Genetic Control of Parthenogenesis in Kentucky Bluegrass: Results from a Sexual x Apomictic Cross

Apomixis, as it exists in Poa pratensis L., permits to combine genotype fixation with propagation by seed. The process of apomictic seed production involves the formation of embryo sacs without meiotic reduction (apospory) and embryos without egg cell fertilization (parthenogenesis). Further information on the genetic control of apomixis was obtained by analyzing aposporous parthenogenesis and the segregation of molecular markers in a progeny resulting from a “sexual” (S) x “apomictic”(A) cross. Data from the 35 F1 plants examined so far have shown that parthenogenesis segregated 1:1, confirming control by a dominant gene, simplex in the parthenogenetic parent. Analysis of variance and regression were used to find single markers from the A and S parents affecting the trait in the 15 parthenogenetic progenies. A minimum of 4 genes from the sexual parent and 1 from the apomictic parent influencing the expression of parthenogenesis appeared to segregate in this cross

Line-field confocal optical coherence tomography: a new tool for non-invasive differential diagnosis of pustular skin disorders

Background The spectrum of pustular skin disorders (PSD) is large and particularly challenging, including inflammatory, infectious and amicrobial diseases. Moreover, although pustules represent the unifying clinical feature, they can be absent or not fully developed in the early stage of the disease. The line-field confocal optical coherence tomography (LC-OCT) is a recently developed imaging technique able to perform a non-invasive, in vivo, examination of the epidermis and upper dermis, reaching very high image resolution and virtual histology. Objectives We aimed to investigate the potentialities of LC-OCT in the non-invasive differential diagnosis of a series of 11 PSD with different aetiology, microscopic features, body location and incidence rates. Materials and Methods Complete LC-OCT imaging (i.e. 2D/3D frames, videos) was performed on a total of 19 patients (10 females and 9 males) aged between 35 and 79 years. Images were blindly evaluated and compared with corresponding histopathologic findings. Results The LC-OCT imaging was able to detect with high accuracy the pustule structure including shape, margins, morphology and cellular content, along with peculiar epidermal and adnexal alterations in each condition, including: Acute Generalized Exanthematous Pustulosis, Generalized pustular psoriasis, Generalized pustular figurate erythema, Subcorneal Pustular Dermatosis, Intraepidermal IgA pustulosis, Palmoplantar pustulosis, Palmoplantar pustular psoriasis. Herpetic whitlow, Acrodermatitis continua of Hallopeau, Vesicopustular Sweet syndrome and Vesicopustular Eosinophilic cellulitis, with pustular appearance, were also compared. Conclusions The new LC-OCT can represent a rapid, non-invasive and painless tool which can help differentiating among PSD of different aetiology and microscopic morphology in clinical mimickers in daily practice

Maraviroc Intensification Modulates Atherosclerotic Progression in HIV-Suppressed Patients at High Cardiovascular Risk. A Randomized, Crossover Pilot Study

Background Experimental CCR5 antagonism with maraviroc in atherosclerosis-prone mice and preliminary data in humans suggest an anti-atherosclerotic effect of the drug. We assessed the impact of maraviroc treatment in persons living with HIV on subclinical indicators of atherosclerosis. Methods Persons living with HIV on effective antiretroviral therapy (ART) including only protease inhibitors were recruited if they had a Framingham risk score >20% and brachial flow-mediated dilation (bFMD) <4%, as indices of high cardiovascular risk. Maraviroc (300 mg per os for 24 weeks) was administered, in addition to ongoing ART, to all patients using a crossover design. Brachial FMD, carotid-femoral pulse wave velocity (cfPWV), and carotid intima-media thickness (cIMT) were measured as markers of atherosclerosis. Vascular competence—as expressed by the ratio of circulating endothelial microparticles (EMPs) to endothelial progenitor cells (EPCs)—and markers of systemic inflammation and monocyte and platelet activation were assessed. Results Maraviroc treatment significantly improved bFMD, cfPWV, and cIMT by 66%, 11%, and 13%, respectively (P = .002, P = .022, P = .038, respectively). We also found a beneficial effect of maraviroc on the EMP/EPC ratio (P < .001) and platelet/leucocyte aggregates (P = .013). No significant changes in markers of systemic inflammation, monocyte activation, and microbial translocation were observed. Conclusions Maraviroc led to significant improvements in several markers for cardiovascular risk, endothelial dysfunction, arterial stiffness, and early carotid atherosclerosis, which was accompanied by an increase of vascular competence, without seeming to affect systemic inflammation. Our data support the need for larger studies to test for any effects of maraviroc on preventing atherosclerosis-driven pathologies

The Plasticizer Bisphenol A Perturbs the Hepatic Epigenome: A Systems Level Analysis of the miRNome

Ubiquitous exposure to bisphenol A (BPA), an endocrine disruptor (ED), has raised concerns for both human and ecosystem health. Epigenetic factors, including microRNAs (miRNAs), are key regulators of gene expression during cancer. The effect of BPA exposure on the zebrafish epigenome remains poorly characterized. Zebrafish represents an excellent model to study cancer as the organism develops a disease that resembles human cancer. Using zebrafish as a systems toxicology model, we hypothesized that chronic BPA-exposure impacts the miRNome in adult zebrafish and establishes an epigenome more susceptible to cancer development. After a 3 week exposure to 100 nM BPA, RNA from the liver was extracted to perform high throughput mRNA and miRNA sequencing. Differential expression (DE) analyses comparing BPA-exposed to control specimens were performed using established bioinformatics pipelines. In the BPA-exposed liver, 6188 mRNAs and 15 miRNAs were differently expressed (q ≤ 0.1). By analyzing human orthologs of the DE zebrafish genes, signatures associated with non-alcoholic fatty liver disease (NAFLD), oxidative phosphorylation, mitochondrial dysfunction and cell cycle were uncovered. Chronic exposure to BPA has a significant impact on the liver miRNome and transcriptome in adult zebrafish with the potential to cause adverse health outcomes including cancer

Novel Harmonization Method for Multi-Centric Radiomic Studies in Non-Small Cell Lung Cancer

The purpose of this multi-centric work was to investigate the relationship between radiomic features extracted from pre-treatment computed tomography (CT), positron emission tomography (PET) imaging, and clinical outcomes for stereotactic body radiation therapy (SBRT) in early-stage non-small cell lung cancer (NSCLC). One-hundred and seventeen patients who received SBRT for early-stage NSCLC were retrospectively identified from seven Italian centers. The tumor was identified on pre-treatment free-breathing CT and PET images, from which we extracted 3004 quantitative radiomic features. The primary outcome was 24-month progression-free-survival (PFS) based on cancer recurrence (local/non-local) following SBRT. A harmonization technique was proposed for CT features considering lesion and contralateral healthy lung tissues using the LASSO algorithm as a feature selector. Models with harmonized CT features (B models) demonstrated better performances compared to the ones using only original CT features (C models). A linear support vector machine (SVM) with harmonized CT and PET features (A1 model) showed an area under the curve (AUC) of 0.77 (0.63-0.85) for predicting the primary outcome in an external validation cohort. The addition of clinical features did not enhance the model performance. This study provided the basis for validating our novel CT data harmonization strategy, involving delta radiomics. The harmonized radiomic models demonstrated the capability to properly predict patient prognosis

Stereotactic radiotherapy for lung oligometastases

30–60% of cancer patients develop lung metastases, mostly from primary tumors in the colon-rectum, lung, head and neck area, breast and kidney. Nowadays, stereotactic radiotherapy (SRT) is considered the ideal modality for treating pulmonary metastases. When lung metastases are suspected, complete disease staging includes a total body computed tomography (CT) and/or positron emission tomography-computed tomography (PET-CT) scan. PET-CT has higher specificity and sensitivity than a CT scan when investigating mediastinal lymph nodes, diagnosing a solitary lung lesion and detecting distant metastases. For treatment planning, a multi-detector planning CT scan of the entire chest is usually performed, with or without intravenous contrast media or esophageal lumen opacification, especially when central lesions have to be irradiated. Respiratory management is recommended in lung SRT, taking the breath cycle into account in planning and delivery. For contouring, co-registration and/or matching planning CT and diagnostic images (as provided by contrast enhanced CT or PET-CT) are useful, particularly for central tumors. Doses and fractionation schedules are heterogeneous, ranging from 33 to 60 Gy in 3–6 fractions. Independently of fractionation schedule, a BED10 > 100 Gy is recommended for high local control rates. Single fraction SRT (ranges 15–30 Gy) is occasionally administered, particularly for small lesions. SRT provides tumor control rates of up to 91% at 3 years, with limited toxicities. The present overview focuses on technical and clinical aspects related to treatment planning, dose constraints, outcome and toxicity of SRT for lung metastases.

The future of Cybersecurity in Italy: Strategic focus area

This volume has been created as a continuation of the previous one, with the aim of outlining a set of focus areas and actions that the Italian Nation research community considers essential. The book touches many aspects of cyber security, ranging from the definition of the infrastructure and controls needed to organize cyberdefence to the actions and technologies to be developed to be better protected, from the identification of the main technologies to be defended to the proposal of a set of horizontal actions for training, awareness raising, and risk management

An integrated framework for quantifying immune-tumour interactions in a 3D co-culture model

Investigational in vitro models that reflect the complexity of the interaction between the immune system and tumours are limited and difficult to establish. Herein, we present a platform to study the tumour-immune interaction using a co-culture between cancer spheroids and activated immune cells. An algorithm was developed for analysis of confocal images of the co-culture to evaluate the following quantitatively; immune cell infiltration, spheroid roundness and spheroid growth. As a proof of concept, the effect of the glucocorticoid stress hormone, cortisol was tested on 66CL4 co-culture model. Results were comparable to 66CL4 syngeneic in vivo mouse model undergoing psychological stress. Furthermore, administration of glucocorticoid receptor antagonists demonstrated the use of this model to determine the effect of treatments on the immune-tumour interplay. In conclusion, we provide a method of quantifying the interaction between the immune system and cancer, which can become a screening tool in immunotherapy design