasmic localization of IRF2BP2 during muscle differentiation

A Novel Unstable Duplication Upstream of HAS2 Predisposes to a Breed-Defining Skin Phenotype and a Periodic Fever Syndrome in Chinese Shar-Pei Dogs

Hereditary periodic fever syndromes are characterized by recurrent episodes of fever and inflammation with no known pathogenic or autoimmune cause. In humans, several genes have been implicated in this group of diseases, but the majority of cases remain unexplained. A similar periodic fever syndrome is relatively frequent in the Chinese Shar-Pei breed of dogs. In the western world, Shar-Pei have been strongly selected for a distinctive thick and heavily folded skin. In this study, a mutation affecting both these traits was identified. Using genome-wide SNP analysis of Shar-Pei and other breeds, the strongest signal of a breed-specific selective sweep was located on chromosome 13. The same region also harbored the strongest genome-wide association (GWA) signal for susceptibility to the periodic fever syndrome (praw = 2.3×10−6, pgenome = 0.01). Dense targeted resequencing revealed two partially overlapping duplications, 14.3 Kb and 16.1 Kb in size, unique to Shar-Pei and upstream of the Hyaluronic Acid Synthase 2 (HAS2) gene. HAS2 encodes the rate-limiting enzyme synthesizing hyaluronan (HA), a major component of the skin. HA is up-regulated and accumulates in the thickened skin of Shar-Pei. A high copy number of the 16.1 Kb duplication was associated with an increased expression of HAS2 as well as the periodic fever syndrome (p<0.0001). When fragmented, HA can act as a trigger of the innate immune system and stimulate sterile fever and inflammation. The strong selection for the skin phenotype therefore appears to enrich for a pleiotropic mutation predisposing these dogs to a periodic fever syndrome. The identification of HA as a major risk factor for this canine disease raises the potential of this glycosaminoglycan as a risk factor for human periodic fevers and as an important driver of chronic inflammation

The potential role of three-dimensional surface imaging as a tool to evaluate aesthetic outcome after Breast Conserving Therapy (BCT)

To establish whether objective measurements of symmetry of volume and shape using three-dimensional surface imaging (3D-SI) can be used as surrogate markers of aesthetic outcome in patients who have undergone breast conserving therapy (BCT). Women who had undergone unilateral BCT in the preceding 1-6 years were invited to participate. Participants completed a satisfaction questionnaire (BREAST-Q) and underwent 3D-SI. Volume and surface symmetry were measured on the images. Assessment of aesthetic outcome was undertaken by a panel of clinicians. The Kruskal-Wallis test was used to assess the relationship between volume and shape symmetry measurements with the panel score. Spearman's rho correlations were used to assess the relationship between the measurements and patient satisfaction. 200 women participated. Median volume symmetry was 87% (IQR 78-93) and shape symmetry was 5.9 mm (IQR 4.2-8.0). The participants were grouped according to panel assessment of aesthetic outcome (poor, fair, good, excellent) and the median volume and shape symmetry was calculated for each group. Volume symmetry significantly differed between the groups. Post hoc pairwise comparisons demonstrated that these differences existed between panel scores of fair versus good and good versus excellent. Median shape symmetry also differed according to patient panel groups with four significant pairwise comparisons between poor versus good, poor versus excellent, fair versus good and fair versus excellent. There was a significant but weak correlation of both volume symmetry and surface asymmetry with BREAST-Q scores (correlation coefficients 0.187 and -0.229, respectively). Breast volume and shape symmetry are both associated with panel assessment scores and patient satisfaction. The objective volume and shape symmetry measures were strongly associated with panel assessment scores, such that a 3D-SI tool could replace panel assessment as a faster and more objective method of evaluating aesthetic outcomes

Fungal Planet description sheets : 951–1041

Novel species of fungi described in this study include those from various countries as follows: Antarctica,Apenidiella antarctica from permafrost, Cladosporium fildesense from an unidentified marine sponge. Argentina,Geastrum wrightii on humus in mixed forest. Australia, Golovinomyces glandulariae on Glandularia aristigera,Neoanungitea eucalyptorum on leaves of Eucalyptus grandis, Teratosphaeria corymbiicola on leaves of Corymbiaficifolia, Xylaria eucalypti on leaves of Eucalyptus radiata. Brazil, Bovista psammophila on soil, Fusarium awaxy onrotten stalks of Zea mays, Geastrum lanuginosum on leaf litter covered soil, Hermetothecium mikaniae-micranthae(incl. Hermetothecium gen. nov.) on Mikania micrantha, Penicillium reconvexovelosoi in soil, Stagonosporopsis vannacciifrom pod of Glycine max. British Virgin Isles, Lactifluus guanensis on soil. Canada, Sorocybe oblongisporaon resin of Picea rubens. Chile, Colletotrichum roseum on leaves of Lapageria rosea. China, Setophoma cavernafrom carbonatite in Karst cave. Colombia, Lareunionomyces eucalypticola on leaves of Eucalyptus grandis. CostaRica, Psathyrella pivae on wood. Cyprus, Clavulina iris on calcareous substrate. France, Chromosera ambiguaand Clavulina iris var. occidentalis on soil. French West Indies, Helminthosphaeria hispidissima on dead wood.Guatemala, Talaromyces guatemalensis in soil. Malaysia, Neotracylla pini (incl. Tracyllales ord. nov. and Neotracyllagen. nov.) and Vermiculariopsiella pini on needles of Pinus tecunumanii. New Zealand, Neoconiothyriumviticola on stems of Vitis vinifera, Parafenestella pittospori on Pittosporum tenuifolium, Pilidium novae-zelandiaeon Phoenix sp. Pakistan, Russula quercus-floribundae on forest floor. Portugal, Trichoderma aestuarinum fromsaline water. Russia, Pluteus liliputianus on fallen branch of deciduous tree, Pluteus spurius on decaying deciduous wood or soil. South Africa, Alloconiothyrium encephalarti, Phyllosticta encephalarticola and Neothyrostromaencephalarti (incl. Neothyrostroma gen. nov.) on leaves of Encephalartos sp., Chalara eucalypticola on leaf spots ofEucalyptus grandis x urophylla, Clypeosphaeria oleae on leaves of Olea capensis, Cylindrocladiella postalofficiumon leaf litter of Sideroxylon inerme, Cylindromonium eugeniicola (incl. Cylindromonium gen. nov.) on leaf litter ofEugenia capensis, Cyphellophora goniomatis on leaves of Gonioma kamassi, Nothodactylaria nephrolepidis (incl.Nothodactylaria gen. nov. and Nothodactylariaceae fam. nov.) on leaves of Nephrolepis exaltata, Falcocladiumeucalypti and Gyrothrix eucalypti on leaves of Eucalyptus sp., Gyrothrix oleae on leaves of Olea capensis subsp.macrocarpa, Harzia metro-sideri on leaf litter of Metrosideros sp., Hippopotamyces phragmitis (incl. Hippopotamycesgen. nov.) on leaves of Phragmites australis, Lectera philenopterae on Philenoptera violacea, Leptosilliamayteni on leaves of Maytenus heterophylla, Lithohypha aloicola and Neoplatysporoides aloes on leaves of Aloesp., Millesimomyces rhoicissi (incl. Millesimomyces gen. nov.) on leaves of Rhoicissus digitata, Neodevriesiastrelitziicola on leaf litter of Strelitzia nicolai, Neokirramyces syzygii (incl. Neokirramyces gen. nov.) on leaf spots of Syzygium sp., Nothoramichloridium perseae (incl. Nothoramichloridium gen. nov. and Anungitiomycetaceae fam.nov.) on leaves of Persea americana, Paramycosphaerella watsoniae on leaf spots of Watsonia sp., Penicilliumcuddlyae from dog food, Podocarpomyces knysnanus (incl. Podocarpomyces gen. nov.) on leaves of Podocarpusfalcatus, Pseudocercospora heteropyxidicola on leaf spots of Heteropyxis natalensis, Pseudopenidiella podocarpi,Scolecobasidium podocarpi and Ceramothyrium podocarpicola on leaves of Podocarpus latifolius, Scolecobasidiumblechni on leaves of Blechnum capense, Stomiopeltis syzygii on leaves of Syzygium chordatum, Strelitziomycesknysnanus (incl. Strelitziomyces gen. nov.) on leaves of Strelitzia alba, Talaromyces clemensii from rotting wood ingoldmine, Verrucocladosporium visseri on Carpobrotus edulis. Spain, Boletopsis mediterraneensis on soil, Calycinacortegadensisi on a living twig of Castanea sativa, Emmonsiellopsis tuberculata in fluvial sediments, Mollisia cortegadensison dead attached twig of Quercus robur, Psathyrella ovispora on soil, Pseudobeltrania lauri on leaf litterof Laurus azorica, Terfezia dunensis in soil, Tuber lucentum in soil, Venturia submersa on submerged plant debris.Thailand, Cordyceps jakajanicola on cicada nymph, Cordyceps kuiburiensis on spider, Distoseptispora caricis onleaves of Carex sp., Ophiocordyceps khonkaenensis on cicada nymph. USA, Cytosporella juncicola and Davidiellomycesjuncicola on culms of Juncus effusus, Monochaetia massachusettsianum from air sample, Neohelicomycesmelaleucae and Periconia neobrittanica on leaves of Melaleuca styphelioides x lanceolata, Pseudocamarosporiumeucalypti on leaves of Eucalyptus sp., Pseudogymnoascus lindneri from sediment in a mine, Pseudogymnoascusturneri from sediment in a railroad tunnel, Pulchroboletus sclerotiorum on soil, Zygosporium pseudomasonii onleaf of Serenoa repens. Vietnam, Boletus candidissimus and Veloporphyrellus vulpinus on soil. Morphological andculture characteristics are supported by DNA barcodes

Chemical genetics strategies for identification of molecular targets

Chemical genetics is an emerging field that can be used to study the interactions of chemical compounds, including natural products, with proteins. Usually, the identification of molecular targets is the starting point for studying a drug’s mechanism of action and this has been a crucial step in understanding many biological processes. While a great variety of target identification methods have been developed over the last several years, there are still many bioactive compounds whose target proteins have not yet been revealed because no routine protocols can be adopted. This review contains information concerning the most relevant principles of chemical genetics with special emphasis on the different genomic and proteomic approaches used in forward chemical genetics to identify the molecular targets of the bioactive compounds, the advantages and disadvantages of each and a detailed list of successful examples of molecular targets identified with these approaches