bluuebunny/crossref_metadata_2025 huggingface dataset:
Suppressive role of endogenous regucalcin in the enhancement of nitric oxide synthase activity in liver cytosol of normal and regucalcin transgenic rats
Authors: Yamaguchi Masayoshi , Takahashi Hiroko , Tsurusaki Yoshinori
Published: March 2003

The suppressive role of endogenous regucalcin, which is a regulatory protein of calcium signaling, in the enhancement of nitric oxide (NO) synthase activity in the liver cytosol of rats was investigated. The enzyme activity was measured in a reaction mixture containing either vehicle or calcium chloride (1–20 μM) in the absence or presence of regucalcin (0.1, 0.25, or 0.5 μM). NO synthase activity was significantly increased by the addition of calcium (5–20 μM). This increase was completely abolished in the presence of trifluoperazine (TFP; 10–50 μM), an antagonist of Ca2+/calmodulin. The addition of regucalcin (0.1–0.5 μM) caused a significant fall in the calcium‐increased enzyme activity. The effect of regucalcin (0.25 μM) in decreasing NO synthase activity was seen in the presence of ethylene glycol bis‐(2‐aminoethylether) N,N,N′,N′‐tetraacetic acid (EGTA, 1 mM) or TFP (20 μM), indicating that regucalcin acts independent on Ca2+/calmodulin. NO synthase activity was significantly raised in the presence of anti‐regucalcin monoclonal antibody (10–50 ng/ml) in the reaction mixture. The effect of the antibody (50 ng/ml) or calcium (10 μM) in elevating NO synthase activity in the liver cytosol of normal rats was not seen in the liver cytosol obtained from regucalcin transgenic rats. Moreover, the increase in NO synthase activity in the liver cytosol of normal rats induced by a single intraperitoneal administration of calcium (5.0 mg/100 g body weight) was significantly enhanced in the presence of anti‐regucalcin monoclonal antibody (50 ng/ml) in the reaction mixture. The administration of calcium caused a significant increase in regucalcin level in the liver cytosol of normal rats. The present study demonstrated that endogenous regucalcin plays a suppressive role in the enhancement of NO synthase activity in the liver cytosol of rats. J. Cell. Biochem. 88: 1226–1234, 2003. © 2003 Wiley‐Liss, Inc.
Progression of chondrogenesis in C3H10T1/2 cells is associated with prolonged and tight regulation of ERK1/2
Authors: Seghatoleslami M. Reza , Roman‐Blas Jorge A. , Rainville Anne M. , Modaressi Rozbeh , Danielson Keith G. , Tuan Rocky S.
Published: March 2003

Close contact of mesenchymal cells in vivo and also in super dense micromass cultures in vitro results in cellular condensation and alteration of existing cellular signaling required for initiation and progression of chondrogenesis. To investigate chondrogenesis related changes in the activity of ubiquitous cell signaling mediated by mitogen‐activated protein kinases (MAP kinase), we have compared the effect of cell seeding of pluripotent C3H10T1/2 mesenchymal cells as monolayers (non‐chondrogenic culture) or high density micromass cultures (chondrogenic) on the regulation and phosphorylation state of extracellular signal‐regulated kinase 1 and 2 (ERK1/2) and also on regulation of ERK1/2 nuclear targets, namely, activation protein‐1 (AP‐1) and serum response factor (SRF). Increasing cell density resulted in reduced DNA binding as well as activity of AP‐1. SRF activity, on the other hand, was up‐regulated in confluent monolayer cultures but like AP‐1 was inhibited in micromass cultures. Low levels of PD 98059 (5 μM), a specific inhibitor of ERK1/2, resulted in delayed induction of AP‐1 and SRF activity whereas higher concentrations of this inhibitor (10–50 μM) conferred an opposite effect. Increasing concentrations of the PD 98059 inhibitor in long term monolayer or micromass cultures (2.5 day) resulted in differential regulation of c‐Fos and c‐Jun protein levels as well as total expression and phosphorylation levels of ERK1/2. PD 98059 treatment of C3H10T1/2 micromass cultures also resulted in up‐regulation of type IIB collagen and Sox9 gene expression. While high expression of aggrecan and type IIB collagen genes were dependent on BMP‐2 signaling, ERK inhibition of BMP‐2 treated micromass cultures resulted in reduced activity of both genes. Our findings show that the activity of ERK1/2 in chondrogenic cultures of C3H10T1/2 cells is tightly controlled and can cross interact with other signaling activities mediated by BMP‐2 to positively regulate chondrogensis. J. Cell. Biochem. 88: 1129–1144, 2003. Published 2003 Wiley‐Liss, Inc.
Direct and indirect induction of apoptosis in human mesenchymal stem cells in response to titanium particles
Authors: Wang Mark L. , Tuli Richard , Manner Paul A. , Sharkey Peter F. , Hall David J. , Tuan Rocky S.
Published: March 2003

The most frequent complication of total joint arthroplasty is periprosthetic osteolysis initiated by an inflammatory response to orthopaedic wear debris, which if left untreated, can result in implant instability and failure, eventually requiring revision surgery. We have previously reported that osteogenic differentiation of human marrow stroma‐derived mesenchymal stem cells (hMSCs) is suppressed upon exposure to titanium particles, accompanied by reduced bone sialoprotein (BSP) gene expression, diminished production of collagen type I and BSP, decreased cellular viability and proliferation, and inhibition of extracellular matrix mineralization. In this study, we have further investigated hMSC cytotoxicity upon exposure to submicron particles of commercially pure titanium (cpTi) and zirconium oxide (ZrO2). Our results showed that direct exposure to cpTi and ZrO2 particles compromises cell viability through the induction of apoptosis, eliciting increased levels of the tumor suppressor proteins p53 and p73, in a manner dependent on material composition, particle dosage, and time. Additionally, conditioned medium collected from hMSCs exposed to cpTi particles, but not to ZrO2 particles, is cytotoxic to hMSCs, inducing apoptosis in the absence of particles. These findings demonstrate that exposure to orthopaedically derived wear particles can compromise hMSC viability through the direct and indirect induction of apoptosis. Thus, prolonged in vivo exposure of marrow‐derived hMSCs to implant‐derived wear debris is likely to reduce the population of viable osteoprogenitor cells, and may contribute to poor periprosthetic bone quality and implant loosening. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
A new case of CDG‐x with stereotyped dystonic hand movements and optic atrophy
Authors: Prietsch V. , Peters V. , Hackler R. , Jakobi R. , Assmann B. , Fang J. , Körner C. , Helwig‐Rolig A. , Schaefer J. R. , Hoffmann G. F.
Published: March 2003

We report the clinical findings and the diagnostic work‐up of a 17‐month‐old girl with CDG‐x. Predominant clinical signs were, besides psychomotor retardation and truncal hypotonia, stereotyped dystonic hand movements and ophthalmological abnormalities such as optic atrophy, nystagmus and strabismus. Other symptoms that are often found in patients with CDG were not present, such as seizures, microcephaly, cerebellar hypoplasia, dysmorphic features, hepatointestinal disease, coagulopathy or multiorgan involvement. Isoelectric focusing (IEF) of the patient's serum showed a marked elevation of disialotransferrin, thus confirming an IEF type 1 pattern. A generalized glycosylation defect was confirmed also by IEF of a further glycoprotein (α1‐antitrypsin), an increased carbohydrate deficient transferrin (CDT) serum concentration and an increased CDT/transferrin ratio. All known types of CDG‐I, secondary glycosylation abnormalities and variants of amino acid sequence were excluded.
3‐Hydroxyglutarate excretion is increased in ketotic patients: Implications for glutaryl‐CoA dehydrogenase deficiency testing
Authors: Pitt J. , Carpenter K. , Wilcken B. , Boneh A.
Published: March 2003

Three patients with ketosis had increased excretion of 3‐hydroxyglutarate (21.8–37.9 μmol/mmol creatinine; controls 2.3 ± 1.6), an indicator of glutaryl‐CoA dehydrogenase deficiency (GDHD), which normalized when the patients were nonketotic. Clinical assessment of all three patients and enzyme studies in one patient were not consistent with GDHD. These findings were compared with those of other ketotic patients, who showed statistically significant increases in 3‐hydroxyglutarate excretion (9.4 ± 5.0 μmol/mmol creatinine; p < 0.01), and with those of a child with confirmed GDHD when she was both ketotic and nonketotic. Secondary increase in 3‐hydroxyglutarate excretion during ketosis is a potential confounder in the diagnosis of GDHD.
Subcellular Localization and Characterization of Nucleoside Diphosphate Kinase in Rat Retina: Effect of Diabetes
Authors: Kowluru Anjaneyulu , Kowluru Renu A.
Published: March 2003

Nucleoside diphosphate kinase (NDP kinase) catalyzes the transfer of terminal phosphate from nucleotide triphosphates (e.g. ATP) to nucleotide diphosphates (e.g. GDP) to yield nucleotide triphosphates (e.g. GTP). Since guanine nucleotides play critical role(s) in GTP-binding protein (G-protein)-mediated signal transduction mechanisms in retina, we quantitated NDP kinase activity in subcellular fraction-derived from normal rat retina. A greater than 85% of the total specific activity was present in the soluble fraction, which was stimulated (up to 7 fold) by 2 mM magnesium. NDP kinase exhibited saturation kinetics towards di- and tri-phosphate substrates, and was inhibited by known inhibitors of NDP kinase, uridine diphosphate (UDP) or cromoglycate (CRG). We have previously reported significant abnormalities in the activation of G-proteins in streptozotocin (STZ)-diabetic rat retina (Kowluru et al. Diabetologia35:624–631, 1992). Since NDP kinase hasbeen implicated in direct interaction with and/or activation of various G-proteins, we quantitated both basal and magnesium-stimulated NDP kinase activity in soluble and particulate fractions of retina derived from STZ-diabetic rats to examine whether abnormalities in G-protein function in diabetes are attributable to alterations in retinal NDP kinase. There was no effect of diabetes either on the basal or the magnesium-activated retinal NDP kinase activity. This study represents the first characterization of NDP kinase activity in rat retina, and suggests that in diabetes, this enzyme may not be rate-limiting and/or causal for the observed alterations in retinal G-protein functions.
Glycotargeting: Influence of the Sugar Moiety on Both the Uptake and the Intracellular Trafficking of Nucleic Acid Carried by Glycosylated Polymers
Authors: Monsigny Michel , Midoux Patrick , Mayer Roger , Roche Annie-Claude
Published: March 2003

Nucleic acids (plasmids as well as oligonucleotides) used to specifically express or modulate the expression of a gene, must reach the cytosol and/or the nucleus. Several systems have been developed to increase their uptake and their efficiency. Glycosylated polylysines have been shown to specifically help nucleic acids to be taken up in cells expressing a given cell surface membrane lectin. However, it appeared that the efficiency of the imported nucleic acid was not directly related to the extent of the uptake. Indeed, some glycosylated polylysines bearing sugar moities which are poor ligands of the cell surface lectins of a given cell were found to be more efficient than those bearing better sugar ligands. The interpretation of this paradoxal result is discussed with regards to the nature of the compartment allowing the nucleic acid to cross the membrane and to be delivered in the cytosol on the one hand, and to the presence of intracellular lectins on the other hand.
The relationship between somatic and PTSD symptoms among Bhutanese refugee torture survivors: Examination of comorbidity with anxiety and depression
Authors: Van Ommeren Mark , Sharma Bhogendra , Sharma Gyanendra K. , Komproe Ivan , Cardeña Etzel , de Jong Joop T. V. M.
Published: March 2003

Previous research has indicated a relationship between posttraumatic stress disorder (PTSD) and somatic complaints. We examined whether this relationship is a result of shared comorbidity with anxiety and depression. Local doctors interviewed a random, community sample of 526 tortured and 526 nontortured Bhutanese refugees living in U.N. refugee camps in Nepal. The interview covered demographics, torture, somatic complaints, and PTSD, depression, and anxiety measures. Number of PTSD symptoms, independent of depression and anxiety, predicted both number of reported somatic complaints and number of organ systems involving such complaints. Physicians need to screen for PTSD when survivors of extreme stressors present nonspecific somatic complaints.
Complex Roles of CpG in Liposomal Delivery of DNA and Oligonucleotides
Authors: Wilson Annette , Pitt Bruce , Li Song
Published: March 2003

Unmethylated CpG in bacterial DNA has recently been recognized as a danger signal to the mammalian immune system. This CpG signal can be greatly amplified when DNA is delivered via a lipidic vector. The CpG effects are affected by the administration route, and can be either beneficial or harmful. In this review, we will summarize our current understanding about the mechanism of action of the immunostimulatory motifs. Emphasis will be placed on the discussion of the complicated roles of CpG when CpG DNA or oligonucleotides are administered in vivo using liposomes as a delivery vehicle.
Tumor-Directed Targeting of Liposomes
Authors: Park Yong Serk
Published: March 2003

Tumor-specific targeting is a critical goal in the research area of liposomal drug delivery. Identification of the specific interactions between ligands and target tumor cells is a principle prerequisite in achieving this goal. Generally, tumor cells aberrantly express tumor-associated antigens that can be utilized as appropriate target molecules. Monoclonal antibodies against tumor-associated antigens have been successfully adopted for targeting to various types of cancer cells. The incorporation of humanized monoclonal antibodies or single chain human antibodies, instead of rodent antibodies into immunoliposomes has resulted in better clinical applicability. Tumor-specific ligands other than monoclonal antibodies have also been investigated as in vivo tumor-directing molecules. However, the number of pre-clinical studies of anticancer treatments using tumor-specific liposomal drugs reporting successful targeting and enhanced therapeutic efficacy has been limited. Further refinement of tumor-specific interactions and liposomal formulations will be necessary for the application of the tumor-specific liposomal drug strategy for anticancer chemotherapy or gene therapy.
Structure of the Ductin Channel
Authors: Finbow Malcolm E. , Pitts John D.
Published: March 2003

Gap junctions appear to be essential components of metazoan animals providing a means of direct means of communication between neighboring cells. They are sieve-like structures which allow cell–cell movement of cytosolic solutes below 1000 MW. The major role of gap junctions would appear to be homeostatic giving rise to groups of cells which act as functional units. Ductin is the major core component of gap junctions and recent structural data shows it to be a four alpha-helical bundle which fits particularly well into a low resolution model of the gap junction channel. Ductin is also the main membrane component of the vacuolar H+-ATPase that is found in all eukaryotes and it seems likely that the gap junction channel first evolved as a housing for the rotating spindle of these proton pumps. Because ductin protrudes little from the membrane, other proteins are required to bring cell surfaces close enough together to form gap junctions. Such proteins may include connexins, a large family of proteins found in vertebrates.
The Behaviour of Ions in Narrow Water-Filled Pores
Authors: Edmonds D. T.
Published: March 2003

Today, the equilibrium behavior of ions in solution may be predicted with some confidence, essentially because rapid ionic diffusion over small distances ensures homogeneity throughout the solution. Equilibrium concepts such as ionic strength and pH apply. However, when attempting to understand the behavior of ions passing rapidly through narrow pores such as ion channels, no such equilibrium state may be assumed. The passing solution may have been in equilibrium with conditions at the mouth of the pore but will not be in equilibrium with charged molecules on the pore wall. In addition, the water in narrow pores will be partially ordered by contact with the pore walls and will not behave like bulk water.

To illustrate this difference, a simple equilibrium calculation of the ion concentrations near a plastic sheet penetrated by narrow pores and containing in its surface partially ionized carboxyl groups is shown to be in good agreement with experiment. However, to predict the non-equilibrium behavior within the narrow pores is much more difficult. To illustrate the difficulty, a Monte Carlo computer model is described which attempts to predict the rapid switching of ion current observed experimentally with these narrow pores.
Inhibition of Mitochondrial Permeability Transition by Low pH is Associated with Less Extensive Membrane Protein Thiol Oxidation
Authors: Teixeira Bruna M. A. R. , Kowaltowski Alicia J. , Castilho Roger F. , Vercesi Anibal E.
Published: March 2003

Ca2+ and inorganic phosphate-induced mitochondrial swelling and membrane protein thiol oxidation, which are associated with mitochondrial permeability transition, are inhibited by progressively decreasing the incubation medium pH between 7.2 and 6.0. Nevertheless, the detection of mitochondrial H2O2 production under these conditions is increased. Permeability transition induced by phenylarsine oxide, which promotes membrane protein thiol cross-linkage in a process independent of Ca2+ or reactive oxygen species, is also strongly inhibited in acidic incubation media. In addition, we observed that the decreased protein thiol reactivity with phenylarsine oxide or phenylarsine oxide-induced swelling at pH 6.0 is reversed by diethyl pyrocarbonate, in a hydroxylamine-sensitive manner. These results provide evidence that the inhibition of mitrochondrial permeability transition observed at lower incubation medium pH is mediated by a decrease in membrane protein thiol reactivity, related to the protonation of protein histidyl residues.
Sodium Channel Fragments: Contributions to Voltage Sensitivity and Ion Selectivity
Authors: Duclohier Hervé , Helluin Olivier , Cosette Pascal , Bendahhou Saïd
Published: March 2003

The peptide strategy was employed to resolve structure-function relationships in the voltage-dependent sodium channel. Two families of motifs were studied: the four voltage sensors S4 extended with the short cytoplasmic linkers L45 and the four P-regions, between S5 and S6, each from the homologous domains of the electric eel sodium channel. Macroscopic conductance experiments conducted with synthetic S4L45s in neutral lipid planar bilayers pointed to a moderate voltage-sensitivity for repeat IV which has no proline, whereas S4L45 of repeats I and II (Pro 19) and especially of repeat III (Pro 14) were much more voltage-sensitive. The influence both of Pro and its position within the sequence was confirmed by comparing the human skeletal muscle channel isoform D4/S4 wild-type and the R4P analogue. Circular dichroism spectroscopy shows highest and lowest helicities for repeats IV and III. The conformational transition (from helix to extended, mainly beta forms), which occurs when the solvent dielectric constant increases, was broader with repeat III. These structural and functional correlates suggest alternative gating mechanisms. The different contributions of each repeat also have effects at the level of the main selectivity filter, which suggests self-recognition between the four P-regions is a key component of intact sodium channel selectivity. In addition, the P-region from domain III is significantly voltage-sensitive and molecular dynamics simulations show that the C-terminal part of P-regions is mainly helical whilst the N-terminus tends to unfold. Such specializations of the four domains both in gating and selectivity are independently confirmed in recent electrophysiological studies.
Evidence of Mucin Secretion in Human Lung Adenocarcinoma Cell Lines NCIH650 and NCIH2077 and Effect of Select Secretagogues on Mucin Secretion
Authors: Sharma Prerna M. , Sarkar Mangala G. , Virmani Arvind K. , Gazdar Adi F. , Sachdev Goverdhan P.
Published: March 2003

Mucins comprise an important class of tumor-associated antigens. The objectives of the present study were (a) to establish an in vitro model system using human non-small cell lung adenocarcinoma cell lines NCIH650 and NCIH2077 (b) provide evidence that these cell lines secrete mucin in culture conditions and (c) investigate the effects of select secretagogues on mucin secretion. The cell lines were established in ACL-4 medium containing several growth factors and retinoic acid and 5% fetal calf serum. The high molecular weight glycoconjugates secreted in the culture medium were purified by ammonium sulfate precipitation and Superose 6 and Superose 12 FPLC chromatography. The purified high molecular weight glycoconjugate fraction and the carcinoma cells were shown to have mucin by dot blot, Western blot and immunohistochemical analysis, respectively, using specific antibodies to purified major mucin, HTM-1. Also, incorporation experiments with mucin precursor 3H-glucosamine demonstrated that the cells indeed synthesize high molecular weight mucins. The effects of secretagogues such as, 8-bromocyclic AMP, ionomycin, phorbol-12-myristate-13-acetate and neutrophil elastase on mucin secretion were also investigated. Only 8-bromocyclic AMP and neutrophil elastase influenced mucin secretion. These studies provided strong evidence that the lung adenocarcinoma cell lines secrete high molecular weight mucins in culture conditions and only two of the four tested secretagogues significantly increased mucin secretion. Thus, this in vitro model system may be useful in determining alterations in mucin structure, if any, in lung adenocarcinomas as well as in studying the regulation of mucin gene expression.
Fluorescence Studies of the Nicotinic Acetylcholine Receptor in its Membrane Environment
Authors: Barrantes Francisco J. , Antollini Silvia , Massol Ramiro
Published: March 2003

Since the discovery of the fraction of immobilized lipid in contact with the nicotinic acetylcholine receptor (AChR), the lipid-belt region around this protein has become the focus of a variety of biophysical studies aimed at defining its properties. Here we summarize recent spectroscopic studies from our laboratory using Laurdan fluorescence to characterize distinct sites for lipids and to describe their effect on the AChR microenvironment.
Biogenesis and Evolution of Photosynthetic (Thylakoid) Membranes
Authors: Herrmann Reinhold G.
Published: March 2003

Work in molecular phylogeny during the past few years has documented that the biogenesis, maintenance, adaptation, and controlled resorption of thylakoid (photosynthetic) membranes are by far more complex than the requirements for maintaining their function, especially in plants (eukaryotic photoautotrophs). Plants, due to their genome compartmentation that originated in a cohabitation of cells (endosymbiotic events), have evolved an exquisite set of regulatory mechanisms for their energy-transducing organelles. These operate in concert with basically ancient regulatory circuits originating in the organelle ancestors. It appears that the biogenesis of thylakoid membranes, as that of chloroplasts in general, cannot be understood without knowledge of the history of the cells.
Role of Peripheral Benzodiazepine Receptors on Secretion of Surfactant in Guinea Pig Alveolar Type II Cells
Authors: Das Salil K. , Mukherjee Shyamali
Published: March 2003

Granular type II cells located in the alveolar epithelium synthesize and secrete pulmonary surfactant and have specialized ion transport system. Alveolar type II cells are stimulated to secrete pulmonary surfactant by a variety of agonists. One mechanism by which extracellular signals are perceived by cells is the mobilization of intracellular Ca2+. Peripheral benzodiazepine receptors (PBRs) are present in both peripheral tissues and central nervous system. We have previously reported the presence of high density PBRs in lung and alveolar type II cells. It is known that both PBRs and beta-adrenergic receptors (beta-ARs) play an important role in cellular Ca2+ transport. Furthermore, we have suggested earlier that PBRs are someway functionally associated with the beta-ARs. The objective of the present study was to determine whether PBRs play any role in the secretion of surfactant by alveolar type II cells. Alveolar type II cells were isolated from normal weanling guinea pigs by panning method and incubated with 3H-palmitic acid in minimum essential medium to synthesize labelled dipalmitoyl phosphatidylcholine (DPPC). After washing, the cells were treated at 37°C for one hour with 10 μM isoproterenol (IP) in the presence and absence of 10 μM Ro 5-4864, an agonist for PBRs. After one hour, the release of labelled DPPC in the medium was analyzed. The control cells released DPPC without any addition of a ligand. However, the treatment of cells with IP, Ro 5-4864 and IP + Ro 5-4864 caused 24, 52 and 171% increase in the secretion of DPPC, respectively. In another experiment, type II cells were loaded with Fura-2 dye and treated with either IP or epineprine or Ro 5-4864. Both isoproterenol and epinephrine caused a significant increase in the level of cytosolic free Ca2+. However, Ro 5-4864 caused not only a decrease in the level of cytosolic free Ca2+ but also counteracted the stimulatory effect of IP. This may suggest that while ligands for ARs stimulate Ca2+ release into cytosol, the ligand for PBRs stimulates efflux of Ca2+ in alveolar type cells. Thus, the increased secretion of surfactant by the ligand of PBRs in alveolar type II cells may be mediated through its effects on increased Ca2+ efflux.
Arterial and Portal Circulation and Parenchymal Changes in Budd–Chiari Syndrome: A Study in 17 Explanted Livers
Authors: Cazals-Hatem Dominique , Vilgrain Valérie , Genin Pascal , Denninger Marie-Hélène , Durand François , Belghiti Jacques , Valla Dominique , Degott Claude
Published: March 2003

Hepatic parenchymal changes associated with Budd–Chiari syndrome (BCS) have been tentatively explained by combined arterial and portal perfusion disturbances in addition to the complete occlusion of hepatic veins. The aim of this study was to correlate pretransplant course and vascular imaging with pathologic findings in livers explanted for BCS. Seventeen consecutive white patients who underwent transplantation for severe classic BCS were retrospectively analyzed. Pretransplant course was 1 year or less in 8 patients and more than 1 year in 9 patients. Thrombophilia was found in 16 patients (94%). Imaging showed decreased portal perfusion in 16 patients (94%) and increased arterial perfusion in 9 patients. Histology showed obstructive portal venopathy and nodular regenerative hyperplasia (NRH) aspects in all cases, large regenerative nodules resembling focal nodular hyperplasia (FNH) in 9 cases, and cirrhosis in 2 cases. Patients with increased arterial inflow had large regenerative nodules and a protracted pretransplant course. Patients with acute thrombi in portal veins had parenchymal infarcts (2 cases) and a short pretransplant course. In conclusion, patients with severe BCS have a constant impaired perfusion inflow unrelated to progression of cirrhosis but related to the outcome. An early decrease in portal perfusion is observed in the short term and is responsible for NRH or infarcts if complicated with large thrombi. An increase in arterial perfusion compensates impaired portal flow in chronic BCS. Arterial hyperemia contributes to the development of large regenerative nodules that are FNH–like. This pathologic situation offers an interesting vascular model to further understand the parenchymal response to changes in hepatic blood flow.
Hepatocyte Nuclear Factor 1α: A Key Mediator of the Effect of Bile Acids on Gene Expression
Authors: Jung Diana , Kullak-Ublick Gerd A.
Published: March 2003

Bile acids regulate the expression of genes involved in cholesterol homeostasis. They are ligands of the farnesoid X receptor, which induces small heterodimer partner (SHP)–1, a transcriptional repressor of bile acid synthetic enzymes. In cholestatic liver disease, hepatic bile acid concentrations are elevated and expression of the major Na+-independent bile acid uptake system, organic anion transporting polypeptide (OATP)–C (solute carrier gene family SLC21A6), is markedly decreased. Because the OATP–C gene is transcriptionally dependent on the hepatocyte nuclear factor (HNF) 1α, we hypothesized that bile acids decrease OATP–C expression through direct repression of HNF1α. To test this hypothesis, we studied the regulation of the human HNF1α gene by bile acids. HNF1α expression in cultured hepatoma cells was decreased ˜50% after 12 hours' exposure to 100 μmol/L chenodeoxycholic acid (CDCA). Characterization of the human HNF1α gene promoter identified a consensus bile acid response element that binds and is activated by HNF4α. Mutagenesis of the HNF4α site abolished baseline HNF1α promoter activity. The central mechanism by which bile acids repress HNF1α is decreased activation by HNF4α. SHP directly inhibits HNF4α–mediated transactivation of the HNF1α promoter in cotransfection assays. In addition, HNF4α nuclear binding activity is decreased by CDCA and the human HNF4α gene promoter is repressed by CDCA through an SHP–independent mechanism. In conclusion, we show that repression of HNF1α is an important new mechanism by which bile acids regulate the expression of HNF1α–dependent genes in man. This explains the suppressive effect of bile acids on the OATP–C gene promoter, leading to decreased expression in cholestatic liver disease.
Glucose-6-Phosphate Dehydrogenase Overexpression Decreases Endothelial Cell Oxidant Stress and Increases Bioavailable Nitric Oxide
Authors: Leopold Jane A. , Zhang Ying-Yi , Scribner Anne W. , Stanton Robert C. , Loscalzo Joseph
Published: March 2003

Objective—

Glucose-6-phosphate dehydrogenase (G6PD), the principal source of NADPH, serves as an antioxidant enzyme to modulate the redox milieu and nitric oxide synthase activity. Deficient G6PD activity is associated with increased endothelial cell oxidant stress and diminished bioavailable nitric oxide (NO
·
). Therefore, we examined whether overexpression of G6PD would decrease reactive oxygen species accumulation and increase bioavailable NO
·
in endothelial cells.

Methods and Results—

Adenoviral-mediated gene transfer of G6PD increased G6PD expression, activity, and NADPH levels in bovine aortic endothelial cells (BAECs). BAECs overexpressing G6PD demonstrated a significant reduction in reactive oxygen species accumulation when exposed to hydrogen peroxide, xanthine-xanthine oxidase, or tumor necrosis factor-α compared with BAECs with basal levels of G6PD. BAECs overexpressing G6PD maintained intracellular glutathione stores when exposed to oxidants because of increased activity of glutathione reductase, an effect that was not observed in endothelial cells with normal G6PD activity. Overexpression of G6PD was also associated with enhanced nitric oxide synthase activity, resulting in elevated levels of cGMP, nitrate, and nitrite, and this response was increased after stimulation with bradykinin.

Conclusions—

Overexpression of G6PD in vascular endothelial cells decreases reactive oxygen species accumulation in response to exogenous and endogenous oxidant stress and improves levels of bioavailable NO
·
.
GATA-6 Is Involved in PPARγ-Mediated Activation of Differentiated Phenotype in Human Vascular Smooth Muscle Cells
Authors: Abe Mitsuru , Hasegawa Koji , Wada Hiromichi , Morimoto Tatsuya , Yanazume Tetsuhiko , Kawamura Teruhisa , Hirai Maretoshi , Furukawa Yutaka , Kita Toru
Published: March 2003

Objective—

Peroxisome proliferator-activated receptor-γ (PPARγ) is a member of the nuclear receptor superfamily involved in the growth and differentiation of many cell types. Although the activation of PPARγ in human vascular smooth muscle cells (VSMCs) inhibits the growth of these cells, the precise mechanism of this effect is unknown. PPARγ-mediated growth inhibition of VSMCs is associated with the induction of the differentiated phenotype. A zinc finger transcription factor, GATA-6, has been implicated in the maintenance of the differentiated phenotype in VSMCs.

Methods and Results—

The administration of 15-deoxy-Δ
12,14
-prostaglandin J
2
(15d-PGJ
2
), a naturally occurring PPARγ ligand, and troglitazone, a thiazolidinedione derivative, induced the expression of smooth muscle myosin heavy chain and smooth muscle α-actin, highly specific markers for differentiated VSMCs. Stimulation of proliferative VSMCs with PPARγ ligands also increased the activity of the transfected wild-type smooth muscle myosin heavy chain promoter but not that of the mutant promoter, in which a GATA-6 binding site was mutated. Compatible with the role of GATA-6, both 15d-PGJ
2
and troglitazone upregulated the DNA binding activity of GATA-6 in proliferative VSMCs.

Conclusions—

The activation of PPARγ-dependent pathways induces the differentiated phenotype in proliferative VSMCs, and this induction is mediated, in part, through a GATA-6–dependent transcriptional mechanism.
Erythrasma
Authors: Pan Sharon , Ryan Michael P. , Rapini Ronald P.
Published: January 2024

This case report describes well-demarcated brown plaques with overlying fine scale in the bilateral axillae, inframammary folds, and inguinal folds and widespread coral-red fluorescence.
US Obstetrician-Gynecologists' Perceived Impacts of Post–Dobbs v Jackson State Abortion Bans
Authors: Sabbath Erika L. , McKetchnie Samantha M. , Arora Kavita S. , Buchbinder Mara
Published: January 2024

Importance

Following the Dobbs v Jackson Women’s Health Organization decision in June 2022, 17 US states have functionally banned abortion except in narrow circumstances, and physicians found in violation of these laws face felony charges, loss of their medical license, fines, and prison sentences. Patient impacts are being studied closely, but less research has focused on the consequences for obstetrician-gynecologists (OB-GYNs), for whom medically necessary care provision may now carry serious personal and professional consequences.

Objective

To characterize perceptions of the impact of abortion restrictions on clinical practice, moral distress, mental health, and turnover intention among US OB-GYNs practicing in states with functional bans on abortion.

Design, Setting, and Participants

This qualitative study included semistructured, remote interviews with OB-GYNs from 13 US states with abortion bans. Volunteer sample of 54 OB-GYNs practicing in states that had banned abortion as of March 2023.

Exposure

State abortion bans enacted between June 2022 and March 2023.

Main Outcomes and Measures

OB-GYNs’ perceptions of clinical and personal impacts of abortion bans.

Results

This study included 54 OB-GYNs (mean [SD] age, 42 [7] years; 44 [81%] female participants; 3 [6%] non-Hispanic Black or African American participants; 45 [83%] White participants) who practiced in general obstetrics and gynecology (39 [72%]), maternal-fetal medicine (7 [13%]), and complex family planning (8 [15%]). Two major domains were identified in which the laws affected OB-GYNs: (1) clinical impacts (eg, delays in care until patients became more sick or legal sign-off on a medical exception to the ban was obtained; restrictions on counseling patients on pregnancy options; inability to provide appropriate care oneself or make referrals for such care); and (2) personal impacts (eg, moral distress; fears and perceived consequences of law violation; intention to leave the state; symptoms of depression and anxiety).

Conclusions and relevance

In this qualitative study of OB-GYNs practicing under abortion bans, participants reported deep and pervasive impacts of state laws, with implications for workforce sustainability, physician health, and patient outcomes. In the context of public policies that restrict physicians’ clinical autonomy, organization-level supports for physicians are essential to maintain workforce sustainability, clinician health and well-being, and availability of timely and accessible health care throughout the US.
Carbon Dots as Ligand Operons to Expand Cluster Size Distribution for High Load‐bearing Liquid Superlubricity
Authors: Liang Hongyu , Liu Manqiang , Yin Tianqiang , Zou Shijing , Xia Xiaojie , Hua Xijun , Fu Yonghong , Zhang Junyan , Bu Yongfeng , Ren Xudong
Published: January 2024

Adding additives (e.g., carbon dots, CDs) to liquid lubricants is an effective method for enhancing their load‐bearing capacity and friction reduction. However, it is challenging to simultaneously impart high load‐bearing capacity and superlubricity for them (e.g., ionic liquid analogs, ILAs) through this strategy due to strong Coulombic interactions. With CDs as a competing ligand operon, the cluster size distribution can be expanded, conferring superlubricity with ultrahigh load‐bearing capacity (>705 MPa, the highest value of CDs‐based superlubricious materials thus far) for CDs/ILAs. In particular, methodologies such as Raman, 1H‐NMR, fourier transform infrared spectroscopy, and laser particle size analysis are employed to characterize the evolution of their H‐bonding interactions and particle size distribution. CDs can act as competing ligands and enable CDs/ILAs to form systems with ultra‐low coefficient of friction and wear consisting of a mixture of large and small clusters. The mixed and expanded size clusters facilitate the reduction of the viscosity for CDs/ILAs under shear, thereby reducing the interfacial shear resistance during superlubricity, while the CDs within them efficiently transfer the normal bearing loads. The progress is made from the perspective of cluster particle size distribution rather than individual additive properties, providing a new avenue for designing ILAs‐based superlubricious materials.
Water‐Soluble Ionic Liquid‐Containing Sulfur Polymers for Mercury Capture, Demulsification, and Antibacterial Activity
Authors: Deng Xi , Dop Romy A. , Cai Diana , Neill Daniel R. , Hasell Tom
Published: January 2024

Sulfur polymers, prepared by inverse vulcanization using elemental sulfur and vinylic monomers, are emerging functional materials of current research interest; however, sulfur polymers suffer from limited water solubility due to the hydrophobic nature of conventional comonomers and sulfur. Herein, the preparation of ionic liquid (IL)‐containing sulfur polymers are reported using the hydrophilic ionic liquid, 1‐allyl‐3‐vinylimidazolium chloride (AVImCl) as a comonomer. The introduction of IL significantly enhances the hydrophilicity of sulfur polymers, enabling them to dissolve in water. Benefiting from the thorough contact with aqueous mercury ions, the resultant sulfur polymer possesses high uptake capacity (436 mg g−1). After binding mercury, a coordination complex is formed and precipitated. The charged sulfur polymers gain a new application in demulsification. The polymer quickly breaks oil‐in‐water (O/W) emulsions through anion exchange between Cl− of the polymer and dodecylbenzenesulfonate (DBS−) of the surfactant. In addition, the polymer has a growth inhibitory effect against Staphylococcus aureus. The integration of IL and elemental sulfur provides a novel approach to modifying the wettability of sulfur polymers. Also, this novel water‐soluble IL‐containing sulfur polymer, with mercury capture, demulsification, and antibacterial activity, can be considered as a multifunctional material in practical water purification.
Bright Circularly Polarized Mechanoluminescence from 0D Hybrid Manganese Halides
Authors: He Xin , Zheng Yuantian , Luo Zhishan , Wei Yi , Liu Yulian , Xie Chenlong , Li Chen , Peng Dengfeng , Quan Zewei
Published: January 2024

Hybrid metal halides (HMHs) with efficient circularly polarized luminescence (CPL) have application prospects in many fields, due to their abundant host–guest structures and high photoluminescence quantum yield (PLQY). However, CPLs in HMHs are predominantly excited by light or electricity, limiting their use in multivariate environments. It is necessary to explore a novel excitation method to extend the application of chiral HMHs as smart stimuli‐responsive optical materials. In this work, an enantiomeric pair of 0D hybrid manganese bromides, [H2(2R,4R)‐(+)/(2S,4S)‐(−)‐2,4‐bis(diphenylphosphino)pentane]MnBr4 [(R/S)‐1] is presented, which exhibits efficient CPL emissions with near‐unity PLQYs and high dissymmetry factors of ± 2.0 × 10−3. Notably, (R/S)‐1 compounds exhibit unprecedented and bright circularly polarized mechanoluminescence (CPML) emissions under mechanical stimulation. Moreover, (R/S)‐1 possess high mechanical force sensitivities with mechanoluminescence (ML) emissions detectable under 0.1 N force stimulation. Furthermore, this ML emission exhibits an extraordinary antithermal quenching effect in the temperature range of 300–380 K, which is revealed to originate from a thermal activation energy compensation mechanism from trap levels to Mn(II) 4T1 level. Based on their intriguing optical properties, these compounds as chiral force‐responsive materials are demonstrated in multilevel confidential information encryption.
Repeatedly Programmable Liquid Crystal Dielectric Elastomer with Multimodal Actuation
Authors: Zhang Chengcheng , Chen Guancong , Zhang Kaihang , Jin Binjie , Zhao Qian , Xie Tao
Published: January 2024

Dielectric elastomers (DEs) are actuatable under an electric field, whose large strain and fast response speed compare favorably with natural muscles. However, the actuation of DE‐based devices is generally limited to a single mode and cannot be reconfigured after fabrication, which pales in comparison to biological counterparts given the ability to alter actuation modes according to external conditions. To address this, liquid crystal dielectric elastomers (LC‐DEs) that can alter the dielectric actuation modes based on the thermally triggered shape‐changing are prepared. Specifically, the two shapes through the LC phase transition possess different bending stiffness, which leads to distinct actuation modes after an electric field is applied. Moreover, the two shapes can be individually programmed/reprogrammed, that is, the one before the transition is regulated through force‐directed solvent evaporation and the one after the transition is via bond exchange‐enabled stress relaxation. As such, the multimodal dielectric actuation behaviors upon temperature change can be readily diversified. Meanwhile, the space charge mechanism endows LC‐DEs with the significantly reduced driving e‐field (8 V µm−1) and bidirectional actuation manners. It is believed this unique adaptivity in the actuation modes under a low electric field shall offer versatile designs for practical soft robots.
Toward Next‐Generation Smart Windows: An In‐depth Analysis of Dual‐Band Electrochromic Materials and Devices
Authors: Wang Junkai , Wang Zhipeng , Zhang Mei , Huo Xiangtao , Guo Min
Published: January 2024

As the proportion of buildings energy consumption increases, the issue of low energy utilization efficiency becomes increasingly prominent. Approximately 45% of the energy is lost through doors and windows, a significant concern that has drawn society's attention to the potential of electrochromic technology, which can regulate light transmittance and absorption effectively. Specifically, dual‐band electrochromic materials offer a promising solution to this issue, as they can manipulate the transmission ratios of visible (VIS) and near‐infrared (NIR) light to obtain “bright,” “cold,” “warm,” and “dark” independent modes. However, research on dual‐band electrochromic materials and smart windows is still infant, and many challenges including performance and assembly issues, are significant obstacles to the advancement and application of this technology. This review clarifies the basic characteristics of dual‐band electrochromic materials and smart windows, including configurations, operational mechanisms, and performance assessment parameters. In‐depth examination of potential dual‐band electrochromic materials and methods for achieving independent modulation is provided, along with an analysis of the challenges and potential solutions for performance and assembly issues. Finally, the future prospects of dual‐band electrochromic smart windows (ESWs) are underscored. The hope is to eventually facilitate the commercial application of these windows, which can significantly contribute to the creation of modern, energy‐efficient buildings.
Improved Light Soaking and Thermal Stability of Organic Solar Cells by Robust Interfacial Modification
Authors: Mbilo Mwende , Haris Muhammad , Ryu Du Hyeon , Mwabora Julius Mwakondo , Musembi Robinson Juma , Lee Seungjin , Song Chang Eun , Shin Won Suk
Published: January 2024

The most widely used material in electron transport layers (ETL) of inverted organic solar cells (iOSCs) is zinc oxide (ZnO). However, the brittleness, inorganic nature, surface defects, and photocatalytic activity of ZnO lead to poor stability in iOSCs. Herein, the light‐soaking and thermal stability of iOSCs are substantially improved by modifying ZnO surface with polyurethane diacrylate (SAR) or urethane acrylate (OCS)‐based ultraviolet (UV) resins. The UV resins significantly reduce the energy barrier, suppress surface defects, and improve interfacial contact between ZnO ETL and the organic photoactive layer. Notably, the SAR and OCS resins mitigate the photocatalytic activity of ZnO, electrical leakage, and interfacial resistance during photoaging of OSCs. As a result, iOSCs based on modified ZnOs retain over 80% of initial efficiency under 1 sun illumination for light soaking 1000 h. Furthermore, SAR and OCS resins on ZnO surfaces form a robust crosslinked network with excellent solvent resistant properties, which result in enhanced thermal stability. These results reveal that this simple and effective approach is a promising procedure to fabricate high‐performance iOSCs.
Data from electronic healthcare records expand our understanding of X‐linked genetic diseases
Authors: Tinker Rory J. , Bastarache Lisa , Ezell Kimberly , Neumann Serena M. , Furuta Yutaka , Morgan Karee A. , Phillips John A.
Published: January 2024

Disease specific cohort studies have reported details on X linked (XL) disorders affecting females. We investigated the spectrum and penetrance of XL disorders seen in electronic health records (EHR). We generated a cohort of individuals diagnosed with XL disorders at Vanderbilt University Medical Center over 20 years. Our cohort included 477 males and 203 females diagnosed with 108 different XL genetic disorders. We found large differences between the female/male (F/M) ratios for various XL disorders regardless of their OMIM annotated mode of inheritance. We identified four XL recessive disorders affecting women previously only described in men. Biomarkers for XL disease had unique gender‐specific patterns differing between modes of inheritance. EHRs provide large cohorts of XL genetic disorders that give new insights compared to the literature. Differences in the F/M ratios and biomarkers of XL disorders observed likely result from disease specific and sex dependent penetrance. We conclude that observed gender ratios associated with specific XL disorders may be more useful than those predicted by Mendelian genetics provided by OMIM. Our findings of a gender specific penetrance and severity for XL disorders show unexpected differences from Mendelian predictions. Further work is required to validate our findings in larger combined EHR cohorts.