Fungicidal activity of some o-nitrophenyl-hydrazones

The antimycotic activity of 16 o-nitrophenylhydrazones against strains of Hansenula anomala, Saccharomyces cerevisiae, Candida parapsyliosis, and Cryptococcus albidus was tested. All 16 compounds inhibited growth of the yeast strains. The inhibitory activity of the 4 methyl-derivatives substituted on the aromatic nucleus was particularly significant

Origin and distribution of the BRCA2-8765delAG mutation in breast cancer

Background: The BRCA2-8765delAG mutation was firstly described in breast cancer families from French-Canadian and Jewish-Yemenite populations; it was then reported as a founder mutation in Sardinian families. We evaluated both the prevalence of the BRCA2-8765delAG variant in Sardinia and the putative existence of a common ancestral origin through a haplotype analysis of breast cancer family members carrying such a mutation. Methods: Eight polymorphic microsatellite markers (D13S1250, centromeric, to D13S267, telomeric) spanning the BRCA2 gene locus were used for the haplotype analysis. Screening for the 8765delAG mutation was performed by PCR-based amplification of BRCA2-exon 20, followed by automated sequencing. Results: Among families with high recurrence of breast cancer (≥ 3 cases in first-degree relatives), those from North Sardinia shared the same haplotype whereas the families from French Canadian and Jewish-Yemenite populations presented distinct genetic assets at the BRCA2 locus. Screening for the BRCA2-8765delAG variant among unselected and consecutively-collected breast cancer patients originating from the entire Sardinia revealed that such a mutation is present in the northern part of the island only [9/648 (1.4%) among cases from North Sardinia versus 0/493 among cases from South Sardinia]. Conclusion: The BRCA2-8765delAG has an independent origin in geographically and ethnically distinct populations, acting as a founder mutation in North but not in South Sardinia. Since BRCA2- 8765delAG occurs within a triplet repeat sequence of AGAGAG, our study further confirmed the existence of a mutational hot-spot at this genomic position (additional genetic factors within each single population might be involved in generating such a mutation)

Development of new technologies to study gut microbiomes

Metaproteomics allows the qualitative and quantitative evaluation of the protein complement of an environment at a given time. Given the youth of this research field, significant efforts are needed to optimize sample preparation and data analysis workflows for metaproteome analysis. A major task is aimed at developing novel, rapid and efficient workflows for shotgun metaproteomic analysis. In the present PhD Thesis the investigation of a number of experimental methods have been developed to optimize sample preparation and its MS analysis. Methods were assessed on mock and real gut microbiome samples, combining bead-beating/freeze-thawing for protein extraction, FASP for clean-up and digestion, and single-run LC-MS/MS for peptide separation and identification. The impact of different sequence databases on data analysis was evaluated using mock microbial mixtures. Upon comparison of experimental metagenomic-derived and publicly deposited databases, complementary results suggested the use of iterative searches and suitable taxonomy filters to improve metaproteomic analysis. According to data obtained, the workflow enables protein identification also from fungi, showing high reproducibility (&gt;99%), sensitivity (&lt;104 bacterial CFUs) and dynamic range (&gt;104). Finally, this workflow was successfully applied to investigate the sheep fecal metaproteome, obtaining the identification of more than 35,000 proteins belonging to more than 700 microbial species (10 % of which fungi).</br

Primary dermal melanoma in a patient with a history of multiple malignancies: a case report with molecular characterization

Introduction: Primary dermal melanoma (PDM) is a recently described clinical entity accounting for less than 1% of all melanomas. Histologically, it is located in the dermis or subcutaneous tissue, and it shows no connections with the overlying epidermis. The differential diagnosis is principally made along with that of metastatic cutaneous melanoma. Case Report: A 72-year-old Caucasian woman with a history of multiple cancers (metachro-nous bilateral breast cancer, meningioma, clear cell renal cell carcinoma, uterine fibromatosis and intestinal adenomatous polyposis), came to our attention with a nodular lesion on her back. After removal of the lesion, the histology report indicated malignant PDM or metastatic malignant melanoma. The clinical and instrumental evaluation of the patient did not reveal any other primary tumour, suggesting the primitive nature of the lesion. The absence of an epithelial component argued for a histological diagnosis of PDM. Subsequently, the patient underwent a wide surgical excision with sentinel node biopsy, which was positive for metastatic melanoma. Finally, the mutational status was studied in the main genes that regulate proliferation, apoptosis and cellular senescence. No pathogenetic mutations in CDKN2A, BRAF, NRAS, KRAS, cKIT, TP53 and PTEN genes were observed. This suggests that alternative pathways and low-frequency alterations may be involved. Conclusions: The differential diagnosis between PDM and isolated metastatic melanoma depends on the negativity of imaging studies and clinical findings for other primary lesions. This distinction is important because 5-year survival rates in such cases are higher than in metastatic cases (80– 100 vs. 5–20%, respectively)

A Simulation Tool to Evaluate the Feasibility of a gasification-I.C.E. System to Produce Heat and Power for Industrial Applications☆

Abstract Combined heat and power (CHP) systems fed by renewable sources are of great interest for efficient and greener energy production in industrial applications. In order to reduce fossil fuel consumption, biomass gasification coupled with I.C.E. is a viable way for ensure constant and accurately predictable renewable energy production. The aim of this work is to evaluate the integration in an industrial context of a CHP system fed by syngas produced from woody biomass gasification in a downdraft reactor. The feasibility study was developed thorough the combination of two simulation programs. Aspen Plus was used for simulating the biomass gasification unit and was exploited in order to determine the syngas composition and flow rate. Results have been employed in TRNSYS, that has instead been chosen for the modeling of the complete CHP system

Epidemiology and Genetic Susceptibility of Breast and Ovarian Cancer in Sardinian Population

The objective of this population-based study is to describe epidemiological and genetic features of breast and ovarian cancer in North Sardinia, Italy. Patients who carry a high-risk mutation in one or both of the BRCA genes (BRCA1 or BRCA2) have a significantly increased risk of developing breast/ovarian cancer (BOC) and other cancers (e.g., prostate cancer in male). Epidemiological data on incidence distribution of breast/ovarian cancer from 2016 to 2019 in North Sardinia are obtained from the local tumor registry and from the cumulative results of 209 genetic testing for BRCA gene mutations performed in all young breast cancer patients and all women (over 50 years) with family history of BOC (total of 164 cases); further, 45 genetic testing is performed, on ovarian cancer patients, at any age. The results provide a different distribution of fraction mutations carried by women and a higher prevalence of the BRCA2 mutation in the north of Sardinia than the entire population and highlight the presence of specific germline mutation associated with the “founder effect” in distinct genetic subgroups reflecting genetic drift. Advances in next-generation sequencing technology, data analysis, and clinical investigation have revolutionized efforts to identify potential targets for BRCA molecular-based therapeutic agents

The impact of sequence database choice on metaproteomic results in gut microbiota studies

Background: Elucidating the role of gut microbiota in physiological and pathological processes has recently emerged as a key research aim in life sciences. In this respect, metaproteomics, the study of the whole protein complement of a microbial community, can provide a unique contribution by revealing which functions are actually being expressed by specific microbial taxa. However, its wide application to gut microbiota research has been hindered by challenges in data analysis, especially related to the choice of the proper sequence databases for protein identification. Results: Here, we present a systematic investigation of variables concerning database construction and annotation and evaluate their impact on human and mouse gut metaproteomic results. We found that both publicly available and experimental metagenomic databases lead to the identification of unique peptide assortments, suggesting parallel database searches as a mean to gain more complete information. In particular, the contribution of experimental metagenomic databases was revealed to be mandatory when dealing with mouse samples. Moreover, the use of a "merged" database, containing all metagenomic sequences from the population under study, was found to be generally preferable over the use of sample-matched databases. We also observed that taxonomic and functional results are strongly database-dependent, in particular when analyzing the mouse gut microbiota. As a striking example, the Firmicutes/Bacteroidetes ratio varied up to tenfold depending on the database used. Finally, assembling reads into longer contigs provided significant advantages in terms of functional annotation yields. Conclusions: This study contributes to identify host- and database-specific biases which need to be taken into account in a metaproteomic experiment, providing meaningful insights on how to design gut microbiota studies and to perform metaproteomic data analysis. In particular, the use of multiple databases and annotation tools has to be encouraged, even though this requires appropriate bioinformatic resources

[1,2,3]triazolo[4,5-<i>H</i>]chinoloni: una nuova classe di promettenti chemioterapici antitubercolari

Alcuni acidi triazolo[4,5-h] e [4,5-f]chinoloncarbossilici angolari, sintetizzati in precedenza come antiinfettivi del tratto urinario, hanno mostrato interessanti valori di MIC90 nei confronti di M. tuberculosis H37Rv. Allo scopo di approfondire le nostre conoscenze sui rapporti struttura-attività di questa classe, abbiamo pertanto preparato una nuove serie di derivati

Learning mutational graphs of individual tumour evolution from single-cell and multi-region sequencing data

Background. A large number of algorithms is being developed to reconstruct evolutionary models of individual tumours from genome sequencing data. Most methods can analyze multiple samples collected either through bulk multi-region sequencing experiments or the sequencing of individual cancer cells. However, rarely the same method can support both data types. Results. We introduce TRaIT, a computational framework to infer mutational graphs that model the accumulation of multiple types of somatic alterations driving tumour evolution. Compared to other tools, TRaIT supports multi-region and single-cell sequencing data within the same statistical framework, and delivers expressive models that capture many complex evolutionary phenomena. TRaIT improves accuracy, robustness to data-specific errors and computational complexity compared to competing methods. Conclusions. We show that the application of TRaIT to single-cell and multi-region cancer datasets can produce accurate and reliable models of single-tumour evolution, quantify the extent of intra-tumour heterogeneity and generate new testable experimental hypotheses

Accurate pHEMT nonlinear modeling in the presence of low-frequency dispersive effects

Low-frequency (LF) dispersive phenomena due to device self-heating and/or the presence of "traps" (i.e., surface state densities and bulk spurious energy levels) must be taken into account in the large-signal dynamic modeling of III-V field-effect transistors when accurate performance predictions are pursued, since these effects cause important deviations between direct current (dc) and dynamic drain current characteristics. In this paper, a new model for the accurate characterization of these phenomena above their cutoff frequencies is presented, which is able to fully exploit, in the identification phase, large-signal current-voltage (I-V) measurements carried out under quasi-sinusoidal regime using a recently proposed setup. Detailed experimental results for model validation under LF small- and large-signal operating conditions are provided. Furthermore, the I-V model proposed has been embedded into a microwave large-signal pseudomorphic high electron-mobility transistor (pHEMT) model in order to point out the strong influence of LF modeling on the degree of accuracy achievable under millimeter-wave nonlinear operation. Large-signal experimental validation at microwave frequencies is provided for the model proposed, by showing the excellent intermodulation distortion (IMD) predictions obtained with different loads despite the very low power level of IMD products involved. Details on the millimeter-wave IMD measurement setup are also provided. Finally, IMD measurements and simulations on a Ka-band highly linear power amplifier, designed by Ericsson using the Triquint GaAs 0.25-/spl mu/m pHEMT process, are shown for further model validation