0000000001212294
AUTHOR
Antonio Rosato
Quality assessment of protein NMR structures.
Biomolecular NMR structures are now routinely used in biology, chemistry, and bioinformatics. Methods and metrics for assessing the accuracy and precision of protein NMR structures are beginning to be standardized across the biological NMR community. These include both knowledge-based assessment metrics, parameterized from the database of protein structures, and model versus data assessment metrics. On line servers are available that provide comprehensive protein structure quality assessment reports, and efforts are in progress by the world-wide Protein Data Bank (wwPDB) to develop a biomolecular NMR structure quality assessment pipeline as part of the structure deposition process. These qu…
Mutant p53 induces Golgi tubulo-vesiculation driving a prometastatic secretome
TP53 missense mutations leading to the expression of mutant p53 oncoproteins are frequent driver events during tumorigenesis. p53 mutants promote tumor growth, metastasis and chemoresistance by affecting fundamental cellular pathways and functions. Here, we demonstrate that p53 mutants modify structure and function of the Golgi apparatus, culminating in the increased release of a pro-malignant secretome by tumor cells and primary fibroblasts from patients with Li-Fraumeni cancer predisposition syndrome. Mechanistically, interacting with the hypoxia responsive factor HIF1α, mutant p53 induces the expression of miR-30d, which in turn causes tubulo-vesiculation of the Golgi apparatus, leading …
Abstract CT261: METAMECH -A Master Observational Trial empowering mechanobiology translational research and mechanobased proof of concept trials in breast cancer
Abstract Background: Breast cancer (BC) is the most frequent tumor in women worldwide. BC lethality is caused by aggressive, therapy-resistant metastases (mBC). Preliminary data have shown that mBC lesions are invariably embedded into a densely packed network of fibrous extracellular matrix, making the metastatic microenvironment a potent inducer of mechanical inputs, ultimately leading to the activation of the transcription factors YAP/TAZ. Aberrant mechano-signaling could thus represent a vulnerability of metastasis, which can be exploited to develop new therapeutic strategies. To investigate how metastatic outgrowth is regulated by the physical properties of the microenvironment, and how…
Skolēnu redzes problēmas
Bakalaura darbs ir uzrakstīts angļu valodā uz 32 drukātām lapām, tas satur 11 tabulas un 5 grafikus . Pētījumi bija veikti Itālijā veicot redzes pārbaudes skolā 138 skolniekiem vecumā no 11 līdz 13 gadiem. Pētījuma laikā tika atklāts, ka lielākai daļai no bērniem ir sūdzības par diskomfortu, ko rada neefektīva redzes sistēmas darbība. Redzes spējas spēlē būtisku lomu daudzās dzīves situācijā, studijās, darbā un sportā. Dažas no šīm spējām ir fundamentālas, lai rakstītu un lasītu bez grūtībām. Optometriskā redzes analīze dod iespēju uzlabot redzes spējas, novērst vai apturēt miopijas progresēšanu un atrisināt astenopijas problēmas parakstot pareizas brilles vai kontaktlēcas, veicot redzes tr…
Analysis of the structural quality of the CASD-NMR 2013 entries
We performed a comprehensive structure validation of both automated and manually generated structures of the 10 targets of the CASD-NMR-2013 effort. We established that automated structure determination protocols are capable of reliably producing structures of comparable accuracy and quality to those generated by a skilled researcher, at least for small, single domain proteins such as the ten targets tested. The most robust results appear to be obtained when NOESY peak lists are used either as the primary input data or to augment chemical shift data without the need to manually filter such lists. A detailed analysis of the long-range NOE restraints generated by the different programs from t…
The second round of Critical Assessment of Automated Structure Determination of Proteins by NMR: CASD-NMR-2013
The second round of the community-wide initiative Critical Assessment of automated Structure Determination of Proteins by NMR (CASD-NMR-2013) comprised ten blind target datasets, consisting of unprocessed spectral data, assigned chemical shift lists and unassigned NOESY peak and RDC lists, that were made available in both curated (i.e. manually refined) or un-curated (i.e. automatically generated) form. Ten structure calculation programs, using fully automated protocols only, generated a total of 164 three-dimensional structures (entries) for the ten targets, sometimes using both curated and un-curated lists to generate multiple entries for a single target. The accuracy of the entries could…
Protein structure prediction assisted with sparse NMR data in CASP13
CASP13 has investigated the impact of sparse NMR data on the accuracy of protein structure prediction. NOESY and 15 N-1 H residual dipolar coupling data, typical of that obtained for 15 N,13 C-enriched, perdeuterated proteins up to about 40 kDa, were simulated for 11 CASP13 targets ranging in size from 80 to 326 residues. For several targets, two prediction groups generated models that are more accurate than those produced using baseline methods. Real NMR data collected for a de novo designed protein were also provided to predictors, including one data set in which only backbone resonance assignments were available. Some NMR-assisted prediction groups also did very well with these data. CAS…