The impact of demographic changes on the epidemiology of herpes zoster: Spain as a case study

Varicella zoster virus (VZV) causes varicella upon first exposure and may reactivate later in life into herpes zoster (HZ), with a risk that is thought to be reduced by re-exposures to VZV. Given the decades-long time scales of reactivation and its dependence on the accumulation of re-exposure episodes, adopting a long-term perspective may be useful to correctly interpret current epidemiological trends of VZV. In this study, we investigate the possible impact of demographic changes on varicella and HZ in Spain, using an age-structured mathematical model informed with historical demographic data and calibrated against age-specific profiles of varicella seroprevalence and HZ incidence data. The model qualitatively reproduces the remarkable growth of HZ incidence observed in Spain between 1997 and 2004, before the introduction of varicella vaccination programmes. We demonstrate that this growth may be partially ascribed to the reduction of varicella circulation that followed the overall decline of the birth rate in the twentieth century. Model predictions further suggest that, even under the most optimistic projections, HZ incidence will continue its rise until at least 2040. Considering the effect of demographic changes can help interpreting variations in epidemiological trends of HZ, contributing to a more accurate evaluation of vaccination programmes against VZV.     

A complex species complex: The controversial role of ecology and biogeography in the evolutionary history of Syllis gracilis Grube, 1840 (Annelida,Syllidae)

The cryptic diversity in the polychaete Syllis gracilis Grube, 1840, in the Mediterranean Sea was examined with an integrative morpho-molecular approach. Individuals of S. gracilis were collected at eleven Mediterranean localities to provide an insight into the role of brackish environments in inducing cryptic speciation. The examination of morphological features combined with a molecular genetic analysis based on a partial sequence of the 16S rRNA gene highlighted discrepancies between morphological and molecular diversity. Morphological data allowed to identify a morphotype with short appendages occurring in coralline algae communities and another one with long appendages observed in brackish-water environments and Sabellaria reefs. Multivariate analyses showed that sampling localities were the greatest source of morphological divergence, suggesting that phenotypic plasticity may play a role in local adaptations of S. gracilis populations. Molecular data showed the occurrence of four divergent lineages not corresponding to morphological clusters. Different species delimitation tests gave conflicting results, retrieving, however, at least four separated entities. Some lineages occurred in sympatry and were equally distributed in marine and brackish-water environments, excluding a biogeographic or ecological explanation of the observed pattern and suggesting instead ancient separation between lineages and secondary contact. The co-occurrence of different lineages hindered the identification of the lineage corresponding to S. gracilis sensu stricto. The discrepancy between morphological and molecular diversity suggests that different environmental and biogeographic features may interact in a complex and unpredictable way in shaping diversity patterns. An integrative approach is needed to provide a satisfactory insight on evolutionary processes in marine invertebrates.     

Dispersal ability rather than ecological tolerance drives differences in range size between lentic and lotic water beetles (Coleoptera: Hydrophilidae)

Aim In aquatic ecosystems, standing (lentic) and running (lotic) waters differ fundamentally in their stability and persistence, shaping the comparative population genetic structure, geographical range size and speciation rates of lentic versus lotic lineages. While the drivers of this pattern remain incompletely understood, the suite of traits making up the ability of a species to establish new populations is instrumental in determining such differences. Here we explore the degree to which the association between habitat type and geographical range size results from differences in dispersal ability or fundamental niche breadth in the members of the Enochrus bicolor complex, an aquatic beetle clade with species across the lentic–lotic divide. Location Western Mediterranean, with a special focus on North Africa, the Iberian Peninsula and Sicily. Methods DNA sequences for four loci were obtained from species of the E. bicolor complex and analysed using phylogenetic inference. Dispersal and establishment abilities were assessed in lentic–lotic species pairs of the complex, using flight wing morphometrics and thermal tolerance ranges as surrogates, respectively. Results There were clear differences in range size between the lotic and lentic taxa of the complex, which appears to have had a lotic origin with two transitions to standing waters. Only small differences were observed in temperature tolerance and acclimation ability between the two lotic–lentic sister species studied. By contrast, wing morphometrics revealed clear, consistent differences between lotic and lentic Enochrus species pairs, the latter having a higher dispersal capacity. Main conclusions We hypothesize that there have been two habitat shifts from lotic to lentic waters, which have allowed marked expansions in geographical range size in western Mediterranean species of the E. bicolor complex. Differences in dispersal rather than in establishment ability appear to underlie differences in geographical range extent, as transitions to lentic waters were associated with changes in wing morphology, but not in thermal tolerance range. In this lineage of water beetles, selection for dispersal in geologically short‐lived lentic systems has driven the evolution of larger range sizes in lentic taxa compared with those of their lotic relatives.     

RAC1 induces nuclear alterations through the LINC complex to enhance melanoma invasiveness

RHO GTPases are key regulators of the cytoskeletal architecture, which impact a broad range of biological processes in malignant cells including motility, invasion, and metastasis, thereby affecting tumor progression. One of the constraints during cell migration is the diameter of the pores through which cells pass. In this respect, the size and shape of the nucleus pose a major limitation. Therefore, enhanced nuclear plasticity can promote cell migration. Nuclear morphology is determined in part through the cytoskeleton, which connects to the nucleoskeleton through the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex. Here, we unravel the role of RAC1 as an orchestrator of nuclear morphology in melanoma cells. We demonstrate that activated RAC1 promotes nuclear alterations through its effector PAK1 and the tubulin cytoskeleton, thereby enhancing migration and intravasation of melanoma cells. Disruption of the LINC complex prevented RAC1-induced nuclear alterations and the invasive properties of melanoma cells. Thus, RAC1 induces nuclear morphology alterations through microtubules and the LINC complex to promote an invasive phenotype in melanoma cells.     

Testosterone metabolism in brain cells and membranes

The central nervous system (CNS) is considered a target structure for the action of all the classes of hormonal steroids produced by the organism. Well-characterized genomic and less well-understood membrane mechanisms of action are probably involved in the steroid modulation of brain activities. Moreover, some classes of steroids need to be converted into “active” metabolites before interacting with their effector systems. In particular, testosterone (T) exerts many of its effects after conversion to 5-dihydrotestosterone (DHT) and estrogens. The CNS possesses both the 5-reductase, the enzyme which produces DHT and the aromatase which transforms T into estrogens; however, the relative role and distribution of these enzymes in the various structural components of the CNS has not been clarified so far. The 5-reductase has been found to be present in high concentrations in brain white matter structures because these are particularly rich in myelin membranes, to which the enzymatic activity appears to be associated. This membrane localization might suggest a possible involvement of steroidal 5-reduced metabolites in membrane-mediated events in the CNS. Moreover, the distribution of 5-reductase was studied in neurons, astrocytes and oligodendrocytes isolated from the brain of male rats by density gradient ultracentrifugation, as well as in neurons and glial cells grown in culture. The aromatase activity was also evaluated in neurons and glial cells grown in culture and in isolated oligodendrocytes. Among the three cell types isolated, neurons appear to be more active than oligodendrocytes and astrocytes, respectively, in converting T into DHT. Also, in cell culture experiments, neurons are more active in forming DHT than glial cells. Only neurons possess aromatase activity, while glial cells are apparently unable to aromatize T.     

PRMT5 silencing selectively affects MTAP-deleted mesothelioma: In vitro evidence of a novel promising approach

Malignant mesothelioma (MM) is an aggressive asbestos-related cancer of the serous membranes. Despite intensive treatment regimens, MM is still a fatal disease, mainly due to the intrinsic resistance to current therapies and the lack of predictive markers and new valuable molecular targets. Protein arginine methyltransferase 5 (PRMT5) inhibition has recently emerged as a potential therapy against methylthioadenosine phosphorylase (MTAP)-deficient cancers, in which the accumulation of the substrate 5'-methylthioadenosine (MTA) inhibits PRMT5 activity, thus sensitizing the cells to further PRMT5 inhibition. Considering that the MTAP gene is frequently codeleted with the adjacent cyclin-dependent kinase inhibitor 2A (CDKN2A) locus in MM, we assessed whether PRMT5 could represent a therapeutic target also for this cancer type. We evaluated PRMT5 expression, the MTAP status and MTA content in normal mesothelial and MM cell lines. We found that both administration of exogenous MTA and stable PRMT5 knock-down, by short hairpin RNAs (shRNAs), selectively reduced the growth of MTAP-deleted MM cells. We also observed that PRMT5 knock-down in MTAP-deficient MM cells reduced the expression of E2F1 target genes involved in cell cycle progression and of factors implicated in epithelial-to-mesenchymal transition. Therefore, PRMT5 targeting could represent a promising new therapeutic strategy against MTAP-deleted MMs.     

Cheap and Nasty? The Potential Perils of Using Management Costs to Identify Global Conservation Priorities

The financial cost of biodiversity conservation varies widely around the world and such costs should be considered when identifying countries to best focus conservation investments. Previous global prioritizations have been based on global models for protected area management costs, but this metric may be related to other factors that negatively influence the effectiveness and social impacts of conservation. Here we investigate such relationships and first show that countries with low predicted costs are less politically stable. Local support and capacity can mitigate the impacts of such instability, but we also found that these countries have less civil society involvement in conservation. Therefore, externally funded projects in these countries must rely on government agencies for implementation. This can be problematic, as our analyses show that governments in countries with low predicted costs score poorly on indices of corruption, bureaucratic quality and human rights. Taken together, our results demonstrate that using national-level estimates for protected area management costs to set global conservation priorities is simplistic, as projects in apparently low-cost countries are less likely to succeed and more likely to have negative impacts on people. We identify the need for an improved approach to develop global conservation cost metrics that better capture the true costs of avoiding or overcoming such problems. Critically, conservation scientists must engage with practitioners to better understand and implement context-specific solutions. This approach assumes that measures of conservation costs, like measures of conservation value, are organization specific, and would bring a much-needed focus on reducing the negative impacts of conservation to develop projects that benefit people and biodiversity.     

Neuropathological findings processed by artificial neural networks (ANNs) can perfectly distinguish Alzheimer's patients from controls in the Nun Study

Background  

Many reports have described that there are fewer differences in AD brain neuropathologic lesions between AD patients and control subjects aged 80 years and older, as compared with the considerable differences between younger persons with AD and controls. In fact some investigators have suggested that since neurofibrillary tangles (NFT) can be identified in the brains of non-demented elderly subjects they should be considered as a consequence of the aging process. At present, there are no universally accepted neuropathological criteria which can mathematically differentiate AD from healthy brain in the oldest old.