Strains of Rodents and the Pharmacology of Learning and Memory

Mendelian genetic tools have extensively been used to improve the description of the pharmacological mechanisms involved in learning and memory. The first part of this short review describes experiments involving the bidirectional selection of rats or mice for extreme behavioral characteristics or for sensitivity to pharmacological treatments. The second part focuses specifically on inbreeding. In conclusion, the advantages and the limits of a Mendelian pharmacogenetic approach of learning and memory are discussed

It’s about the type of career: The political ambition gender gap among youth wing members

One of the main supply-side explanations for women's underrepresentation in politics is the gender gap in nascent political ambition. While this has been examined in terms of electoral ambition, the aspiration to pursue non-electoral careers within parties has been overlooked. In our study, we therefore investigate whether both types of ambition – electoral and non-electoral – vary among young women and men participating in a key entry point for political careers in Western democracies: party youth wings. To do so, we surveyed almost 2,000 members of six centre-left and centre-right youth wings in Australia, Italy and Spain. We find that while, as expected, women in youth wings display lower levels of electoral ambition, they are almost as likely as men to express non-electoral ambition. Furthermore, and contrary to our expectations, we show that women in centre-right youth wings are no less interested in pursuing electoral and non-electoral political careers than women in centre-left ones. Our study thus provides new insights into the gendered nature of political ambition, highlighting that women's lower interest in electoral office does not necessarily reflect reduced interest in a political career

No. 1: Migration and Development in Africa: An Overview

Migration is clearly a major issue across Africa. Indeed, migration – both within countries and across borders – can be seen as an integral part of labour markets and livelihoods across much of the continent for at least the last century. Over time, and in different places, migration has taken a number of different forms. It has cut across class and skill boundaries, and exists in widely different geographical and demographic contexts. Migration represents an important livelihood strategy for poor households seeking to diversify their sources of income, but is also characteristic of the better off, and indeed of many African elites. In practice, however, the link between migration and poverty is often viewed more negatively. It is assumed across much of the continent that it is poverty that forces poor people to migrate, rather than migration being a potential route out of poverty. The poor are also generally seen as those worst affected by conflict-induced migration, itself a prominent feature in Africa. The movement of skilled and/or wealthy Africans is also generally viewed negatively (e.g. there is long-standing concern on the African continent with the impact of the ‘brain drain’ of African professionals). Only slowly, and in relatively few quarters, is understanding emerging of the potentially positive role that migration itself can play in reducing poverty, or of the possibilities for ‘mobilisation’ of the African diaspora in the fight against poverty. Meanwhile, public policy remains a long way from building effectively on such understanding. The aim of this study is to synthesise existing research on migration in Africa, and its relationship to development policy. The report focuses on the relationship between migration, poverty and pro-poor development policy. Pro-poor policy is taken here to mean policies that are context-specific, listen and react to poor people’s voices, and/or seek to assist poor people to become less vulnerable and build up their income and assets. Government health and education policies might not be considered intrinsically pro-poor, but become so where they are targeted at widening access to health and education services, and especially basic health and education services (e.g. primary care, vaccination campaigns, primary schooling), or at responding to the specific needs of the poor. Pro-poor policies might also seek to identify and support poor people’s livelihoods, through the promotion of social protection mechanisms (ranging from pensions, health insurance, maternity benefit and unemployment benefits to food aid and other social assistance) or enhancement and enforcement of poor people’s rights. In turn, our focus is not only on the policies of developing country governments, but also on those of non-government and intergovernmental organisations, and of donor nations. In terms of migration, the study covers both international and internal migration. In the sections that follow, issues are dealt with first in relation to sub-Saharan Africa as a whole, and then in detail for three regions – West Africa, East Africa and Southern Africa. The sections on Africa as a whole, and on West and East Africa were completed by researchers at the Sussex Centre for Migration Research at the University of Sussex, whilst the section on Southern Africa was written by researchers at the Southern African Migration Project

eEF1Bγ binds the Che-1 and TP53 gene promoters and their transcripts

Background: We have previously shown that the eukaryotic elongation factor subunit 1B gamma (eEF1Bγ) interacts with the RNA polymerase II (pol II) alpha-like subunit “C” (POLR2C), alone or complexed, in the pol II enzyme. Moreover, we demonstrated that eEF1Bγ binds the promoter region and the 3’ UTR mRNA of the vimentin gene. These events contribute to localize the vimentin transcript and consequentially its translation, promoting a proper mitochondrial network. Methods: With the intent of identifying additional transcripts that complex with the eEF1Bγ protein, we performed a series of ribonucleoprotein immunoprecipitation (RIP) assays using a mitochondria-enriched heavy membrane (HM) fraction. Results: Among the eEF1Bγ complexed transcripts, we found the mRNA encoding the Che-1/AATF multifunctional protein. As reported by other research groups, we found the tumor suppressor p53 transcript complexed with the eEF1Bγ protein. Here, we show for the first time that eEF1Bγ binds not only Che-1 and p53 transcripts but also their promoters. Remarkably, we demonstrate that both the Che-1 transcript and its translated product localize also to the mitochondria and that eEF1Bγ depletion strongly perturbs the mitochondrial network and the correct localization of Che-1. In a doxorubicin (Dox)-induced DNA damage assay we show that eEF1Bγ depletion significantly decreases p53 protein accumulation and slightly impacts on Che-1 accumulation. Importantly, Che-1 and p53 proteins are components of the DNA damage response machinery that maintains genome integrity and prevents tumorigenesis. Conclusions: Our data support the notion that eEF1Bγ, besides its canonical role in translation, is an RNA-binding protein and a key player in cellular stress responses. We suggest for eEF1Bγ a role as primordial transcription/translation factor that links fundamental steps from transcription control to local translatio

Electrophysiology of glioma: a Rho GTPase-activating protein reduces tumor growth and spares neuron structure and function

Background. Glioblastomas are the most aggressive type of brain tumor. A successful treatment should aim at halting tumor growth and protecting neuronal cells to prevent functional deficits and cognitive deterioration. Here, we exploited a Rho GTPase-activating bacterial protein toxin, cytotoxic necrotizing factor 1 (CNF1), to interfere with glioma cell growth in vitro and vivo. We also investigated whether this toxin spares neuron structure and function in peritumoral areas. Methods. We performed a microarray transcriptomic and in-depth proteomic analysis to characterize the molecular changes triggered by CNF1 in glioma cells. We also examined tumor cell senescence and growth in vehicle-and CNF1-treated glioma-bearing mice. Electrophysiological and morphological techniques were used to investigate neuronal alterations in peritumoral cortical areas. Results. Administration of CNF1 triggered molecular and morphological hallmarks of senescence in mouse and human glioma cells in vitro. CNF1 treatment in vivo induced glioma cell senescence and potently reduced tumor volumes. In peritumoral areas of glioma-bearing mice, neurons showed a shrunken dendritic arbor and severe functional alterations such as increased spontaneous activity and reduced visual responsiveness. CNF1 treatment enhanced dendritic length and improved several physiological properties of pyramidal neurons, demonstrating functional preservation of the cortical network. Conclusions. Our findings demonstrate that CNF1 reduces glioma volume while at the same time maintaining the physiological and structural properties of peritumoral neurons. These data indicate a promising strategy for the development of more effective antiglioma therapies

Acute and chronic effects of Cr(VI) on Hypsiboas pulchellus embryos and tadpoles

In the last few years there has been great concern about declines in the abundance of several species of amphibians around the world. Among amphibians, anurans have a biphasic life cycle, with aquatic tadpoles and generally terrestrial adults, and they have an extremely permeable skin, making them excellent indicators of the health of the environment. A number of different causes have been suggested for the global decline of anurans, the pollution of their habitat by chemical stressors being considered one of the major factors. Among chemical stressors, heavy metals are known for their high toxicity at very low concentrations. This study assessed short- (96 h, 'acute') and long-term (1272 h, 'chronic') exposure to Cr(VI) at lethal (3 to 90 mg l-1) and sublethal concentrations (0.001 to 12 mg l-1) on Hypsiboas pulchellus (previously called Hyla pulchella; see Faivovich et al. 2005) tadpoles (Fam. Hylidae) from central eastern Argentina. Fertilized eggs collected from a clean pond near La Plata (Buenos Aires Province) were used for acute and chronic toxicity testing. Assays were done under controlled laboratory conditions. Results of chronic exposure were used to assess the effect of factors such as toxicant concentration and age of organisms at the beginning of exposure on the response variables (growth, development and survival until metamorphosis). Results indicated a higher sensitivity to Cr(VI) of individuals first exposed as tadpoles than those first exposed as embryos during acute and chronic exposure. Exposure to the highest sublethal concentrations (6 to 12 mg l-1) of the toxicant showed early inhibitory effects on growth of all treated organisms compensated at longer exposure periods with an increase in the growth rate compared to the control groups.Centro de Investigaciones del Medio Ambient

Granulocytic myeloid-derived suppressor cells increased in early phases of primary HIV infection depending on TRAIL plasma level

Background It has been demonstrated that Myeloid Derived Suppressor Cells (MDSC) are expanded in HIV-1 infected individuals and correlated with disease progression. The phase of HIV infection during which MDSC expansion occurs, and the mechanisms that regulate this expansion remain to be established. In this study we evaluated the frequency of MDSC in patients during primary HIV infection, and factors involved in MDSC control. Methods Patients with primary (PHI) and chronic (CHI) HIV infection were enrolled. PHI staging was performed according to Fiebig classification, and circulating MDSC frequency and function were evaluated by flow cytometry. Cytokine levels were evaluated by Luminex technology. Results We found that granulocytic MDSC (Gr-MDSC) frequency was higher in PHI compared to healthy donors, but lower than CHI. Interestingly, Gr-MDSC expansion was observed in the early phases of HIV infection (Fiebig II/III), but it was not associated to HIV viral load and CD4 T cell count. Interestingly, in PHI Gr-MDSC frequency was inversely correlated with plasmatic level of TRAIL, while a direct correlation was observed in CHI. Further, lower level of GMCSF was observed in PHI compared with CHI. In vitro experiments demonstrated that, differently from CHI, recombinant TRAIL induced apoptosis of Gr-MDSC from PHI, can effect that can be abrogated by GM-CSF. Conclusion We found that Gr-MDSC are expanded early during primary HIV infection and may be regulated by TRAIL and GM-CSF levels. These findings shed light on the fine mechanisms regulating the immune system during HIV infection, and open new perspectives for immune-based strategies

Classi e ceti nella società italiana. Studi e Ricerche

Studi sulla struttura sociale italiana: caratteristiche e dinamiche dal secondo dopoguerra a metà anni settanta.- Presentazione, Marcello Pacini #7- Indice #11- 1. Una breve cronaca bibliografica #15- 2. Le immagini della struttura di classe #37- 3. La distribuzione della ricchezza e del reddito #43- 4. Le posizioni sociali e il prestigio #49- 5. Potere, consenso e preferenze politiche #57- 6. Le tendenze generali e quelle odierne #6

Adherence in HIV-positive patients treated with single-tablet regimens and multi-pill regimens: findings from the COMPACT study

The use of Combination AntiRetroviral Therapy (cART) has decreased the morbidity and mortality of patients infected with HIV. However, adherence to cART remains crucial to prevent virological failure and disease progression. The aim of this study was to assess adherence to treatment among patients treated with Single Tablet Regimen (STR) or with multi-pill regimens based on Protease Inhibitors (PI), Non-Nucleoside Reverse-Transcriptase Inhibitors (NNRTI), or raltegravir (RAL). An observational retrospective cohort analysis based on administrative and clinical databases was conducted at the National Institute for Infectious Diseases (Rome, Italy). HIV-positive patients treated with a cART between Jan 1st, 2008–Dec 31st, 2010 were included. Patients were followed-up for one year since the first prescription during the inclusion period or up to death or switch of at least one drug of the regimen. Adherence and selective non-adherence (days without backbone or 3rd drug) were calculated using pharmacy refill compliance [1]. cART regimens were classified based on number of daily pills (STR vs multi-pill regimen) and on type of third drug. Viral Load (VL) and CD4 cell counts at the end of the follow-up were evaluated. A total of 1,604 patients were analyzed, 70.0% male, age 45.0±8.7, 14.3% newly treated. Patients on STR were 159 (9.9%), PI 878 (54.7%), NNRTI 523 (32.6%), RAL 44 (2.7%). Presence of at least one AIDS-defining conditions (according to Centers for Disease Control classification) was 30% in the STR group, 34% PI, 26% NNRTI, 34% RAL (p=n.s.). Adherence was 80.4±14.7% for STR, 71.8±21.8% PI, 77.1±20.3% NNRTI, 74.0±22.4% RAL. Selective non-adherence was 5.5% (18 days) PI, 2.8% (8 days) NNRTI, 12.5% (43 days) RAL (Figure 1). At the end of the follow-up, VL/CD4 values were available among 709 patients (44%); CD4 count >500 cell/mm3 was observed among 61% of patients on STR, 44% PI, 48% NNRTI, 42% RAL and VL < 50 copies/ml was observed among 96% of patients on STR, 78% PI, 88% NNRTI, 87% RAL. Interruptions in cART refill remain a relevant problem across all cART regimens. Patients on STR displayed a higher adherence rate compared to multi-pill regimes (PI, NNRTI, and RAL), primarily due to lack of selective non-adherence. Patients on STR experienced also higher rates of VL < 50 and CD4 > 500. The use of an STR regimen appears an effective therapeutic option to avoid selective non-adherence and, consequently, to prevent virological failure and disease progression

Non-adherence to ivabradine and placebo and outcomes in chronic heart failure: an analysis from SHIFT

Aims In heart failure, non-adherence increases events; in turn, the effect of hospitalization on adherence is incompletely understood. We explored the relationship of non-adherence to outcomes, hospitalizations with non-adherence, and the influence of non-adherence on treatment effects of heart rate lowering with ivabradine. Methods and results In the randomized, controlled Systolic Heart failure treatment with the If-inhibitor ivabradine Trial (SHIFT), we studied the effect of non-adherence (n = 1287) compared with adherence (n = 5204) on cardiovascular outcomes. After adjustment, non-adherence was associated with the primary composite endpoint of cardiovascular death and heart failure hospitalization (hazard ratio 3.47, 95% confidence interval 2.91–4.13, P < 0.0001). No interaction with the treatment groups of placebo or ivabradine (P for interaction 0.54) occurred. Similar results for cardiovascular death and heart failure hospitalization, as well as for cardiovascular hospitalization, heart failure death, and total death were observed. The effect of ivabradine was maintained in patients being adherent or becoming non-adherent during the trial (P for interaction = 0.54). Patients with a previous hospitalization were more likely to become non-adherent thereafter. Conclusions Non-adherence identifies a group at particularly high cardiovascular event risk independent of treatment allocation. Non-adherent patients in the ivabradine group maintain a treatment benefit. Patients with previous hospitalizations are more likely to become non-adherent and represent a group of particularly high-risk patients in whom special attention to stimulate adherence may be valuable