bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of Transient Receptor Potential Vanilloid 4-Mediated Membrane Currents and Synaptic Transmission by Protein Kinase C
Authors: Cao De-Shou , Yu Shuang-Quan , Premkumar Louis S 
Published: February 2009

Background Transient receptor potential Vanilloid (TRPV) receptors are involved in nociception and are expressed predominantly in sensory neurons. TRPV1, a non-selective cation channel has been extensively studied and is responsible for inflammatory thermal hypersensitivity. In this study, the expression and function of TRPV4 have been characterized and compared with those of TRPV1. Results Immunohistochemical studies revealed that both TRPV1 and TRPV4 were co-expressed in dorsal root ganglion (DRG) neuronal cell bodies and in the central terminals of laminae I and II of the spinal dorsal horn (DH). In Ca2+ fluorescence imaging and whole-cell patch-clamp experiments, TRPV1- and TRPV4-mediated responses were observed in a population of the same DRG neurons. Sensitization of TRPV1 has been shown to be involved in inflammatory pain conditions. Incubation with phorbol 12, 13-dibutyrate (PDBu), a PKC activator, resulted in a significant potentiation of TRPV4 currents in DRG neurons. In TRPV4 expressing HEK 293T cells, PDBu increased 4α-phorbol 12, 13-didecanoate (4α-PDD)-induced single-channel activity in cell-attached patches, which was abrogated by bisindolylmaleimide (BIM), a selective PKC inhibitor. TRPV4 is also expressed at the central terminals of sensory neurons. Activation of TRPV4 by 4α-PDD increased the frequency of miniature excitatory post synaptic currents (mEPSCs) in DRG-DH neuronal co-cultures. 4α-PDD-induced increase in the frequency of mEPSCs was further enhanced by PDBu. The expression of TRP channels has been shown in other areas of the CNS; application of 4α-PDD significantly increased the mEPSC frequency in cultured hippocampal neurons, which was further potentiated by PDBu, whereas, TRPV1 agonist capsaicin did not modulate synaptic transmission. Conclusion: These results indicate that TRPV4 and TRPV1 are co-expressed in certain DRG neurons and TRPV4 can be sensitized by PKC not only in DRG neuronal cell bodies, but also in the central sensory and non-sensory nerve terminals. Co-expression of TRPV1 and TRPV4 ion channels, their modulation of synaptic transmission and their sensitization by PKC may synergistically play a role in nociception.
An in vitrostudy investigating the survival and phenotype of mesenchymal stem cells following injection into nucleus pulposus tissue
Authors: Le Maitre Christine L , Baird Pauline , Freemont Anthony J , Hoyland Judith A 
Published: February 2009

Abstract
Introduction
The decreased disc height characteristic of intervertebral disc (IVD) degeneration has often been linked to low back pain, and thus regeneration strategies aimed at restoring the disc extracellular matrix and ultimately disc height have been proposed as potential treatments for IVD degeneration. One such therapy under investigation by a number of groups worldwide is the use of autologous mesenchymal stem cells (MSCs) to aid in the regeneration of the IVD extracellular matrix. To date, however, the optimum method of application of these cells for regeneration strategies for the IVD is unclear, and few studies have investigated the direct injection of MSCs alone into IVD tissues. In the present article, we investigated the survival and phenotype of human MSCs, sourced from aged individuals, following injection into nucleus pulposus (NP) tissue explant cultures.

Methods
Human MSCs extracted from bone marrow were expanded in monolayer culture and, after labelling with adenoviral vectors carrying the green fluorescent protein transcript, were injected into NP tissue explants (sourced from bovine caudal discs) and maintained in culture for 2, 7, 14 and 28 days post injection. Following fixation and paraffin embedding, cell viability was assessed using in situ hybridisation for polyA-mRNA and using immunohistochemistry for caspase 3. Immunohistochemistry/fluorescence for aggrecan, Sox-9 and types I, II and X collagen together with Alizarin red staining was employed to investigate the MSC phenotype and matrix formation.

Results
MSCs were identified in all injected tissue samples and cell viability was maintained for the 4 weeks investigated. MSCs displayed cellular staining for Sox-9, and displayed cellular and matrix staining for aggrecan and type II collagen that increased during culture. No type I collagen, type X collagen or Alizarin red staining was observed at any time point.

Conclusions
MSCs from older individuals differentiate spontaneously into chondrocyte-like NP cells upon insertion into NP tissue in vitro, and thus may not require additional stimulation or carrier to induce differentiation. This is a key finding, as such a strategy would minimise the level of external manipulation required prior to insertion into the patient, thus simplifying the treatment strategy and reducing costs.
Effects of interventional lung assist on haemodynamics and gas exchange in cardiopulmonary resuscitation: a prospective experimental study on animals with acute respiratory distress syndrome
Authors: Zick Günther , Schädler Dirk , Elke Gunnar , Pulletz Sven , Bein Berthold , Scholz Jens , Frerichs Inéz , Weiler Norbert 
Published: February 2009

Abstract
Introduction
Interventional lung assist (ILA), based on the use of a pumpless extracorporeal membrane oxygenator, facilitates carbon dioxide (CO2) elimination in acute respiratory distress syndrome (ARDS). It is unclear whether an ILA system should be clamped during cardiopulmonary resuscitation (CPR) in patients with ARDS or not. The aim of our study was to test the effects of an ILA on haemodynamics and gas exchange during CPR on animals with ARDS and to establish whether the ILA should be kept open or clamped under these circumstances.

Methods
The study was designed to be prospective and experimental. The experiments were performed on 12 anaesthetised and mechanically ventilated pigs (weighing 41 to 58 kg). One femoral artery and one femoral vein were cannulated and connected to an ILA. ARDS was induced by repeated bronchoalveolar lavage. An indwelling pacemaker was used to initiate ventricular fibrillation and chest compressions were immediately started and continued for 30 minutes. In six animals, the ILA was kept open and in the other six it was clamped.

Results
Systolic and mean arterial pressures did not differ significantly between the groups. With the ILA open mean ± standard deviation systolic blood pressures were 89 ± 26 mmHg at 5 minutes, 71 ± 28 mmHg at 10 minutes, 63 ± 33 mmHg at 20 minutes and 83 ± 23 mmHg at 30 minutes. The clamped ILA system resulted in systolic pressures of 77 ± 30 mmHg, 90 ± 23 mmHg, 72 ± 11 mmHg and 72 ± 22 mmHg, respectively. In the group with the ILA system open, arterial partial pressure of CO2 was significantly lower after 10, 20 and 30 minutes of CPR and arterial partial pressure of oxygen was higher 20 minutes after the onset of CPR (191 ± 140 mmHg versus 57 ± 14 mmHg). End-tidal partial pressure of CO2 decreased from 46 ± 23 Torr (ILA open) and 37 ± 9 Torr (ILA clamped) before intervention to 8 ± 5 Torr and 8 ± 10 Torr, respectively, in both groups after 30 minutes of CPR.

Conclusions
Our results indicate that in an animal model of ARDS, blood pressures were not impaired by keeping the ILA system open during CPR compared with the immediate clamping of the ILA with the onset of CPR. The effect of ILA on gas exchange implied a beneficial effect.
Genetic Influences on Type 2 Diabetes and Metabolic Syndrome Related Quantitative Traits in Mauritius
Authors: Jowett Jeremy B. , Diego Vincent P. , Kotea Navaratnam , Kowlessur Sudhir , Chitson Pierrot , Dyer Thomas D. , Zimmet Paul , Blangero John 
Published: February 2009

AbstractEpidemiological studies report a high prevalence of type 2 diabetes and metabolic syndrome in the island nation of Mauritius. The Mauritius Family Study was initiated to examine heritable factors that contribute to these high rates of prevalence and consists of 400 individuals in 24 large extended multigenerational pedigrees. Anthropometric and biochemical measurements relating to the metabolic syndrome were undertaken in addition to family and lifestyle based information for each individual. Variance components methods were used to determine the heritability of the type 2 diabetes and metabolic syndrome related quantitative traits. The cohort was made up of 218 females (55%) and 182 males with 22% diagnosed with type 2 diabetes and a further 30% having impaired glucose tolerance or impaired fasting glucose. Notably BMI was not significantly increased in those with type 2 diabetes (P= .12), however a significant increase in waist circumference was observed in these groups (P= .02). The heritable proportion of trait variance was substantial and greater than values previously published for hip circumference, LDL and total cholesterol, diastolic and systolic blood pressure and serum creatinine. Height, weight and BMI heritabilities were all in the upper range of those previously reported. The phenotypic characteristics of the Mauritius family cohort are similar to those previously reported in the Mauritian population with a high observed prevalence rate of type 2 diabetes. A high heritability for key type 2 diabetes and metabolic syndrome related phenotypes (range 0.23 to 0.68), suggest the cohort will have utility in identifying genes that influence these quantitative traits.
Der Familienname als Nationalsymbol. Über den Untergang deutscher Familiennamen im Ungarn des 19. Jahrhunderts
Authors: Maitz Péter , Farkas Tamás 
Published: February 2009

Abstract
As a result of German-Hungarian societal bilingualism German family names had been present in multilingual 19th century Hungary for centuries. Magyarizations of family names in the second half of the 19th century mostly affected the German and Yiddish speech communities bearing German family names. This paper explores the causes and characteristics of this phenomenon by examining the social, psychological, and ideological factors influencing the use of family names. After giving the numerical description of family name changes, the authors examine the sociolinguistic background of family name use, focusing on the situation of ethnolinguistic communities whose members bore German family names. By analysing the semantic structure of family names, the authors present how and why these family names could become tools of linguistic nationalism in contemporary Hungary, generating the claim of changing foreign-sounding family names to Hungarian ones. The political and social background of family name changes as well as social stratification of the applicants are also examined. The authors describe the movement of family name Magyarizations as a behavioural pattern of middle-class people ready to accept social mobility and willing to take part in assimilation. The aesthetic, functional and linguistic principles found behind these family name changes are also discussed. After briefly presenting the history of German family names in 20th century Hungary, the authors deduce some basic theoretical and methodological conclusions.
Contact Resistivity of NiPtSi on n-doped Silicon Activated by Laser Annealing
Authors: Pagette Francois , Solomon Paul M , Kozlowski Paul M , Topol Anna W , Haensch Wilfried 
Published: February 2009

AbstractReducing specific contact resistivity of the silicide to silicon interface is advantageous to achieve high planar density and high drive current FET devices. Measuring the differential resistivities at different low voltage bias conditions of four terminal Kelvin test structures with a range of contact sizes has proven particularly effective in characterizing the linearity behavior and specific contact resistivity. This study shows that adding laser activation annealing for an n+ doped silicon contacted by a standard NiPt silicide is found to significantly improve the contact electrical properties. Initial results with only rapid thermal anneal activation show a size dependence of the contact resistivity with non-linear behavior exhibiting maximum resistance at zero bias, and contact resistivities ranging from 4×10-8 &#937;-cm2 to 4×10-7 &#937;-cm2. Adding laser anneal after the rapid thermal anneal gives ohmic behavior, for contact down to 50nm in size, with a specific contact resistivity of 1×10-8 &#937;-cm2. The metal-to-silicide contact resistance was measured separately using a novel test structure and it was confirmed to be negligible. We describe our device structure, our experimental methodology, and the implications of our results for future devices.
Cost Savings From the Provision of Specific Methods of Contraception in a Publicly Funded Program
Authors: Foster Diana Greene , Rostovtseva Daria P. , Brindis Claire D. , Biggs M. Antonia , Hulett Denis , Darney Philip D. 
Published: February 2009

Objectives. We examined the cost-effectiveness of contraceptive methods dispensed in 2003 to 955 000 women in Family PACT (Planning, Access, Care and Treatment), California's publicly funded family planning program. Methods. We estimated the number of pregnancies averted by each contraceptive method and compared the cost of providing each method with the savings from averted pregnancies. Results. More than half of the 178 000 averted pregnancies were attributable to oral contraceptives, one fifth to injectable methods, and one tenth each to the patch and barrier methods. The implant and intrauterine contraceptives were the most cost-effective, with cost savings of more than $7.00 for every $1.00 spent in services and supplies. Per $1.00 spent, injectable contraceptives yielded savings of $5.60; oral contraceptives, $4.07; the patch, $2.99; the vaginal ring, $2.55; barrier methods, $1.34; and emergency contraceptives, $1.43. Conclusions. All contraceptive methods were cost-effective—they saved more in public expenditures for unintended pregnancies than they cost to provide. Because no single method is clinically recommended to every woman, it is medically and fiscally advisable for public health programs to offer all contraceptive methods.
Loss-of-Function Mutation in Myostatin Reduces Tumor Necrosis Factor α Production and Protects Liver Against Obesity-Induced Insulin Resistance
Authors: Wilkes Jason J. , Lloyd David J. , Gekakis Nick 
Published: February 2009

OBJECTIVEInsulin resistance develops in tandem with obesity. Ablating myostatin (Mstn) prevents obesity, so we investigated if Mstn deficiency could improve insulin sensitivity. A loss-of-function mutation (MstnLn) in either one or both alleles of the Mstn gene shows how Mstn deficiency protects whole-body insulin sensitivity.RESEARCH DESIGN AND METHODSMstnLn/Ln mice were weaned onto a high-fat diet (HFD) or standard diet. HFD-fed MstnLn/Ln mice exhibited high lean, low-fat body compositions compared with wild types. Wild-type and heterozygous and homozygous mutant mice were bled to determine basal levels of insulin, glucose, and homeostasis model assessment of insulin resistance. To evaluate postprandial insulin sensitivity between animals of a similar size, glucose and insulin tolerance tests and hyperinsulinemic-euglycemic clamp studies were performed with heterozygous and homozygous mutant mice. Quantitative RT-PCR quantified TNF∝, IL-6, IL-1β, F4/80, GPR43, and CD36 expression in muscle, fat, and liver. Histological analysis measured hepatosteatosis.RESULTSHomozygous mutants were glucose tolerant and protected against overall insulin resistance compared with heterozygous mice. Hyperinsulinemic-euglycemic clamp studies revealed a dramatically improved glucose infusion rate, glucose disposal rate, and hepatic glucose production in 11-month-old MstnLn/Ln mice on an HFD. Improvements to muscle and liver insulin sensitivity (∼200–400%) correlated with 50–75% decreased tumor necrosis factor (TNF)α production and coincided with severe Mstn deficiency. Hepatosteatosis appeared to be ameliorated. Short-term treatment of MstnLn/Ln mice with recombinant Mstn led to increased plasma TNFα and insulin resistance.CONCLUSIONSWe find that severe Mstn deficiency caused by Ln (lean) mutations in HFD-fed mice protects muscle and liver against obesity-induced insulin resistance.
Activation of Insulin-Reactive CD8 T-Cells for Development of Autoimmune Diabetes
Authors: Wong F. Susan , Khai Siew Lai , Scott Gwen , Thomas Ian J. , Chapman Stephen , Viret Christophe , Wen Li 
Published: February 2009

OBJECTIVEWe have previously reported a highly diabetogenic CD8 T-cell clone, G9C8, in the nonobese diabetic (NOD) mouse, specific to low-avidity insulin peptide B15-23, and cells responsive to this antigen are among the earliest islet infiltrates. We aimed to study the selection, activation, and development of the diabetogenic capacity of these insulin-reactive T-cells.RESEARCH DESIGN AND METHODSWe generated a T-cell receptor (TCR) transgenic mouse expressing the cloned TCR Vα18/Vβ6 receptor of the G9C8 insulin-reactive CD8 T-cell clone. The mice were crossed to TCRCα−/− mice so that the majority of the T-cells expressed the clonotypic TCR, and the phenotype and function of the cells was investigated.RESULTSThere was good selection of CD8 T-cells with a predominance of CD8 single-positive thymocytes, in spite of thymic insulin expression. Peripheral lymph node T-cells had a naïve phenotype (CD44lo, CD62Lhi) and proliferated to insulin B15-23 peptide and to insulin. These cells produced interferon-γ and tumor necrosis factor-α in response to insulin peptide and were cytotoxic to insulin peptide–coated targets. In vivo, the TCR transgenic mice developed insulitis but not spontaneous diabetes. However, the mice developed diabetes on immunization, and the activated transgenic T-cells were able to transfer diabetes to immunodeficient NOD.scid mice.CONCLUSIONSAutoimmune CD8 T-cells responding to a low-affinity insulin B-chain peptide escape from thymic negative selection and require activation in vivo to cause diabetes.
Mechanisms of Podocyte Injury in Diabetes
Authors: Eid Assaad A. , Gorin Yves , Fagg Bridget M. , Maalouf Rita , Barnes Jeffrey L. , Block Karen , Abboud Hanna E. 
Published: February 2009

OBJECTIVE
We investigated the role of cytochrome P450 of the 4A family (CYP4A), its metabolites, and NADPH oxidases both in reactive oxygen species (ROS) production and apoptosis of podocytes exposed to high glucose and in OVE26 mice, a model of type 1 diabetes.

RESEARCH DESIGN AND METHODS
Apoptosis, albuminuria, ROS generation, NADPH superoxide generation, CYP4A and Nox protein expression, and mRNA levels were measured in vitro and in vivo.

RESULTS
Exposure of mouse podocytes to high glucose resulted in apoptosis, with approximately one-third of the cells being apoptotic by 72 h. High-glucose treatment increased ROS generation and was associated with sequential upregulation of CYP4A and an increase in 20-hydroxyeicosatetraenoic acid (20-HETE) and Nox oxidases. This is consistent with the observation of delayed induction of NADPH oxidase activity by high glucose. The effects of high glucose on NADPH oxidase activity, Nox proteins and mRNA expression, and apoptosis were blocked by N-hydroxy-N′-(4-butyl-2-methylphenol) formamidine (HET0016), an inhibitor of CYP4A, and were mimicked by 20-HETE. CYP4A and Nox oxidase expression was upregulated in glomeruli of type 1 diabetic OVE26 mice. Treatment of OVE26 mice with HET0016 decreased NADPH oxidase activity and Nox1 and Nox4 protein expression and ameliorated apoptosis and albuminuria.

CONCLUSIONS
Generation of ROS by CYP4A monooxygenases, 20-HETE, and Nox oxidases is involved in podocyte apoptosis in vitro and in vivo. Inhibition of selected cytochrome P450 isoforms prevented podocyte apoptosis and reduced proteinuria in diabetes.
Hyperglycemia Induces a Dynamic Cooperativity of Histone Methylase and Demethylase Enzymes Associated With Gene-Activating Epigenetic Marks That Coexist on the Lysine Tail
Authors: Brasacchio Daniella , Okabe Jun , Tikellis Christos , Balcerczyk Aneta , George Prince , Baker Emma K. , Calkin Anna C. , Brownlee Michael , Cooper Mark E. , El-Osta Assam 
Published: February 2009

OBJECTIVE
Results from the Diabetes Control Complications Trial (DCCT) and the subsequent Epidemiology of Diabetes Interventions and Complications (EDIC) Study and more recently from the U.K. Prospective Diabetes Study (UKPDS) have revealed that the deleterious end-organ effects that occurred in both conventional and more aggressively treated subjects continued to operate &gt;5 years after the patients had returned to usual glycemic control and is interpreted as a legacy of past glycemia known as “hyperglycemic memory.” We have hypothesized that transient hyperglycemia mediates persistent gene-activating events attributed to changes in epigenetic information.

RESEARCH DESIGN AND METHODS
Models of transient hyperglycemia were used to link NFκB-p65 gene expression with H3K4 and H3K9 modifications mediated by the histone methyltransferases (Set7 and SuV39h1) and the lysine-specific demethylase (LSD1) by the immunopurification of soluble NFκB-p65 chromatin.

RESULTS
The sustained upregulation of the NFκB-p65 gene as a result of ambient or prior hyperglycemia was associated with increased H3K4m1 but not H3K4m2 or H3K4m3. Furthermore, glucose was shown to have other epigenetic effects, including the suppression of H3K9m2 and H3K9m3 methylation on the p65 promoter. Finally, there was increased recruitment of the recently identified histone demethylase LSD1 to the p65 promoter as a result of prior hyperglycemia.

CONCLUSIONS
These studies indicate that the active transcriptional state of the NFκB-p65 gene is linked with persisting epigenetic marks such as enhanced H3K4 and reduced H3K9 methylation, which appear to occur as a result of effects of the methyl-writing and methyl-erasing histone enzymes.
Muscle Microvascular Dysfunction in Central Obesity Is Related to Muscle Insulin Insensitivity but Is Not Reversed by High-Dose Statin Treatment
Authors: Clough Geraldine F. , Turzyniecka Magdalena , Walter Lara , Krentz Andrew J. , Wild Sarah H. , Chipperfield Andrew J. , Gamble John , Byrne Christopher D. 
Published: February 2009

OBJECTIVE
To test the hypotheses that decreased insulin-mediated glucose disposal in muscle is associated with a reduced muscle microvascular exchange capacity (Kf) and that 6 months of high-dose statin therapy would improve microvascular function in people with central obesity.

RESEARCH DESIGN AND METHODS
We assessed skeletal muscle microvascular function, visceral fat mass, physical activity levels, fitness, and insulin sensitivity in skeletal muscle in 22 female and 17 male volunteers with central obesity whose age (mean ± SD) was 51 ± 9 years. We tested the effect of atorvastatin (40 mg daily) on muscle microvascular function in a randomized, double-blind, placebo-controlled trial lasting 6 months.

RESULTS
K f was negatively associated with a measure of glycemia (A1C; r = −0.44, P = 0.006) and positively associated with insulin sensitivity (the ratio of insulin-stimulated glucose effectiveness, or M value, to the mean insulin concentration, or I value; r = 0.39, P = 0.02). In regression modeling, A1C, visceral fat mass, and M:I explained 38% of the variance in Kf (in a linear regression model with Kf as the outcome [R2 = 0.38, P = 0.005]). M:I was associated with Kf independently of visceral fat mass (B coefficient 3.13 [95% CI 0.22–6.02], P = 0.036). Although 6 months' treatment with atorvastatin decreased LDL cholesterol by 51% (P &lt; 0.001) and plasma high-sensitivity C-reactive protein by 75% (P = 0.02), microvascular function was unchanged.

CONCLUSIONS
Decreased insulin-mediated glucose uptake in skeletal muscle is associated with impaired muscle microvascular exchange capacity (Kf), independently of visceral fat mass. Muscle microvascular function is not improved by 6 months of high-dose statin treatment, despite marked statin-mediated improvements in lipid metabolism and decreased inflammation.