829 research outputs found
Glycerol confined in zeolitic imidazolate frameworks: The temperature-dependent cooperativity length scale of glassy freezing
In the present work, we employ broadband dielectric spectroscopy to study the
molecular dynamics of the prototypical glass former glycerol confined in two
microporous zeolitic imidazolate frameworks (ZIF-8 and ZIF-11) with
well-defined pore diameters of 1.16 and 1.46 nm, respectively. The spectra
reveal information on the modified alpha relaxation of the confined supercooled
liquid, whose temperature dependence exhibits clear deviations from the typical
super-Arrhenius temperature dependence of the bulk material, depending on
temperature and pore size. This allows assigning well-defined cooperativity
length scales of molecular motion to certain temperatures above the glass
transition. We relate these and previous results on glycerol confined in other
host systems to the temperature-dependent length scale deduced from nonlinear
dielectric measurements. The combined experimental data can be consistently
described by a critical divergence of this correlation length as expected
within theoretical approaches assuming that the glass transition is due to an
underlying phase transition.Comment: 14 pages, 5 figures + Supplemental Material (4 pages, 6 figures).
Final version as accepted for publicatio
Symmetries of pp-Waves with Distributional Profile
We generalize the classification of (non-vacuum) pp-waves \cite{JEK} based on
the Killing-algebra of the space-time by admitting distribution-valued profile
functions. Our approach is based on the analysis of the (infinite-dimensional)
group of ``normal-form-preserving'' diffeomorphisms.Comment: 10 pages, latex2e, no figures, statement about the combination of
symmetry classes of impulsive waves correcte
Induction of the intrinsic apoptotic pathway via a new antimitotic agent in an esophageal carcinoma cell line
BACKGROUND : 2-Ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16) is a unique, in silico-designed compound
with possible anticancer properties, which were identified in our laboratory. This compound is capable of
interfering with microtubule dynamics and is believed to have potential carbonic anhydrase IX inhibiting activity.
In this study, it was investigated whether ESE-16 is capable of inducing apoptosis in vitro in the esophageal
carcinoma SNO cell line via the intrinsic pathway at a concentration of 0.2 ΞΌM with an exposure time of 24 hours.
RESULTS : Qualitative results were obtained via light microscopy, transmission electron microscopy and confocal
microscopy. Results showed hallmarks of apoptosis in the ESE-16-treated cells. In addition, data revealed an increase
in the number of ESE-16-treated cells blocked in metaphase. Cell death via apoptosis in the ESE-16-treated cells was
confirmed by studying the internal ultrastructure of the cells via transmission electron microscopy, while confocal
microscopy revealed abnormal spindle formation and condensed chromatin in ESE-16-treated cells, thus confirming
metaphase block.
Quantitative results were obtained via flow cytometry and spectrophotometry. Cell death via apoptosis in ESE-16-treated
cells was quantitatively confirmed by the Annexin V-FITC apoptosis detection assay. Flow cytometry and
spectrophotometry revealed dissipation of mitochondrial membrane potential and an increase in superoxide
levels in the ESE-16-treated cells when compared to the relevant controls. Both initiator caspase 9 and effector
caspase 3 activities were increased, which demonstrates that ESE-16 causes cell death in a caspase-dependent manner.
CONCLUSIONS : This was the first in vitro study conducted to investigate the action mechanism of ESE-16 on an
esophageal carcinoma cell line. The results provided valuable information on the action mechanism of this
potential anticancer agent. It can be concluded that the novel in silico-designed compound exerts an anti-proliferative
effect on the esophageal carcinoma SNO cell line by disrupting microtubule function resulting in metaphase block.
This culminates in apoptotic cell death via the intrinsic apoptotic pathway. This research provided cellular targets
warranting in vivo assessment of ESE-16βs potential as an anticancer agent.Medical Research Council of South Africa, the Cancer Association of South Africa, Research Committee of the University of Pretoria (RESCOM), the National Research Foundation (NRF), the Institute for Cellular and Molecular Medicine (ICMM) and the
Struwig- Germeshuysen Cancer Research Trust of South Africa.http://www.cellandbioscience.comhb201
Tetramethylbenzidine-TetrafluoroTCNQ: A narrow-gap semiconducting salt with room temperature relaxor ferroelectric behavior
We present an extension and revision of the spectroscopic and structural data
of the mixed stack charge transfer (CT) crystal
3,3,5,5-tetramethylbenzidine--tetrafluoro-tetracyanoquinodimethane
(TMB-TCNQF4), associated with new electric and dielectric measurements.
Refinement of syncrotron structural data at low temperature has led to revise
the previously reported [Phys. Rev. Mat. 2, 024602 (2018)] structure.
The revised structure is , with two dimerized stacks per unit cell, and
is consistent with the vibrational data. However, polarized Raman data in the
low-frequency region also indicate that by increasing temperature above 200 K
the structure presents an increasing degree of disorder mainly along the stack
axis. X-ray diffraction data at room temperature have confirmed that the
correct structure is -- no phase transitions -- but did not allow to
definitely substantiate the presence of disorder. On the other hand, dielectric
measurement have evidenced a typical relaxor ferroelectric behavior already at
room temperature, with a peak in real part of dielectric constant
around 200 K and 0.1 Hz. The relaxor behavior is explained
in terms of the presence of spin solitons separating domains of opposite
polarity that yield to ferroelectric nanodomains. TMB-TCNQF4 is confirmed to be
a narrow gap band semiconductor ( eV) with room temperature
conductivity of cm.Comment: 21 pages, including the Supporting Information in the same file.
Version 3 updates the x-ray structural data at room temperatur
Plane torsion waves in quadratic gravitational theories
The definition of the Riemann-Cartan space of the plane wave type is given.
The condition under which the torsion plane waves exist is found. It is
expressed in the form of the restriction imposed on the coupling constants of
the 10-parametric quadratic gravitational Lagrangian. In the mathematical
appendix the formula for commutator of the variation operator and Hodge
operator is proved. This formula is applied for the variational procedure when
the gravitational field equations are obtained in terms of the exterior
differential forms.Comment: 3 May 1998. - 11
In vitro evaluation of ESE-15-ol, an Estradiol analogue with nanomolar antimitotic and carbonic anhydrase inhibitory activity
Antimitotic compounds are still one of the most widely used chemotherapeutic anticancer drugs in the clinic today. Given
their effectiveness against cancer it is beneficial to continue enhancing these drugs. One way is to improve the bioavailability and efficacy by synthesizing derivatives that reversibly bind to carbonic anhydrase II (CAII) in red blood cells followed by a slow release into the blood circulation system. In the present study we describe the in vitro biological activity of a reduced derivative of 2-ethyl-3-O-sulphamoyl-estradiol (2EE), 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10),15-tetraen-17-ol
(ESE-15-ol). ESE-15-ol is capable of inhibiting carbonic anhydrase activity in the nanomolar range and is selective towards a
mimic of carbonic anhydrase IX when compared to the CAII isoform. Docking studies using Autodock Vina suggest that the
dehydration of the D-ring plays a role towards the selectivity of ESE-15-ol to CAIX and that the binding mode of ESE-15-ol is
substantially different when compared to 2EE. ESE-15-ol is able to reduce cell growth to 50% after 48 h at 50β75 nM in MCF-
7, MDA-MB-231, and MCF-12A cells. The compound is the least potent against the non-tumorigenic MCF-12A cells. In vitro mechanistic studies demonstrate that the newly synthesized compound induces mitochondrial membrane depolarization, abrogates the phosphorylation status of Bcl-2 and affects gene expression of genes associated with cell death and mitosis.Grants from the Medical Research Council of South Africa (AG374, AK076), the Cancer Association of South Africa
(AK246), National Research Foundation (NRF) (AL239), the Research Committee of the Faculty of Health Sciences (RESCOM) of University of Pretoria, and the Struwig-Germeshuysen Cancer Research Trust of South Africa (AJ038, AN074).http://www.plosone.orgam2013ay201
Signaling pathways of ESE-16, an antimitotic and anticarbonic anhydrase estradiol analog, in breast cancer cells
The aim of this study was to characterize the in vitro action of 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16) on
non-tumorigenic MCF-12A, tumorigenic MCF-7 and metastatic MDA-MB-231 breast cancer cells. ESE-16 is able to inhibit the activity of a carbonic anhydrase II and a mimic of carbonic anhydrase IX in the nanomolar range. Gene and protein expression studies using various techniques including gene and antibody microarrays and various flow cytometry assays yielded valuable information about the mechanism of action of ESE-16. The JNK pathway was identified as an important pathway mediating the effects of ESE-16 while the p38 stress-induced pathway is more important in MDA-MB-231 cells exposed to ESE-16. Lysosomal rupture and iron metabolism was identified as important mediators of mitochondrial membrane depolarization. Abrogation of Bcl-2 phosphorylation status as a result of ESE-16 also plays a role in inducing
mitochondrial membrane depolarization. The study provides a basis for future research projects to develop the newly synthesized compound into a clinically usable anticancer agent either alone or in combination with other agents. Keywords:
Antimitotic, anticarbonic anhydrase IX, apoptosis, autophagy, cell cycle arrest, Bcl-2, JNK, p38, mitochondrial
membrane depolarization, flow cytometry, gene expression and protein microarray, anticancer.This research was supported by grants from the Medical Research Council of South Africa (AG374, AK076), the Cancer Association of South Africa (AK246), National Research Foundation (NRF) (AL239), the Research Committee of the Faculty of Health Sciences (RESCOM) of University of Pretoria and the
Struwig-Germeshuysen Cancer Research Trust of South Africa (AJ038, AN074).http://www.plosone.orgam2013ay201
Severe thrombocytosis and anemia associated with celiac disease in a young female patient: a case report
<p>Abstract</p> <p>Introduction</p> <p>Platelet counts exceeding 1.000 Γ 10<sup>3</sup>/ΞΌl are usually considered secondary to another cause, particularly to chronic myeloproliferative disease (CMPD). Reactive thrombocytosis due to iron deficiency rarely exceeds platelet counts of 700 Γ 10<sup>3</sup>/ΞΌl.</p> <p>Case presentation</p> <p>Here we report the case of a young woman presenting with clinical signs of severe anemia. Laboratory findings confirmed an iron-deficiency anemia associated with severe thrombocytosis of 1703 Γ 10<sup>3</sup>/ΞΌl. Macroscopic gastrointestinal and genitourinary tract bleeding was excluded. The excessive elevation of platelets, slightly elevated lactate dehydrogenase and slightly elevated leukocytes along with the absence of other inflammation parameters raised the suspicion of an underlying hematological disease. However, bone marrow evaluation could not prove the suspected diagnosis of a CMPD, especially essential thrombocythemia (ET). In the further clinical course the platelet count returned to normal after raising the hemoglobin to a level close to normal range with erythrocyte transfusion, and normalization of serum iron and decline of erythropoietin. Finally, following small bowel biopsy, despite the absence of typical clinical signs, celiac disease was diagnosed. After discharge from hospital the patient was commenced on a gluten-free diet and her hemoglobin almost completely normalized in the further follow-up period.</p> <p>Conclusion</p> <p>This case illustrates the rare constellation of an extreme thrombocytosis most likely secondary to iron deficiency due to celiac disease. This represents, to the best of the authors' knowledge, the highest reported platelet count coincident with iron deficiency. A potential mechanism for the association of iron-deficiency anemia and thrombocytosis is discussed. Even in the presence of 'atypically' high platelets one should consider the possibility of reactive thrombocytosis. Extreme thrombocytosis could emerge in the case of iron deficiency secondary to celiac disease.</p
Novel estradiol analogue induces apoptosis and autophagy in esophageal carcinoma cells
Cancer is the second leading cause of death in South Africa. The
critical role that microtubules play in cell division makes them an ideal target
for the development of chemotherapeutic drugs that prevent the
hyperproliferation of cancer cells. The new in silico-designed estradiol
analogue 2-ethyl-3-O-sulfamoyl-estra-1,3,5(10)16-tetraene (ESE-16) was
investigated in terms of its in vitro antiproliferative effects on the esophageal
carcinoma SNO cell line at a concentration of 0.18 ΞΌM and an exposure
time of 24 h. Polarization-optical differential interference contrast and
triple fluorescent staining (propidium iodide, Hoechst 33342 and acridine
orange) revealed a decrease in cell density, metaphase arrest, and the
occurrence of apoptotic bodies in the ESE-16-treated cells when compared to
relevant controls. Treated cells also showed an increase in the presence of
acidic vacuoles and lysosomes, suggesting the occurrence ofMedical Research Council of South Africa, the Cancer Association of South Africa, Research Committee of the University of Pretoria (RESCOM), the National Research Foundation (NRF),the Institute of Cellular and Molecular Medicine (ICMM), and the Struwig-Germeshuysen Cancer Research Trust of South Africa.http://link.springer.com/journal/11658hb201
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