2,977 research outputs found
Unifying thermodynamic and kinetic descriptions of single-molecule processes: RNA unfolding under tension
We use mesoscopic non-equilibrium thermodynamics theory to describe RNA
unfolding under tension. The theory introduces reaction coordinates,
characterizing a continuum of states for each bond in the molecule. The
unfolding considered is so slow that one can assume local equilibrium in the
space of the reaction coordinates. In the quasi-stationary limit of high
sequential barriers, our theory yields the master equation of a recently
proposed sequential-step model. Non-linear switching kinetics is found between
open and closed states. Our theory unifies the thermodynamic and kinetic
descriptions and offers a systematic procedure to characterize the dynamics of
the unfolding processComment: 13 pages, 3 figure
Regulation of Antigen-Experienced T Cells: Lessons from the Quintessential Memory Marker CD44
Despite the widespread use of the cell-surface receptor CD44 as a marker for antigen (Ag)-experienced, effector and memory T cells, surprisingly little is known regarding its function on these cells. The best-established function of CD44 is the regulation of cell adhesion and migration. As such, the interactions of CD44, primarily with its major ligand, the extracellular matrix (ECM) component hyaluronic acid (HA), can be crucial for the recruitment and function of effector and memory T cells into/within inflamed tissues. However, little is known about the signaling events following engagement of CD44 on T cells and how cooperative interactions of CD44 with other surface receptors affect T cell responses. Recent evidence suggests that the CD44 signaling pathway(s) may be shared with those of other adhesion receptors, and that these provide contextual signals at different anatomical sites to ensure the correct T cell effector responses. Furthermore, CD44 ligation may augment T cell activation after Ag encounter and promote T cell survival, as well as contribute to regulation of the contraction phase of an immune response and the maintenance of tolerance. Once the memory phase is established, CD44 may have a role in ensuring the functional fitness of memory T cells. Thus, the summation of potential signals after CD44 ligation on T cells highlights that migration and adhesion to the ECM can critically impact the development and homeostasis of memory T cells, and may differentially affect subsets of T cells. These aspects of CD44 biology on T cells and how they might be modulated for translational purposes are discussed
Effect of Cytisus multiflorus in the control of Type-2 Diabetes
Medicinal plants display diverse pharmacological activities with marked therapeutic effects. Type-2 diabetes (T2D) remains a major health problem among industrialized countries, therefore the investigation of formulas to prevent or attenuate the metabolic syndrome, including new therapeutic agents. Currently the interest of medicinal plants is increasing. Portuguese native flora includes several plants known for their hypoglycemic properties.
The aim of this work was to study the pharmacological effect of Cytisus multiflorus, one plant from the Portuguese flora traditionally used as an ethnopharmacological agent in diabetes control
Distribution of dwell times of a ribosome: effects of infidelity, kinetic proofreading and ribosome crowding
Ribosome is a molecular machine that polymerizes a protein where the sequence
of the amino acid residues, the monomers of the protein, is dictated by the
sequence of codons (triplets of nucleotides) on a messenger RNA (mRNA) that
serves as the template. The ribosome is a molecular motor that utilizes the
template mRNA strand also as the track. Thus, in each step the ribosome moves
forward by one codon and, simultaneously, elongates the protein by one amino
acid. We present a theoretical model that captures most of the main steps in
the mechano-chemical cycle of a ribosome. The stochastic movement of the
ribosome consists of an alternating sequence of pause and translocation; the
sum of the durations of a pause and the following translocation is the time of
dwell of the ribosome at the corresponding codon. We derive the analytical
expression for the distribution of the dwell times of a ribosome in our model.
Whereever experimental data are available, our theoretical predictions are
consistent with those results. We suggest appropriate experiments to test the
new predictions of our model, particularly, the effects of the quality control
mechanism of the ribosome and that of their crowding on the mRNA track.Comment: This is an author-created, un-copyedited version of an article
accepted for publication in Physical Biology. IOP Publishing Ltd is not
responsible for any errors or omissions in this version of the manuscript or
any version derived from it. The definitive publisher authenticated version
is available online at DOI:10.1088/1478-3975/8/2/02600
Acoustic-like dynamics of amorphous drugs in the THz regime
The high frequency dynamics of Indomethacin and Celecoxib glasses has been investigated by inelastic x-ray scattering, accessing a momentum-energy region still unexplored in amorphous pharmaceuticals. We find evidence of phonon-like acoustic dynamics, and determine the THz behavior of sound velocity and acoustic attenuation. Connections with ordinary sound propagation are discussed, along with the relation between fast and slow degrees of freedom as represented by non-ergodicity factor and kinetic fragility, respectively
Probing protein sequences as sources for encrypted antimicrobial peptides
Starting from the premise that a wealth of potentially biologically active peptides may lurk within proteins, we describe here a methodology to identify putative antimicrobial peptides encrypted in protein sequences. Candidate peptides were identified using a new screening procedure based on physicochemical criteria to reveal matching peptides within protein databases. Fifteen such peptides, along with a range of natural antimicrobial peptides, were examined using DSC and CD to characterize their interaction with phospholipid membranes. Principal component analysis of DSC data shows that the investigated peptides group according to their effects on the main phase transition of phospholipid vesicles, and that these effects correlate both to antimicrobial activity and to the changes in peptide secondary structure. Consequently, we have been able to identify novel antimicrobial peptides from larger proteins not hitherto associated with such activity, mimicking endogenous and/or exogenous microorganism enzymatic processing of parent proteins to smaller bioactive molecules. A biotechnological application for this methodology is explored. Soybean (Glycine max) plants, transformed to include a putative antimicrobial protein fragment encoded in its own genome were tested for tolerance against Phakopsora pachyrhizi, the causative agent of the Asian soybean rust. This procedure may represent an inventive alternative to the transgenic technology, since the genetic material to be used belongs to the host organism and not to exogenous sources
Structure of Polyelectrolytes in Poor Solvent
We present simulations on charged polymers in poor solvent. First we
investigate in detail the dilute concentration range with and without imposed
extension constraints. The resulting necklace polymer conformations are
analyzed in detail. We find strong fluctuations in the number of pearls and
their sizes leading only to small signatures in the form factor and the
force-extension relation. The scaling of the peak in the structure factor with
the monomer density shows a pertinent different behavior from good solvent
chains.Comment: 7 pages, 5 figures. submitted to EP
Electronic and phononic properties of the chalcopyrite CuGaS2
The availability of ab initio electronic calculations and the concomitant
techniques for deriving the corresponding lattice dynamics have been profusely
used for calculating thermodynamic and vibrational properties of
semiconductors, as well as their dependence on isotopic masses. The latter have
been compared with experimental data for elemental and binary semiconductors
with different isotopic compositions. Here we present theoretical and
experimental data for several vibronic and thermodynamic properties of CuGa2, a
canonical ternary semiconductor of the chalcopyrite family. Among these
properties are the lattice parameters, the phonon dispersion relations and
densities of states (projected on the Cu, Ga, and S constituents), the specific
heat and the volume thermal expansion coefficient. The calculations were
performed with the ABINIT and VASP codes within the LDA approximation for
exchange and correlation and the results are compared with data obtained on
samples with the natural isotope composition for Cu, Ga and S, as well as for
isotope enriched samples.Comment: 9 pages, 8 Figures, submitted to Phys. Rev
Advanced tools and techniques to add value to soil stabilization practice
The aim of this paper is to demonstrate the advanced tools and techniques used for adding value to the soil stabilization practice. The tools presented involve advanced laboratory tests and modeling using codes and soft computing to evaluate the mechanical behavior of stabilized soils with cement, ranging from short-term to long-term behavior. More precisely, these tools are able to: 1. Predict the mechanical behavior of the stabilized soils over time from data obtained in the early ages saving time in laboratory tests; 2. Predict the mechanical behavior of the stabilized soils over time based on basic parameters of soil type and binder using historical accurate data, avoiding mechanical laboratory tests. 3. Incorporate the serviceability limit state concept in a novel proposal to estimate the design modulus in function of the uniaxial compressive strength and the strain level, making more economic and sustainable geotechnical solutions.This work was supported by FCTâââFundação para a CiĂȘncia e a Tecnologiaââ, within ISISE, project UID/ECI/04029/2013 and through the post doctoral Grant fellowship with reference SFRH/BPD/94792/2013. This work was also partly financed by FEDER funds through the Competitivity Factors Operational ProgrammeâCOMPETE and by national funds through FCT within the scope of the project POCI-01-0145-FEDER-007633.info:eu-repo/semantics/publishedVersio
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