288 research outputs found
Anomalous Behavior of the Zero Field Susceptibility of the Ising Model on the Cayley Tree
It is found that the zero field susceptibility chi of the Ising model on the
Cayley tree exhibits unusually weak divergence at the critical point Tc. The
susceptibility amplitude is found to diverge at Tc proportionally to the tree
generation level n, while the behavior of chi is otherwise analytic in the
vicinity of Tc, with the critical exponent gamma=0.Comment: 3 pages, 2 figure
Phase transitions in biological membranes
Native membranes of biological cells display melting transitions of their
lipids at a temperature of 10-20 degrees below body temperature. Such
transitions can be observed in various bacterial cells, in nerves, in cancer
cells, but also in lung surfactant. It seems as if the presence of transitions
slightly below physiological temperature is a generic property of most cells.
They are important because they influence many physical properties of the
membranes. At the transition temperature, membranes display a larger
permeability that is accompanied by ion-channel-like phenomena even in the
complete absence of proteins. Membranes are softer, which implies that
phenomena such as endocytosis and exocytosis are facilitated. Mechanical signal
propagation phenomena related to nerve pulses are strongly enhanced. The
position of transitions can be affected by changes in temperature, pressure, pH
and salt concentration or by the presence of anesthetics. Thus, even at
physiological temperature, these transitions are of relevance. There position
and thereby the physical properties of the membrane can be controlled by
changes in the intensive thermodynamic variables. Here, we review some of the
experimental findings and the thermodynamics that describes the control of the
membrane function.Comment: 23 pages, 15 figure
Volume-energy correlations in the slow degrees of freedom of computer-simulated phospholipid membranes
Constant-pressure molecular-dynamics simulations of phospholipid membranes in
the fluid phase reveal strong correlations between equilibrium fluctuations of
volume and energy on the nanosecond time-scale. The existence of strong
volume-energy correlations was previously deduced indirectly by Heimburg from
experiments focusing on the phase transition between the fluid and the ordered
gel phases. The correlations, which are reported here for three different
membranes (DMPC, DMPS-Na, and DMPSH), have volume-energy correlation
coefficients ranging from 0.81 to 0.89. The DMPC membrane was studied at two
temperatures showing that the correlation coefficient increases as the phase
transition is approached
From supported membranes to tethered vesicles: lipid bilayers destabilisation at the main transition
We report results concerning the destabilisation of supported phospholipid
bilayers in a well-defined geometry. When heating up supported phospholipid
membranes deposited on highly hydrophilic glass slides from room temperature
(i.e. with lipids in the gel phase), unbinding was observed around the main gel
to fluid transition temperature of the lipids. It lead to the formation of
relatively monodisperse vesicles, of which most remained tethered to the
supported bilayer. We interpret these observations in terms of a sharp decrease
of the bending rigidity modulus in the transition region, combined
with a weak initial adhesion energy. On the basis of scaling arguments, we show
that our experimental findings are consistent with this hypothesis.Comment: 11 pages, 3 figure
Profiling of Glycan Receptors for Minute Virus of Mice in Permissive Cell Lines Towards Understanding the Mechanism of Cell Recognition
The recognition of sialic acids by two strains of minute virus of mice (MVM), MVMp (prototype) and MVMi (immunosuppressive), is an essential requirement for successful infection. To understand the potential for recognition of different modifications of sialic acid by MVM, three types of capsids, virus-like particles, wild type empty (no DNA) capsids, and DNA packaged virions, were screened on a sialylated glycan microarray (SGM). Both viruses demonstrated a preference for binding to 9-O-methylated sialic acid derivatives, while MVMp showed additional binding to 9-O-acetylated and 9-O-lactoylated sialic acid derivatives, indicating recognition differences. The glycans recognized contained a type-2 Galβ1-4GlcNAc motif (Neu5Acα2-3Galβ1-4GlcNAc or 3′SIA-LN) and were biantennary complex-type N-glycans with the exception of one. To correlate the recognition of the 3′SIA-LN glycan motif as well as the biantennary structures to their natural expression in cell lines permissive for MVMp, MVMi, or both strains, the N- and O-glycans, and polar glycolipids present in three cell lines used for in vitro studies, A9 fibroblasts, EL4 T lymphocytes, and the SV40 transformed NB324K cells, were analyzed by MALDI-TOF/TOF mass spectrometry. The cells showed an abundance of the sialylated glycan motifs recognized by the viruses in the SGM and previous glycan microarrays supporting their role in cellular recognition by MVM. Significantly, the NB324K showed fucosylation at the non-reducing end of their biantennary glycans, suggesting that recognition of these cells is possibly mediated by the Lewis X motif as in 3′SIA-LeX identified in a previous glycan microarray screen
On the action potential as a propagating density pulse and the role of anesthetics
The Hodgkin-Huxley model of nerve pulse propagation relies on ion currents
through specific resistors called ion channels. We discuss a number of
classical thermodynamic findings on nerves that are not contained in this
classical theory. Particularly striking is the finding of reversible heat
changes, thickness and phase changes of the membrane during the action
potential. Data on various nerves rather suggest that a reversible density
pulse accompanies the action potential of nerves. Here, we attempted to explain
these phenomena by propagating solitons that depend on the presence of
cooperative phase transitions in the nerve membrane. These transitions are,
however, strongly influenced by the presence of anesthetics. Therefore, the
thermodynamic theory of nerve pulses suggests a explanation for the famous
Meyer-Overton rule that states that the critical anesthetic dose is linearly
related to the solubility of the drug in the membranes.Comment: 13 pages, 8 figure
The influence of anesthetics, neurotransmitters and antibiotics on the relaxation processes in lipid membranes
In the proximity of melting transitions of artificial and biological
membranes fluctuations in enthalpy, area, volume and concentration are
enhanced. This results in domain formation, changes of the elastic constants,
changes in permeability and slowing down of relaxation processes. In this study
we used pressure perturbation calorimetry to investigate the relaxation time
scale after a jump into the melting transition regime of artificial lipid
membranes. This time corresponds to the characteristic rate of domain growth.
The studies were performed on single-component large unilamellar and
multilamellar vesicle systems with and without the addition of small molecules
such as general anesthetics, neurotransmitters and antibiotics. These drugs
interact with membranes and affect melting points and profiles. In all systems
we found that heat capacity and relaxation times are related to each other in a
simple manner. The maximum relaxation time depends on the cooperativity of the
heat capacity profile and decreases with a broadening of the transition. For
this reason the influence of a drug on the time scale of domain formation
processes can be understood on the basis of their influence on the heat
capacity profile. This allows estimations of the time scale of domain formation
processes in biological membranes.Comment: 12 pages, 6 figure
Neuropsychological outcome after cardiac arrest: a prospective case control sub-study of the Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest trial (TTM2)
Background:
This study is designed to provide detailed knowledge on cognitive impairment after out-of-hospital cardiac arrest (OHCA) and its relation to associated factors, and to validate the neurocognitive screening of the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest trial (TTM2-trial), assessing effectiveness of targeted temperature management after OHCA.
Methods:
This longitudinal multi-center clinical study is a sub-study of the TTM2-trial, in which a comprehensive neuropsychological examination is performed in addition to the main TTM2-trial neurocognitive screening. Approximately 7 and 24 months after OHCA, survivors at selected study sites are invited to a standardized assessment, including performance-based tests of cognition and questionnaires of emotional problems, fatigue, executive function and insomnia. At 1:1 ratio, a matched control group from a cohort of acute myocardial infarction (MI) patients is recruited to perform the same assessment. We aim to include 100 patients per group. Potential differences between the OHCA patients and the MI controls at 7 and 24 months will be analyzed with a linear regression, using composite z-scores per cognitive domain (verbal, visual/constructive, working memory, episodic memory, processing speed, executive functions) as primary outcome measures. Results from OHCA survivors on the main TTM2-trial neurocognitive screening battery will be compared with neuropsychological test results at 7 months, using sensitivity and specificity analyses.
Discussion:
In this study we collect detailed information on cognitive impairment after OHCA and compare this to a control group of patients with acute MI. The validation of the TTM2 neurocognitive screening battery could justify its inclusion in routine follow-up. Our results may have a potential to impact on the design of future follow-up strategies and interventions after OHCA
Coexpression of VEGF-C and COX-2 and its association with lymphangiogenesis in human breast cancer
<p>Abstract</p> <p>Background</p> <p>Lymphangiogenesis has become a new research frontier in tumor metastasis since the discovery of reliable lymphatic markers that have allowed observation and isolation of lymphatic endothelium. Cyclooxygenase-2 (COX-2) has been reported to be involved in the critical steps in carcinogenesis. However, possible role of COX-2 in lymphangiogenesis and lymphatic metastasis is still poorly understood. In present study, we aimed to investigate the relationship between vascular endothelial growth factor-C (VEGF-C) and COX-2 in human breast cancer, and correlations with lymphangiogenesis and prognosis.</p> <p>Methods</p> <p>Tissue samples of primary tumors from 70 patients undergoing intentionally curative surgical resections for breast cancer were immunohistochemically examined for VEGF-C, COX-2, and D2-40 expressions. The association between COX-2 and VEGF-C expressions and clinicopathological parameters as well as prognosis were analysised. To demonstrate the presence of proliferating lymphatic endothelial cells, 10 random cases with high LVD counts were selected for D2-40/Ki-67 double immunostaining.</p> <p>Results</p> <p>A significant correlation was found between the expression of VEGF-C and COX-2 (<it>r </it>= 0.529, <it>P </it>< 0.001), and both elevated VEGF-C expression and elevated COX-2 expression were associated with higher lymph vessel density (LVD), lymph node metastasis and D2-40 positive lymphatic invasion (LVI) as well as worse disease free survival (DFS) and overall survival (OS) in a univariate analysis. In the double immunostain for the lymph vessel marker D2-40 and the proliferation marker Ki-67, the results confirmed Ki-67-positive nuclei in a proportion of lymph vessel endothelial cells.</p> <p>Conclusion</p> <p>There is indeed lymphangiogenesis in breast cancer, the most compelling evidence being the presence of proliferating lymphatic endothelial cells. VEGF-C and COX-2 are coexpressed and significantly associated with lymphangiogenesis and prognosis in invasive breast cancer. Suggesting COX-2 may up-regulate VEGF-C expression and thus promote lymph node metastasis via lymphangiogenesis pathway in human breast cancer.</p
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