Has Immigration Really Led to an Increase in Crime in Italy?

Immigration has been a key topic in Italy’s election campaign, with several candidates arguing that the flow of people into the country during the migration crisis has increased the risk of crime. But has immigration really generated more crime in Italy? Drawing on data from the Italian National Institute of Statistics, Donato Di Carlo, Julia Schulte-Cloos and Giulia Saudelli illustrate that crime rates across Italian regions and the share of crimes committed by foreigners have both fallen significantly over the last decade

Evaluating dynamics in affect structure with latent Markov factor analysis

In intensive longitudinal research, researchers typically consider the structure of affect to be stable across individuals and contexts. Based on an assumed theoretical structure (e.g., one bipolar or two separate positive and negative affect constructs), researchers create affect scores from items (e.g., sum or factor scores) and use them to examine the dynamics therein. However, researchers usually ignore that the affect structure itself is dynamic and varies across individuals and contexts. Understanding these dynamics provides valuable insights into individuals’ affective experiences. This study uses latent Markov factor analysis (LMFA) to study what affect structures underlie individuals’ responses, how individuals transition between structures, and whether their individual transition patterns differ. Moreover, we explore whether the intensity of negative events and the personality trait neuroticism relate to momentary transitions and individual differences in transition patterns, respectively. Applying LMFA to experience sampling data (N = 153; age: mean = 22; SD = 7.1; range = 17–66), we identified two affect structures—one with three and one with four dimensions. The main difference was the presence of negative emotionality, and the affect dimensions became more inversely related when the affect structure included negative emotionality. Moreover, we identified three latent subgroups that differed in their transition patterns. Higher negative event intensity increased the probability of adopting an affect structure with negative emotionality. However, neuroticism was unrelated to subgroup-membership. Summarized, we propose a way to incorporate contextual and individual differences in affect structure, contributing to advancing the theoretical basis of affect dynamics research. (PsycInfo Database Record (c) 2023 APA, all rights reserved

Inherited susceptibility to bleomycin-induced chromatid breaks in cultured peripheral blood lymphocytes

Background: Susceptibility to bleomycin-induced chromatid breaks in cultured peripheral blood lymphocytes may reflect the way a person deals with carcinogenic challenges. This susceptibility (also referred to as mutagen sensitivity) has been found to be increased in patients with environmentally related cancers, including cancers of the head and neck, lung, and colon, and, in combination with carcinogenic exposure, this susceptibility can greatly influence cancer risk. The purpose of this study was to assess the heritability of mutagen sensitivity. Methods: Heritability was determined by use of a maximum likelihood method that employed the FISHER package of pedigree analysis. Bleomycin-induced breaks per cell values for 135 healthy volunteers without cancer were determined. These individuals were from 53 different pedigrees and included 25 monozygotic twin pairs (n = 50), 14 pairs of dizygotes (twin pairs and siblings, n = 28), and 14 families selected on the basis of a first-degree relative who was successfully treated for head and neck cancer and who had no sign of recurrence for at least 1 year. All data were analyzed simultaneously, and different models of familial resemblance were fitted to the data. All P values are two-sided. Results: Our results showed no evidence for the influence of a shared family environment on bleomycin-induced chromatid breaks. Genetic influences, however, were statistically significant (P = .036) and accounted for 75% of the total variance. Conclusions: The high heritability estimate of the susceptibility to bleomycin-induced chromatid breaks indicates a clear genetic basis. The findings of this study support the notion that a common genetic susceptibility to DNA damage - and thereby a susceptibility to cancer - may exist in the general population

TARP as immunotherapeutic target in AML expressed in the LSC compartment

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Serum N-Terminal propeptide of collagen type I is associated with the number of bone Metastases in breast and prostate cancer and correlates to other bone related markers

Background A number of biomarkers have been proven potentially useful for their ability to indicate bone metastases (BM) in cancer patients. The aim of this study was to investigate the relative utility of a newly developed N-terminal propeptide of collagen type I (PINP) human serum assay for the detection of BM in cancer patients. This assay has a corresponding rat PINP assay which in the future might help in translational science between rodent and human trials. Methods Participants were 161 prostate, lung and breast cancer patients stratified by number of BM(Soloway score). PINP was assessed and correlated to number of BM. Additionally, the PINP marker was correlated to bone resorption of young (ALPHA CTX-I)- and aged bone (BETA CTX-I); number of osteoclasts (Tartrate-resistant acid phosphatase 5b, TRACP5B) and osteoclast activity (CTX-I/TRACP5B). Results PINP was significantly elevated in breast- and prostate cancer patients +BM, compared to –BM ( P < 0.001), however not in lung cancer patients. A strong linear association was seen between PINP and the number of BMs. Significant elevation of PINP was observed at Soloway scores 1–4 (<0 BM) compared with score 0 (0 BM) ( P < 0.001). The correlation between bone resorption of young bone or aged bone and bone formation was highly significant in patients +BM and –BM ( P < 0.0001). Conclusions Data suggest that the present PINP potentially could determine skeletal involvement in patients with breast or prostate cancer. Correlations suggested that coupling between bone resorption and bone formation was maintained in breast- and prostate cancer patients

Regulation of stem cell differentiation by histone methyltransferases and demethylases

The generation of different cell types from stem cells containing identical genetic information and their organization into tissues and organs during development is a highly complex process that requires defined transcriptional programs. Maintenance of such programs is epigenetically regulated and the factors involved in these processes are often essential for development. The activities required for cell-fate decisions are frequently deregulated in human tumors, and the elucidation of the molecular mechanisms that regulate these processes is therefore important for understanding both developmental processes and tumorigenesis

Genome-Wide Studies of Histone Demethylation Catalysed by the Fission Yeast Homologues of Mammalian LSD1

In order to gain a more global view of the activity of histone demethylases, we report here genome-wide studies of the fission yeast SWIRM and polyamine oxidase (PAO) domain homologues of mammalian LSD1. Consistent with previous work we find that the two S. pombe proteins, which we name Swm1 and Swm2 (after SWIRM1 and SWIRM2), associate together in a complex. However, we find that this complex specifically demethylates lysine 9 in histone H3 (H3K9) and both up- and down-regulates expression of different groups of genes. Using chromatin-immunoprecipitation, to isolate fragments of chromatin containing either H3K4me2 or H3K9me2, and DNA microarray analysis (ChIP-chip), we have studied genome-wide changes in patterns of histone methylation, and their correlation with gene expression, upon deletion of the swm1+ gene. Using hyper-geometric probability comparisons we uncover genetic links between lysine-specific demethylases, the histone deacetylase Clr6, and the chromatin remodeller Hrp1. The data presented here demonstrate that in fission yeast the SWIRM/PAO domain proteins Swm1 and Swm2 are associated in complexes that can remove methyl groups from lysine 9 methylated histone H3. In vitro, we show that bacterially expressed Swm1 also possesses lysine 9 demethylase activity. In vivo, loss of Swm1 increases the global levels of both H3K9me2 and H3K4me2. A significant accumulation of H3K4me2 is observed at genes that are up-regulated in a swm1 deletion strain. In addition, H3K9me2 accumulates at some genes known to be direct Swm1/2 targets that are down-regulated in the swm1¿ strain. The in vivo data indicate that Swm1 acts in concert with the HDAC Clr6 and the chromatin remodeller Hrp1 to repress gene expression. In addition, our in vitro analyses suggest that the H3K9 demethylase activity requires an unidentified post-translational modification to allow it to act. Thus, our results highlight complex interactions between histone demethylase, deacetylase and chromatin remodelling activities in the regulation of gene expression

Overcoming bortezomib resistance in human B cells by anti-CD20/rituximab-mediated complement-dependent cytotoxicity and epoxyketone-based irreversible proteasome inhibitors

UNLABELLED: BACKGROUND: In clinical and experimental settings, antibody-based anti-CD20/rituximab and small molecule proteasome inhibitor (PI) bortezomib (BTZ) treatment proved effective modalities for B cell depletion in lymphoproliferative disorders as well as autoimmune diseases. However, the chronic nature of these diseases requires either prolonged or re-treatment, often with acquired resistance as a consequence. METHODS: Here we studied the molecular basis of acquired resistance to BTZ in JY human B lymphoblastic cells following prolonged exposure to this drug and examined possibilities to overcome resistance by next generation PIs and anti-CD20/rituximab-mediated complement-dependent cytotoxicity (CDC). RESULTS: Characterization of BTZ-resistant JY/BTZ cells compared to parental JY/WT cells revealed the following features: (a) 10-12 fold resistance to BTZ associated with the acquisition of a mutation in the PSMB5 gene (encoding the constitutive $β$5 proteasome subunit) introducing an amino acid substitution (Met45Ile) in the BTZ-binding pocket, (b) a significant 2-4 fold increase in the mRNA and protein levels of the constitutive $β$5 proteasome subunit along with unaltered immunoproteasome expression, (c) full sensitivity to the irreversible epoxyketone-based PIs carfilzomib and (to a lesser extent) the immunoproteasome inhibitor ONX 0914. Finally, in association with impaired ubiquitination and attenuated breakdown of CD20, JY/BTZ cells harbored a net 3-fold increase in CD20 cell surface expression, which was functionally implicated in conferring a significantly increased anti-CD20/rituximab-mediated CDC. CONCLUSIONS: These results demonstrate that acquired resistance to BTZ in B cells can be overcome by next generation PIs and by anti-CD20/rituximab-induced CDC, thereby paving the way for salvage therapy in BTZ-resistant disease