A statistical model to predict the reduction of lichenification in atopic dermatitis

Acute symptoms of atopic dermatitis (AD), such as erythema, oedema/papulations and excoriations, respond quickly to topical corticosteroid treatment. Conversely, lichenification is regarded as a troublesome non-acute symptom of chronic AD which can take months of treatment before any improvement is seen. However, very little data actually support this opinion. Here, we analyse lichenification scores in 3 multicentre, short-term studies of nearly similar design. Two of these studies were active comparator dosage trials administered with either fluticasone propionate cream or ointment once or twice daily, the third study was a placebo control. In each of these 4-weeks studies lichenification was measured weekly. For the evaluation of the lichenification score over time a random-coefficients regression model was used. In all active treatments lichenification significantly improved (p 80% of patients scoring no, very mild or mild lichenification after 4 weeks. We developed a model in which the lichenification score drops off linearly with the square root of time. The resulting convexly-shaped downward time trend of lichenification was significant during all treatments. This effect was significantly stronger during active treatment than with placebo. Fluticasone propionate can improve moderate to severe lichenification in a relative short period of time

Resilience to aging in the regeneration-capable flatworm Macrostomum lignano

Animals show a large variability of lifespan, ranging from short-lived as Caenorhabditis elegans to immortal as Hydra. A fascinating case is flatworms, in which reversal of aging by regeneration is proposed, yet conclusive evidence for this rejuvenation-by-regeneration hypothesis is lacking. We tested this hypothesis by inducing regeneration in the sexual free-living flatworm Macrostomum lignano. We studied survival, fertility, morphology, and gene expression as a function of age. Here, we report that after regeneration, genes expressed in the germline are upregulated at all ages, but no signs of rejuvenation are observed. Instead, the animal appears to be substantially longer lived than previously appreciated, and genes expressed in stem cells are upregulated with age, while germline genes are downregulated. Remarkably, several genes with known beneficial effects on lifespan when overexpressed in mice and C. elegans are naturally upregulated with age in M. lignano, suggesting that molecular mechanism for offsetting negative consequences of aging has evolved in this animal. We therefore propose that M. lignano represents a novel powerful model for molecular studies of aging attenuation, and the identified aging gene expression patterns provide a valuable resource for further exploration of anti-aging strategies

TIM29 is required for enhanced stem cell activity during regeneration in the flatworm Macrostomum lignano

TIM29 is a mitochondrial inner membrane protein that interacts with the protein import complex TIM22. TIM29 was shown to stabilize the TIM22 complex but its biological function remains largely unknown. Until recently, it was classified as one of the Domain of Unknown Function (DUF) genes, with a conserved protein domain DUF2366 of unclear function. Since characterizing DUF genes can provide novel biological insight, we used previously established transcriptional profiles of the germline and stem cells of the flatworm Macrostomum lignano to probe conserved DUFs for their potential role in germline biology, stem cell function, regeneration, and development. Here, we demonstrate that DUF2366/TIM29 knockdown in M. lignano has very limited effect during the normal homeostatic condition but prevents worms from adapting to a highly proliferative state required for regeneration

Robust Bichromatic Classification using Two Lines

Given two sets $\mathit{R}$ and $\mathit{B}$ of at most $\mathit{n}$ points in the plane, we present efficient algorithms to find a two-line linear classifier that best separates the "red" points in $\mathit{R}$ from the "blue" points in $B$ and is robust to outliers. More precisely, we find a region $\mathit{W}_\mathit{B}$ bounded by two lines, so either a halfplane, strip, wedge, or double wedge, containing (most of) the blue points $\mathit{B}$, and few red points. Our running times vary between optimal $O(n\log n)$ and $O(n^4)$, depending on the type of region $\mathit{W}_\mathit{B}$ and whether we wish to minimize only red outliers, only blue outliers, or both.Comment: 19 pages, 11 figures. Updated to include new result

Simvastatin inhibits interferon-γ-induced MHC class II up-regulation in cultured astrocytes

Based on their potent anti-inflammatory properties and a preliminary clinical trial, statins (HMG-CoA reductase inhibitors) are being studied as possible candidates for multiple sclerosis (MS) therapy. The pathogenesis of MS is unclear. One theory suggests that the development of autoimmune lesions in the central nervous system may be due to a failure of endogenous inhibitory control of MHC class II expression on astrocytes, allowing these cells to adapt an interferon (IFN)-γ-induced antigen presenting phenotype. By using immunocytochemistry in cultured astrocytes derived from newborn Wistar rats we found that simvastatin at nanomolar concentrations inhibited, in a dose-response fashion, up to 70% of IFN-γ-induced MHC class II expression. This effect was reversed by the HMG-CoA reductase product mevalonate. Suppression of the antigen presenting function of astrocytes might contribute to the beneficial effects of statins in MS

Dual Infection and Superinfection Inhibition of Epithelial Skin Cells by Two Alphaherpesviruses Co-Occur in the Natural Host

Hosts can be infected with multiple herpesviruses, known as superinfection; however, superinfection of cells is rare due to the phenomenon known as superinfection inhibition. It is believed that dual infection of cells occurs in nature, based on studies examining genetic exchange between homologous alphaherpesviruses in the host, but to date, this has not been directly shown in a natural model. In this report, gallid herpesvirus 2 (GaHV-2), better known as Marek’s disease virus (MDV), was used in its natural host, the chicken, to determine whether two homologous alphaherpesviruses can infect the same cells in vivo. MDV shares close similarities with the human alphaherpesvirus, varicella zoster virus (VZV), with respect to replication in the skin and exit from the host. Recombinant MDVs were generated that express either the enhanced GFP (eGFP) or monomeric RFP (mRFP) fused to the UL47 (VP13/14) herpesvirus tegument protein. These viruses exhibited no alteration in pathogenic potential and expressed abundant UL47-eGFP or -mRFP in feather follicle epithelial cells in vivo. Using laser scanning confocal microscopy, it was evident that these two similar, but distinguishable, viruses were able to replicate within the same cells of their natural host. Evidence of superinfection inhibition was also observed. These results have important implications for two reasons. First, these results show that during natural infection, both dual infection of cells and superinfection inhibition can co-occur at the cellular level. Secondly, vaccination against MDV with homologous alphaherpesvirus like attenuated GaHV-2, or non-oncogenic GaHV-3 or meleagrid herpesvirus (MeHV-1) has driven the virus to greater virulence and these results implicate the potential for genetic exchange between homologous avian alphaherpesviruses that could drive increased virulence. Because the live attenuated varicella vaccine is currently being administered to children, who in turn could be superinfected by wild-type VZV, this could potentiate recombination events of VZV as well

Factors Affecting Trypanosome Maturation in Tsetse Flies

Trypanosoma brucei brucei infections which establish successfully in the tsetse fly midgut may subsequently mature into mammalian infective trypanosomes in the salivary glands. This maturation is not automatic and the control of these events is complex. Utilising direct in vivo feeding experiments, we report maturation of T. b. brucei infections in tsetse is regulated by antioxidants as well as environmental stimuli. Dissection of the maturation process provides opportunities to develop transmission blocking vaccines for trypanosomiasis. The present work suggests L-cysteine and/or nitric oxide are necessary for the differentiation of trypanosome midgut infections in tsetse

Interspecifieke konkurrentie als mogelijke verklaring voor aantalsfluktuaties van twee grondelsoorten in de Grevelingen (Pomatoschistus minutus en P. microps)

Aantalsfluctuaties, waarbij in het Grevelingenmeer afwisselend Pomatoschistus minutus of P. microps domineerde, gaven aanleiding om interspecifieke concurrentie te veronderstellen. De overlap van de verspreidingsgebieden van beide soorten is in het stagnante Grevelingenmeer groter dan in een getijdengebied. Hun dichtheden zijn relatief hoog. Door middel van maaginhoud-analyses is de voedselsamenstelling van beide grondelsoorten onderzocht in de maanden september, oktober en november 1980. In het gebied waar het dikkopje en de brakwatergrondel naast elkaar voorkomen zijn de voedselsamenstellingen vrijwel aan elkaar gelijk. De meest voorkomende prooidieren zijn achtereenvolgens: copepoden, Praunus flexuosus, Gammarus locusta en Idotea chelipes. Kleine vissen eten hoofdzakelijk copepoden. Met toenemende grootte wordt geleidelijk overgeschakeld op de grotere crustaceeën. Deze grotere crustaceeën worden vooral veel gegeten in het slibrijke en met zeegras en wieren begroeide oostelijk deel van het Grevelingenmeer. Het totale voedselspectrum van een dikkopje is zeer breed. Tenslotte is een schatting gemaakt van de predatie door beide soorten op de epibenthische fauna. Er zijn aanwijzingen gevonden voor intraspecifieke concurrentie bij P. minutus. Maar hoewel interspecifieke concurrentie mogelijk kan worden geacht, zijn er onvoldoende aanwijzingen om de aantalsfluctuaties zoals die bij beide grondelsoorten voorkomen met interspecifieke concurrentie te kunnen verklaren.