A simplified model of chromatin dynamics drives differentiation process in Boolean models of GRN

Cellular types of multicellular organisms are the stable results of complex intertwined processes that occur in biological cells. Among the many others, chromatin dynamics significantly contributes\u2014by modulating access to genes\u2014to differential gene expression, and ultimately to determine cell types. Here, we propose a dynamical model of differentiation based on a simplified bio-inspired methylation mechanism in Boolean models of GRNs. Preliminary results show that, as the number of methylated nodes increases, there is a decrease in attractor number and networks tend to assume dynamical behaviours typical of ordered ensembles. At the same time, results show that this mechanism does not affect the possibility of generating path dependent differentiation: cell types determined by the specific sequence of methylated genes

Pricing financial derivatives with neural networks

Abstract Neural network algorithms are applied to the problem of option pricing and adopted to simulate the nonlinear behavior of such financial derivatives. Two different kinds of neural networks, i.e. multi-layer perceptrons and radial basis functions, are used and their performances compared in detail. The analysis is carried out both for standard European options and American ones, including evaluation of the Greek letters, necessary for hedging purposes. Detailed numerical investigation show that, after a careful phase of training, neural networks are able to predict the value of options and Greek letters with high accuracy and competitive computational time

Phytosociology and taxonomic notes on some endemic-rich associations of the Naples Gulf

The Gulf of Naples is an important centre of endemism, well known from the floristic point of view, but much less from the phytosociological one. In this paper we investigated the non-forest vegetation focusing on communities rich in endemics. We described two communities as new: Eryngio amethystini-Santolinetum neapolitanae for the garrigues on limestone, Globulario neapolitanae-Loniceretum stabianae for the vegetation on dolomitic rocks, both from the Lattari mountains, and we extend the area of Crithmo maritimi-Limonietum cumani for the vegetation on volcanic rocks and rarely on limestones along the coast, which was known for a few localities. The syntaxonomical position and the phytogeographical context of these communities are discussed. A few taxonomic notes are added on rare or interesting species retrieved in the course of the enquiry

Impact of bisphenol A (BPA) on early embryo development in the marine mussel Mytilus galloprovincialis: Effects on gene transcription.

Bisphenol A (BPA), a monomer used in plastic manufacturing, is weakly estrogenic and a potential endocrine disruptor in mammals. Although it degrades quickly, it is pseudo-persistent in the environment because of continual inputs, with reported concentrations in aquatic environments between 0.0005 and 12 \u3bcg/L. BPA represents a potential concern for aquatic ecosystems, as shown by its reproductive and developmental effects in aquatic vertebrates. In invertebrates, endocrine-related effects of BPA were observed in different species and experimental conditions, with often conflicting results, indicating that the sensitivity to this compound can vary considerably among related taxa. In the marine mussel Mytilus galloprovincialis BPA was recently shown to affect early development at environmental concentrations. In this work, the possible effects of BPA on mussel embryos were investigated at the molecular level by evaluating transcription of 13 genes, selected on the basis of their biological functions in adult mussels. Gene expression was first evaluated in trocophorae and D-veligers (24 and 48 h post fertilization) grown in physiological conditions, in comparison with unfertilized eggs. Basal expressions showed a general up-regulation during development, with distinct transcript levels in trocophorae and D-veligers. Exposure of fertilized eggs to BPA (10 \u3bcg/L) induced a general upregulation at 24 h pf, followed by down regulation at 48 h pf. Mytilus Estrogen Receptors, serotonin receptor and genes involved in biomineralization (Carbonic Anydrase and Extrapallial Protein) were the most affected by BPA exposure. At 48 h pf, changes in gene expression were associated with irregularities in shell formation, as shown by scanning electron microscopy (SEM), indicating that the formation of the first shelled embryo, a key step in mussel development, represents a sensitive target for BPA. Similar results were obtained with the natural estrogen 17\u3b2-estradiol. The results demonstrate that BPA and E2 can affect Mytilus early development through dysregulation of gene transcription

Exploring Machine Learning for Untargeted Metabolomics Using Molecular Fingerprints

Background Metabolomics, the study of substrates and products of cellular metabolism, offers valuable insights into an organism's state under specific conditions and has the potential to revolutionise preventive healthcare and pharmaceutical research. However, analysing large metabolomics datasets remains challenging, with available methods relying on limited and incompletely annotated metabolic pathways. Methods This study, inspired by well-established methods in drug discovery, employs machine learning on metabolite fingerprints to explore the relationship of their structure with responses in experimental conditions beyond known pathways, shedding light on metabolic processes. It evaluates fingerprinting effectiveness in representing metabolites, addressing challenges like class imbalance, data sparsity, high dimensionality, duplicate structural encoding, and interpretable features. Feature importance analysis is then applied to reveal key chemical configurations affecting classification, identifying related metabolite groups. Results The approach is tested on two datasets: one on Ataxia Telangiectasia and another on endothelial cells under low oxygen. Machine learning on molecular fingerprints predicts metabolite responses effectively, and feature importance analysis aligns with known metabolic pathways, unveiling new affected metabolite groups for further study. Conclusion In conclusion, the presented approach leverages the strengths of drug discovery to address critical issues in metabolomics research and aims to bridge the gap between these two disciplines. This work lays the foundation for future research in this direction, possibly exploring alternative structural encodings and machine learning models

Responses of Mytilus galloprovincialis to challenge with the emerging marine pathogen Vibrio coralliilyticus

Vibrio coralliilyticus has emerged as a coral pathogen of concern throughout the Indo-Pacific reef. The interest towards understanding its ecology and pathogenic potential has increased since V. coralliilyticus was shown to be strongly virulent also for other species; in particular, it represents a serious threat for bivalve aquaculture, being one of the most important emerging pathogen responsible for oyster larval mortalities worldwide. V. coralliilyticus has a tightly regulated temperature-dependent virulence and it has been related to mass mortalities events of benthic invertebrates also in the temperate northwestern Mediterranean Sea. However, no data are available on the effects of V. coralliilyticus in the mussel Mytilus galloprovincialis, the most abundant aquacultured species in this area. In this work, responses of M. galloprovincialis to challenge with V. coralliilyticus (ATCC BAA-450) were investigated. In vitro, short term responses of mussel hemocytes were evaluated in terms of lysosomal membrane stability, bactericidal activity, lysozyme release, ROS and NO production, and ultrastructural changes, evaluated by TEM. In vivo, hemolymph parameters were measured in mussels challenged with V. coralliilyticus at 24h p.i. Moreover, the effects of V. coralliilyticus on mussel early embryo development (at 48 hpf) were evaluated. The results show that both in vitro and in vivo, mussels were unable to activate immune response towards V. coralliilyticus, and that challenge mainly induced lysosomal stress in the hemocytes. Moreover, V. coralliilyticus showed a strong and concentration-dependent embryotoxicity. Overall, the results indicate that, although M. galloprovincialis is considered a resistant species to vibrio infections, the emerging pathogen V. coralliilyticus can represent a potential threat to mussel aquaculture

Multiple photon corrections to the neutral-current Drell-Yan process

Precision studies of single W and Z production processes at hadron colliders require progress in the calculation of electroweak radiative corrections. To this end, higher-order QED corrections to the neutral-current Drell-Yan process, due to multiple photon radiation in Z leptonic decays, are calculated. Particular attention is paid to the effects induced by such corrections on the experimental observables which are relevant for high-precision measurements of the W-boson mass at the Tevatron Run II and the LHC. The calculation is implemented in the Monte Carlo event generator HORACE, which is available for data analysis.Comment: 16 pages, 4 figures, 3 tables, JHEP3 styl

Unsupervised machine learning and geometric morphometrics as tools for the identification of inter and intraspecific variations in the Anopheles Maculipennis complex

Geometric morphometric analysis was combined with two different unsupervised machine learning algorithms, UMAP and HDBSCAN, to visualize morphological differences in wing shape among and within four Anopheles sibling species (An. atroparvus, An. melanoon, An. maculipennis s.s. and An. daciae sp. inq.) of the Maculipennis complex in Northern Italy. Specifically, we evaluated: (1) wing shape variation among and within species; (2) the consistencies between groups of An. maculipennis s.s. and An. daciae sp. inq. identified based on COI sequences and wing shape variability; and (3) the spatial and temporal distribution of different morphotypes. UMAP detected at least 13 main patterns of variation in wing shape among the four analyzed species and mapped intraspecific morphological variations. The relationship between the most abundant COI haplotypes of An. daciae sp. inq. and shape ordination/variation was not significant. However, morphological variation within haplotypes was reported. HDBSCAN also recognized different clusters of morphotypes within An. daciae sp. inq. (12) and An. maculipennis s.s. (4). All morphotypes shared a similar pattern of variation in the subcostal vein, in the anal vein and in the radio-medial cross-vein of the wing. On the contrary, the marginal part of the wings remained unchanged in all clusters of both species. Any spatial-temporal significant difference was observed in the frequency of the identified morphotypes. Our study demonstrated that machine learning algorithms are a useful tool combined with geometric morphometrics and suggest to deepen the analysis of inter and intra specific shape variability to evaluate evolutionary constrains related to wing functionality

Continuing trastuzumab beyond disease progression: outcomes analysis in patients with metastatic breast cancer

INTRODUCTION: We performed a retrospective analysis of HER2-overexpressing metastatic breast cancer patients to describe clinical outcomes of those who, despite progression of the disease (PD), maintained trastuzumab for multiple chemotherapy lines. We also compared survival of these patients with that of those who halted trastuzumab at first PD. METHODS: We identified 101 patients treated between July 2000 and January 2007. Nineteen were still receiving the first-line trastuzumab-based treatment without evidence of PD and were not included in this analysis. Of the remaining 82 patients, 59 retained trastuzumab for one or more additional lines of chemotherapy after PD, according to our institution policy. Twenty-three patients who changed treating institution and stopped trastuzumab at first progression were used as a control group. RESULTS: For patients retaining trastuzumab, the median follow-up was 39.6 months. Clinical outcomes showed the typical degradation between first and second lines of therapy which we would expect by halting trastuzumab at first progression. Response rates were 35\% and 16\% and median times to progression were 7.25 and 5.25 months for the first and second lines of trastuzumab therapy, respectively. The median overall survival (OS) rates were 70 months for patients who retained trastuzumab and 56 months for patients who halted the drug (hazard ratio [HR] 0.87, 95\% confidence interval [CI] 0.51 to 1.18; P = 0.52). If we consider OS from the start of trastuzumab therapy, the figures are 53.9 and 34.8 months, respectively (HR 0.78, 95\% CI 0.58 to 1.32; P = 0.2). CONCLUSION: A nonstatistically significant trend of improved survival for patients retaining trastuzumab is observed. This is in line with most retrospective analyses and recent randomized data. Retaining trastuzumab after progression is a reasonable option, but further randomized data are warranted to better define its role in comparison with other available options.

Un settore di 'Campagna Romana' a rischio di urbanizzazione (Valle Fontana - Valle delle Campanelle; Roma; Italia centrale). Un primo inquadramento finalizzato alla tutela

We carried out a first arrangement (by field study and literature) aimed at developing a local conservation strategy. Direct and indirect evidence were collected for 53 breeding bird species (23 from the original field study), with a significant dominance of the agro-forest species, including species declining at a regional/national level (e.g., Emberiza calandra). The area was recently indicated as the subject of anthropogenic changes by urbanization. In this regard, there is an urgent need for its inclusion in the natural reserve system of RomaNatura Protected Areas