CALCIUM HOMEOSTASIS AND POLYCYSTIN-2 EXPRESSION IN T-LYMPHOBLASTS OF PKD SUBJECTS

Mutations of polycystin-1 (PC1) and polycystin-2 (PC2), coded by PKD1 and PKD2 genes, account for approximately 85 and 15% of Autosomal Dominant Polycystic Kidney Disease (ADPKD) cases, a common and important inherited kidney disorder. PC2 is a calcium-permeable and -regulated channel, interacting with the membrane receptor PC1, both colocalizing in the ‘primary cilium’ of epithelial cells as a flow-sensitive mechanosensor involved in signal-transduction. Diagnostic tools to decrease ADPKD are little in progress. Renal ultrasound, the principal diagnostic procedure, not allows an early diagnosis. The molecular characterization of the mutations can have a prognostic value, the progression to ESRD occurring more rapidly in PKD1 patients. The genetic test is, however, very expensive, time consuming, many missense variants remaining without a known function. This study is addressed to define whether PC1 and PC2 are expressed and play some functional role in T-lymphoblasts (HTL). These cells are easily obtainable from peripheral blood, differently from kidney cells and transgenic mice that represent canonical models for the study of PKD gene expression and function. In particular, attention has been focused on the possible relation between abnormal PCs levels and Ca2+ homeostasis in HTL obtained from ADPKD patients and thus carrying a mutation of either PKD1 or PKD2 gene. Expression studies have also considered fibrocystin/polyductin (FC1), mutated in the recessive form of the disease, known to be functionally related to PCs in vivo. Reduced cytoplasmic Ca2+ levels or other cellular abnormalities in ADPKD HTL will provide further information on the extrarenal role of PCs. Moreover, as HTL are easily and quickly obtainable from peripheral blood cells, positive results may lead to an ADPKD diagnosis based on quantitative and functional evaluation of PC1/PC2 channel complex. Peripheral blood samples from 31 (13 F) controls and 34 PKD patients (21 F) including some genetically characterized ADPKD1 subjects, have been considered in the present study and compared to B-lymphoblastoid cell lines (LCLs) and human adult and embryonal kidney cell lines. Results obtained demonstrate that PC1 and PC2 are expressed in HTL, although at a lower level than in kidney cells. Since PC1 is not correctly quantifiable in HTL, no comparison between PC1 levels in ADPKD HTL and controls is reported. On the contrary, the degree of PC2 expression in HTL, which appear comparable to that of B-LCLs, does not differ in ADPKD and non-ADPKD HTL (PC2 relative abitrary units, 0.572 ± 0.228 SD vs 0.553 ± 0.176 SD). Few cases with very low PC2 levels (lower than 2 fold the SD of ADPKD1 average values) and showing a less severe disease because entered in dialysis very late (over 70 y. o.), may carry a PKD2 mutation, which should be expected in 15% of ADPKD. Also the investigation of FC1, mutated in the recessive form of PKD, and of FCL, its homologue highly expressed in activated T-cells, does not reveal quantitative alteration in the level of combined FC1/FCL proteins in ADPKD HTL. As far as the function of PC1/PC2 channel complex is concerning, in HTL average values of PAF-evoked [Ca2+] are lower in ADPKD than in non-ADPKD (78.96 ± 9.67 SE nM vs 124.51 ± 16.87 nM, p<0.05), and a same reduction is present in ADPKD PBL (112.03 ± 13.87 nM SE vs 183.32 ± 20.54 nM, p<0.01). These results show that PCs have a functional role in T-cells. However, the large and overlapping distribution of the data in both PBL and HTL does not allow the use of [Ca2+] differences to distinguish individual ADPKD and non-ADPKD cases. A further marked cellular abnormality observed in ADPKD HTL is consistent with the anti-apoptotic action of PC1: ADPKD HTL death is higher compared to normal HTL (after 2 days of culture the % of trypan blue positve cells is 7.6 ± 2.8 SD vs 24.1 ± 9.7, p<0.05). Moreover, the observation of a larger size of cell aggregates in ADPKD compared to control HTL, is consistent with the PCs-dependent positive control of cell scattering/migration of renal epithelial cells. Alterations, presumably located at membrane level, are also present in ADPKD neutrophils which are basically more activated, but less responsive to stimuli, than control cells. Overall these findings indicate that aploinsufficiency of PKD1, the more probable involved gene in these patients, is detectable in HTL as an impairment of the PC1/PC2 channel, reduced cell survival and altered aggregation, thus playing PC1/PC2 a still undefined role in HTL. Aploinsufficiency in these cells seems, however, not sufficient to discriminate between unique ADPKD and not ADPKD subjects

Second contribution to the knowledge of the Lithosiini of Gabon: the genus Nanna Birket-Smith (Lepidoptera, Erebidae, Arctiinae)

The presence of the genus Nanna in Gabon is treated. Four species are recorded, two of which are new to science (N. molouba sp. nov. and N. semigrisea sp. nov.), and the hitherto unknown female of Nannaa ceratopygia is described. A checklist and a key to the species of the genus Nanna are provided

The Shadow of the Italian Colonial Experience: The Impact of Collective Emotions on Intentions to Help the Victims’ Descendants

Recalling the Italian colonial experience elicits the collective emotions of guilt, shame, and ingroup-focused anger. We expected that these emotions would predict different reparation intentions in favor of the colonized populations' descendants. Students and non-students were recruited (N = 152) and asked to rate their emotions of collective guilt, shame, and anger for the violence that their ingroup had perpetrated against colonized people. Results showed that shame affected intentions to provide economic compensation to current inhabitants of the ex-colonies. This relationship was mediated by concerns of damage for the ingroup's image. Anger toward the ingroup predicted intentions to help immigrants from the ex-colonies now living in Italy. Interestingly, empathy toward the outgroup mediated the latter relation. Finally, collective guilt was not reliably associated with any reparation strategy. These findings have implications for theory and for the historical collective memory of Italian colonialism

Picturing the Other: Targets of Delegitimization across Time

Italian Fascist propaganda was compared with contemporary right-wing material to explore how political propaganda depicts specific target groups in different historical periods. Taking the theory of delegitimization as the theoretical framework, we analyzed visual images concerning despised social groups used by the Fascist regime and current images of contemporary targets of social resentment used by Lega Nord (currently part of the governing coalition). Images of Jewish and Black people published in the Fascist magazine La Difesa della Razza were classified according to eight delegitimizing strategies, as were images of immigrants used on Lega Nord propaganda posters. Although the target group has changed, six of the eight strategies of delegitimization were used in both periods. In most cases, overlap was found in the way target groups were portrayed in the past and in the present

Effects of objective and subjective indicators of economic inequality on subjective well-being: Underlying mechanisms

Much research found that economic inequality - the dispersion of incomes distribution among individuals in a society - affects subjective well-being (SWB). As a meta-analysis has shown, the association between economic inequality, commonly measured by the Gini index, and individuals' SWB is weak and not significant. Psychosocial research suggests that the situational perception, rather than objective reality, has a greater impact on individuals. Our aim was to investigate whether and how objective and subjective measures of economic inequality affect the subjective individuals' well-being, both in its affective and cognitive components. A representative Italian sample (N = 1446, 51% women; average age = 42.42 years, SD = 12.87) answered an online survey. Multilevel regressions detected a negative and significant effect of the inequality perception on well-being. In contrast, the Gini index showed no effect. Two psychological mechanisms explain the association between perceived inequality and well-being: Perceived anger toward inequality and individuals' economic vulnerability. The parallel mediation models showed that the effect of perceived inequality is conveyed by cognitive (economic vulnerability) and emotional (anger) processing of inequality. Findings also highlighted the role of the ongoing COVID-19 pandemic

Total and Partial Fragmentation Cross-Section of 500 MeV/nucleon Carbon Ions on Different Target Materials

By using an experimental setup based on thin and thick double-sided microstrip silicon detectors, it has been possible to identify the fragmentation products due to the interaction of very high energy primary ions on different targets. Here we report total and partial cross-sections measured at GSI (Gesellschaft fur Schwerionenforschung), Darmstadt, for 500 MeV/n energy $^{12}C$ beam incident on water (in flasks), polyethylene, lucite, silicon carbide, graphite, aluminium, copper, iron, tin, tantalum and lead targets. The results are compared to the predictions of GEANT4 (v4.9.4) and FLUKA (v11.2) Monte Carlo simulation programs.Comment: 10pages, 13figures, 4table

Author Correction: 3D measurement techniques for the hindfoot alignment angle from weight-bearing CT in a clinical population

Cone-beam CT (CBCT) scans now enable accurate measurements on foot skeletal structures with the advantage of observing these in 3D and in weight-bearing. Among the most common skeletal deformities, the varus/valgus of the hindfoot is the most complex to be represented, and a number of measure proposals have been published. This study aims to analyze and to compare these measurements from CBCT scans in a real clinical population with large such deformity. Ten patients with severe acquired adult fatfoot and indication for surgery underwent CBCT scans (Carestream, USA) while standing on that leg, before and after surgical correction. Corresponding 3D shape of each bone of the distal shank and hindfoot were defned (Materialise, Belgium). Six diferent techniques from the literature were used to calculate the varus/valgus deformity, i.e. the inclination of the hindfoot in the frontal plane of the shank. Standard clinical measurements by goniometers were taken for comparison. According to these techniques, and starting from a careful 3D reconstruction of the relevant foot skeletal structures, a large spectrum of measurements was found to represent the same hindfoot alignment angle. Most of them were very diferent from the traditional clinical measures. The assessment of the pre-operative valgus deformity and of the corresponding post-operative correction varied considerably. CBCT fnally allows 3D assessment of foot deformities in weight-bearing. Measurements from the diferent available techniques do not compare well, as they are based on very diferent approaches. It is recommended to be aware of the anatomical and functional concepts behind these techniques before clinical and surgical conclusions

Integrated Approach of Life Cycle Assessment and Experimental Design in the Study of A Model Organic Reaction: New Perspectives in Renewable Vanillin-Derived Chemicals

This work is focused on performing a quantitative assessment of the environmental impacts associated with an organic synthesis reaction, optimized using an experimental design approach. A nucleophilic substitution reaction was selected, employing vanillin as the substrate, a phenolic compound widely used in the food industry and of pharmaceutical interest, considering its antioxidant and antitumoral potential. To carry out the reaction, three different solvents have been chosen, namely acetonitrile (ACN), acetone (Ace), and dimethylformamide (DMF). The syntheses were planned with the aid of a multivariate experimental design to estimate the best reaction conditions, which simultaneously allow a high product yield and a reduced environmental impact as computed by Life Cycle Assessment (LCA) methodology. The experimental results highlighted that the reactions carried out in DMF resulted in higher yields with respect to ACN and Ace; these reactions were also the ones with lower environmental impacts. The multilinear regression models allowed us to identify the optimal experimental conditions able to guarantee the highest reaction yields and lowest environmental impacts for the studied reaction. The identified optimal experimental conditions were also validated by experimentally conducting the reaction in those conditions, which indeed led to the highest yield (i.e., 93%) and the lowest environmental impacts among the performed experiments. This work proposes, for the first time, an integrated approach of DoE and LCA applied to an organic reaction with the aim of considering both conventional metrics, such as reaction yield, and unconventional ones, such as environmental impacts, during its lab-scale optimization

Association between proton-pump inhibitors (PPI) and metronomic capecitabine (MCAP) as salvage treatment for patients with advanced gastro-intestinal tumoursa. A randomized phase II study

Background: Several researches have shown that acidification of tumor microenvironment is the basis for tumor invasiveness, ability to metastasize S382 Abstracts and cytotoxic agents resistance; therefore proton pump inhibitors (PPI) could significantly increase the chemosensitivity. In our retrospective work we have investigated the role of capecitabine (mCAP) at metronomic dosage of 1500 mg/die as salvage chemotherapy in patients with metastatic colorectal cancer, showing a moderately activity and well tolerability. In this prospective study we evaluated safety and activity of mCAP in the advanced gastro-intestinal patients and the putative chemosensitizing activity of a specific PPI (Rabeprazole) in association to this therap