The African hind's (Cephalopholis taeniops, serranidae) use of artificial reefs off Sal Island (Cape Verde): a preliminary study based on acoustic telemetry

The African hind Cephalopholis taeniops (Valenciennes, 1828) is one of the most important commercial demersal species caught in the Cape Verde archipelago. The species is closely associated with hard substrate and is one of the main attractions for SCUBA divers. In January 2006 a former Soviet fishing vessel - the Kwarcit - was sunk off Santa Maria Bay (Sal Island). Young C. taeniops are commonly observed in this artificial reef (AR). In order to investigate the species' use of the AR, 4 specimens were captured and surgically implanted underwater with Vemco brand acoustic transmitters. The fish were monitored daily with an active telemetry receiver for one week after release. Simultaneously, an array of 3 passive VR2 / VR2W receivers was set for 63 days, registering data that allowed an analysis of spatial, daily and short term temporal activity patterns. The results showed site fidelity to the AR, with no migrations to the nearby natural reef. The method used allowed to register a consistent higher activity during daytime and a preference for the area opposite the dominant current

The Presence of Essential and Non-Essential Stratum Corneum Proteases: The Vital Need for Protease Inhibitors

Dry skin is one of the most important concerns of consumers worldwide. Despite huge efforts over several decades, the personal care industry still does not offer complete solutions that satisfy the unmet needs of consumers for moisturizing treatments. The paucity of data for the underlying biochemical problems in and the effects of moisturizers on facial skin biology and physiology may partly explain this. Our recent color mapping studies based on bio-instrumental evaluations of skin capacitance and transepidermal water loss have revealed the complexity of facial skin. However, the biomolecular reasons for these subtle differences in the different zones of the face are unknown so far. As the maturation of the stratum corneum is vital for skin moisturization and optimal barrier function, we believe that the protease / proteaseinhibitor balance particularly of the plasminogen system may be key in these processes. Thus, our aim was to develop a specific dual plasmin and urokinase inhibitor for topical application to barrier-impaired skin and demonstrate its efficac

Spin dependent scattering of a domain-wall of controlled size

Magnetoresistance measurements in the CPP geometry have been performed on single electrodeposited Co nanowires exchange biased on one side by a sputtered amorphous GdCo layer. This geometry allows the stabilization of a single domain wall in the Co wire, the thickness of which can be controlled by an external magnetic field. Comparing magnetization, resistivity, and magnetoresistance studies of single Co nanowires, of GdCo layers, and of the coupled system, gives evidence for an additional contribution to the magnetoresistance when the domain wall is compressed by a magnetic field. This contribution is interpreted as the spin dependent scattering within the domain wall when the wall thickness becomes smaller than the spin diffusion length.Comment: 9 pages, 13 figure

Detection of K-Ras mutations in tumour samples of patients with non-small cell lung cancer using PNA-mediated PCR clamping

Non-small cell lung cancers (NSCLC), in particular adenocarcinoma, are often mixed with normal cells. Therefore, low sensitivity of direct sequencing used for K-Ras mutation analysis could be inadequate in some cases. Our study focused on the possibility to increase the detection of K-Ras mutations in cases of low tumour cellularity. Besides direct sequencing, we used wild-type hybridisation probes and peptide-nucleic-acid (PNA)-mediated PCR clamping to detect mutations at codons 12 and 13, in 114 routine consecutive NSCLC frozen surgical tumours untreated by targeted drugs. The sensitivity of the analysis without or with PNA was 10 and 1% of tumour DNA, respectively. Direct sequencing revealed K-Ras mutations in 11 out of 114 tumours (10%). Using PNA-mediated PCR clamping, 10 additional cases of K-Ras mutations were detected (21 out of 114, 18%, P<0.005), among which five in samples with low tumour cellularity. In adenocarcinoma, K-Ras mutation frequency increased from 7 out of 55 (13%) by direct sequencing to 15 out of 55 (27%) by clamped-PCR (P<0.005). K-Ras mutations detected by these sensitive techniques lost its prognostic value. In conclusion, a rapid and sensitive PCR-clamping test avoiding macro or micro dissection could be proposed in routine analysis especially for NSCLC samples with low percentage of tumour cells such as bronchial biopsies or after neoadjuvant chemotherapy

Ex vivo drug response profiling detects recurrent sensitivity patterns in drug-resistant acute lymphoblastic leukemia

Drug sensitivity and resistance testing on diagnostic leukemia samples should provide important functional information to guide actionable target and biomarker discovery. We provide proof of concept data by profiling 60 drugs on 68 acute lymphoblastic leukemia (ALL) samples mostly from resistant disease in cocultures of bone marrow stromal cells. Patient-derived xenografts retained the original pattern of mutations found in the matched patient material. Stromal coculture did not prevent leukemia cell cycle activity, but a specific sensitivity profile to cell cycle-related drugs identified samples with higher cell proliferation both in vitro and in vivo as leukemia xenografts. In patients with refractory relapses, individual patterns of marked drug resistance and exceptional responses to new agents of immediate clinical relevance were detected. The BCL2inhibitor venetoclax was highly active below 10 nM in B-cell precursor ALL (BCP-ALL) subsets, including MLL-AF4 and TCF3-HLF ALL, and in some T-cell ALLs (T-ALLs), predicting in vivo activity as a single agent and in combination with dexamethasone and vincristine. Unexpected sensitivity to dasatinib with half maximal inhibitory concentration values below 20 nM was detected in 2 independent T-ALL cohorts, which correlated with similar cytotoxic activity of the SRC inhibitor KX2-391 and inhibition of SRC phosphorylation. A patient with refractory T-ALL was treated with dasatinib on the basis of drug profiling information and achieved a 5-month remission. Thus, drug profiling captures disease-relevant features and unexpected sensitivity to relevant drugs, which warrants further exploration of this functional assay in the context of clinical trials to develop drug repurposing strategies for patients with urgent medical needs.Peer reviewe

Towards an international language for incontinence-associated dermatitis (IAD): design and evaluation of psychometric properties of the Ghent Global IAD Categorization Tool (GLOBIAD) in 30 countries

Background Incontinence-associated dermatitis (IAD) is a specific type of irritant contact dermatitis with different severity levels. An internationally accepted instrument to assess the severity of IAD in adults, with established diagnostic accuracy, agreement and reliability, is needed to support clinical practice and research. Objectives To design the Ghent Global IAD Categorization Tool (GLOBIAD) and evaluate its psychometric properties. Methods The design was based on expert consultation using a three-round Delphi procedure with 34 experts from 13 countries. The instrument was tested using IAD photographs, which reflected different severity levels, in a sample of 823 healthcare professionals from 30 countries. Measures for diagnostic accuracy (sensitivity and specificity), agreement, interrater reliability (multirater Fleiss kappa) and intrarater reliability (Cohen’s kappa) were assessed. Results The GLOBIAD consists of two categories based on the presence of persistent redness (category 1) and skin loss (category 2), both of which are subdivided based on the presence of clinical signs of infection. The agreement for differentiating between category 1 and category 2 was 0 86 [95% confidence interval (CI) 0 86–0 87], with a sensitivity of 90% and a specificity of 84%. The overall agreement was 0 55 (95% CI 0 55–0 56). The Fleiss kappa for differentiating between category 1 and category 2 was 0 65 (95% CI 0 65–0 65). The overall Fleiss kappa was 0 41 (95% CI 0 41–0 41). The Cohen’s kappa for differentiating between category 1 and category 2 was 0 76 (95% CI 0 75–0 77). The overall Cohen’s kappa was 0 61 (95% CI 0 59–0 62). Conclusions The development of the GLOBIAD is a major step towards a better systematic assessment of IAD in clinical practice and research worldwide. However, further validation is needed.info:eu-repo/semantics/acceptedVersio

Flavaglines Alleviate Doxorubicin Cardiotoxicity: Implication of Hsp27

Background: Despite its effectiveness in the treatment of various cancers, the use of doxorubicin is limited by a potentially fatal cardiomyopathy. Prevention of this cardiotoxicity remains a critical issue in clinical oncology. We hypothesized that flavaglines, a family of natural compounds that display potent neuroprotective effects, may also alleviate doxorubicininduced cardiotoxicity. Methodology/Principal Findings: Our in vitro data established that a pretreatment with flavaglines significantly increased viability of doxorubicin-injured H9c2 cardiomyocytes as demonstrated by annexin V, TUNEL and active caspase-3 assays. We demonstrated also that phosphorylation of the small heat shock protein Hsp27 is involved in the mechanism by which flavaglines display their cardioprotective effect. Furthermore, knocking-down Hsp27 in H9c2 cardiomyocytes completely reversed this cardioprotection. Administration of our lead compound (FL3) to mice attenuated cardiomyocyte apoptosis and cardiac fibrosis, as reflected by a 50 % decrease of mortality. Conclusions/Significance: These results suggest a prophylactic potential of flavaglines to prevent doxorubicin-induce

Filaggrin Genotype Determines Functional and Molecular Alterations in Skin of Patients with Atopic Dermatitis and Ichthyosis Vulgaris

BACKGROUND: Several common genetic and environmental disease mechanisms are important for the pathophysiology behind atopic dermatitis (AD). Filaggrin (FLG) loss-of-function is of great significance for barrier impairment in AD and ichthyosis vulgaris (IV), which is commonly associated with AD. The molecular background is, however, complex and various clusters of genes are altered, including inflammatory and epidermal-differentiation genes. OBJECTIVE: The objective was to study whether the functional and molecular alterations in AD and IV skin depend directly on FLG loss-of-function, and whether FLG genotype determines the type of downstream molecular pathway affected. METHODS AND FINDINGS: Patients with AD/IV (n = 43) and controls (n = 15) were recruited from two Swedish outpatient clinics and a Swedish AD family material with known FLG genotype. They were clinically examined and their medical history recorded using a standardized questionnaire. Blood samples and punch biopsies were taken and trans-epidermal water loss (TEWL) and skin pH was assessed with standard techniques. In addition to FLG genotyping, the STS gene was analyzed to exclude X-linked recessive ichthyosis (XLI). Microarrays and quantitative real-time PCR were used to compare differences in gene expression depending on FLG genotype. Several different signalling pathways were altered depending on FLG genotype in patients suffering from AD or AD/IV. Disease severity, TEWL and pH follow FLG deficiency in the skin; and the number of altered genes and pathways are correlated to FLG mRNA expression. CONCLUSIONS: We emphasize further the role of FLG in skin-barrier integrity and the complex compensatory activation of signalling pathways. This involves inflammation, epidermal differentiation, lipid metabolism, cell signalling and adhesion in response to FLG-dependent skin-barrier dysfunction