Shaping Epigenetic Memory via Genomic Bookmarking

Reconciling the stability of epigenetic patterns with the rapid turnover of histone modifications and their adaptability to external stimuli is an outstanding challenge. Here, we propose a new biophysical mechanism that can establish and maintain robust yet plastic epigenetic domains via genomic bookmarking (GBM). We model chromatin as a recolourable polymer whose segments bear non-permanent histone marks (or colours) which can be modified by "writer" proteins. The three-dimensional chromatin organisation is mediated by protein bridges, or "readers", such as Polycomb Repressive Complexes and Transcription Factors. The coupling between readers and writers drives spreading of biochemical marks and sustains the memory of local chromatin states across replication and mitosis. In contrast, GBM-targeted perturbations destabilise the epigenetic patterns. Strikingly, we demonstrate that GBM alone can explain the full distribution of Polycomb marks in a whole Drosophila chromosome. We finally suggest that our model provides a starting point for an understanding of the biophysics of cellular differentiation and reprogramming.Comment: Published in Nucleic Acids Research; Supplementary Movies can be found at this url: https://www2.ph.ed.ac.uk/~dmichiel/ShapingEpigeneticMemory.html or https://www.youtube.com/watch?v=xY-DNP58yB

The ALICE experiment at the CERN LHC

ALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model. It is designed to address the physics of strongly interacting matter and the quark-gluon plasma at extreme values of energy density and temperature in nucleus-nucleus collisions. Besides running with Pb ions, the physics programme includes collisions with lighter ions, lower energy running and dedicated proton-nucleus runs. ALICE will also take data with proton beams at the top LHC energy to collect reference data for the heavy-ion programme and to address several QCD topics for which ALICE is complementary to the other LHC detectors. The ALICE detector has been built by a collaboration including currently over 1000 physicists and engineers from 105 Institutes in 30 countries. Its overall dimensions are 161626 m3 with a total weight of approximately 10 000 t. The experiment consists of 18 different detector systems each with its own specific technology choice and design constraints, driven both by the physics requirements and the experimental conditions expected at LHC. The most stringent design constraint is to cope with the extreme particle multiplicity anticipated in central Pb-Pb collisions. The different subsystems were optimized to provide high-momentum resolution as well as excellent Particle Identification (PID) over a broad range in momentum, up to the highest multiplicities predicted for LHC. This will allow for comprehensive studies of hadrons, electrons, muons, and photons produced in the collision of heavy nuclei. Most detector systems are scheduled to be installed and ready for data taking by mid-2008 when the LHC is scheduled to start operation, with the exception of parts of the Photon Spectrometer (PHOS), Transition Radiation Detector (TRD) and Electro Magnetic Calorimeter (EMCal). These detectors will be completed for the high-luminosity ion run expected in 2010. This paper describes in detail the detector components as installed for the first data taking in the summer of 2008

Understanding the potential role played by major flavonoid components of apple leaves in plant defense against herbivorous arthropods

Field, greenhouse, and laboratory studies were conducted with the following objectives: (1) develop an efficient extraction and analytical method for determining concentration of major flavonoids in apple (Malus domestica Borkh.) leaves, (2) determine if differences exist in levels of these components in leaves of ten apple cultivars and if these differences explain variation in cultivar susceptibility to spider mites ( Acari: Tetranychidae), (3) understand the effects of varying light and nutritional regimes on apple leaf flavonoid levels, (4) assess if the flavonoid phloridzin, when applied to bush bean plants, affects Two Spotted Spider Mite population density, and (5) Determine if summer pruning of mature, field-grown apple trees influences levels of foliar phloridzin. An efficient extraction and HPLC analytical method is presented using commonly available and least toxic solvents and an isocratic HPLC run of short duration allowing calculation of unknown concentrations with a high degree of accuracy. Different cultivars showed significant differences in mite susceptibility and in phloridzin concentration in leaves. However, phloridzin differences do not appear to explain variation in cultivar susceptibility to spider mites. Greenhouse trials indicated that phloridzin concentration was significantly lower in leaves of potted trees of the four cultivars tested under 70% shade cloth than under full sun. All cultivars responded similarly to sun or shade in regard to percent dry weight phloridzin. Nutrition treatments appeared to have an effect on phloridzin levels only in 1995. Horticultural bush bean plants (Phaeseolus vulgaris) were either sprayed or injected through a cotton wick with 0.01 M phloridzin or distilled water, and seeded with 5 gravid female Tetranychus urticae mites. Phloridzin, either when applied topically to bean plants, or when introduced into the transpirational stream via a cotton wick, resulted in smaller numbers of T. urticae compared to plants which were not treated with phloridzin. Summer pruning of mature, field grown “McIntosh” apple had no effect on phloridzin concentration, likely indicating that summer pruning is not a stimulus of induced changes in flavonoid content

Immunocytochemical evaluation of thyroid neoplasms on thin-layer smears from fine-needle aspiration biopsies.

BACKGROUND: Fine-needle aspiration biopsy (FNAB) is the most reliable diagnostic tool for thyroid nodules. A difficult cytologic diagnosis may be supported by an immunocytochemical study. The efficacy of a panel made up of RET, HBME-1, and Galectin-3 antibodies was evaluated in smears processed by thin-layer cytology (TLC). DESIGN: Thyroid FNABs (n = 99) with both conventional (CS) and thin-layer cytology (TLC) smears were studied. The cases were diagnosed as follows: 5 benign lesions (BL), 13 papillary carcinomas (PC), and 81 follicular proliferations (FP). The category of FP was divided into three subgroups according to nuclear features of follicular cells: Follicular neoplasm (FN NOS), oxyphilic follicular neoplasm (OFN), and follicular lesion with nuclear pleomorphism (FLWNP). Immunostains for HBME-1, Galectin-3, and RET were carried out on TLC slides. RESULTS: Among 49 cases undergoing surgery, all 10 PC and 2 BL were histologically confirmed, whereas 15 out of 37 FP (40.5%) were malignant. The complete immunocytochemical panel (ICCP) was positive in 9 of 10 malignancies (90%) and negative in both BLs. Out of 37 FP, the ICCP yielded positive in 15 cases (4 benign, 11 malignant) and negative in 11 (all benign). In the FLWNP subgroup, the ICCP was positive in 11 (84.6%) and negative in 2 histologically benign cases. CONCLUSION: The combined panel of antibodies and the nuclear pleomorphism of follicular cells were effective in distinguishing between thyroid nodules requiring surgery from thyroid nodules requiring just follow-up. 2005 American Cancer Society

Groin Pain Syndrome Italian Consensus Conference update 2023.

Groin pain syndrome (GPS) is a controversial topic in Sports Medicine. The GPS Italian Consensus Conference on terminology, clinical evaluation and imaging assessment of groin pain in athletes was organized by the Italian Society of Arthroscopy in Milan, on 5 February 2016. In this Consensus Conference (CC) GPS etiology was divided into 11 different categories for a total of 63 pathologies. The GPS Italian Consensus Conference update 2023 is an update of the 2016 CC. The CC was based on a sequential, two-round online Delphi survey, followed by a final CC in the presence of all panelists. The panel was composed of 55 experts from different scientific and clinical backgrounds. Each expert discussed 6 different documents, one of which regarded the clinical and imaging definition of sports hernias, and the other 5 dealt with 5 new clinical situations thought to result in GPS. The panelists came to an agreement on the definition of a sports hernia. Furthermore, an agreement was reached, recognizing 4 of the 5 possible proposed pathologies as causes to GPS. On the contrary, the sixth pathology discussed did not find consensus given the insufficient evidence in the available scientific literature. The final document includes a new clinical and imaging definition of sports hernia. Furthermore, the etiology of GPS was updated compared to the previous CC of 2016. The new taxonomic classification includes 12 categories (versus 11 in the previous CC) and 67 pathologies (versus 63 in the previous CC)