Identifying the molecular components that matter: a statistical modelling approach to linking functional genomics data to cell physiology

Functional genomics technologies, in which thousands of mRNAs, proteins, or metabolites can be measured in single experiments, have contributed to reshape biological investigations. One of the most important issues in the analysis of the generated large datasets is the selection of relatively small sub-sets of variables that are predictive of the physiological state of a cell or tissue. In this thesis, a truly multivariate variable selection framework using diverse functional genomics data has been developed, characterized, and tested. This framework has also been used to prove that it is possible to predict the physiological state of the tumour from the molecular state of adjacent normal cells. This allows us to identify novel genes involved in cell to cell communication. Then, using a network inference technique networks representing cell-cell communication in prostate cancer have been inferred. The analysis of these networks has revealed interesting properties that suggests a crucial role of directional signals in controlling the interplay between normal and tumour cell to cell communication. Experimental verification performed in our laboratory has provided evidence that one of the identified genes could be a novel tumour suppressor gene. In conclusion, the findings and methods reported in this thesis have contributed to further understanding of cell to cell interaction and multivariate variable selection not only by applying and extending previous work, but also by proposing novel approaches that can be applied to any functional genomics data

Molecular evolution and expression profile of the chemerine encoding gene RARRES2 in baboon and chimpanzee

BACKGROUND: Chemerin, encoded by the retinoic acid receptor responder 2 (RARRES2) gene is an adipocytesecreted protein with autocrine/paracrine functions in adipose tissue, metabolism and inflammation with a recently described function in vascular tone regulation, liver, steatosis, etc. This molecule is believed to represent a critical endocrine signal linking obesity to diabetes. There are no data available regarding evolution of RARRES2 in non-human primates and great apes. Expression profile and orthology in RARRES2 genes are unknown aspects in the biology of this multigene family in primates. Thus; we attempt to describe expression profile and phylogenetic relationship as complementary knowledge in the function of this gene in primates. To do that, we performed A RT-PCR from different tissues obtained during necropsies. Also we tested the hypotheses of positive evolution, purifying selection, and neutrality. And finally a phylogenetic analysis was made between primates RARRES2 protein. RESULTS: RARRES2 transcripts were present in liver, lung, adipose tissue, ovary, pancreas, heart, hypothalamus and pituitary tissues. Expression in kidney and leukocytes were not detectable in either species. It was determined that the studied genes are orthologous. CONCLUSIONS: RARRES2 evolution fits the hypothesis of purifying selection. Expression profiles of the RARRES2 gene are similar in baboons and chimpanzees and are also phylogenetically related

Global attitudes in the management of acute appendicitis during COVID-19 pandemic: ACIE Appy Study

Background: Surgical strategies are being adapted to face the COVID-19 pandemic. Recommendations on the management of acute appendicitis have been based on expert opinion, but very little evidence is available. This study addressed that dearth with a snapshot of worldwide approaches to appendicitis. Methods: The Association of Italian Surgeons in Europe designed an online survey to assess the current attitude of surgeons globally regarding the management of patients with acute appendicitis during the pandemic. Questions were divided into baseline information, hospital organization and screening, personal protective equipment, management and surgical approach, and patient presentation before versus during the pandemic. Results: Of 744 answers, 709 (from 66 countries) were complete and were included in the analysis. Most hospitals were treating both patients with and those without COVID. There was variation in screening indications and modality used, with chest X-ray plus molecular testing (PCR) being the commonest (19\ub78 per cent). Conservative management of complicated and uncomplicated appendicitis was used by 6\ub76 and 2\ub74 per cent respectively before, but 23\ub77 and 5\ub73 per cent, during the pandemic (both P < 0\ub7001). One-third changed their approach from laparoscopic to open surgery owing to the popular (but evidence-lacking) advice from expert groups during the initial phase of the pandemic. No agreement on how to filter surgical smoke plume during laparoscopy was identified. There was an overall reduction in the number of patients admitted with appendicitis and one-third felt that patients who did present had more severe appendicitis than they usually observe. Conclusion: Conservative management of mild appendicitis has been possible during the pandemic. The fact that some surgeons switched to open appendicectomy may reflect the poor guidelines that emanated in the early phase of SARS-CoV-2

Publisher Correction: Unveiling the strong interaction among hadrons at the LHC

Correction to: Nature https://doi.org/10.1038/s41586-020-3001-6Published online 09 December 2020 In Fig. 1c of this Article, owing to an error during the production process, the equation incorrectly began ‘C(k*, r*) = …’ instead of ‘C(k*) = …’. In addition, in affiliation 71 ‘Dipartimento di Fisica dell’Università degli studi di Bari Aldo Moro’ has been corrected to read ‘Dipartimento di Fisica dell’Università degli studi di Cagliari’. The original Article has been corrected online

Measurement of isolated photon–hadron correlations in √sNN = 5.02 TeV pp and p–Pb collisions

This paper presents isolated photon-hadron correlations using pp and p-Pb data collected by the ALICE detector at the LHC. For photons with |η| < 0.67 and 12 < pT < 40 GeV/c, the associated yield of charged particles in the range |η| < 0.80 and 0.5 < pT < 10 GeV/c is presented. These momenta are much lower than previous measurements at the LHC. No significant difference between pp and p-Pb is observed, with PYTHIA 8.2 describing both data sets within uncertainties. This measurement constrains nuclear effects on the parton fragmentation in p-Pb collisions, and provides a benchmark for future studies of Pb-Pb collisions

Jet fragmentation transverse momentum distributions in pp and p–Pb collisions at √sNN = 5.02 TeV

Jet fragmentation transverse momentum (jT) distributions are measured in proton-proton (pp) and proton-lead (p-Pb) collisions at sNN−−−√ = 5.02 TeV with the ALICE experiment at the LHC. Jets are reconstructed with the ALICE tracking detectors and electromagnetic calorimeter using the anti-kT algorithm with resolution parameter R=0.4 in the pseudorapidity range |η|<0.25. The jT values are calculated for charged particles inside a fixed cone with a radius R=0.4 around the reconstructed jet axis. The measured jT distributions are compared with a variety of parton-shower models. Herwig and PYTHIA 8 based models describe the data well for the higher jT region, while they underestimate the lower jT region. The jT distributions are further characterised by fitting them with a function composed of an inverse gamma function for higher jT values (called the "wide component"), related to the perturbative component of the fragmentation process, and with a Gaussian for lower jT values (called the "narrow component"), predominantly connected to the hadronisation process. The width of the Gaussian has only a weak dependence on jet transverse momentum, while that of the inverse gamma function increases with increasing jet transverse momentum. For the narrow component, the measured trends are successfully described by all models except for Herwig. For the wide component, Herwig and PYTHIA 8 based models slightly underestimate the data for the higher jet transverse momentum region. These measurements set constraints on models of jet fragmentation and hadronisation

Energy dependence of φ meson production at forward rapidity in pp collisions at the LHC

The production of ϕ mesons has been studied in pp collisions at LHC energies with the ALICE detector via the dimuon decay channel in the rapidity region 2.5<y<4. Measurements of the differential cross section d2σ/dydpT are presented as a function of the transverse momentum (pT) at the center-of-mass energies s√=5.02, 8 and 13 TeV and compared with the ALICE results at midrapidity. The differential cross sections at s√=5.02 and 13 TeV are also studied in several rapidity intervals as a function of pT, and as a function of rapidity in three pT intervals. A hardening of the pT-differential cross section with the collision energy is observed, while, for a given energy, pT spectra soften with increasing rapidity and, conversely, rapidity distributions get slightly narrower at increasing pT. The new results, complementing the published measurements at s√=2.76 and 7 TeV, allow one to establish the energy dependence of ϕ meson production and to compare the measured cross sections with phenomenological models. None of the considered models manages to describe the evolution of the cross section with pT and rapidity at all the energies

Elliptic flow of electrons from beauty-hadron decays in Pb–Pb collisions at √sNN = 5.02 TeV

The elliptic flow of electrons from beauty hadron decays at midrapidity (|y| < 0.8) is measured in Pb-Pb collisions at sNN−−−√ = 5.02 TeV with the ALICE detector at the LHC. The azimuthal distribution of the particles produced in the collisions can be parameterized with a Fourier expansion, in which the second harmonic coefficient represents the elliptic flow, v2. The v2 coefficient is measured for the first time in transverse momentum (pT) range 1.3-6 GeV/c in the centrality class 30-50%. The measurement of electrons from beauty-hadron decays exploits their larger mean proper decay length cτ≈ 500 μm compared to that of charm hadrons and most of the other background sources. The v2 of electrons from beauty hadron decays at midrapidity is found to be positive with a significance of 3.75σ. The results provide insights on the degree of thermalization of beauty quarks in the medium. A model assuming full thermalization of beauty quarks is strongly disfavoured by the measurement at high pT, but is in agreement with the results at low pT. Transport models including substantial interactions of beauty quarks with an expanding strongly-interacting medium describe the measurement

J/ψ elliptic and triangular flow in Pb–Pb collisions at √sNN = 5.02 TeV

The inclusive J/ψ elliptic (v2) and triangular (v3) flow coefficients measured at forward rapidity (2.5 <y< 4) and the v2 measured at midrapidity (|y|< 0.9) in Pb-Pb collisions at sNN−−−√ = 5.02 TeV using the ALICE detector at the LHC are reported. The entire Pb-Pb data sample collected during Run 2 is employed, amounting to an integrated luminosity of 750 μb−1 at forward rapidity and 93 μb−1 at midrapidity. The results are obtained using the scalar product method and are reported as a function of transverse momentum pT and collision centrality. At midrapidity, the J/ψ v2 is in agreement with the forward rapidity measurement. The centrality averaged results indicate a positive J/ψ v3 with a significance of more than 5σ at forward rapidity in the pT range 2<pT<5 GeV/c. The forward rapidity v2, v3, and v3/v2 results at low and intermediate pT (pT≲8 GeV/c) exhibit a mass hierarchy when compared to pions and D mesons, while converging into a species-independent curve at higher pT. At low and intermediate pT, the results could be interpreted in terms of a later thermalization of charm quarks compared to light quarks, while at high pT, path-length dependent effects seem to dominate. The J/ψ v2 measurements are further compared to a microscopic transport model calculation. Using a simplified extension of the quark scaling approach involving both light and charm quark flow components, it is shown that the D-meson vn measurements can be described based on those for charged pions and J/ψ flow

Production of muons from heavy−flavour hadron decays at high transverse momentum in Pb−Pb collisions at √sNN = 5.02 and 2.76 TeV

Measurements of the production of muons from heavy-flavour hadron decays in Pb−Pb collisions at sNN−−−√ = 5.02 and 2.76 TeV using the ALICE detector at the LHC are reported. The nuclear modification factor RAA at sNN−−−√ = 5.02 TeV is measured at forward rapidity (2.5<y<4) as a function of transverse momentum pT in central, semi-central, and peripheral collisions over a wide pT interval, 3<pT<20 GeV/c, in which a significant contribution of muons from beauty-hadron decays is expected at high pT. With a significantly improved precision compared to the measurements at lower collision energy, the RAA shows an increase of the suppression of the yields of muons from heavy-flavour hadron decays with increasing centrality. A suppression by a factor of about three is observed in the 10% most central collisions. The RAA at sNN−−−√ = 5.02 is similar to that reported at 2.76 TeV in a broader pT interval and with an improved accuracy with respect to previously published measurements. The precise RAA results have the potential to distinguish between model predictions implementing different mechanisms of parton energy loss in the high-density medium formed in heavy-ion collisions. The results place stringent constraints on the relative energy loss between charm and beauty quarks