DNA Methylation Signatures of Bone Metabolism in Osteoporosis and Osteoarthritis Aging-Related Diseases: An Updated Review

DNA methylation is one of the most studied epigenetic mechanisms that play a pivotal role in regulating gene expression. The epigenetic component is strongly involved in aging-bone diseases, such as osteoporosis and osteoarthritis. Both are complex multi-factorial late-onset disorders that represent a globally widespread health problem, highlighting a crucial point of investigations in many scientific studies. In recent years, new findings on the role of DNA methylation in the pathogenesis of aging-bone diseases have emerged. The aim of this systematic review is to update knowledge in the field of DNA methylation associated with osteoporosis and osteoarthritis, focusing on the specific tissues involved in both pathological conditions.     

Resveratrol as Chemosensitizer Agent: State of Art and Future Perspectives

Resistance to chemotherapy still remains a major challenge in the clinic, impairing the quality of life and survival rate of patients. The identification of unconventional chemosensitizing agents is therefore an interesting aspect of cancer research. Resveratrol has emerged in the last decades as a fascinating molecule, able to modulate several cancer-related molecular mechanisms, suggesting a possible application as an adjuvant in cancer management. This review goes deep into the existing literature concerning the possible chemosensitizing effect of resveratrol associated with the most conventional chemotherapeutic drugs. Despite the promising effects observed in different cancer types in in vitro studies, the clinical translation still presents strong limitations due to the low bioavailability of resveratrol. Recently, efforts have been moved in the field of drug delivery to identifying possible strategies/formulations useful for a more effective administration. Despite the necessity of a huge implementation in this research area, resveratrol appears as a promising molecule able to sensitize resistant tumors to drugs, suggesting its potential use in therapy-refractory cancer patients.     

DILIGENT: integrating digital library and Grid technologies for a new Earth observation research infrastructure

This paper introduces DILIGENT, a digital library infrastructure built by integrating digital library and Grid technologies and resources. This infrastructure allows different communities to dynamically build specialised digital libraries capable to support the entire e-Science knowledge production and consumption life-cycle by using shared computing, storage, content, and application resources. The paper presents some of the main software services that implement the DILIGENT system. Moreover, it exemplifies the provided features by presenting how the DILIGENT infrastructure is being exploited in supporting the activity of user communities working in the Earth Science Environmental sector. This work is partially funded by the European Commission in the context of the DILIGENT project, under the 2nd call of FP6 IST priority.     

Acetohydroxy acid synthase and threonine deaminase activities, and the biosynthesis of isoleucine-leucine-valine in Streptococcus bovis

Acetohydroxy acid synthase (AHAS) and threonine deaminase (TD) activities were found in Streptococcus bovis and shown to be involved in the biosynthesis of the branched chain amino acids isoleucine, leucine and valine. Apparent lack of repression of AHAS synthesis by the end-products and reduced sensitivity of S. bovis growth to analogues of the branched chain amino acids suggested that secretion of isoleucine, leucine and valine in the growth medium may be a consequence of the regulatory features of AHAS. A glycyl-leucine-resistant mutant with reduced TD activity secreted a reduced amount of isoleucine and an increased amount of valine, which might be a result of the reduced rate of synthesis of the isoleucine precursor alpha-ketobutyrate and of a consequent preferential carbon flow through the valine branch of the pathway.     

The effect of cytokines, including IL4, IL7, stem cell factor, insulin-like growth factor on childhood acute lymphoblastic leukemia

We have investigated the effects of some interleukins, such as interleukin (IL) 4, IL7, stem cell factor (SCF) and insulin-like growth factor (IGF-1), known to be involved in human lymphopoiesis, on proliferation, clonal growth and differentiation of cells from two acute lymphoblastic leukemia (ALL) derived pre-B cell lines, that is, Nalm 1, Nalm 6 and purified blasts from 37 childhood ALL. IL4 did not display any promoting activity, an inhibitory effect being observed in two patients. IL7 showed an heterogeneous responsiveness, not related to immunophenotype or cytogenetic features, proliferation and clonal growth being observed in a minority of ALL. In other patients no or even inhibitory effects on proliferation were observed. In one case this inhibition of DNA synthesis was accompanied by maturation of the cells, as demonstrated by the induced expression of surface immunoglobulins (slg); other IL7 treated samples failed to express slg, but showed a decreased expression of terminal deoxynucleotidyl transferase and cALL antigen, suggesting that the cells have a potential of limited maturation by IL7. SCF, known to synergize with IL7 in the most primitive stages of normal B cell development, did not enhance the IL7 response in B cell precursor ALL. Finally IGF-1 failed to induce a proliferative response and clonal growth in BCP ALL either alone or in combination with IL7.     

The impact of risk and protective factors on online teaching experience in high school Italian teachers during the COVID-19 pandemic

The lockdown due to COVID-19 in Italy resulted in the sudden closure of schools, with a shift from traditional teaching to the online one. Through an online questionnaire, this survey explores teachers' experience of online teaching, the level of risk factors (e.g., stress) and protective factors (e.g., locus of control) and their impact on satisfaction levels during the social distancing. One hundred seven high school teachers from Lombardy, an Italian region very affected by the COVID-19 outbreak, participated. Results show that depression and stress are the main predictors of satisfaction levels for online teaching. In addition, coping, locus of control and self-efficacy emerge as important protective factors. Finally, although there is great satisfaction with the online teaching experience, critical elements emerged. This study is relevant because it describes the critical elements of the online teaching experience, and identifies some protective factors and the main risk factors in teachers operating in an area strongly marked by social restrictions imposed by the pandemic. High school teachers emerge as a sub-group of the general population with specific psychological reactions. Considering the results, it is possible to suggest providing high-quality educational support and crisis-psychological oriented services to teachers, and help to maintain the psychological well-being.     

Wrinkling of epoxy powder coatings

Differential scanning calorimetry (DSC) and mechanical profilometry were used to study wrinkle formation in curing epoxy powder coatings. Powder coating formulations were studied that contained solid epoxy resins, methylene disalicylic acid (MDSA) crosslinker, and an amine‐blocked Lewis acid catalyst. Both the crosslinker (MDSA) and the amine‐blocked catalyst are required for wrinkle formation. Evaporation of the blocking amine from the free surface of the coating generated a depthwise gradient in the extent of polymerization and crosslinking, and hence in the degree of solidification, as evidenced by the formation of a mechanical skin prior to wrinkling. It is hypothesized that compressive elastic stress develops in the still swellable skin when unreacted low‐molecular‐weight material from beneath diffuses up into the monomer‐ or oligomer‐depleted crosslinking skin and swells it. This compressive stress, if above a critical value, buckles the skin to produce wrinkles. Experimentally observed compositional requirements for wrinkle formation were consistent with the proposed mechanism. The size of the wrinkles can be controlled by varying formulation parameters such as the amount of catalyst or crosslinker. Increasing the amount of catalyst decreased both the wavelength and the amplitude of the wrinkle pattern. Increasing the amount of crosslinker initially increased the amplitude of the wrinkles; after reaching a maximum level, the wrinkle amplitude decreased. DSC was a useful tool to understand the critical reactions responsible for wrinkling in this system. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 116–129, 2005     

Reducing control selection errors associated with underground bolting equipment

Selecting the incorrect control during the operation of underground bolting and drilling equipment causes serious injuries. Shape coding and the layout of dual control banks are two aspects of control design which require further examination. The aims of this research were: (i) to determine whether arbitrary shape coding was effective in reducing selection error rates in a virtual analogy of roof-bolting; and (ii) to determine whether any advantages exist for mirror or place layouts for dual control situations in this situation. Two experiments were conducted to address these questions. No benefits of arbitrary shape coding were evident while control location remained constant. When control location was altered, shape coding did provide a significant reduction in selection error rate. No differences between mirror or place arrangements were detected and this question remains open.     

Examining working memory load and congruency effects on affordances and conventions

Although there is a debate about whether designers should draw a distinction between perceptual affordances and cultural conventions, there are few behavioral studies. We examined the impact of working memory load and expected button-to-action mapping congruency on affordances and conventions. The findings suggest both sides of the debate are correct. Learned conventions were found to structure responses towards expected actions, just like affordances, but affordance-based interactions were not affected by memory load while convention-based actions were. Therefore, designers ought to employ perceptual affordances when possible and when not feasible they ought to reuse established conventions. Additionally, evidence is presented that violating expected affordance-based and convention-based button-to-action mappings caused a similar performance cost. We believe that after the initial learning period, conventions play a critical role in the perception of a design’s available actions just as perceptual affordances do.     

Urinary proteomic analysis of chronic allograft nephropathy

The pathogenesis of progressive renal allograft injury, which is termed chronic allograft nephropathy (CAN), remains obscure and is currently defined by histology. Prospective protocol-biopsy trials have demonstrated that clinical and standard laboratory tests are insufficiently sensitive indicators of the development and progression of CAN. The study aim was to determine if CAN could be characterized by urinary proteomic data and identify the proteins associated with disease. The urinary proteome of 75 renal transplant recipients and 20 healthy volunteers was analyzed using surface enhanced laser desorption and ionization MS. Patients could be classified into subgroups with normal histology and Banff CAN grades 2-3 with a sensitivity of 86% and a specificity of 92% by applying the classification algorithm Adaboost to urinary proteomic data. Several urinary proteins associated with advanced CAN were identified including α1-microglobulin, β2-microglobulin, prealbumin, and endorepellin, the antiangiogenic C-terminal fragment of perlecan. Increased urinary endorepellin was confirmed by ELISA and increased tissue expression of the endorepellin/perlecan ratio by immunofluoresence analysis of renal biopsies. In conclusion, analysis of urinary proteomic data has further characterized the more severe CAN grades and identified urinary endorepellin, as a potential biomarker of advanced CAN.