Modulation of the UVA activation of haem oxygenase, collagenase and cyclooxygenase gene expression by epigallocatechin in human skin cells

AbstractWe have investigated the modifying effects of epigallocatechin, a major polyphenolic constituent of green tea, on ultraviolet-A-activated gene expression in human fibroblasts and keratinocytes using the stress responsive enzymes: haem oxygenase-1, interstitial collagenase and cyclooxygenase-2. Although epigallocatechin strongly reduced ultraviolet-A-induced haem oxygenase-1 activation in skin-derived fibroblasts, the same compound activated collagenase and cyclooxygenase expression. In a keratinocyte cell line, ultraviolet-A-mediated haem oxygenase-1 over-expression was low and epigallocatechin failed to modulate it further. In contrast to the results with fibroblasts, ultraviolet-A activation of cyclooxygenase in keratinocytes was reduced by epigallocatechin. The results indicate that the effect of this green tea polyphenol on cellular stress responses is complex and may involve direct effects on signal transduction as well as changes that may be associated with its antioxidant activity

Flavonoid glycosides from Persea caerulea. Unraveling their interactions with SDS-micelles through matrix-assisted DOSY, PGSE, mass spectrometry, and NOESY

Two flavonoid glycosides derived from rhamnopyranoside (1) and arabinofuranoside (2) have been isolated from leaves of Persea caerulea for the first time. The structures of 1 and 2 have been established by 1H NMR, 13C NMR, and IR spectroscopy, together with LC–ESI–TOF and LC–ESI–IT MS spectrometry. From the MS and MS/MS data, the molecular weights of the intact molecules as well as those of quercetin and kaempferol together with their sugar moieties were deduced. The NMR data provided information on the identity of the compounds, as well as the α and β configurations and the position of the glycosides on quercetin and kaempferol. We have also explored the application of sodium dodecyl sulfate (SDS) normal micelles in binary aqueous solution, at a range of concentrations, to the diffusion resolution of these two glycosides, by the application of matrix‐assisted diffusion ordered spectroscopy (DOSY) and pulse field gradient spin echo (PGSE) methodologies, showing that SDS micelles offer a significant resolution which can, in part, be rationalized in terms of differing degrees of hydrophobicity, amphiphilicity, and steric effects. In addition, intra‐residue and inter‐residue proton–proton distances using nuclear Overhauser effect build‐up curves were used to elucidate the conformational preferences of these two flavonoid glycosides when interacting with the micelles. By the combination of both diffusion and nuclear Overhauser spectroscopy techniques, the average location site of kaempferol and quercetin glycosides has been postulated, with the former exhibiting a clear insertion into the interior of the SDS‐micelle, whereas the latter is placed closer to the surface.Junta de Andalucía P12-FQM-266

Diabetes Complications at Presentation and One Year by Glycated Haemoglobin at Diagnosis in a Multiethnic and Diverse Socioeconomic Population: Results from the South London Diabetes Study

Background. WHO's recommendation of HbA 1c ≥ 48 mmol/mol (6.5%) as diagnostic for type 2 diabetes mellitus (T2DM) was adopted by three UK London boroughs in May 2012. The South London Diabetes (SOUL-D) study has recruited people with newly diagnosed T2DM since 2008. We compared participants diagnosed before May 2012 with HbA 1c < 48 mmol/mol to those with diagnostic HbA 1c ≥ 48 mmol/mol. Methods. A prospective cohort study of newly diagnosed T2DM participants from 96 primary care practices, comparing demographic and biomedical variables between those with diagnostic HbA 1c < 48 mmol/mol or HbA 1c ≥ 48 mmol/mol at recruitment and after one year. Results. Of 1488 participants, 22.8% had diagnostic HbA 1c < 48 mmol/mol. They were older and more likely to be white ( < 0.05). At recruitment and one year, there were no between-group differences in the prevalence of diabetic complications, except that those diagnosed with HbA 1c < 48 mmol/mol had more sensory neuropathy at recruitment ( = 0.039) and, at one year, had new myocardial infarction ( = 0.012) but less microalbuminuria ( = 0.012). Conclusions. Use of HbA 1c ≥ 48 mmol/mol as the sole T2DM diagnostic criterion may miss almost a quarter of those previously diagnosed in South London yet HbA 1c < 48 mmol/mol may not exclude clinically important diabetes

A systematic review of controlled trials on visual stress using Intuitive Overlays or the Intuitive Colorimeter

Claims that coloured filters aid reading date back 200 years and remain controversial. Some claims, for example, that more than 10% of the general population and 50% of people with dyslexia would benefit from coloured filters lack sound evidence and face validity. Publications with such claims typically cite research using methods that have not been described in the scientific literature and lack a sound aetiological framework. Notwithstanding these criticisms, some researchers have used more rigorous selection criteria and methods of prescribing coloured filters that were developed at a UK Medical Research Council unit and which have been fully described in the scientific literature. We review this research and disconfirm many of the more extreme claims surrounding this topic. This literature indicates that a minority subset of dyslexics (circa 20%) may have a condition described as visual stress which most likely results from a hyperexcitability of the visual cortex. Visual stress is characterised by symptoms of visual perceptual distortions, headaches, and eyestrain when viewing repetitive patterns, including lines of text. This review indicates that visual stress is distinct from, although sometimes co-occurs with, dyslexia. Individually prescribed coloured filters have been shown to improve reading performance in people with visual stress, but are unlikely to influence the phonological and memory deficits associated with dyslexia and therefore are not a treatment for dyslexia. This review concludes that larger and rigorous randomised controlled trials of interventions for visual stress are required. Improvements in the diagnosis of the condition are also a priority

Acinetobacter baumannii from grass: novel but non-resistant clones

Acinetobacter baumannii is one the most worrisome nosocomial pathogens, which has long been considered almost mainly as a hospital-associated bacterium. There have been some studies about animal and environmental isolates over the last decade. However, little effort has been made to determine if this pathogen dwells in the grass. Here, we aim to determine the evolutionary relationships and antibiotic resistance of clones of A. baumannii sampled from grass to the major human international clones and animal clones. Two hundred and forty genomes were considered in total from four different sources for this study. Our core and accessory genomic epidemiology analyses showed that grass isolates cluster in seven groups well differentiated from one another and from the major human and animal isolates. Furthermore, we found new sequence types under both multilocus sequence typing schemes: two under the Pasteur scheme and seven for the Oxford scheme. The grass isolates contained fewer antibiotic-resistance genes and were not resistant to the antibiotics tested. Our results demonstrate that these novel clones appear to have limited antibiotic resistance potential. Given our findings, we propose that genomic epidemiology and surveillance of A. baumannii should go beyond the hospital settings and consider the environment in an explicit One Health approach

Structural connectivity in a single case of progressive prosopagnosia: The role of the right inferior longitudinal fasciculus

Progressive prosopagnosia (PP) is a clinical syndrome characterized by a progressive and selective inability to recognize and identify faces of familiar people. Here we report a patient (G.S.) with PP, mainly related to a prominent deficit in recognition of familiar faces, without a semantic (cross-modal) impairment. An in-depth evaluation showed that his deficit extended to other classes of objects, both living and non-living. A follow-up neuropsychological assessment did not reveal substantial changes after about 1 year. Structural MRI showed predominant right temporal lobe atrophy. Diffusion tensor imaging was performed to elucidate structural connectivity of the inferior longitudinal fasciculus (ILF) and the inferior fronto-occipital fasciculus (IFOF), the two major tracts that project through the core fusiform region to the anterior temporal and frontal cortices, respectively. Right ILF was markedly reduced in G.S., while left ILF and IFOFs were apparently preserved. These data are in favour of a crucial role of the neural circuit subserved by right ILF in the pathogenesis of PP

Genomic Profiling of Childhood Tumor Patient-Derived Xenograft Models to Enable Rational Clinical Trial Design.

Accelerating cures for children with cancer remains an immediate challenge as a result of extensive oncogenic heterogeneity between and within histologies, distinct molecular mechanisms evolving between diagnosis and relapsed disease, and limited therapeutic options. To systematically prioritize and rationally test novel agents in preclinical murine models, researchers within the Pediatric Preclinical Testing Consortium are continuously developing patient-derived xenografts (PDXs)-many of which are refractory to current standard-of-care treatments-from high-risk childhood cancers. Here, we genomically characterize 261 PDX models from 37 unique pediatric cancers; demonstrate faithful recapitulation of histologies and subtypes; and refine our understanding of relapsed disease. In addition, we use expression signatures to classify tumors for TP53 and NF1 pathway inactivation. We anticipate that these data will serve as a resource for pediatric oncology drug development and will guide rational clinical trial design for children with cancer

Origin of Carboniferous sandstones fringing the northern margin of the Wales-Brabant Massif: insights from detrital zircon ages

A study of detrital zircon age populations in Namurian–Westphalian (Carboniferous) sandstones in the southern Central Pennine Basin of the UK has revealed considerable complexity in their provenance history. The Pendleian–Marsdenian Morridge Formation, which is known to have been derived from the Wales-Brabant Massif to the south on the basis of palaeocurrent and petrographic information, is dominated by zircons ultimately derived from the Caledonian belt to the north. These zircons were recycled from sandstones of northern origin that had been previously deposited over the massif during Middle to Late Devonian times. The Morridge Formation also includes Late Neoproterozoic zircons of local Wales-Brabant Massif origin. The south lobe of the Yeadonian Rough Rock has been previously interpreted as having a complex provenance including sediment of northern origin interbedded with sediment ascribed to a Wales-Brabant Massif source. However, the zircon spectrum lacks a Late Neoproterozoic component that would have been diagnostic of input from the Wales-Brabant Massif, and the provenance history of the Rough Rock south lobe therefore remains enigmatic. The Langsettian Ludgbridge Conglomerate is dominated by Late Neoproterozoic zircons of Wales-Brabant Massif origin, but even in this evidently proximal deposit, the provenance is complex since the main zircon group (ca. 640 Ma) cannot be matched with known local Neoproterozoic basement sources. The data either indicate the presence of hitherto-unknown magmatic rocks of this age adjacent to the South Staffordshire coalfield or indicate that the zircons were recycled from sediment with a more distal origin. Finally, the Duckmantian Top Hard Rock contains zircons that can be reconciled with a source in the Irish Caledonides, consistent with the palaeocurrent evidence, supplemented by zircons derived from the Wales-Brabant Massif, possibly including the Monian Composite Terrane of Anglesey. The study reinforces the important message that failure to recognize the presence of recycled zircon could lead to erroneous reconstructions of sediment provenance and transport history

Nitric oxide production and antioxidant function during viral infection of the coccolithophore Emiliania huxleyi

Emiliania huxleyi is a globally important marine phytoplankton that is routinely infected by viruses. Understanding the controls on the growth and demise of E. huxleyi blooms is essential for predicting the biogeochemical fate of their organic carbon and nutrients. In this study, we show that the production of nitric oxide (NO), a gaseous, membrane-permeable free radical, is a hallmark of early-stage lytic infection in E. huxleyi by Coccolithoviruses, both in culture and in natural populations in the North Atlantic. Enhanced NO production was detected both intra- and extra-cellularly in laboratory cultures, and treatment of cells with an NO scavenger significantly reduced viral production. Pre-treatment of exponentially growing E. huxleyi cultures with the NO donor S-nitroso-N-acetylpenicillamine (SNAP) prior to challenge with hydrogen peroxide (H2O2) led to greater cell survival, suggesting that NO may have a cellular antioxidant function. Indeed, cell lysates generated from cultures treated with SNAP and undergoing infection displayed enhanced ability to detoxify H2O2. Lastly, we show that fluorescent indicators of cellular ROS, NO, and death, in combination with classic DNA- and lipid-based biomarkers of infection, can function as real-time diagnostic tools to identify and contextualize viral infection in natural E. huxleyi blooms