Far-reaching changes to the structure and function of the Earth's natural systems represent a growing threat to human health. And yet, global health has mainly improved as these changes have gathered ...pace. What is the explanation? As a Commission, we are deeply concerned that the explanation is straightforward and sobering: we have been mortgaging the health of future generations to realise economic and development gains in the present.
The Database and Expert Systems Applications (DEXA) conferences bring together researchers and practitioners from all over the world to exchange ideas, experiences and opinions in a friendly and ...stimulating environment. The papers are at once a record of what has been achieved and the first steps towards shaping the future of information systems. DEXA covers a broad field, and all aspects of database, knowledge base and related technologies and their applications are represented. Once again there were a good number of submissions: 241 papers were submitted and of these the programme committee selected 103 to be presented. DEXA’99 took place in Florence and was the tenth conference in the series, following events in Vienna, Berlin, Valencia, Prague, Athens, London, Zurich, Toulouse and Vienna. The decade has seen many developments in the areas covered by DEXA, developments in which DEXA has played its part. I would like to express thanks to all the institutions which have actively supported and made possible this conference, namely: • University of Florence, Italy • IDG CNR, Italy • FAW – University of Linz, Austria • Austrian Computer Society • DEXA Association In addition, we must thank all the people who have contributed their time and effort to make the conference possible. Special thanks go to Maria Schweikert (Technical University of Vienna), M. Neubauer and G. Wagner (FAW, University of Linz). We must also thank all the members of the programme committee, whose careful reviews are important to the quality of the conference.
Pustular psoriasis (PP) is a group of inflammatory skin conditions characterized by infiltration of neutrophil granulocytes in the epidermis to such an extent that clinically visible sterile pustules ...develop. Because of clinical co‐incidence, PP is currently grouped with psoriasis vulgaris (PV). However, PP and PV are phenotypically different, respond differently to treatments and seem to be distinct on the genetic level. In contrast to PV, the phenotypes of PP are not well defined. Descriptions of each form of PP are discordant among standard dermatology textbooks Saurat Dermatologie 2016, Rook's Dermatology 2016, Fitzpatrick's 2012 and Braun‐Falco 2012, encumbering the collection of phenotypically well‐matched groups of patients as well as clinical trials. The European Rare and Severe Psoriasis Expert Network (ERASPEN) was founded to define consensus criteria for diagnosis, deeply phenotype large groups of PP patients, analyse the genetics and pathophysiology and prepare for prospective clinical trials. This work reviews historical aspects of these conditions, new genetic findings and presents our initial considerations on the phenotypes of PP and a consensus classification of clinical phenotypes that will be used as a baseline for further, prospective studies of PP. Generalized pustular psoriasis (GPP) is defined as primary, sterile, macroscopically visible pustules on non‐acral skin (excluding cases where pustulation is restricted to psoriatic plaques). GPP can occur with or without systemic inflammation, with or without PV and can either be a relapsing (>1 episode) or persistent (>3 months) condition. Acrodermatitis continua of Hallopeau (ACH) is characterized by primary, persistent (>3 months), sterile, macroscopically visible pustules affecting the nail apparatus. Palmoplantar pustulosis (PPP) has primary, persistent (>3 months), sterile, macroscopically visible pustules on palms and/or soles and can occur with or without PV.
Summary Massive slums have become major features of cities in many low-income and middle-income countries. Here, in the first in a Series of two papers, we discuss why slums are unhealthy places with ...especially high risks of infection and injury. We show that children are especially vulnerable, and that the combination of malnutrition and recurrent diarrhoea leads to stunted growth and longer-term effects on cognitive development. We find that the scientific literature on slum health is underdeveloped in comparison to urban health, and poverty and health. This shortcoming is important because health is affected by factors arising from the shared physical and social environment, which have effects beyond those of poverty alone. In the second paper we will consider what can be done to improve health and make recommendations for the development of slum health as a field of study.
In reviewing a selection of recent case studies from our laboratory, we revealed some lessons learned and benefits accrued from the application of mass spectrometry (MS/MS) molecular networking in ...the field of marine sponge natural products. Molecular networking proved pivotal to our discovery of many new natural products and even new classes of natural product, some of which were opaque to alternate dereplication and prioritization strategies. Case studies included the discovery of: (i) trachycladindoles, an exceptionally rare class of bioactive indole alkaloid previously only known from a single southern Australia sample of
; (ii) dysidealactams, an unprecedented class of sesquiterpene glycinyl-lactam and glycinyl-imide from a
sp., a sponge genera often discounted as having been exhaustively studied; (iii) cacolides, an unprecedented family of sesterterpene α-methyl-γ-hydroxybutenolides from a
sp., all too easily mischaracterized and deprioritized during dereplication as a well-known class of sponge sesterterpene tetronic acids; and (iv) thorectandrins, a new class of indole alkaloid which revealed unexpected insights into the chemical and biological properties of the aplysinopsins, one of the earliest and more extensively reported class of sponge natural products.
Co-cultivation of Chaunopycnis sp. (CMB-MF028) and Trichoderma hamatum (CMB-MF030), fungal strains co-isolated from the inner tissue of an intertidal rock platform mollusc (Siphonaria sp), resulted ...in transcriptional activation of a rare class of 2-alkenyl-tetrahydropyran, chaunopyran A (7), and biotransformation and deactivation of the antifungal pyridoxatin (1), to methyl-pyridoxatin (8). This study illustrates the complexity of offensive and counter-offensive molecular defenses encountered during fungal co-cultivation, and the opportunities for activating new, otherwise transcriptionally silent secondary metabolites.
ATP binding cassette (ABC) transporters, such as P-gp, BCRP and MRP1, can increase efflux of clinical chemotherapeutic agents and lead to multi-drug resistance (MDR) in cancer cells. While the ...discovery and development of clinically useful inhibitors has proved elusive to date, this molecular target nevertheless remains a promising strategy for addressing and potentially overcoming MDR. In a search for new classes of inhibitor, we used fluorescent accumulation and efflux assays supported by cell flow cytometry and MDR reversal assays, against a panel of sensitive and MDR human cancer cell lines, to evaluate the marine sponge co-metabolites 1-12 as inhibitors of P-gp, BCRP or MRP1 initiated MDR. These studies identified and characterized lamellarin O (11) as a selective inhibitor of BCRP mediated drug efflux. A structure-activity relationship analysis inclusive of the natural products 1-12 and the synthetic analogues 13-19, supported by in silico docking studies, revealed key structural requirements for the lamellarin O (11) BCRP inhibitory pharmacophore.
This study showcases the application of an integrated workflow of molecular networking chemical profiling (GNPS), together with miniaturized microbioreactor cultivation profiling (MATRIX) to ...successfully detect, dereplicate, prioritize, optimize the production, isolate, characterize, and identify a diverse selection of new chemically labile natural products from the Queensland sheep pasture soil-derived fungus
sp. CMB-MRF324. More specifically, we report the new tryptamine enamino tripeptide aspergillamides E-F (
-
), dihydroquinoline-2-one aflaquinolones H-I (
-
), and prenylated phenylbutyrolactone aspulvinone Y (
), along with an array of known co-metabolites, including asterriquinones SU5228 (
) and CT5 (
), terrecyclic acid A (
), and aspulvinones N-CR (
), B (
), D (
), and H (
). Structure elucidation was achieved by a combination of detailed spectroscopic and chemical analysis, biosynthetic considerations, and in the case of
an X-ray crystallographic analysis.
Glutamate-gated chloride channel receptors (GluClRs) mediate inhibitory neurotransmission at invertebrate synapses and are primary targets of parasites that impact drastically on agriculture and ...human health. Ivermectin (IVM) is a broad-spectrum pesticide that binds and potentiates GluClR activity. Resistance to IVM is a major economic and health concern, but the molecular and synaptic mechanisms of resistance are ill-defined. Here we focus on GluClRs of the agricultural endoparasite, Haemonchus contortus. We demonstrate that IVM potentiates inhibitory input by inducing a tonic current that plateaus over 15 minutes and by enhancing post-synaptic current peak amplitude and decay times. We further demonstrate that IVM greatly enhances the active durations of single receptors. These effects are greatly attenuated when endogenous IVM-insensitive subunits are incorporated into GluClRs, suggesting a mechanism of IVM resistance that does not affect glutamate sensitivity. We discovered functional groups of IVM that contribute to tuning its potency at different isoforms and show that the dominant mode of access of IVM is via the cell membrane to the receptor.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Psoriasis is a common inflammatory skin disease caused by the interplay between multiple genetic and environmental risk factors. This review summarises recent progress in elucidating the genetic ...basis of psoriasis, particularly through large genome-wide association studies. We illustrate the power of genetic analyses for disease stratification. Psoriasis can be stratified by phenotype (common plaque versus rare pustular variants), or by outcome (prognosis, comorbidities, response to treatment); recent progress has been made in delineating the genetic contribution in each of these areas. We also highlight how genetic data can directly inform the development of effective psoriasis treatments.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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