The Comparison of Forensic-Psychiatric Traits between Female and Male Perpetrators of Murder or Attempted Murder

The aim of this investigation was to define more clearly specific forensic-psychiatric characteristics of female murder or attempted murder perpetrators. The retrospective method applied was based on the comparison of the data from forensic-psychiatric assessments carried out in the Center for Forensic Psychiatry, Psychiatric Hospital Vrapče, Zagreb, from 1983 to 1997 (including 70 female and 70 male subjects – who committed murder or attempted murder). Compared with men, female offenders were most often in some way emotionally related to their victims, and they were more often victimized themselves before committing the crime. In men alcoholism was a more significant circumstantial factor in the assessment of their accountability. Psychiatric security measures were more often given to male offenders. The intensity of aggression was lower in females than in males. This investigation reveals that there are some sex specific forensic-psychiatric traits of murder or attempted murder perpetrators. The obtained results could be of help in everyday forensic-psychiatric practice, both in assessments and treatment

The Comparison of Forensic-Psychiatric Traits between Female and Male Perpetrators of Murder or Attempted Murder

The aim of this investigation was to define more clearly specific forensic-psychiatric characteristics of female murder or attempted murder perpetrators. The retrospective method applied was based on the comparison of the data from forensic-psychiatric assessments carried out in the Center for Forensic Psychiatry, Psychiatric Hospital Vrapče, Zagreb, from 1983 to 1997 (including 70 female and 70 male subjects – who committed murder or attempted murder). Compared with men, female offenders were most often in some way emotionally related to their victims, and they were more often victimized themselves before committing the crime. In men alcoholism was a more significant circumstantial factor in the assessment of their accountability. Psychiatric security measures were more often given to male offenders. The intensity of aggression was lower in females than in males. This investigation reveals that there are some sex specific forensic-psychiatric traits of murder or attempted murder perpetrators. The obtained results could be of help in everyday forensic-psychiatric practice, both in assessments and treatment

Glycophenotype of breast and prostate cancer stem cells treated with thieno[2,3-b]pyridine anticancer compound

Angela Mastelić,1 Vedrana Čikeš Čulić,1 Nikolina Režić Mužinić,1 Milena Vuica-Ross,2 David Barker,3 Euphemia Y Leung,4,5 Jóhannes Reynisson,3 Anita Markotić1 1Department of Medical Chemistry and Biochemistry, University of Split School of Medicine, Split, Croatia; 2Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA; 3School of Chemical Sciences, The University of Auckland, 4Auckland Cancer Society Research Centre, The University of Auckland, 5Molecular Medicine and Pathology Department, The University of Auckland, Auckland, New Zealand Abstract: Tumor progression may be driven by a small subpopulation of cancer stem cells (CSCs characterized by CD44+/CD24- phenotype). We investigated the influence of a newly developed thienopyridine anticancer compound (3-amino-5-oxo-N-naphthyl-5,6,7,8-tetrahydrothieno[2,3-b]quinoline-2-carboxamide, 1) on the growth, survival and glycophenotype (CD15s and GM3 containing neuraminic acid substituted with acetyl residue, NeuAc) of breast and prostate cancer stem/progenitor-like cell population. MDA-MB-231 and Du-145 cells were incubated with compound 1 alone or in combination with paclitaxel. The cellular metabolic activity was determined by the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay. The type of cell death induced by 48-h treatment was assessed using a combination of Annexin-V-FITC and propidium iodide staining. Flow cytometric analysis was performed to detect the percentage of CD44+/CD24- cells, and GM3 and CD15s positive CSCs, as well as the expression of GM3 and CD15s per one CSC, in both cell lines. Compound 1 produces a dose- and time-dependent cytotoxicity, mediated mainly by apoptosis in breast cancer cells, and slightly (2.3%) but statistically significant lowering breast CSC subpopulation. GM3 expression per one breast CSC was increased, and the percentage of prostate GM3+ CSC subpopulation was decreased in cells treated with compound 1 compared with non-treated cells. The percentage of CD15s+ CSCs was lower in both cell lines after treatment with compound 1. Considering that triple-negative breast cancers are characterized by an increased percentage of breast CSCs and knowing their association with an increased risk of metastasis and mortality, compound 1 is a potentially effective drug for triple-negative breast cancer treatment. Keywords: breast, prostate, cancer stem cells, CD44+/CD24-, GM3, CD15

Epigenetic silencing of HNF1A associates with changes in the composition of the human plasma N-glycome.

Protein glycosylation is a ubiquitous modification that affects the structure and function of proteins. Our recent genome wide association study identified transcription factor HNF1A as an important regulator of plasma protein glycosylation. To evaluate the potential impact of epigenetic regulation of HNF1A on protein glycosylation we analyzed CpG methylation in 810 individuals. The association between methylation of four CpG sites and the composition of plasma and IgG glycomes was analyzed. Several statistically significant associations were observed between HNF1A methylation and plasma glycans, while there were no significant associations with IgG glycans. The most consistent association with HNF1A methylation was observed with the increase in the proportion of highly branched glycans in the plasma N-glycome. The hypothesis that inactivation of HNF1A promotes branching of glycans was supported by the analysis of plasma N-glycomes in 61 patients with inactivating mutations in HNF1A, where the increase in plasma glycan branching was also observed. This study represents the first demonstration of epigenetic regulation of plasma glycome composition, suggesting a potential mechanism by which epigenetic deregulation of the glycome may contribute to disease development

Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers

Contains fulltext : 118733.pdf (publisher's version ) (Open Access)Glycosylation of immunoglobulin G (IgG) influences IgG effector function by modulating binding to Fc receptors. To identify genetic loci associated with IgG glycosylation, we quantitated N-linked IgG glycans using two approaches. After isolating IgG from human plasma, we performed 77 quantitative measurements of N-glycosylation using ultra-performance liquid chromatography (UPLC) in 2,247 individuals from four European discovery populations. In parallel, we measured IgG N-glycans using MALDI-TOF mass spectrometry (MS) in a replication cohort of 1,848 Europeans. Meta-analysis of genome-wide association study (GWAS) results identified 9 genome-wide significant loci (P<2.27 x 10(-9)) in the discovery analysis and two of the same loci (B4GALT1 and MGAT3) in the replication cohort. Four loci contained genes encoding glycosyltransferases (ST6GAL1, B4GALT1, FUT8, and MGAT3), while the remaining 5 contained genes that have not been previously implicated in protein glycosylation (IKZF1, IL6ST-ANKRD55, ABCF2-SMARCD3, SUV420H1, and SMARCB1-DERL3). However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). Follow-up functional experiments in haplodeficient Ikzf1 knock-out mice showed the same general pattern of changes in IgG glycosylation as identified in the meta-analysis. As IKZF1 was associated with multiple IgG N-glycan traits, we explored biomarker potential of affected N-glycans in 101 cases with SLE and 183 matched controls and demonstrated substantial discriminative power in a ROC-curve analysis (area under the curve = 0.842). Our study shows that it is possible to identify new loci that control glycosylation of a single plasma protein using GWAS. The results may also provide an explanation for the reported pleiotropy and antagonistic effects of loci involved in autoimmune diseases and haematological cancer