200 research outputs found
Molecular Dynamics Simulations of Solutions at Constant Chemical Potential
Molecular Dynamics studies of chemical processes in solution are of great
value in a wide spectrum of applications, which range from nano-technology to
pharmaceutical chemistry. However, these calculations are affected by severe
finite-size effects, such as the solution being depleted as the chemical
process proceeds, which influence the outcome of the simulations. To overcome
these limitations, one must allow the system to exchange molecules with a
macroscopic reservoir, thus sampling a Grand-Canonical ensemble. Despite the
fact that different remedies have been proposed, this still represents a key
challenge in molecular simulations.
In the present work we propose the Constant Chemical Potential Molecular
Dynamics (CMD) method, which introduces an external force that controls
the environment of the chemical process of interest. This external force,
drawing molecules from a finite reservoir, maintains the chemical potential
constant in the region where the process takes place. We have applied the
CMD method to the paradigmatic case of urea crystallization in aqueous
solution. As a result, we have been able to study crystal growth dynamics under
constant supersaturation conditions, and to extract growth rates and
free-energy barriers.Comment: 8 pages, 8 figures (Supplementary Information: 6 pages, 7 figures).
Typos and labelling corrected Ver. 3: Minor comments added in Sec. 3.
References 13,36,38 added. Minor text changes and typos correcte
Cytotoxic activity of Ciona intestinalis (Tunicata) hemocytes: Properties of the in vitro reaction against erythrocyte targets
Hemocytes (effectors) of Ciona intestinalis showed a natural cytotoxic capacity (HCA) when assayed in vitro against erythrocytes (targets). Cytotoxic cells lysed, to a variable extent, rabbit (RE), human (A, B, O), guinea pig, and sheep (SE) erythrocytes. Hemocyte cytotoxic activity (HCA) assayed against SE is a calcium-dependent reaction, occurs rapidly (15-30 min), at 25-37°C over a wide range of pH (5.4-8.0). Assays were carried out using: 1) the medium in which hemocytes were maintained, 2) the soluble portion of hemocyte lysates, and 3) debris prepared from hemocyte lysates. Results suggest that HCA is a cell-mediated process that requires effector-target cell contacts. Anti-SE (calcium-dependent) and anti-RE (calcium-independent) agglutinins were also found in the reaction medium, probably released by hemocytes as a consequence of the in vitro experiments. The occurrence of HCA was independent of any allogeneic reaction between mixed hemocytes. Various levels of cytotoxic activity reveal hemocyte specificity. © 1993
Overcoming timescale and finite-size limitations to compute nucleation rates from small scale Well Tempered Metadynamics simulations
Condensation of a liquid droplet from a supersaturated vapour phase is
initiated by a prototypical nucleation event. As such it is challenging to
compute its rate from atomistic molecular dynamics simulations. In fact at
realistic supersaturation conditions condensation occurs on time scales that
far exceed what can be reached with conventional molecular dynamics methods.
Another known problem in this context is the distortion of the free energy
profile associated to nucleation due to the small, finite size of typical
simulation boxes. In this work the problem of time scale is addressed with a
recently developed enhanced sampling method while contextually correcting for
finite size effects. We demonstrate our approach by studying the condensation
of argon, and showing that characteristic nucleation times of the order of
magnitude of hours can be reliably calculated, approaching realistic
supersaturation conditions, thus bridging the gap between what standard
molecular dynamics simulations can do and real physical systems.Comment: 9 pages, 7 figures, additional figures and data provided as
supplementary information. Submitted to the Journal of Chemical Physisc
In Vitro Release of Lectins From Phallusia mamillata Hemocytes After Their Fractionation on a Density Gradient
Hemocytes were fractionated by centrifugation on a discontinuous Percoll density
gradient from the hemolymph of Phallusia mamillata. Results obtained from microcultures of the
fractionated hemocytes, sugar-inhibition experiments, SDS-PAGE, and immunoblotting indicate that
"compartment cells" release cellular-type (CL) lectins that are specific for a-lactose and lactulose.
The released lectins have the same properties as the CL lectins that were previously isolated from
sonicated unfractionated hemocytes, but they differ in terms of some molecular and immunological
properties from the lectins (SL) purified from the serum. SLs were never found in the supernatants
from microcultures ofthe fractionated hemocytes
Cell cooperation in coelomocyte cytotoxic activity of Paracentrotus lividus coelomocytes
The coelomic fluid from the sea urchin Paracentrotus lividus contains several coelomocyte types including amoebocytes and uncoloured
spherulocytes involved in immune defences. In the present paper, we show a Ca2+-dependent cytotoxic activity for the unfractionated
coelomocytes assayed in vitro, with rabbit erythrocytes and the K562 tumour cell line. In a plaque-forming assay, whole coelomocyte preparations
as well as density gradient separated coelomocyte populations revealed that cell populations enriched in uncoloured spherulocytes, exerted high
cytotoxic activity by releasing lysins in the presence of amoebocytes. This cooperative effect could be dependent on soluble factors released by
amoebocytes. With regard to this, we show that an enhanced cytotoxic activity was found by adding the supernatant from sonicated amoebocytes
or hemocyte culture medium into spherulocyte preparations
Ciona intestinalis peroxinectin is a novel component of the peroxidase– cyclooxygenase gene superfamily upregulated by LPS
Peroxinectins function as hemoperoxidase and cell adhesion factor involved in invertebrate immune reac-
tion. In this study, the ascidian (Ciona intestinalis) peroxinectin gene (CiPxt) and its expression during the inflammatory response have been examined. CiPxt is a new member of the peroxidase–cyclooxygenase gene superfamily that contains both the peroxidase domain and the integrin KGD (Lys-Gly-Asp) binding motif. A phylogenetic tree showed that CiPxt is very close to the chordate group and appears to be the out-group ofmammalianMPO, EPO and TPO clades. The CiPxtmolecular structuremodel resulted superimposable to the human myeloperoxidase. The CiPxt mRNA expression is upregulated by LPS inoculation suggesting it is involved in C. intestinalis inflammatory response. The CiPxt was expressed in hemocytes (compartment/morula cells), vessel epithelium, and unilocular refractile granulocytes populating the inflamed tunic matrix and in the zones 7, 8 and 9 of the endostyle, a special pharynx organs homolog to the vertebrate thyroid glan
Inducible galectins are expressed in the inflamed pharynx of the ascidian Ciona intestinalis
Although ascidians belong to a key group in chordate phylogenesis, amino acid sequences of Ciona
intestinalis galectin-CRDs (CiLgals-a and -b) have been retained too divergent from vertebrate galectins.
In the present paper, to contribute in disclosing Bi-CRD galectin evolution a novel attempt was carried
out on CiLgals-a and -b CRDs phylogenetic analysis, and their involvement in ascidian inflammatory
responses was shown. CiLgals resulted aligned with Bi-CRD galectins from vertebrates (Xenopus tropicalis,
Gallus gallus, Mus musculus, Homo sapiens), cephalochordates (Branchiostoma floridae), echinoderms
(Strongylocentrotus purpuratus) and a mono-CRD galectin from the ascidian Clavelina picta. The CiLgalsa
N-terminal and C-terminal CRDs contain the signature sequence involved in carbohydrate binding,
whereas the CiLgals-b C-CRD presents only three out of seven key aminoacids and it could not be suitable
as sugar binding motif. Sequence similarity between clusters suggests an evolutionary model based on
CRD domain gene duplication and sequence diversification. In particular CiLgals-b N-CRD and C-CRD
were similar to each other and both grouped with the ascidian C. picta mono-CRD. Homology modeling
process shows a CiLgals molecular structure superimposed to chicken and mouse galectins. The CiLgalsa
and CiLgals-b genes were upregulated by LPS inoculation suggesting that they are inducible and
expressed in the inflamed pharynx as revealed by real-time PCR analysis. Finally, in situ hybridization and
immunohistochemical assays showed their localization in the inflamed tissues, while immunoblotting
analysis indicated that CiLgals can form oligomer
A Concerted Variational Strategy for Investigating Rare Events
A strategy for finding transition paths connecting two stable basins is
presented. The starting point is the Hamilton principle of stationary action;
we show how it can be transformed into a minimum principle through the addition
of suitable constraints like energy conservation. Methods for improving the
quality of the paths are presented: for example, the Maupertuis principle can
be used for determining the transition time of the trajectory and for coming
closer to the desired dynamic path. A saddle point algorithm (conjugate
residual method) is shown to be efficient for reaching a ``true'' solution of
the original variational problem.Comment: 3 figures, accepted for publication in Journal of Chemical Physic
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