4 research outputs found
A GROMOS Force Field for Furanose-Based Carbohydrates
No full textThe
article describes a GROMOS force field parameter set for molecular
dynamics simulations of furanose carbohydrates. The proposed united-atom
force field is designed and validated with respect to the conformational
properties of furanose mono-, di-, oligo-, and polymers in aqueous
solvent. The set accounts for the possibility of arbitrary glycosidic
linkage connectivity between units, O-alkylation, as well as of different
anomery. The compatibility with the already existing, pyranose-dedicated
GROMOS 56A6CARBO/CARBO_R set allows one to use the presently
proposed extension for studying more diverse and biologically relevant
carbohydrates that exploit both pyranose and furanose units. The validation
performed against the quantum-mechanical and experimental data concerning
the structural and conformational features shows that the newly developed
set is capable to reproduce conformational equilibrium within the
furanose ring, relative free energies of anomers, hydroxymethyl rotamers,
and glycosidic linkage conformers. Additionally, the results concerning
the conformation of the furanose ring with relation to the two-state
model as well as other conformational features of furanose-containing
saccharides are discussed
Just-In-Time eTraining Applied To Emergency Medical Services
No full textWhile the applications of just-in-time training are more and
more spread, the ubiquitous mobile technology has not found
practical uses of this training strategy. As an original example
of services for healthcare, we present in this work an
application of eTraining that makes use of mobile telephones
to transmit medical and on-site information content to
emergency medical personnel that attend and emergency. The
state-of-the-art in related technologies, overall architecture, and
functioning of JITTER (for Just-In-Time Training for
Emergency Responders) is described in this work.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. This work has been funded by the FIT-350100-2006-400
PROFIT project of the Spanish Ministerio de Industria,
Turismo y Comercio, American NSF grant DMI-0239180,
NIEHS (National Institute for Environmental Health
Sciences) grant 1R41ES014793-01, BanDeMar Networks,
Inc., the healthcare company iSOFT Sanidad, S.A., and the
CITIC Technology Centre
Functional mammalian spliceosomal complex E contains SMN complex proteins in addition to U1 and U2 snRNPs
No full textCopyright @ 2011 The Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.Spliceosomes remove introns from primary gene transcripts. They assemble de novo on each intron through a series of steps that involve the incorporation of five snRNP particles and multiple non-snRNP proteins. In mammals, all the intermediate complexes have been characterized on one transcript (MINX), with the exception of the very first, complex E. We have purified this complex by two independent procedures using antibodies to either U1-A or PRPF40A proteins, which are known to associate at an early stage of assembly. We demonstrate that the purified complexes are functional in splicing using commitment assays. These complexes contain components expected to be in the E complex and a number of previously unrecognized factors, including survival of motor neurons (SMN) and proteins of the SMN-associated complex. Depletion of the SMN complex proteins from nuclear extracts inhibits formation of the E complex and causes non-productive complexes to accumulate. This suggests that the SMN complex stabilizes the association of U1 and U2 snRNPs with pre-mRNA. In addition, the antibody to PRPF40A precipitated U2 snRNPs from nuclear extracts, indicating that PRPF40A associates with U2 snRNPs
Isoforms of U1-70k control subunit dynamics in the human spliceosomal U1 snRNP
No full textMost human protein-encoding genes contain multiple exons that are spliced together, frequently in alternative arrangements, by the spliceosome. It is established that U1 snRNP is an essential component of the spliceosome, in human consisting of RNA and ten proteins, several of which are post- translationally modified and exist as multiple isoforms. Unresolved and challenging to investigate are the effects of these post translational modifications on the dynamics, interactions and stability of the particle. Using mass spectrometry we investigate the composition and dynamics of the native human U1 snRNP and compare native and recombinant complexes to isolate the effects of various subunits and isoforms on the overall stability. Our data reveal differential incorporation of four protein isoforms and dynamic interactions of subunits U1-A, U1-C and Sm-B/B’. Results also show that unstructured post- ranslationally modified C-terminal tails are
responsible for the dynamics of Sm-B/B’ and U1-C and that their interactions with the Sm core are controlled by binding to different U1-70k isoforms and their phosphorylation status in vivo. These results therefore provide the important functional link between proteomics and structure as well as insight into the dynamic quaternary structure of the native U1 snRNP important for its function.This work was funded by: BBSRC (OVM), BBSRC and EPSRC (HH and NM), EU Prospects (HH), European Science Foundation (NM), the Royal Society (CVR), and fellowship from JSPS and HFSP (YM and DAPK respectively)
