Current Status of Human Papillomavirus-Related Head and Neck Cancer: From Viral Genome to Patient Care

Virologica Sinica - Human papillomavirus (HPV) infection identified as a definitive human carcinogen is increasingly being recognized for its role in carcinogenesis of human cancers. Up to...     

A muscle controlled finite-element model of laryngeal abduction and adduction

A three-dimensional finite-element model was developed to simulate the complex movement of the laryngeal cartilages during vocal fold abduction and adduction. The model consists of cricoid and arytenoid cartilages, as well as the intralaryngeal muscles and vocal folds. The active and passive properties of the muscles were idealised by one-dimensional elements based on the Hill theory. Its controlling input value is a time dependent stimulation rate. Optimisation loops have been carried out for the arrangement of the individual stimulation rates. Since in vivo measurements are not feasible, the developed biomechanical model shall be used to analyse the force distribution within the laryngeal muscles during phonatory manoeuvres. Simulations of abduction and adduction in different pitches of voice lead to realistic tensions of the vocal folds. The model is a first step to analyse motional vocal fold diseases and to predict the consequences of phonosurgical interventions.     

Laccase-catalyzed decolorization of the synthetic azo-dye diamond black PV 200 and of some structurally related derivatives

The kinetics of laccase-catalyzed transformation of the azo-dye Diamond Black PV 200 (CI Mordant Black 9) and various related synthesized derivatives were analyzed for dependence on pH and substrate structure. The reaction mixture of Diamond Black PV 200 was analyzed by HPLC/MS–MS and it was shown that upon laccase oxidation, reactive chinoid fragments of lower molecular weight were formed. These may further oligomerize as indicated by the appearance of a number of compounds with increased molecular weight. The pH optimum for the decolorization was pH 5 for Diamond Black PV 200 which did not change significantly when the substitution pattern of its basic structure was varied. Biodegradability, however, was strongly dependent on the structure of the dyes.     

Noncanonical Role of the 9-1-1 Clamp in the Error-Free DNA Damage Tolerance Pathway

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Highlights? 9-1-1 and Exo1 are components of the error-free RAD6 pathway ? 9-1-1 promotes postreplicative template switching ? Polyubiquitylated PCNA and 9-1-1 cooperate in the error-free RAD6 pathway ? 9-1-1’s role in the error-free RAD6 pathway is uncoupled from checkpoint functions     

Wnk kinases are positive regulators of canonical Wnt/β-catenin signalling

Wnt/β-catenin signalling is central to development and its regulation is essential in preventing cancer. Using phosphorylation of Dishevelled as readout of pathway activation, we identified Drosophila Wnk kinase as a new regulator of canonical Wnt/β-catenin signalling. WNK kinases are known for regulating ion co-transporters associated with hypertension disorders. We demonstrate that wnk loss-of-function phenotypes resemble canonical Wnt pathway mutants, while Wnk overexpression causes gain-of-function canonical Wnt-signalling phenotypes. Importantly, knockdown of human WNK1 and WNK2 also results in decreased Wnt signalling in mammalian cell culture, suggesting that Wnk kinases have a conserved function in ensuring peak levels of canonical Wnt signalling.     

Stereocontrolled Facile Synthesis and Biological Evaluation of (3′S) and (3′R)-3′-Amino (and Azido)-3′-Deoxy Pyranonucleosides

This article describes the synthesis of (3 ′S) and (3 ′R)-3 ′-amino-3 ′-deoxy pyranonucleosides and their precursors (3 ′S) and (3 ′R)-3 ′-azido-3 ′-deoxy pyranonucleosides. Azidation of 1,2:5,6-di-O-isopropylidene-3-O-toluenesulfonyl-α-D-allofuranose followed by hydrolysis and subsequent acetylation afforded 3-azido-3-deoxy-1,2,4,6-tetra-O-acetyl-D-glucopyranose, which upon coupling with the proper silylated bases, deacetylation, and catalytic hydrogenation, obtained the target 3 ′-amino-3 ′-deoxy-β-D-glucopyranonucleosides. The desired 1-(3 ′-amino-3 ′-deoxy-β-D-allopyranosyl)5-fluorouracil was readily prepared from the suitable imidazylate sugar after azidation followed by a protection/deprotection sequence and reduction of the unprotected azido precursor. No antiviral activity was observed for the novel nucleosides. Moderate cytostatic activity was recorded for the 5-fluorouracil derivatives.     

Driving factors of a vegetation shift from Scots pine to pubescent oak in dry Alpine forests

An increasing number of studies have reported on forest declines and vegetation shifts triggered by drought. In the Swiss Rhone valley (Valais), one of the driest inner‐Alpine regions, the species composition in low elevation forests is changing: The sub‐boreal Scots pine (Pinus sylvestris L.) dominating the dry forests is showing high mortality rates. Concurrently the sub‐Mediterranean pubescent oak (Quercus pubescens Willd.) has locally increased in abundance. However, it remains unclear whether this local change in species composition is part of a larger‐scale vegetation shift. To study variability in mortality and regeneration in these dry forests we analysed data from the Swiss national forest inventory (NFI) on a regular grid between 1983 and 2003, and combined it with annual mortality data from a monitoring site. Pine mortality was found to be highest at low elevation (below 1000 m a.s.l.). Annual variation in pine mortality was correlated with a drought index computed for the summer months prior to observed tree death. A generalized linear mixed‐effects model indicated for the NFI data increased pine mortality on dryer sites with high stand competition, particularly for small‐diameter trees. Pine regeneration was low in comparison to its occurrence in the overstorey, whereas oak regeneration was comparably abundant. Although both species regenerated well at dry sites, pine regeneration was favoured at cooler sites at higher altitude and oak regeneration was more frequent at warmer sites, indicating a higher adaptation potential of oaks under future warming. Our results thus suggest that an extended shift in species composition is actually occurring in the pine forests in the Valais. The main driving factors are found to be climatic variability, particularly drought, and variability in stand structure and topography. Thus, pine forests at low elevations are developing into oak forests with unknown consequences for these ecosystems and their goods and services.     

Multiple introductions and no loss of genetic diversity: invasion history of Japanese Rose, Rosa rugosa, in Europe

The shrub Rosa rugosa (Japanese Rose), native to East Asia, is considered one of the most troublesome invasive plant species in natural or semi-natural habitats of northern Europe and has proven very difficult to control. We aimed at disentangling the species’ invasion history in Europe, including determining the number of introductions and their geographic origin, and at investigating whether populations in the introduced and native ranges differ in genetic diversity, structure and degree of differentiation. We found that introduced (n = 16) and native (n = 16) populations had similar levels of genetic diversity at seven nuclear SSR (microsatellite) loci. European populations lack isolation by distance and are less genetically differentiated than are populations in East Asia. Multiple and at least three independent colonization events, one of which was particularly successful, gave rise to current R. rugosa populations in Europe. The geographic distribution patterns of these three genetic clusters could not be explained by natural dispersal alone, indicating that human mediated secondary dispersal is driving the expansion in Europe. One cluster representing three of the European populations was most likely derived from NW Japan, whereas the origin of the remaining thirteen populations could not clearly be resolved. The introduction and expansion in Europe occurred with no significant loss of genetic diversity. We conclude that high propagule pressure at the primary establishment phase is the most parsimonious explanation for this pattern. A potential for long distance seed dispersal, coastal habitat connectivity and an outcrossing breeding system are factors likely to have enabled populations of R. rugosa to avoid detrimental effects of genetic bottlenecks and will further increase the species’ range size and abundance in Europe. We recommend that human-mediated dispersal should be prevented in order to halt the continued expansion.