356 research outputs found
Inferring DNA sequences from mechanical unzipping: an ideal-case study
We introduce and test a method to predict the sequence of DNA molecules from
in silico unzipping experiments. The method is based on Bayesian inference and
on the Viterbi decoding algorithm. The probability of misprediction decreases
exponentially with the number of unzippings, with a decay rate depending on the
applied force and the sequence content.Comment: Source as TeX file with ps figure
A glance into mthfr deficiency at a molecular level
MTHFR deficiency still deserves an investigation to associate the phenotype to protein structure variations. To this aim, considering the MTHFR wild type protein structure, with a catalytic and a regulatory domain and taking advantage of state‐of‐the‐art computational tools, we explore the properties of 72 missense variations known to be disease associated. By computing the thermodynamic ΔΔG change according to a consensus method that we recently introduced, we find that 61% of the disease‐related variations destabilize the protein, are present both in the catalytic and regulatory domain and correspond to known biochemical deficiencies. The propensity of solvent accessible residues to be involved in protein‐protein interaction sites indicates that most of the interacting residues are located in the regulatory domain, and that only three of them, located at the interface of the functional protein homodimer, are both disease‐related and destabilizing. Finally, we compute the protein architecture with Hidden Markov Models, one from Pfam for the catalytic domain and the second computed in house for the regulatory domain. We show that patterns of disease‐associated, physicochemical variation types, both in the catalytic and regulatory domains, are unique for the MTHFR deficiency when mapped into the protein architecture
Inferring DNA sequences from mechanical unzipping data: the large-bandwidth case
The complementary strands of DNA molecules can be separated when stretched
apart by a force; the unzipping signal is correlated to the base content of the
sequence but is affected by thermal and instrumental noise. We consider here
the ideal case where opening events are known to a very good time resolution
(very large bandwidth), and study how the sequence can be reconstructed from
the unzipping data. Our approach relies on the use of statistical Bayesian
inference and of Viterbi decoding algorithm. Performances are studied
numerically on Monte Carlo generated data, and analytically. We show how
multiple unzippings of the same molecule may be exploited to improve the
quality of the prediction, and calculate analytically the number of required
unzippings as a function of the bandwidth, the sequence content, the elasticity
parameters of the unzipped strands
The X-Gamma Imaging Spectrometer (XGIS) onboard THESEUS
A compact and modular X and gamma-ray imaging spectrometer (XGIS) has been
designed as one of the instruments foreseen on-board the THESEUS mission
proposed in response to the ESA M5 call. The experiment envisages the use of
CsI scintillator bars read out at both ends by single-cell 25 mm 2 Silicon
Drift Detectors. Events absorbed in the Silicon layer (lower energy X rays) and
events absorbed in the scintillator crystal (higher energy X rays and
Gamma-rays) are discriminated using the on-board electronics. A coded mask
provides imaging capabilities at low energies, thus allowing a compact and
sensitive instrument in a wide energy band (~2 keV up to ~20 MeV). The
instrument design, expected performance and the characterization performed on a
series of laboratory prototypes are discussed.Comment: To be published in the Proceedings of the THESEUS Workshop 2017
(http://www.isdc.unige.ch/theseus/workshop2017.html), Journal of the Italian
Astronomical Society (Mem.SAIt), Editors L. Amati, E. Bozzo, M. Della Valle,
D. Gotz, P. O'Brien. Details on the THESEUS mission concept can be found in
the white paper Amati et al. 2017 (arXiv:171004638) and Stratta et al. 2017
(arXiv:1712.08153
Loss of PALB2 predicts poor prognosis in acute myeloid leukemia and suggests novel therapeutic strategies targeting the DNA repair pathway
Dear Editor,
Acute myeloid leukemia (AML) patients carrying complex karyotype or aneuploidies have a very poor prognosis, with a 5-year overall survival (OS) <20%1. We and others have shown that these patients are characterized by high genomic instability, along with defects of DNA damage response (DDR) genes2,3
Ceramide and palmitic acid inhibit macrophage-mediated epithelial-mesenchymal transition in colorectal cancer
Accumulating evidence indicates that ceramide (Cer) and palmitic acid (PA) possess the ability to modulate switching of macrophage phenotypes and possess anti-tumorigenic effects; however, the underlying molecular mechanisms are largely unknown. The aim of the present study was to investigate whether Cer and PA could induce switching of macrophage polarization from the tumorigenic M2- towards the pro-inflammatory M1-phenotype, and whether this consequently altered the potential of colorectal cancer cells to undergo epithelial-mesenchymal transition (EMT), a hallmark of tumor progression. Our study showed that Cer- and PA-treated macrophages increased expression of the macrophage 1 (M1)-marker CD68 and secretion of IL-12 and attenuated expression of the macrophage 2 (M2)-marker CD163 and IL-10 secretion. Moreover, Cer and PA abolished M2 macrophage-induced EMT and migration of colorectal cancer cells. At the molecular level, this coincided with inhibition of SNAI1 and vimentin expression and upregulation of E-cadherin. Furthermore, Cer and PA attenuated expression levels of IL-10 in colorectal cancer cells co-cultured with M2 macrophages and downregulated STAT3 and NF-kappa B expression. For the first time, our findings suggest the presence of an IL-10-STAT3-NF-kappa B signaling axis in colorectal cancer cells co-cultured with M2 macrophages, mimicking the tumor microenvironment. Importantly, PA and Cer were powerful inhibitors of this signaling axis and, consequently, EMT of colorectal cancer cells. These results contribute to our understanding of the immunological mechanisms that underlie the anti-tumorigenic effects of lipids for future combination with drugs in the therapy of colorectal carcinoma.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas
Development and tests of a new prototype detector for the XAFS beamline at Elettra Synchrotron in Trieste
The XAFS beamline at Elettra Synchrotron in Trieste combines X-ray absorption
spectroscopy and X-ray diffraction to provide chemically specific structural
information of materials. It operates in the energy range 2.4-27 keV by using a
silicon double reflection Bragg monochromator. The fluorescence measurement is
performed in place of the absorption spectroscopy when the sample transparency
is too low for transmission measurements or the element to study is too diluted
in the sample. We report on the development and on the preliminary tests of a
new prototype detector based on Silicon Drift Detectors technology and the
SIRIO ultra low noise front-end ASIC. The new system will be able to reduce
drastically the time needed to perform fluorescence measurements, while keeping
a short dead time and maintaining an adequate energy resolution to perform
spectroscopy. The custom-made silicon sensor and the electronics are designed
specifically for the beamline requirements.Comment: Proceeding of the 6YRM 12th-14th Oct 2015 - L'Aquila (Italy).
Accepted for publication on Journal of Physics: Conference Serie
Ceramide and palmitic acid inhibit macrophage-mediated epithelial-mesenchymal transition in colorectal cancer (vol 468, pg 153, 2020)
Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas
ETV6::ABL1-Positive Myeloid Neoplasm: A Case of a Durable Response to Imatinib Mesylate without Additional or Previous Treatment
ETV6::ABL1 rearranged neoplasms are rare hematological diseases. To date, about 80 cases have been reported, including myeloid and lymphoid leukemias. The ETV6 gene codes for an ETS family transcription factor and several fusion partners have been described. When translocated, ETV6 causes the constitutive activation of the partner genes. Here, we report the case of a 54-year-old woman with a cryptic insertion of the 3′ region of ABL1 in the ETV6 gene. The patient was first diagnosed with idiopathic hypereosinophilic syndrome, according to the clinical history, conventional cytogenetics, standard molecular analyses and pathologist description. Next generation sequencing of diagnosis samples unexpectedly detected both ETV6::ABL1 type A and B fusion transcripts, which were then confirmed by FISH. The diagnosis was Myeloid/Lymphoid neoplasm with ETV6::ABL1 fusion, and the patient received imatinib mesylate treatment. In a follow-up after more than one year, the patient still maintained the molecular and complete hematological responses. This case highlights the importance of timely and proper diagnostics and prompt tyrosine kinase inhibitor treatment
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