Revisiting the role of GSK3, a modulator of innate immunity, in idiopathic inclusion body myositis

Idiopathic or sporadic inclusion body myositis (IBM) is the leading age-related (onset > 50 years of age) autoimmune muscular pathology, resulting in significant debilitation in affected individuals. Once viewed as primarily a degenerative disorder, it is now evident that much like several other neuro-muscular degenerative disorders, IBM has a major autoinflammatory component resulting in chronic inflammation-induced muscle destruction. Thus, IBM is now considered primarily an inflammatory pathology. To date, there is no effective treatment for sporadic inclusion body myositis, and little is understood about the pathology at the molecular level, which would offer the best hopes of at least slowing down the degenerative process. Among the previously examined potential molecular players in IBM is glycogen synthase kinase (GSK)-3, whose role in promoting TAU phosphorylation and inclusion bodies in Alzheimer’s disease is well known. This review looks to re-examine the role of GSK3 in IBM, not strictly as a promoter of TAU and Abeta inclusions, but as a novel player in the innate immune system, discussing some of the recent roles discovered for this well-studied kinase in inflammatory-mediated pathology

Cases of albinism and leucism in amphibians in Italy : new reports

Findings of abnormally pigmented amphibian individuals provide interesting insights on intraspecific phenotypic variability as well as on variation among populations inhabiting different habitats. Amphibian coloration is determined by chromatophores (specific epidermal cells), and a variety of abnormalities related to them have been reported. In this study we reported cases of albinism and leucism in six species of Italian amphibians, including some endemic species. For some taxa, like Hydromantes sarrabusensis, H. flavus, H. supramontis and Bufo viridis, we describe the first observations of albinism and leucism

Variation in Community Structure across Vertical Intertidal Stress Gradients: How Does It Compare with Horizontal Variation at Different Scales?

In rocky intertidal habitats, the pronounced increase in environmental stress from low to high elevations greatly affects community structure, that is, the combined measure of species identity and their relative abundance. Recent studies have shown that ecological variation also occurs along the coastline at a variety of spatial scales. Little is known, however, on how vertical variation compares with horizontal variation measured at increasing spatial scales (in terms of sampling interval). Because broad-scale processes can generate geographical patterns in community structure, we tested the hypothesis that vertical ecological variation is higher than fine-scale horizontal variation but lower than broad-scale horizontal variation. To test this prediction, we compared the variation in community structure across intertidal elevations on rocky shores of Helgoland Island with independent estimates of horizontal variation measured at the scale of patches (quadrats separated by 10s of cm), sites (quadrats separated by a few m), and shores (quadrats separated by 100s to 1000s of m). The multivariate analyses done on community structure supported our prediction. Specifically, vertical variation was significantly higher than patch- and site-scale horizontal variation but lower than shore-scale horizontal variation. Similar patterns were found for the variation in abundance of foundation taxa such as Fucus spp. and Mastocarpus stellatus, suggesting that the effects of these canopy-forming algae, known to function as ecosystem engineers, may explain part of the observed variability in community structure. Our findings suggest that broad-scale processes affecting species performance increase ecological variability relative to the pervasive fine-scale patchiness already described for marine coasts and the well known variation caused by vertical stress gradients. Our results also indicate that experimental research aiming to understand community structure on marine shores should benefit from applying a multi-scale approach

Alternative Splicing, RNA Editing, and the Current Limits of Next Generation Sequencing

The advent of next generation sequencing (NGS) has fostered a shift in basic analytic strategies of a gene expression analysis in diverse pathologies for the purposes of research, pharmacology, and personalized medicine. What was once highly focused research on individual signaling pathways or pathway members has, from the time of gene expression arrays, become a global analysis of gene expression that has aided in identifying novel pathway interactions, the discovery of new therapeutic targets, and the establishment of disease-associated profiles for assessing progression, stratification, or a therapeutic response. But there are significant caveats to this analysis that do not allow for the construction of the full picture. The lack of timely updates to publicly available databases and the “hit and miss” deposition of scientific data to these databases relegate a large amount of potentially important data to “garbage”, begging the question, “how much are we really missing?” This brief perspective aims to highlight some of the limitations that RNA binding/modifying proteins and RNA processing impose on our current usage of NGS technologies as relating to cancer and how not fully appreciating the limitations of current NGS technology may negatively affect therapeutic strategies in the long run

Comparison between epiphyte assemblages of leaves and rhizomes of the seagrass Posidonia oceanica subjected to different levels of anthropogenic eutrophication

This paper aimed to compare epiphyte assemblages of leaves and rhizomes of Posidonia oceanica exposed to different levels of concentration of nutrients. The same design including a potentially impacted meadow and two reference meadows was used in each of two locations, characterized by the presence of a city or of suspended cages of a fish farm, respectively. This allowed to test for the consistency of responses of epiphytic assemblages to different sources of eutrophication. In both studies, results documented differences in patterns of composition and abundance of epiphytic assemblages on leaves between disturbed and reference meadows, while assemblages on rhizomes did not appear sensitive to this kind of disturbance. Moreover, in potentially impacted meadows, both assemblages showed different patterns of spatial variability compared to reference assemblages. Species composition and abundance of epiphyte assemblages seemed suitable for detecting moderate nutrient increases, even if adequate sampling designs are needed to separate patterns related to the large natural spatial variability of these systems from those related to changes in environmental conditions

Dynamic modelling and energy performance analysis of an innovative dual-source heat pump system

In this paper the energy performance of a Dual-Source Heat Pump (DSHP) system able to use both air and ground as external heat source is analysed by using TRNSYS and the experimental data obtained by testing a DSHP prototype. The DSHP seasonal and annual performance factors are compared with those offered by the same DSHP in which only ground (ground-source mode) or only external air (air-source mode) is used as external heat source in order to evaluate the benefits achievable with the exploitation of a double external heat source (ground and air) with the same unit. Yearly dynamic simulations have been carried out by coupling the DSHP to a detached residential building located in Bologna, characterized by unbalanced heating and cooling loads, and coupled to a geothermal loop based on borehole heat exchangers (BHEs). With the help of the dynamic simulations it has been demonstrated that DSHPs can be very useful in order to solve the problems linked to the ground temperature drift which can be originated by the presence of an undersized borehole heat exchanger field and/or by unbalanced heating and cooling loads. In fact, the use of external air as auxiliary heat source with respect to ground during the most severe season enables to obtain more stable energy performance even in presence of undersized BHEs. In this paper it is shown how an optimal trade-off in terms of annual energy performance and investment costs can be obtained by reducing the size of the DSHP borehole field of 15\u201355% with respect to the borehole field needed by a conventional ground-coupled heat pump having the same size. In this way the DSHP can be used during the retrofitting of thermal plants based on ground-coupled heat pumps in which an undersized BHEs field is present

Effects of enhanced loads of nutrients on epiphytes on leaves and rhizomes of Posidonia oceanica

The increase of anthropogenic activities has severely altered both terrestrial and aquatic systems. Urbanisation, excessive use of agricultural fertilisers, organic runoff and climate change have caused an increase of nutrients in coastal waters, altering the diversity and food-web structure of benthic assemblages. The aims of the present paper were to text if an experimentally increased availability of nutrients, primarily nitrogen and phosphorous, in an oligotrophic basin, would affect epiphytic assemblages on leaves and rhizomes of P. oceanica and whether this could change rates of consumption of the plant by herbivores. In particular, we tested the hypothesis i) that changes to species composition and abundance of epiphytic assemblages generated by nutrients enrichment would vary between leaves and rhizomes and that ii) alterations to epiphytic assemblages on leaves might, in turn, modify feeding rates of herbivorous fish. After two years, the structure of both leaf and rhizome epiphytic assemblages responded to changes in nutrient concentrations before the occurrence of drastic alterations to the host plant, but only the former showed significant changes in terms of species composition. Moreover, a larger intensity of grazing on P. oceanica leaves was documented in experimentally enriched areas than in controls. The present findings and conclusions are applicable to other systems where patterns of biodiversity depend on changes in the availability of nutrients due to natural or anthropogenic events, likely interacting with biological processes, such as competition and grazing

Signal transduction in ribosome biogenesis: A recipe to avoid disaster

Energetically speaking, ribosome biogenesis is by far the most costly process of the cell and, therefore, must be highly regulated in order to avoid unnecessary energy expenditure. Not only must ribosomal RNA (rRNA) synthesis, ribosomal protein (RP) transcription, translation, and nuclear import, as well as ribosome assembly, be tightly controlled, these events must be coordinated with other cellular events, such as cell division and differentiation. In addition, ribosome biogenesis must respond rapidly to environmental cues mediated by internal and cell surface receptors, or stress (oxidative stress, DNA damage, amino acid depletion, etc.). This review examines some of the well-studied pathways known to control ribosome biogenesis (PI3K-AKT-mTOR, RB-p53, MYC) and how they may interact with some of the less well studied pathways (eIF2\u3b1 kinase and RNA editing/splicing) in higher eukaryotes to regulate ribosome biogenesis, assembly, and protein translation in a dynamic manner

Nuclear inositide specific phospholipase C signalling - interactions and activity

Evidence accumulated over the past 20 years has highlighted the presence of an autonomous nuclear inositol lipid metabolism, and suggests that lipid signalling molecules are important components of signalling pathways operating within the nucleus. Nuclear polyphosphoinositide (PI) signalling relies on the synthesis and metabolism of phosphatidylinositol 4,5-bisphosphate, which can modulate the activity of effector proteins and is a substrate of signalling enzymes. The regulation of the nuclear PI pool is totally independent from the plasma membrane counterpart, suggesting that the nucleus constitutes a functionally distinct compartment of inositol lipids metabolism. Among the nuclear enzymes involved in PI metabolism, inositide specific phospholipase C (PI-PLC) has been one of the most extensively studied. Several isoforms of PI-PLCs have been identified in the nucleus, namely PI-PLC-\u3b21, \u3b31, \u3b41 and \u3b6; however, the \u3b21 isozyme is the best characterized. In the present review, we focus on the signal transduction-related metabolism of nuclear PI-PLC and review the most convincing evidence for PI-PLC expression and activity being involved in differentiation and proliferation programmes in several cell systems. Moreover, nuclear PI-PLC is an intermediate effector and interactor for nuclear inositide signalling. The inositide cycle exists and shows a biological role inside the nucleus. It is an autonomous lipid-dependent signalling system, independently regulated with respect to the one at the plasma membrane counterpart, and is involved in cell cycle progression and differentiation