3,867 research outputs found
Toxicological evaluation of precocene II isolated from Ageratum conyzoides L. (Asteraceae) in Sprague Dawley rats
Precocene II (6,7-dimethoxy-2,2-dimethyl-2-chromene) was the main constituent isolated from Ageratum conyzoides L. and reportedly possessed antifungal activity. The study investigated the isolation,purification and toxicological effects of precocene II from A. conyzoides in Sprague Dawley rats. Precocene II was isolated from the petroleum ether fraction of the plant and the structure was determined by  1H-,13C-,DEPT-NMR and MS spectral techniques. Three groups of eight rats per group were used for the study. While groups B and C were respectively administered with 25 and 50 mg/kg of precocene II in 0.25% CMC-Na for 11 days by gastric intubation, group A was administered with 0.25% CMC-Na and served as the control group. After the last treatment, animals were fasted overnight and on the 12th day, they were injected intravenously with 0.2 ml/kg body weight of phenobarbital. Animalswere subsequently dissected from the abdominal region; blood was collected from the pulmonary vein into EDTA anti-coagulated and non anti-coagulated tubes. The liver, kidney and spleen tissues wereextracted into separate bottles for histopathological examinations. Results from hematological study indicated that the white blood cell (WBC), red blood cell (RBC), plateletcrit (PCT) and mean corpuscular hemoglobin count (MCHC) were significantly higher across the treated group s. Biochemical result showed that serum glucose level was significantly reduced in the treated groups. No apparent damage was noticed in the liver, kidney and spleen tissues. The result therefore suggests that precocene II possesses hypoglycemic property and could alter some hematopoietic elements but was not toxic to the liver, kidney and spleen tissues
A Role for VEGFR2 Activation in Endothelial Responses Caused by Barrier Disruptive OxPAPC Concentrations
Introduction: Oxidation products of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphatidylcholine (OxPAPC) differentially modulate endothelial cell (EC) barrier function in a dose-dependent fashion. Vascular endothelial growth factor receptor-2 (VEGFR2) is involved in the OxPAPC-induced EC inflammatory activation. This study examined a role of VEGFR2 in barrier dysfunction caused by high concentrations of OxPAPC and evaluated downstream signaling mechanisms resulting from the effect of OxPAPC in EC from pulmonary and systemic circulation
The what and where of adding channel noise to the Hodgkin-Huxley equations
One of the most celebrated successes in computational biology is the
Hodgkin-Huxley framework for modeling electrically active cells. This
framework, expressed through a set of differential equations, synthesizes the
impact of ionic currents on a cell's voltage -- and the highly nonlinear impact
of that voltage back on the currents themselves -- into the rapid push and pull
of the action potential. Latter studies confirmed that these cellular dynamics
are orchestrated by individual ion channels, whose conformational changes
regulate the conductance of each ionic current. Thus, kinetic equations
familiar from physical chemistry are the natural setting for describing
conductances; for small-to-moderate numbers of channels, these will predict
fluctuations in conductances and stochasticity in the resulting action
potentials. At first glance, the kinetic equations provide a far more complex
(and higher-dimensional) description than the original Hodgkin-Huxley
equations. This has prompted more than a decade of efforts to capture channel
fluctuations with noise terms added to the Hodgkin-Huxley equations. Many of
these approaches, while intuitively appealing, produce quantitative errors when
compared to kinetic equations; others, as only very recently demonstrated, are
both accurate and relatively simple. We review what works, what doesn't, and
why, seeking to build a bridge to well-established results for the
deterministic Hodgkin-Huxley equations. As such, we hope that this review will
speed emerging studies of how channel noise modulates electrophysiological
dynamics and function. We supply user-friendly Matlab simulation code of these
stochastic versions of the Hodgkin-Huxley equations on the ModelDB website
(accession number 138950) and
http://www.amath.washington.edu/~etsb/tutorials.html.Comment: 14 pages, 3 figures, review articl
Electrically-driven phase transition in magnetite nanostructures
Magnetite (FeO), an archetypal transition metal oxide, has been
used for thousands of years, from lodestones in primitive compasses[1] to a
candidate material for magnetoelectronic devices.[2] In 1939 Verwey[3] found
that bulk magnetite undergoes a transition at T 120 K from a
high temperature "bad metal" conducting phase to a low-temperature insulating
phase. He suggested[4] that high temperature conduction is via the fluctuating
and correlated valences of the octahedral iron atoms, and that the transition
is the onset of charge ordering upon cooling. The Verwey transition mechanism
and the question of charge ordering remain highly controversial.[5-11] Here we
show that magnetite nanocrystals and single-crystal thin films exhibit an
electrically driven phase transition below the Verwey temperature. The
signature of this transition is the onset of sharp conductance switching in
high electric fields, hysteretic in voltage. We demonstrate that this
transition is not due to local heating, but instead is due to the breakdown of
the correlated insulating state when driven out of equilibrium by electrical
bias. We anticipate that further studies of this newly observed transition and
its low-temperature conducting phase will shed light on how charge ordering and
vibrational degrees of freedom determine the ground state of this important
compound.Comment: 17 pages, 4 figure
Signal pathways underlying homocysteine-induced production of MCP-1 and IL-8 in cultured human whole blood
Aim : To elucidate the mechanisms underlying homocysteine (Hcy)-induced chemokine production. Methods : Human whole blood was pretreated with inhibitors of calmodulin (CaM), protein kinase C (PKC), protein tyrosine kinase (PTK), mitogen-activated protein kinase (MAPK), and NF-ΚB and activators of PPARΓ for 60 min followed by incubation with Hcy 100 Μmol/L for 32 h. The levels of mitogen chemokine protein (MCP)-1 and interleukin-8 (IL-8) were determined by enzyme-linked immunosorbant assay (ELISA). Results : Inhibitors of PKC (calphostin C, 50-500 nmol/L and RO-31-8220, 10–100 nmol/L), CaM (W7, 28–280 Μmol/L), ERK1/2 MAPK (PD 98059, 2–20 Μmol/L), p38 MAPK (SB 203580, 0.6–6 Μmol/L), JNK MAPK (curcumin, 2–10 Μmol/L), and NF-ΚB (PDTC, 10-100 nmol/L) markedly reduced Hcy 100 Μmol/L-induced production of MCP-1 and IL-8 in human cultured whole blood, but the inhibitors of PTK (genistein, 2.6–26 Μmol/L and tyrphostin, 0.5-5 Μmol/L) had no obvious effect on MCP-1 and IL-8 production. PPARΓ activators (ciglitazone 30 Μmol/L and troglitazone 10 Μmol/L) depressed the Hcy-induced MCP-1 production but not IL-8 production in the cultured whole blood. Conclusion : Hcy-induced MCP-1 and IL-8 production is mediated by activated signaling pathways such as PKC, CaM, MAPK, and NF-ΚB. Our results not only provide clues for the signal transduction pathways mediating Hcy-induced chemokine production, but also offer a plausible explanation for a pathogenic role of hyperhomocysteinemia in these diseases.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75644/1/j.1745-7254.2005.00005.x.pd
Semiparametric Multivariate Accelerated Failure Time Model with Generalized Estimating Equations
The semiparametric accelerated failure time model is not as widely used as
the Cox relative risk model mainly due to computational difficulties. Recent
developments in least squares estimation and induced smoothing estimating
equations provide promising tools to make the accelerate failure time models
more attractive in practice. For semiparametric multivariate accelerated
failure time models, we propose a generalized estimating equation approach to
account for the multivariate dependence through working correlation structures.
The marginal error distributions can be either identical as in sequential event
settings or different as in parallel event settings. Some regression
coefficients can be shared across margins as needed. The initial estimator is a
rank-based estimator with Gehan's weight, but obtained from an induced
smoothing approach with computation ease. The resulting estimator is consistent
and asymptotically normal, with a variance estimated through a multiplier
resampling method. In a simulation study, our estimator was up to three times
as efficient as the initial estimator, especially with stronger multivariate
dependence and heavier censoring percentage. Two real examples demonstrate the
utility of the proposed method
Recessive Inheritance of Congenital Hydrocephalus With Other Structural Brain Abnormalities Caused by Compound Heterozygous Mutations in ATP1A3
Background: ATP1A3 encodes the α3 subunit of the Na+/K+ ATPase, a fundamental ion-transporting enzyme. Primarily expressed in neurons, ATP1A3 is mutated in several autosomal dominant neurological diseases. To our knowledge, damaging recessive genotypes in ATP1A3 have never been associated with any human disease. Atp1a3 deficiency in zebrafish results in hydrocephalus; however, no known association exists between ATP1A3 and human congenital hydrocephalus (CH). /
Methods: We utilized whole-exome sequencing (WES), bioinformatics, and computational modeling to identify and characterize novel ATP1A3 mutations in a patient with CH. We performed immunohistochemical studies using mouse embryonic brain tissues to characterize Atp1a3 expression during brain development. /
Results: We identified two germline mutations in ATP1A3 (p. Arg19Cys and p.Arg463Cys), each of which was inherited from one of the patient’s unaffected parents, in a single patient with severe obstructive CH due to aqueductal stenosis, along with open schizencephaly, type 1 Chiari malformation, and dysgenesis of the corpus callosum. Both mutations are predicted to be highly deleterious and impair protein stability. Immunohistochemical studies demonstrate robust Atp1a3 expression in neural stem cells (NSCs), differentiated neurons, and choroid plexus of the mouse embryonic brain. /
Conclusion: These data provide the first evidence of a recessive human phenotype associated with mutations in ATP1A3, and implicate impaired Na+/K+ ATPase function in the pathogenesis of CH
Non-Equilibrium Field Dynamics of an Honest Holographic Superconductor
Most holographic models of superconducting systems neglect the effects of
dynamical boundary gauge fields during the process of spontaneous
symmetry-breaking. Usually a global symmetry gets broken. This yields a
superfluid, which then is gauged "weakly" afterwards. In this work we build
(and probe the dynamics of) a holographic model in which a local boundary
symmetry is spontaneously broken instead. We compute two-point functions of
dynamical non-Abelian gauge fields in the normal and in the broken phase, and
find non-trivial gapless modes. Our AdS3 gravity dual realizes a p-wave
superconductor in (1+1) dimensions. The ground state of this model also breaks
(1+1)-dimensional parity spontaneously, while the Hamiltonian is
parity-invariant. We discuss possible implications of our results for a wider
class of holographic liquids.Comment: 32 pages, 12 figures; v3: string theory derivation of setup added
(section 3.1), improved presentation, version accepted by JHEP; v2: paragraph
added to discussion, figure added, references added, typos correcte
Direct observation of spin-polarised bulk bands in an inversion-symmetric semiconductor
Methods to generate spin-polarised electronic states in non-magnetic solids
are strongly desired to enable all-electrical manipulation of electron spins
for new quantum devices. This is generally accepted to require breaking global
structural inversion symmetry. In contrast, here we present direct evidence
from spin- and angle-resolved photoemission spectroscopy for a strong spin
polarisation of bulk states in the centrosymmetric transition-metal
dichalcogenide WSe. We show how this arises due to a lack of inversion
symmetry in constituent structural units of the bulk crystal where the
electronic states are localised, leading to enormous spin splittings up to
eV, with a spin texture that is strongly modulated in both real and
momentum space. As well as providing the first experimental evidence for a
recently-predicted `hidden' spin polarisation in inversion-symmetric materials,
our study sheds new light on a putative spin-valley coupling in
transition-metal dichalcogenides, of key importance for using these compounds
in proposed valleytronic devices.Comment: 6 pages, 4 figure
Identification of plasma lipid biomarkers for prostate cancer by lipidomics and bioinformatics
Background:
Lipids have critical functions in cellular energy storage, structure and signaling. Many individual lipid molecules have been associated with the evolution of prostate cancer; however, none of them has been approved to be used as a biomarker. The aim of this study is to identify lipid molecules from hundreds plasma apparent lipid species as biomarkers for diagnosis of prostate cancer.
Methodology/Principal Findings:
Using lipidomics, lipid profiling of 390 individual apparent lipid species was performed on 141 plasma samples from 105 patients with prostate cancer and 36 male controls. High throughput data generated from lipidomics were analyzed using bioinformatic and statistical methods. From 390 apparent lipid species, 35 species were demonstrated to have potential in differentiation of prostate cancer. Within the 35 species, 12 were identified as individual plasma lipid biomarkers for diagnosis of prostate cancer with a sensitivity above 80%, specificity above 50% and accuracy above 80%. Using top 15 of 35 potential biomarkers together increased predictive power dramatically in diagnosis of prostate cancer with a sensitivity of 93.6%, specificity of 90.1% and accuracy of 97.3%. Principal component analysis (PCA) and hierarchical clustering analysis (HCA) demonstrated that patient and control populations were visually separated by identified lipid biomarkers. RandomForest and 10-fold cross validation analyses demonstrated that the identified lipid biomarkers were able to predict unknown populations accurately, and this was not influenced by patient's age and race. Three out of 13 lipid classes, phosphatidylethanolamine (PE), ether-linked phosphatidylethanolamine (ePE) and ether-linked phosphatidylcholine (ePC) could be considered as biomarkers in diagnosis of prostate cancer.
Conclusions/Significance:
Using lipidomics and bioinformatic and statistical methods, we have identified a few out of hundreds plasma apparent lipid molecular species as biomarkers for diagnosis of prostate cancer with a high sensitivity, specificity and accuracy
- …