Tomato plants transgenic for an Arabidopsis thaliana cystein proteinase inhibitor (Atcys) impair the life cycle of Helicoverpa armigera (Hüb.)

Atcys tomato (Lycopersicon esculentum Mill.) transgenic plants, expressing a cystein proteinase inhibition level double than the untransformed control (Speranza et al. in press), were used for in vivo assays with H. armigera larvae. This insect pest, extremely polyphagous, has recently caused severe damages to the outdoor tomato crop due to the dropping of infested young fruits and to fruit rotting because of the larval galleries. Plants of the cv. Riogrande (RIG) and of the corresponding Atcys homozygous transgenic line (BG-106) were grown in greenhouse and leaves utilized for feeding H. armigera larvae, reared for four days with artificial diet. The recorded data were larval weight (every two days until the cocoon stage), cocoon sex and morphometric traits, number of adults emerged from the cocoon, number of layed and hatched eggs. The mean weight was generally higher when larvae were fed with BG-106 leaves. By subdividing in three periods the larval life, no difference in mortality was observed between larvae reared with control (RIG) and with BG-106 leaves. The percentage of adults emerged from the cocoon was 81% and 76% for the control and BG-106 respectively. The sex ratio (males/females) was in favour of the female sex both for the RIG (0.87) and BG-106 (0.73) cocoons. On average, the fertility (number of layed eggs) of the BG-106 fed females was 33% lower than the control. By considering the percentage of hatched eggs (emerged larvae), the value obtained was 6.8% for BG-106 against 11% for RIG. According to these data, in Atcys transgenic tomato (BG-106), a level of cystein proteinase inhibition double than the untransformed control, is sufficient to negatively influence the H. armigera biological cycle, even if the weight of the larvae fed with the BG-106 leaves is on average higher than the control (RIG). The last datum is in agreement with similar experiments reported in literature where the effect of proteinase inhibitors is tested in different host-pest systems

Neuronopathic Gaucher disease models reveal defects in cell growth promoted by Hippo pathway activation

Gaucher Disease (GD), the most common lysosomal disorder, arises from mutations in the GBA1 gene and is characterized by a wide spectrum of phenotypes, ranging from mild hematological and visceral involvement to severe neurological disease. Neuronopathic patients display dramatic neuronal loss and increased neuroinflammation, whose molecular basis are still unclear. Using a combination of Drosophila dGBA1b loss-of-function models and GD patient-derived iPSCs differentiated towards neuronal precursors and mature neurons we showed that different GD- tissues and neuronal cells display an impairment of growth mechanisms with an increased cell death and reduced proliferation. These phenotypes are coupled with the downregulation of several Hippo transcriptional targets, mainly involved in cells and tissue growth, and YAP exclusion from nuclei. Interestingly, Hippo knock-down in the GBA-KO flies rescues the proliferative defect, suggesting that targeting the Hippo pathway can be a promising therapeutic approach to neuronopathic GD.A combination of Drosophila dGBA1b loss-of-function models and Gaucher Disease (GD) patient-derived iPSCs reveals an impairment in GD neuronal cell growth and that Hippo pathway hyperactivation contributes to the impairment

Psychopathological factors and personality dimensions on dysfunctional eating behaviors in a sample of individuals with obesity

IntroductionObesity and eating disorders are considered to be part of a broad spectrum of disorders associated with weight issues and maladaptive eating styles. Several studies show that psychopathological and personality characteristics contribute to the development and maintenance of obesity and dysfunctional eating behaviors, showing a bidirectional relationship. The purpose of this study was to understand the role of psychopathological factors and personality dimensions on dysfunctional eating behaviors in a sample of individuals with obesity.MethodsThe study was conducted with 96 individuals with obesity (31 males and 65 females) who underwent psychological assessment. The instruments administered included the Cognitive Behavioral Assessment 2.0 - Primary Scales, the Minnesota Multiphasic Personality Inventory-2, and the Eating Disorder Inventory. Relationships between dysfunctional eating behaviors and personality and psychopathological factors were explored through mediation analysis.Results and discussionOur results showed that difficulties related to impulse control and behavior, along with negative and dysphoric emotions, may be associated with difficulties in eating behavior. Mediation analysis showed that the combination of depressive and obsessive-compulsive symptomatology may exacerbate or contribute to the occurrence of eating disorders. These psychopathological aspects should be taken into account during the assessment of patients who decide to undergo bariatric surgery and should be targets of specific psychological interventions

Comprehensive Genomic Analysis Reveals the Prognostic Role of LRRK2 Copy-Number Variations in Human Malignancies

Genetic alterations of leucine-rich repeat kinase 2 (LRRK2), one of the most important contributors to familial Parkinson’s disease (PD), have been hypothesized to play a role in cancer development due to demographical and preclinical data. Here, we sought to define the prevalence and prognostic significance of LRRK2 somatic mutations across all types of human malignancies by querying the publicly available online genomic database cBioPortal. Ninety-six different studies with 14,041 cases were included in the analysis, and 761/14,041 (5.4%) showed genetic alterations in LRRK2. Among these, 585 (76.9%) were point mutations, indels or fusions, 168 (22.1%) were copy number variations (CNVs), and 8 (1.0%) showed both types of alterations. One case showed the somatic mutation R1441C. A significant difference in terms of overall survival (OS) was noted between cases harboring somatic LRRK2 whole deletions, amplifications, and CNV-unaltered cases (median OS: 20.09, 57.40, and 106.57 months, respectively; p = 0.0008). These results suggest that both LRRK2 amplifications and whole gene deletions could play a role in cancer development, paving the way for future research in terms of potential treatment with LRRK2 small molecule inhibitors for LRRK2-amplified cases

SCARB1 downregulation in adrenal insufficiency with Allgrove syndrome

Abstract Background Allgrove disease is a rare genetic syndrome characterized by adrenal insufficiency, alacrimia, achalasia and complex neurological involvement. Allgrove disease is due to recessive mutations in the AAAS gene, which encodes for the nucleoporin Aladin, implicated in the nucleocytoplasmic transport. The adrenal insufficiency has been suggested to rely on adrenal gland-ACTH resistance. However, the link between the molecular pathology affecting the nucleoporin Aladin and the glucocorticoid deficiency is still unknown. Results By analyzing postmortem patient’s adrenal gland, we identified a downregulation of Aladin transcript and protein. We found a downregulation of Scavenger receptor class B-1 (SCARB1), a key component of the steroidogenic pathway, and SCARB1 regulatory miRNAs (mir125a, mir455) in patient’s tissues. With the hypothesis of an impairment in the nucleocytoplasmic transport of the SCARB1 transcription enhancer cyclic AMP-dependent protein kinase (PKA), we detected a reduction of nuclear Phospho-PKA and a cytoplasmic mislocalization in patient’s samples. Conclusions These results shed a light on the possible mechanisms linking ACTH resistance, SCARB1 impairment, and defective nucleocytoplasmic transport