The Influence of Government Effectiveness and Corruption on the High Levels of Homicide in Latin America

“Most research that has examined the international variation in homicide levels has focused on structural variables, with the suggestion that socio-economic development operates as a cure for violence. In Latin America, development has occurred, but high homicide levels remain, suggesting the involvement of other influencing factors. We posit that government effectiveness and corruption control may contribute to explaining the variation in homicide levels, and in particular in the Latin America region. Our results show that social and economic structural variables are useful but are not conclusive in explaining the variation in homicide levels and that the relationship between homicide, government effectiveness, and corruption control was significant and highly pronounced for countries in the Latin American region. The findings highlight the importance of supporting institutions in improving their effectiveness in Latin America so that reductions in homicide (and improvements in citizen security in general) can be achieved

Immunomodulatory effect of hemodialysis extracorporeal treatment and comparative study of different high flux membranes

Backgroud. L'infiammazione cronica, fattore di rischio cardiovascolare, dipende da fattori non correlati alla dialisi e correlati, come la biocompatibilità della membrana e la permeabilità alle medie molecole (citochine infiammatorie). L'uremia determina una disfunzione immunitaria con tendenza alle infezioni. Questo studio valuta l'effetto immunomodulatorio della singola sessione di dialisi e confronta tre diverse membrane ad alto flusso. Metodi. Sono stati arruolati 35 pazienti in emodialisi cronica trisettimanale e 10 volontari sani. Per due settimane i gruppi A e C sono stati sottoposti a emodialisi con Filtryzer-BGU 1.6 e THERANOVA, il gruppo B a emofiltrazione con HFR17. Cellule mononucleate del sangue periferico (PBMC) sono state raccolte all'inizio (T0) e alla fine (T1) della 5a sessione e all'inizio della 6a (T2) per eseguire citofluorimetria e saggi di proliferazione cellulare e apoptosi. Risultati. Nei pazienti in dialisi i linfociti CD3+, B e T si riducono, per aumento dell'apoptosi. NK, CD8+CD57+ senescenti e Th17 aumentano. Durante la seduta CD3+ subiscono un calo significativo secondario all'apoptosi, per incrementare, non significativamente, in T2. In T1 CD4+ aumentano per proliferazione, così come il rapporto Treg/Th17 e cala alla sessione successiva. CD8+ diminuiscono in T1 e T2, contestualmente ad una riduzione della produzione di IFN-γ. Il rapporto CD4+/CD8+ aumenta in T1 per diminuire nell'intervallo interdialitico. CD8+CD57+ e la produzione di IFN-γ diminuiscono durante il trattamento. NK e monociti diminuiscono durante la sessione per aumentare nell'intervallo interdialitico. Confrontando i filtri non sono state registrate variazioni statisticamente significative. Conclusioni. L’emodialisi rappresenta un trigger infiammatorio in un sistema immunitario iperattivo e disfunzionale, come testimoniato dall’incremento di sottopopolazioni linfocitarie ad elevato potenziale citotossico ed infiammatorio. Il singolo trattamento tende a correggere questo stato rimovendo mediatori dell’infiammazione, con progressivo ripristino delle condizioni basali nel corso dell’intervallo interdialitico. L’impiego di diverse membrane non influenza le sottopopolazioni linfocitarie né dal punto di visa numerico né funzionale.Introduction. Chronic inflammation is a cardiovascular risk factor observed in hemodialysis patients. It depends both on dialysis-unrelated and related factors, as membrane biocompatibility and permeability to middle molecule, including inflammation cytokines. On the other hand, uremia is associated with immune dysfunction and high prevalence of infections. This study focuses on immunomodulatory effect of single dialysis session and compares three different high flux membranes. Methods. 35 maintenance hemodialysis three times per-week patients and 10 healthy volunteers were enrolled. For two weeks group A and C underwent hemodialysis with Filtryzer BGU 1.6 and THERANOVA respectively, group B hemofiltration with HFR17. Peripherical blood mononuclear cells (PBMC) were collected at the beginning (T0) and the end (T1) of the 5th session and starting the 6th session (T2). Previous sessions allowed wash-out from usual treatment. Cytofluorimetry, cellular proliferation and apoptosis essay were performed. Results. CD3+, B and T lymphocytes reduce, according to increased apoptosis in dialysis patients, compared to healthy volunteers. NK, senescence CD8+ CD57+ and Th17 increase. During session CD3+ suffer a significant drop secondary to apoptosis, to rise again, not significantly, on T2. On T1 CD4+ increase due to proliferation, as well as Treg/Th17 ratio and drop on next session. CD8+ decrease on T1 and T2 according to IFN-γ production. CD4+/CD8+ ratio is increased in T1 to decrease in interdialytic interval. CD8+ CD57+ and IFN-γ production drop during treatment, persisting on 6th dialysis. NK and monocytes decrease during session to rise in interdialytic interval. Comparing the three different dialyzer no statistically significant variations were recorded. Conclusions. Replacement therapy represents an acute inflammatory trigger in terminal uremia hyperactive and dysfunctional immune system, as evidenced by the increase in cytotoxic lymphocyte subpopulations compared to healthy population. Single dialysis session attempts to correct dysfunctional inflammatory state, removing mediators, with restoration of basal conditions in interdialytic interval

Evaluation of the impact of transient interruption of antiangiogenic treatment using ultrasound-based techniques in a murine model of hepatocellular carcinoma

BACKGROUND: Development of escape pathways from antiangiogenic treatments was reported to be associated with enhanced tumor aggressiveness and rebound effect was suggested after treatment stop. Aim of the study was to evaluate tumor response simulating different conditions of administration of antiangiogenic treatment (transient or definitive treatment stop) in a mouse model of hepatocellular carcinoma. METHODS: Subcutaneous tumors were created by inoculating 5 7 10(6) Huh7 cells into the right flank of 14 nude mice. When tumor size reached 5-10 mm, mice were divided in 3 groups: group 1 was treated with placebo, group 2 was treated with sorafenib (62 mg/kg via gavage) but temporarily suspended from day +5 to +9, whereas in group 3 sorafenib was definitively stopped at day +5. At day +13 all mice were sacrificed, collecting masses for Western-Blot analyses. Volume was calculated with B-mode ultrasonography at day 0, +5, +9, +11 and +13. VEGFR2-targeted contrast-enhanced ultrasound using BR55 (Bracco Imaging) was performed at day +5 and +13 and elastonosography (Esaote) at day +9 and +11 to assess tumor stiffness. RESULTS: Median growth percentage delta at day +13 versus day 0 was 197% (115-329) in group 1, 81% (48-144) in group 2 and 111% (27-167) in group 3. Median growth delta at day +13 with respect to day +5 was 79% (48-127), 37% (-14128) and 81% (15-87) in groups 1, 2 and 3, respectively. Quantification of targeted-CEUS at day +13 showed higher values in group 3 (509 Arbitrary Units AI, range 293-652) than group 1 (275 AI, range 191-494) and group 2 (181 AI, range 63-318) (p=0.033). Western-Blot analysis demonstrated higher VEGFR2 expression in group 3 with respect to group 1 and 2. CONCLUSIONS: A transient interruption of antiangiogenic treatment does not impede restoration of tumor response, while a definitive interruption tends to stimulate a rebound of angiogenesis to higher level than without treatment

Nodulation in the absence of nod genes induction: alternative mechanisms involved in the symbiotic interaction between Cupriavidus sp. UYMMa02A and Mimosa pudica

Cupriavidus sp. UYMMa02A is a beta-rhizobia strain of the Cupriavidus genus, isolated from nodules of Mimosa magentea in Uruguay. This strain can form effective nodules with several Mimosa species, including its original host. Genome analyses indicate that Cupriavidus sp. UYMMa02A has a highly conserved 35 kb symbiotic island containing nod, nif, and fix operons, suggesting conserved mechanisms for the symbiotic interaction with plant hosts. However, while Cupriavidus sp. UYMMa02A produces functional nodules and promotes Mimosa pudica growth under nitrogen-limiting conditions, nod genes are not induced by luteolin or exposure to Mimosa spp. root exudate. To explore alternative mechanisms implicated in the Cupriavidus-Mimosa interaction, we assessed the proteomic profiles of Cupriavidus sp. UYMMa02A grown in the presence of pure flavonoids and co-culture with M. pudica plants. This approach allowed us to identify 24 differentially expressed proteins potentially involved in bacterial-plant interaction. In light of the obtained results, a possible model for nod-alternative symbiotic interaction is proposed.Agencia Nacional de Investigación e InnovaciónInstituto de Investigaciones Biológicas Clemente EstableProgama del Desarrollo de Ciencias Básica

Aiding the conservation of two wooden Buddhist sculptures with 3D imaging and spectroscopic techniques

The conservation of Buddhist sculptures that were transferred to Europe at some point during their lifetime raises numerous questions: while these objects historically served a religious, devotional purpose, many of them currently belong to museums or private collections, where they are detached from their original context and often adapted to western taste. A scientific study was carried out to address questions from Museo d'Arte Orientale of Turin curators in terms of whether these artifacts might be forgeries or replicas, and how they may have transformed over time. Several analytical techniques were used for materials identification and to study the production technique, ultimately aiming to discriminate the original materials from those added within later interventions

(Dis)integrazioni

CfP n.17 - 05/2017(Dis)integrazionia cura di Daniele Croci, Laura Scarabelli e Marianna Scaramucc

Domain-specific regulation of cerebellar morphogenesis by Zfp423 / ZNF423, a gene implicated in Joubert syndrome and cerebellar vermis hypoplasia

The Zfp423 gene encodes a 30-Zn-finger transcription factor that acts as a scaffold for the assembly of complex transcriptional and cellular machineries regulating neural development. While null Zfp423 mutants feature a sharp decrease in the total number of cerebellar Purkinje cells (PCs), the underlying mechanisms remain unclear. Mutations of the human homolog ZNF423 have been identified in patients carrying cerebellar vermis hypoplasia (CVH) or Joubert Syndrome (JS), associated with other signs of classical ciliopathy outside the central nervous system. To further characterize the role of ZFP423 in cerebellar neurogenesis, we have performed morphological, cellular and molecular studies on two mutant mouse lines carrying allelic in-frame deletions of Zfp423. While both lines exhibit cerebellar hypoplasia, considerable differences are observed between the two mutants, with respect to neural progenitor differentiation, cell survival and morphogenesis. The results of this in vivo and in vitro structure-function analysis point to domain- and context-specific roles played by ZFP423 in different aspects of cerebellar development, and contribute to our understanding of its role as a disease / modifier gene in JS, CVH and other ciliopathies

Editoriale/Editorial/Éditorial/Editorial

Editoriale/Editorial/Éditorial/Editorial AM1

Zinc-finger and helix-loop-helix transcription factors regulate Purkinje neuron neurogenesis and cerebellar corticogenesis

Many regulatory genes have been pinpointed as orchestrators of cerebellar development, from the onset of neurogenesis to the patterning of the adult cerebellar cortex, with a special reference to the development of cerebellar Purkinje cells (PCs). PCs provide the sole output from cerebellar cortical circuits, where each PC integrates myriads of presynaptic inputs, both inhibitory and excitatory. In the murine cerebellar primordium PCs are generated from a pool of ventricular zone progenitors facing the fourth ventricle between embryonic day (E) 10.5 and 13.5. This progenitor pool expands in the ventricular zone (VZ) through symmetric cell division until E10.5, when a gradual switch to asymmetric cell division occurs, regulated by Notch1 (Lutolf et al., 2002) and its interactor (Masserdotti et al., 2010), the Zn-finger TF Zfp423 (Alcaraz et al., 2006; Warming et al., 2006; Croci et al., submitted). Zfp423 was recently implicated in Joubert syndrome and cerebellar vermis hypoplasia (Chaki et al., 2012). Allelic mutations of Zfp423 produce distinct alterations in PC development (Croci et al., submitted). PCs arise from a pool of progenitors positive for the basic-helix-loop-helix transcription factors (TFs) neurogenin (Ngn) 1 and 2 (Zordan et al., 2008; Lundell et al., 2009). Ngn2 regulates cell cycle progression and dendritic arbor generation in PC precursors (Florio et al., 2012). PCs also express HLH transcription factors of the Olf/EBF family. In Ebf2 -/- mutants, PC migration and survival are affected (Croci et al., 2006). Neonatal PC death is due to local downregulation of Igf1 gene expression (Croci et al., 2011). Finally, EBF2 regulates cortical patterning in the adult cerebellum, regulating its subdivision into alternate parasagittal stripes of distinct PC subtypes. Indeed, EBF2 is required to repress the zebrin II+ phenotype in postnatal PCs (Croci et al., 2006; Chung et al., 2008)

Galectin-1 expression imprints a neurovascular phenotype in proliferative retinopathies and delineates responses to anti-VEGF

Neovascular retinopathies are leading causes of irreversible blindness. Although vascular endothelial growth factor (VEGF) inhibitors have been established as the mainstay of current treatment, clinical management of these diseases is still limited. As retinal impairment involves abnormal neovascularization and neuronal degeneration, we evaluated here the involvement of galectin-1 in vascular and non-vascular alterations associated with retinopathies, using the oxygen-induced retinopathy (OIR) model. Postnatal day 17 OIR mouse retinas showed the highest neovascular profile and exhibited neuro-glial injury as well as retinal functional loss, which persisted until P26 OIR. Concomitant to VEGF up-regulation, galectin-1 was highly expressed in P17 OIR retinas and it was mainly localized in neovascular tufts. In addition, OIR induced remodelling of cell surface glycophenotype leading to exposure of galectin-1-specific glycan epitopes. Whereas VEGF returned to baseline levels at P26, increased galectin-1 expression persisted until this time period. Remarkably, although anti-VEGF treatment in P17 OIR improved retinal vascularization, neither galectin-1 expression nor non-vascular and functional alterations were attenuated. However, this functional defect was partially prevented in galectin-1-deficient (Lgals1-/-) OIR mice, suggesting the importance of targeting both VEGF and galectin-1 as non-redundant independent pathways. Supporting the clinical relevance of these findings, we found increased levels of galectin-1 in aqueous humor from patients with proliferative diabetic retinopathy and neovascular glaucoma. Thus, using an OIR model and human samples, we identified a role for galectin-1 accompanying vascular and non-vascular retinal alterations in neovascular retinopathies.Fil: Ridano, Magali Evelin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Subirada Caldarone, Paula Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Paz, Maria Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Lorenc, Valeria Erika. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Stupirski, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Gramajo, Ana Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología - Nodo Bariloche | Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología - Nodo Bariloche; ArgentinaFil: Luna, José Domingo. Clinica de Ojos Romagosa, Fundacion Ver; ArgentinaFil: Croci Russo, Diego Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad Nacional de Córdoba. Facultad de Cs.exactas Físicas y Naturales. Departamento de Química. Cátedra de Química Biologica; ArgentinaFil: Garcia Sanchez, Maria Candela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentin