Systemic and Brain Metabolic Dysfunction as a New Paradigm for Approaching Alzheimer’s Dementia

Since its definition Alzheimer’s disease has been at the centre of consideration for neurologists, psychiatrists, and pathologists. With John P. Blass it has been disclosed a different approach Alzheimer’s disease neurodegeneration understanding not only by the means of neurochemistry but also biochemistry opening new scenarios in the direction of a metabolic system degeneration. Nowadays, the understanding of the role of cholesterol, insulin, and adipokines among the others in Alzheimer’s disease etiopathogenesis is clarifying approaches valuable not only in preventing the disease but also for its therapy. Special issue dedicated to John P. Blass.     

Is the Eco-label EU Decision for hard coverings really capable of capturing the environmental performances of the marble productive chain? A field verification by means of a life cycle approach

Purpose

This work intends to show whether the Eco-label EU Decision for hard coverings, in which marble is contemplated among hard coverings as a natural product, is really capable of capturing the environmental performances of the marble productive chain, in other words whether it is actually viable for the natural products, like marble.

Methods

After a preliminary critical analysis of the suitability for marble of the current EU Decision (2009/607/EC), a classical life cycle assessment (LCA) methodology has been applied on the field to the marble “Perlato di Sicilia.” More specifically, the whole productive chain of a couple of firms treating the “Perlato di Sicilia” marble has been examined. The life cycle analysis is actually a cradle-to-gate analysis which includes the raw material extraction, processing phase, and finishing operations.

Results and discussion

Both the preliminary critical analyses of the structure of the Decision and the in-field checking on the two firms of the Custonaci marble district in Sicily singled out several conflicting points of the Decision for the marble working chain. These difficulties could be reasonably extended to other natural stones, such as granite, for which similar working processes are applied. Based on the outcomes of both these analyses, in the present work, a set of new indicators and modified criteria, already present in the Decision, is proposed as a candidate to be considered for inclusion in a future release of the Decision.

Conclusions

The changes here introduced can represent a useful indication toward a more suitable scheme of the EU Eco-label for marble, at least. Clearly, further investigations need to better assess the proposed scheme, especially in terms of threshold values of pollutant releases and use of explosive that are actually specific for the marble productive chain. The present modified version of the standard has been proposed to the Sicilian administration in order to be voluntarily adopted by marble productive sites of the region, in the aim of extensively verifying its suitability.     

Assessment of total hepatitis C virus (HCV) core protein in HCV-related mixed cryoglobulinemia

Introduction

In hepatitis C virus (HCV)-related mixed cryoglobulinemia (MCG), the nonenveloped HCV core protein (HCV-Cp) is a constituent of the characteristic cold-precipitating immune complexes (ICs). A possible correlation between HCV-Cp, virologic, laboratory, and clinical parameters in both untreated MCG patients and those undergoing specific treatment was explored.

Methods

HCV-Cp was quantified by a fully automated immune assay. Correlations between HCV-Cp and HCV RNA, cryocrit, and virus genotype (gt) were investigated in 102 chronically HCV-infected MCG patients.

Results

HCV-Cp concentrations strongly correlated with HCV RNA levels in baseline samples. An average ratio of 1,425 IU and 12,850 IU HCV RNA per picogram HCV-Cp was estimated in HCV gt-1 and gt-2 patients, respectively. This equation allowed us to estimate that, on average, HCV-Cp was associated with the viral genome in only 3.4% of the former and in 35% of the latter group of patients. The direct relation between HCV-Cp and the cryocrit level suggests that the protein directly influences the amount of cryoprecipitate. Although the therapy with rituximab (RTX) as a single agent resulted in the enhancement of HCV-Cp levels, in patients treated with RTX in combination with a specific antiviral therapy (pegylated interferon-α plus ribavirin), the prompt and effective clearance of HCV-Cp was documented.

Conclusions

Our data provide evidence that HCV-Cp has a direct effect on the cold-precipitation process in a virus genotype-dependence in HCV-related MCG patients.     

Silencing of RB1 and RB2/P130 during adipogenesis of bone marrow stromal cells results in dysregulated differentiation

Bone marrow adipose tissue (BMAT) is different from fat found elsewhere in the body, and only recently have some of its functions been investigated. BMAT may regulate bone marrow stem cell niche and plays a role in energy storage and thermogenesis. BMAT may be involved also in obesity and osteoporosis onset. Given the paramount functions of BMAT, we decided to better clarify the human bone marrow adipogenesis by analyzing the role of the retinoblastoma gene family, which are key players in cell cycle regulation.

Our data provide evidence that the inactivation of RB1 or RB2/P130 in uncommitted bone marrow stromal cells (BMSC) facilitates the first steps of adipogenesis. In cultures with silenced RB1 or RB2/P130, we observed an increase of clones with adipogenic potential and a higher percentage of cells accumulating lipid droplets.

Nevertheless, the absence of RB1 or RB2/P130 impaired the terminal adipocyte differentiation and gave rise to dysregulated adipose cells, with alteration in lipid uptake and release. For the first time, we evidenced that RB2/P130 plays a role in bone marrow adipogenesis.

Our data suggest that while the inactivation of retinoblastoma proteins may delay the onset of last cell division and allow more BMSC to be committed to adipocyte, it did not allow a permanent cell cycle exit, which is a prerequisite for adipocyte terminal maturation.     

On the tracks of Nitrogen deposition effects on temperate forests at their southern European range – an observational study from Italy

We studied forest monitoring data collected at permanent plots in Italy over the period 2000–2009 to identify the possible impact of nitrogen (N) deposition on soil chemistry, tree nutrition and growth. Average N throughfall (N‐NO₃+N‐NH₄) ranged between 4 and 29 kg ha^?1 yr^?1, with Critical Loads (CLs) for nutrient N exceeded at several sites. Evidence is consistent in pointing out effects of N deposition on soil and tree nutrition: topsoil exchangeable base cations (BCE) and pH decreased with increasing N deposition, and foliar nutrient N ratios (especially N : P and N : K) increased. Comparison between bulk openfield and throughfall data suggested possible canopy uptake of N_, levelling out for bulk deposition >4–6 kg ha^?1 yr^?1. Partial Least Square (PLS) regression revealed that ‐ although stand and meteorological variables explained the largest portion of variance in relative basal area increment (BAI_rel 2000–2009) ‐ N‐related predictors (topsoil BCE, C : N, pH; foliar N‐ratios; N deposition) nearly always improved the BAI_rel model in terms of variance explained (from 78.2 to 93.5%) and error (from 2.98 to 1.50%). N deposition was the strongest predictor even when stand, management and atmosphere‐related variables (meteorology and tropospheric ozone) were accounted for. The maximal annual response of BAI_rel was estimated at 0.074–0.085% for every additional kgN. This corresponds to an annual maximal relative increase of 0.13–0.14% of carbon sequestered in the above‐ground woody biomass for every additional kgN, i.e. a median value of 159 kgC per kgN ha^?1 yr^?1 (range: 50–504 kgC per kgN, depending on the site). Positive growth response occurred also at sites where signals of possible, perhaps recent N saturation were detected. This may suggest a time lag for detrimental N effects, but also that, under continuous high N input, the reported positive growth response may be not sustainable in the long‐term.     

A Mathematical-Biological Joint Effort to Investigate the Tumor-Initiating Ability of Cancer Stem Cells

The involvement of Cancer Stem Cells (CSCs) in tumor progression and tumor recurrence is one of the most studied subjects in current cancer research. The CSC hypothesis states that cancer cell populations are characterized by a hierarchical structure that affects cancer progression. Due to the complex dynamics involving CSCs and the other cancer cell subpopulations, a robust theory explaining their action has not been established yet. Some indications can be obtained by combining mathematical modeling and experimental data to understand tumor dynamics and to generate new experimental hypotheses. Here, we present a model describing the initial phase of ErbB2⁺ mammary cancer progression, which arises from a joint effort combing mathematical modeling and cancer biology. The proposed model represents a new approach to investigate the CSC-driven tumorigenesis and to analyze the relations among crucial events involving cancer cell subpopulations. Using in vivo and in vitro data we tuned the model to reproduce the initial dynamics of cancer growth, and we used its solution to characterize observed cancer progression with respect to mutual CSC and progenitor cell variation. The model was also used to investigate which association occurs among cell phenotypes when specific cell markers are considered. Finally, we found various correlations among model parameters which cannot be directly inferred from the available biological data and these dependencies were used to characterize the dynamics of cancer subpopulations during the initial phase of ErbB2⁺ mammary cancer progression.     

Metabolic changes of genetically engineered grapes (<Emphasis Type="Italic">Vitis vinifera</Emphasis> L.) studied by <Superscript>1</Superscript>H-NMR,metabolite heatmaps and <Emphasis Type="Italic">i</Emphasis>PLS

Introduction

The Deficiens Homologue 9-iaaM (DefH9-iaaM) gene is an ovule-specific auxin-synthesizing gene which is expressed specifically in placenta/ovules and promotes auxin-synthesis. It was introduced into the genome of two grape cultivars Thompson Seedless and Silcora and both transgenic cultivars had an increased number of berries per bunch.

Objectives

This study investigates the down-stream metabolic changes of Silcora and Thompson seedless grape cultivars when genetically modified through the insertion of the DefH9-iaaM gene into their genome.

Methods

The effects of the genetic modification upon the grape metabolome were evaluated through ¹H-NMR and exploratory data analysis. Chemometric tools such as Interval Partial Least Squares regression and metabolite heatmaps were employed for scrutinizing the changes in the transgenic metabolome as compared to the wild type one.

Results

The results show that the pleiotropic effect on the grape metabolome as a function of the gene modifications is relatively low, although the insertion of the transgene caused a decrement in malic acid and proline and an increment in p-coumaric acid content. In addition, the concentration of malic acid was successfully correlated with the number of inserted copies of transgene in the Silcora cultivar, proving that the increased production of berries, promoted by the inserted gene, is achieved at the expense of a decrement in malic acid concentration.

Conclusion

NMR together with chemometrics is able to identify specific metabolites that were up- or down regulated in the genetically engineered plants allowing highlighting alterations in the down-stream metabolic pathways due to the up-stream genetic modifications.