Assessment of cetacean–fishery interactions in the marine food web of the Gulf of Taranto (Northern Ionian Sea,Central Mediterranean Sea)

Reviews in Fish Biology and Fisheries - The exploitation of fishery resources acts as a driving force on cetaceans both directly, by determining their fishing mortality or injury as by-catch...     

A biophysically-defined hyaluronic acid-based compound accelerates migration and stimulates the production of keratinocyte-derived neuromodulators

Hyaluronic acid (HA) preparations are widely used in clinical practice and recent data suggest that commercially available HA-based compounds promote ulcer re-epithelialization and induce pain relief. However, the pathophysiological basis of these effects remains poorly understood. In the present study, we investigated the biophysical, biomolecular and functional properties of a HA preparation combined with a pool of collagen precursor synthetic aminoacids, namely l-proline, l-leucine, l-lysine and glycine (Aminogam®). Hydrodynamic characterization of Aminogam® by size exclusion chromatography-triple detector array (SEC-TDA) revealed an average molecular weight in the range of 700–1700 kDa. Rheological measurements of the 1700kDa M_w lot showed a pseoudoplastic behaviour with a zero-shear viscosity (η₀) equal to 90 ± 9 Pa?s at 25°C and 55 ± 6 Pa?s at 37°C. Automated time-lapse videomicroscopy studies in a fibroblast-free system demonstrated that 1% (v/v) Aminogam® significantly reduced the healing time of wounded keratinocyte monolayers. In AKGOS assays, Aminogam® stimulated cellular locomotion (chemokinesis) and directional migration (chemotaxis) of keratinocytes. Analysis of microarray data suggested that keratinocytes had a functional neuroendocrine machinery, and this was confirmed by testing the secretion of six neuroactive molecules by ELISA, namely α-MSH, β-endorphins, melatonin, substance P, cortisol, and neurotensin. Interestingly, Aminogam® regulated the production of several neuropeptides, including β-endorphins. In conclusion, our data shed light on the epithelial-dependent mechanisms that underlie the efficacy of Aminogam®, particularly in reference to wound healing and nociception.     

SUGT1 controls susceptibility to HIV-1 infection by stabilizing microtubule plus-ends

Understanding the viral–host cell interface during HIV-1 infection is a prerequisite for the development of innovative antiviral therapies. Here we show that the suppressor of G2 allele of skp1 (SUGT1) is a permissive factor for human immunodeficiency virus (HIV)-1 infection. Expression of SUGT1 increases in infected cells on human brain sections and in permissive host cells. We found that SUGT1 determines the permissiveness to infection of lymphocytes and macrophages by modulating the nuclear import of the viral genome. More importantly, SUGT1 stabilizes the microtubule plus-ends (+MTs) of host cells (through the modulation of microtubule acetylation and the formation of end-binding protein 1 (EB1) comets). This effect on microtubules favors HIV-1 retrograde trafficking and replication. SUGT1 depletion impairs the replication of HIV-1 patient primary isolates and mutant virus that is resistant to raltegravir antiretroviral agent. Altogether our results identify SUGT1 as a cellular factor involved in the post-entry steps of HIV-1 infection that may be targeted for new therapeutic approaches.Subject terms: Infectious diseases, Immunopathogenesis     

Nonparametric confidence regions for the symmetry point-based optimal cutpoint and associated sensitivity of a continuous-scale diagnostic test

In medical research, diagnostic tests with continuous values are widely employed to attempt to distinguish between diseased and non-diseased subjects. The diagnostic accuracy of a test (or a biomarker) can be assessed by using the receiver operating characteristic (ROC) curve of the test. To summarize the ROC curve and primarily to determine an “optimal” threshold for test results to use in practice, several approaches may be considered, such as those based on the Youden index, on the so-called close-to-(0,1) point, on the concordance probability and on the symmetry point. In this paper, we focus on the symmetry point-based approach, that simultaneously controls the probabilities of the two types of correct classifications (healthy as healthy and diseased as diseased), and show how to get joint nonparametric confidence regions for the corresponding optimal cutpoint and the associated sensitivity (= specificity) value. Extensive simulation experiments are conducted to evaluate the finite sample performances of the proposed method. Real datasets are also used to illustrate its application.