Open Education and OER - A guide and call to action for policy makers

Executive Summary ALT has produced this call to action to highlight to education policy makers and professionals how Open Education and OER can expand inclusive and equitable access to education and lifelong learning, widen participation, and create new opportunities for the next generation of teachers and learners, preparing them to become fully engaged digital citizens. Open Education can also promote knowledge transfer while enhancing quality and sustainability, supporting social inclusion and creating a culture of inter-institutional collaboration and sharing. One of ALT’s three strategic aims is to increase the impact of Learning Technology for the wider community and we are issuing this call to action for policy makers to mandate that publicly funded educational resources are released under open licence to ensure that they reside in the public domain and are freely and openly available to all. This will be of wide benefit, but in particular will enable education providers and learning technology professionals to: Keep up to date with the rapid pace of technological innovation Develop critical, informed approaches to the implementation of Learning Technology and the impact on learners Scale up knowledge sharing and its benefits across sectors.

Catalytic reduction of levulinic acid derivatives to bio-fuel components

Levulinic Acid and its esters are polyfunctional molecules obtained by biomass conversion. The most investigated strategy for the valorization of LA is its hydrogenation towards fuel additives, solvents and other added-value bio-based chemicals and, in this context, heterogeneous and homogeneous catalysts are widely used. Most commonly, it is typically performed with molecular hydrogen (H2) in batch systems, with high H2 pressures and noble metal catalysts. Several works reported the batch liquid-phase hydrogenation of LA and its esters by heterogenous catalysts which contained support with Brønsted acidity in order to obtain valeric acid and its esters. Furthermore, bimetallic and monometallic systems composed by both a metal for hydrogen activation and a promoter were demonstrated to be suitable catalysts for reduction of carboxylic group. However, there were no studies in the literature reporting the hydrogenation of alkyl levulinates to 1-pentanol (1-PAO). Therefore, bimetallic and monometallic catalysts were tested for one-pot hydrogenation of methyl levulinate to 1-PAO. Re-based catalysts were investigated, this way proving the crucial role of the support for promoting the ring-opening of GVL and its consecutive reduction to valeric compounds. All the reactions were performed in neat without the need of any additional solvents. In these conditions, bimetallic Re-Ru-O/HZSM-5 afforded methyl valerate and valeric acid (VA) with a productivity of 512 mmol gmetal-1 h-1, one of the highest reported in literature to date. Rhenium can also promote the reduction of valeric acid/esters to PV through the formation of 1-pentanol and its efficient esterification/transesterification with the starting material. However, it was proved that Re-based catalysts may undergo leaching of active phase in presence of carboxylic acids, especially by working in neat with VA. Furthermore, the over-reduction of rhenium affects catalytic performance, suggesting not only that a pre-reduction step is unnecessary but also that it could be detrimental for catalyst’s activity.

Strategies to hijack MTs dysfunction in neurodegenerative tauopathies: Design and synthesis of novel CNS-disease-modifying tools

Neuronal microtubules assembly and dynamics are regulated by several proteins including (MT)-associated protein tau, whose aberrant hyperphosphorylation promotes its dissociation from MTs and its abnormal deposition into neurofibrillary tangles, a common neurotoxic hallmarks of neurodegenerative tauopathies. To date, no disease-modifying drugs have been approved to combat CNS tau-related diseases. The multifactorial etiology of these conditions represents one of the major limits in the discovery of effective therapeutic options. In addition, tau protein functions are orchestrated by diverse post-translational modifications among which phosphorylation mediated by PKs plays a leading role. In this context, conventional single-target therapies are often inadequate in restoring perturbed networks and fraught with adverse side-effects. This thesis reports two distinct approaches to hijack MT defects in neurons. The first is focused on the rational design and synthesis of first-in-class triple inhibitors of GSK-3β, FYN, and DYRK1A, three close-related PKs, which act as master regulators of aberrant tau hyperphosphorylation. A merged multi-target pharmacophore strategy was applied to simultaneously modulate all three targets and achieve a disease-modifying effect. Optimization of ARN25068 by a computationally and crystallographic driven SAR exploration, allowed to rationalize the key structural modifications to maintain a balanced potency against all three targets and develop a new generation of quite well-balanced analogs exhibiting improved physicochemical properties, a good in vitro ADME profile, and promising cell-based anti-tau phosphorylation activity. In Part II, MT-stabilizing compounds have been developed to compensate MT defects in tau-related pathologies. Intensive chemical effort has been devoted to scaling up BL-0884, identified as a promising MT-normalizing TPD, which exhibited favorable ADME-PK, including brain penetration, oral bioavailability, and brain pharmacodynamic activity. A suitable functionalization of the exposed hydroxyl moiety of BL-0884 was carried out to generate corresponding esters and amides possessing a wide range of applications as prodrugs and active targeting for cancer chemotherapy.

Unveiling the molecular mechanism of BRCA2-RAD51 interaction to tackle cancer onset

Different kinds of lesions can occur to DNA, and among them, one of the most dangerous is the double strand breaks (DSBs). Actually, DSBs can result in mutations, chromosome translocation or deletion. For this kind of lesions, depending on cell cycle phase as well as DNA-end resection, cells have developed specific repair pathways. Among these the error-free homologous recombination (HR) plays a crucial role. HR takes place during S/G2 phases, since the sister chromatids can be used as homologous templates. In this process, hRAD51 and BRCA2 are key players. hRAD51 is a recombinase of 339 amino-acids highly conserved through evolution which displays an intrinsic tendency to form oligomeric structures. BRCA2 is a very large protein of 3418 amino-acids, essential for the recruitment and accumulation of hRAD51 in the nucleus repairing-foci. BRCA2 interacts with hRAD51 through eight, so-called, BRC repeats, composed of 35-40 amino-acids. Mutations within this region have been linked to an increased risk of ovarian cancer development. In particular, several reports highlighted that missense mutations within one BRC repeat can hamper BRCA2 activity. Considering the close homology between the BRC repeats, it is striking how these mutations cannot be counterbalanced by the other non-mutated repeats preserving the function and the interactions of BRCA2 with hRAD51. To date the only interaction that has been structurally elucidated, is the one taking place amid the fourth BRC repeat and hRAD51. Only very little biophysical information is available on the interaction of the other BRC repeats with hRAD51. This thesis aims at elucidating the mechanism of hRAD51-BRCA2 interaction, by means of biophysical and structural approaches.

A 3D biomimetic in vitro model: a novel strategy to investigate glioma biology

Gliomas are one of the most frequent primary malignant brain tumors. Acquisition of stem-like features likely contributes to the malignant nature of high-grade gliomas and may be responsible for the initiation, growth, and recurrence of these tumors. In this regard, although the traditional 2D cell culture system has been widely used in cancer research, it shows limitations in maintaining the stemness properties of cancer and in mimicking the in vivo microenvironment. In order to overcome these limitations, different three-dimensional (3D) culture systems have been developed to mimic better the tumor microenvironment. Cancer cells cultured in 3D structures may represent a more reliable in vitro model due to increased cell-cell and cell-extracellular matrix (ECM) interaction. Several attempts to recreate brain cancer tissue in vitro are described in literature. However, to date, it is still unclear which main characteristics the ideal model should reproduce. The overall goal of this project was the development of a 3D in vitro model able to reproduce the brain ECM microenvironment and to recapitulate pathological condition for the study of tumor stroma interactions, tumor invasion ability, and molecular phenotype of glioma cells. We performed an in silico bioinformatic analysis using GEPIA2 Software to compare the expression level of seven matrix protein in the LGG tumors with healthy tissues. Then, we carried out a FFPE retrospective study in order to evaluate the percentage of expression of selected proteins. Thus, we developed a 3D scaffold composed by Hyaluronic Acid and Collagen IV in a ratio of 50:50. We used two astrocytoma cell lines, HTB-12 and HTB-13. In conclusion, we developed an in vitro 3D model able to reproduce the composition of brain tumor ECM, demonstrating that it is a feasible platform to investigate the interaction between tumor cells and the matrix.

From emerging adults' unmet psychosocial needs to their problematic use of social networking sites: the mediating role of Fear of Missing Out

Fear of Missing Out (FoMO) is a pervasive apprehension that others might be having rewarding experiences from which one is absent. Consequently, individuals experiencing FoMO wish to stay constantly in contact with what others are doing and engage with social networking sites for this purpose. In recent times, FoMO has received increased attention from psychological research, as a minority of users experiencing high levels of FoMO - particularly young people - might develop a problematic social networking site use, defined as the maladaptive and excessive use of social networking sites, resulting in symptoms associated with other addictions. According to the theoretical framework of the Interaction of Person-Affect-Cognition- Execution (I-PACE) model, FoMO and certain motives for use may foster problematic use in individuals who display unmet psychosocial needs. However, to date, the I-PACE model has only conceptualized the general higher-order mechanisms related to the development of problematic use. Consistently, the overall purpose of this dissertation was to deepen the understanding of the mediating role of FoMO between specific predisposing variables and problematic social networking sites use. Adopting a psychological approach, two empirical and exploratory cross-sectional studies, conceived as independent research, were conducted through path analysis.

Contribution of cytokines to the etiology and progression of Primary Myelofibrosis

Primary Myelofibrosis (PMF) is the end-stage of Philadelphia-negative myeloproliferative neoplasms (MPN) and is characterized by fibrosis and hematopoietic failure in bone marrow, with a consequential migration of the malignant hematopoietic stem cells (HSC) in the spleen where they induce ineffective haematopoiesis. To date, available therapies for PMF are still palliative and do not halt the progression of this neoplasm. During my PhD years, our laboratory investigated the factors promoting the onset and progression of PMF. In our PMF mice model, Gata1low mouse, we studied the role of the interaction of HSC niche with megakaryocytes and HSC localization in the bone marrow during their division and cycle. We observed the inflammation and the main protagonists (LNC-2, CXCL1, and TGF-β) of this process and how their level changes before and after the onset of the disease. We investigated the different megakaryocyte populations in the fibrotic environment in different organs (lung and bone marrow) to define the megakaryocytes implicated in this process. In human samples, we described different ultrastructural abnormalities of megakaryocytes from the bone marrow and the spleen, identifying a possible different metabolism in those two populations. In conclusion, we highlighted the intricated crosstalk between the megakaryocytes, the niche and HSC in PMF. We identified megakaryocytes-dependent cytokines altering the homeostasis of the niche and HSC. Those cytokines could be used as alternative therapeutic targets. Furthermore, we observed different megakaryocytic populations in different organs, providing new prospective on the role of megakaryocytes in different microenvironments.

Development And Characterization Of Microsatellite Loci For Tabebuia Cassinoides (bignoniaceae).

Tabebuia cassinoides (Lam.) DC., popularly known as caxeta, is a tree species that belongs to the plant family Bignoniaceae. This species is endemic to the Brazilian Atlantic Forest and is widely exploited commercially. To date, little is known about its genetic structure, preventing the establishment of adequate management plans for this taxon. The objective of this study was to construct a microsatellite-enriched genomic library for T. cassinoides to select polymorphic loci, and standardize polymerase chain reaction amplification conditions. Of the 15 loci examined, 5 were polymorphic. The number of alleles per locus ranged from 2 to 8, with a mean of 4.4. The microsatellite loci described here represent the basis for detailed population genetic studies of this species, which will greatly contribute for the development of better conservation strategies for this taxon.

[strategies For Integration Of Health Care Practices And Sanitary Surveillance In The Context Of The Implementation Of Rede Cegonha - A Brazilian Mother And Infant Health Care Network].

Mother and infant mortality has been the scope of analysis throughout the history of public health in Brazil and various strategies to tackle the issue have been proposed to date. The Ministry of Health has been working on this and the Rede Cegonha strategy is the most recent policy in this context. Given the principle of comprehensive health care and the structure of the Unified Health System in care networks, it is necessary to ensure the integration of health care practices, among which are the sanitary surveillance actions (SSA). Considering that the integration of health care practices and SSA can contribute to reduce mother and infant mortality rates, this article is a result of qualitative research that analyzed the integration of these actions in four cities in the State of São Paulo/Brazil: Campinas, Indaiatuba, Jaguariúna and Santa Bárbara D'Oeste. The research was conducted through interviews with SSA and maternal health managers, and the data were evaluated using thematic analysis. The results converge with other studies, identifying the isolation of health care practices and SSA. The insertion of SSA in collectively-managed areas appears to be a potential strategy for health planning and implementation of actions in the context under scrutiny.

Dyspareunia In Hiv-positive And Hiv-negative Middle-aged Women: A Cross-sectional Study.

To evaluate whether dyspareunia is associated with HIV status in menopausal women and also to assess which factors are associated with dyspareunia in a group of HIV-positive menopausal women. A cross-sectional study was conducted with 178 HIV-negative and 128 HIV-positive women aged 40-60 years. The Short Personal Experiences Questionnaire (SPEQ) was used to collect data. Sociodemographic, clinical, behavioural and reproductive factors were evaluated, as well as factors related to the HIV infection. Dyspareunia was defined as pain during intercourse. A bivariate analysis and Poisson multiple regression analysis were performed. Overall, 41.4% of the HIV-positive women reported dyspareunia compared with 34.8% of the HIV-negative women (p=0.242). In the HIV-positive women, bivariate analysis revealed an association between dyspareunia and having a steady partner (p=0.047); the woman's partner having undergone HIV testing (p=0.020); vaginal dryness (p<0.001); muscle/joint pain (p=0.021); physical/emotional violence (p=0.049); urinary incontinence (p=0.004); and the use of lamivudine/zidovudine (p=0.048). The Poisson multiple regression analysis found an association between dyspareunia and vaginal dryness (prevalence ratio (PR)=1.96, 95% CI 1.10 to 3.50, p=0.023) and urinary incontinence (PR=1.86, 95% CI 1.06 to 3.27, p=0.031). Dyspareunia was common in this group of HIV-positive women and was associated principally with vaginal dryness and urinary incontinence. The importance of treating dyspareunia within the context of sexual health in this group of women should be emphasised and appropriate management of this issue may reduce the likelihood of lesions on the vaginal wall, which may act as a portal of entry for other infections.

Factors Associated With The Age Of The Onset Of Diabetes In Women Aged 50 years Or More: A Population-based Study.

Investigate factors associated with the onset of diabetes in women aged more than 49 years. Cross-sectional, population-based study using self-reports with 622 women. The dependent variable was the age of occurrence of diabetes using the life table method. Cox multiple regression models were adjusted to analyse the onset of diabetes according to predictor variables. Sociodemographic, clinical and behavioural factors were evaluated. Of the 622 women interviewed, 22.7% had diabetes. The mean age at onset was 56 years. The factors associated with the age of occurrence of diabetes were self-rated health (very good, good) (coefficient=-0.792; SE of the coefficient=0.215; p=0.0001), more than two individuals living in the household (coefficient=0.656, SE of the coefficient=0.223; p=0.003), and body mass index (BMI) (kg/m(2)) at 20-30 years of age (coefficient= 0.056, SE of the coefficient=0.023; p=0.014). Self-rated health considered good or very good was associated with a higher rate of survival without diabetes. Sharing a home with two or more other people and a weight increase at 20-30 years of age was associated with the onset of type 2 diabetes.

Genomic Copy Number Alterations Of Primary And Secondary Metastasizing Pleomorphic Adenomas.

Metastasizing pleomorphic adenoma (MPA) is a rare tumour, and its mechanism of metastasis still is unknown. To date, there has been no study on MPA genomics. We analysed primary and secondary MPAs with array comparative genomic hybridization to identify somatic copy number alterations and affected genes. Tumour DNA samples from primary (parotid salivary gland) and secondary (scalp skin) MPAs were subjected to array comparative genomic hybridization investigation, and the data were analysed with NEXUS COPY NUMBER DISCOVERY. The primary MPA showed copy number losses affecting 3p22.2p14.3 and 19p13.3p123, and a complex pattern of four different deletions at chromosome 6. The 3p deletion encompassed several genes: CTNNB1, SETD2, BAP1, and PBRM1, among others. The secondary MPA showed a genomic profile similar to that of the primary MPA, with acquisition of additional copy number changes affecting 9p24.3p13.1 (loss), 19q11q13.43 (gain), and 22q11.1q13.33 (gain). Our findings indicated a clonal origin of the secondary MPA, as both tumours shared a common profile of genomic copy number alterations. Furthermore, we were able to detect in the primary tumour a specific pattern of copy number alterations that could explain the metastasizing characteristic, whereas the secondary MPA showed a more unbalanced genome.

Acupuncture Increases The Diameter And Reorganisation Of Collagen Fibrils During Rat Tendon Healing.

Our previous study showed that electroacupuncture (EA) increases the concentration and reorganisation of collagen in a rat model of tendon healing. However, the ultrastructure of collagen fibrils after acupuncture is unknown. To assess the effect of acupuncture protocols on the ultrastructure of collagen fibrils during tendon healing. Sixty-four rats were divided into the following groups: non-tenotomised (normal group), tenotomised (teno group), tenotomised and subjected to manual acupuncture at ST36 (ST36 group), BL57 (BL57 group) and ST36+BL57 (SB group) and EA at ST36+BL57 (EA group). The mass-average diameter (MAD) and the reorganisation of collagen fibril diameters were determined during the three phases of tendon healing (at 7, 14 and 21 days). The MAD increased during the three phases of healing in the SB group. In the EA group, MAD increased initially but was reduced at day 21. The reorganisation of collagen fibrils was improved in the EA and SB groups at days 14 and 21, respectively. EA at day 21 appeared to reduce the reorganisation. These results indicate that the use of EA up to day 14 and manual acupuncture at ST36+BL57 up to day 21 improve the ultrastructure of collagen fibrils, indicating strengthening of the tendon structure. These data suggest a potential role for acupuncture in rehabilitation protocols.

Bipolar Disorder: Recent Advances And Future Trends In Bioanalytical Developments For Biomarker Discovery.

In this manuscript we briefly describe bipolar disorder (a depressive and manic mental disease), its classification, its effects on the patient, which sometimes include suicidal tendencies, and the drugs used for treatment. We also address the status quo with regard to diagnosis of bipolar disorder and recent advances in bioanalytical approaches for biomarker discovery. These approaches focus on blood samples (serum and plasma) and proteins as the main biomarker targets, and use various strategies for protein depletion. Strategies include use of commercially available kits or other homemade strategies and use of classical proteomics methods for protein identification based on bottom-up or top-down approaches, which used SELDI, ESI, or MALDI as sources for mass spectrometry, and up-to-date mass analyzers, for example Orbitrap. We also discuss some future objectives for treatment of this disorder and possible directions for the correct diagnosis of this still-unclear mental illness.

Atypical antipsychotics in the treatment of pathological aggression in children and adolescents: literature review and clinical recommendations

Objective: To review the literature about the use of atypical antipsychotics in the treatment of pathological aggression in children and adolescents. Method: The databases MEDLINE, SciELO, and LILACS were searched for publications in Portuguese or English from 1992 to August 2011 using the following keywords: mental disease, child, adolescent, treatment, atypical antipsychotic, aggressive behavior, aggression, and violent behavior. Results: Sixty-seven studies of good methodological quality and clinical interest and relevance were identified. Studies including children and adolescents were relatively limited, because few atypical antipsychotics have been approved by the Food and Drug Administration (FDA). All the medications included in this review (risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole and clozapine) have some effectiveness in treating aggression in children and adolescents, and choices should be based on clinical indications and side effects. Conclusions: There are few studies about the effectiveness and safety of atypical antipsychotics for the pediatric population, and further randomized controlled studies with larger groups of patients and more diagnostic categories, such as severe conduct disorder and oppositional defiant disorder, should be conducted to confirm the results reported up to date and to evaluate the impact of long-term use.