bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective and uncoupled role of substrate elasticity in the regulation of replication and transcription in epithelial cells
Authors: Kocgozlu Leyla , Lavalle Philippe , Koenig Géraldine , Senger Bernard , Haikel Youssef , Schaaf Pierre , Voegel Jean-Claude , Tenenbaum Henri , Vautier Dominique
Published: December 2009

Actin cytoskeleton forms a physical connection between the extracellular matrix, adhesion complexes and nuclear architecture. Because tissue stiffness plays key roles in adhesion and cytoskeletal organization, an important open question concerns the influence of substrate elasticity on replication and transcription. To answer this major question, polyelectrolyte multilayer films were used as substrate models with apparent elastic moduli ranging from 0 to 500 kPa. The sequential relationship between Rac1, vinculin adhesion assembly, and replication becomes efficient at above 200 kPa because activation of Rac1 leads to vinculin assembly, actin fiber formation and, subsequently, to initiation of replication. An optimal window of elasticity (200 kPa) is required for activation of focal adhesion kinase through auto-phosphorylation of tyrosine 397. Transcription, including nuclear recruitment of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), occurred above 50 kPa. Actin fiber and focal adhesion signaling are not required for transcription. Above 50 kPa, transcription was correlated with αv-integrin engagement together with histone H3 hyperacetylation and chromatin decondensation, allowing little cell spreading. By contrast, soft substrate (below 50 kPa) promoted morphological changes characteristic of apoptosis, including cell rounding, nucleus condensation, loss of focal adhesions and exposure of phosphatidylserine at the outer cell surface. On the basis of our data, we propose a selective and uncoupled contribution from the substrate elasticity to the regulation of replication and transcription activities for an epithelial cell model.
The intersections betweenO-GlcNAcylation and phosphorylation: implications for multiple signaling pathways
Authors: Zeidan Quira , Hart Gerald W.
Published: December 2009

A paradigm-changing discovery in biology came about when it was found that nuclear and cytosolic proteins could be dynamically glycosylated with a single O-linked β-N-acetylglucosamine (O-GlcNAc) moiety. O-GlcNAcylation is akin to phosphorylation: it occurs on serine and/or threonine side chains of proteins, and cycles rapidly upon cellular activation. O-GlcNAc and phosphate show a complex interplay: they can either competitively occupy a single site or proximal sites, or noncompetitively occupy different sites on a substrate. Phosphorylation regulates O-GlcNAc-cycling enzymes and, conversely, O-GlcNAcylation controls phosphate-cycling enzymes. Such crosstalk is evident in all compartments of the cell, a finding that is congruent with the fundamental role of O-GlcNAc in regulating nutrient- and stress-induced signal transduction. O-GlcNAc transferase is recruited to the plasma membrane in response to insulin and is targeted to substrates by forming transient holoenzyme complexes that have different specificities. Cytosolic O-GlcNAcylation is important for the proper transduction of signaling cascades such as the NFκB pathway, whereas nuclear O-GlcNAc is crucial for regulating the activity of numerous transcription factors. This Commentary focuses on recent findings supporting an emerging concept that continuous crosstalk between phosphorylation and O-GlcNAcylation is essential for the control of vital cellular processes and for understanding the mechanisms that underlie certain neuropathologies.
Integral membrane proteins Brr6 and Apq12 link assembly of the nuclear pore complex to lipid homeostasis in the endoplasmic reticulum
Authors: Hodge Christine A. , Choudhary Vineet , Wolyniak Michael J. , Scarcelli John J. , Schneiter Roger , Cole Charles N.
Published: December 2009

Cells of Saccharomyces cerevisiae lacking Apq12, a nuclear envelope (NE)-endoplasmic reticulum (ER) integral membrane protein, are defective in assembly of nuclear pore complexes (NPCs), possibly because of defects in regulating membrane fluidity. We identified BRR6, which encodes an essential integral membrane protein of the NE-ER, as a dosage suppressor of apq12 Δ. Cells carrying the temperature-sensitive brr6-1 allele have been shown to have defects in nucleoporin localization, mRNA metabolism and nuclear transport. Electron microscopy revealed that brr6-1 cells have gross NE abnormalities and proliferation of the ER. brr6-1 cells were hypersensitive to compounds that affect membrane biophysical properties and to inhibitors of lipid biosynthetic pathways, and displayed strong genetic interactions with genes encoding non-essential lipid biosynthetic enzymes. Strikingly, brr6-1 cells accumulated, in or near the NE, elevated levels of the two classes of neutral lipids, steryl esters and triacylglycerols, and over-accumulated sterols when they were provided exogenously. Although neutral lipid synthesis is dispensable in wild-type cells, viability of brr6-1 cells was fully dependent on neutral lipid production. These data indicate that Brr6 has an essential function in regulating lipid homeostasis in the NE-ER, thereby impacting NPC formation and nucleocytoplasmic transport.
Sonic-hedgehog-mediated proliferation requires the localization of PKA to the cilium base
Authors: Barzi Mercedes , Berenguer Jordi , Menendez Anghara , Alvarez-Rodriguez Ruben , Pons Sebastian
Published: December 2009

Cerebellar granular neuronal precursors (CGNPs) proliferate in response to the mitogenic activity of Sonic hedgehog (Shh), and this proliferation is negatively regulated by activation of cAMP-dependent protein kinase (PKA). In the basal state, the PKA catalytic subunits (C-PKA) are inactive because of their association with the regulatory subunits (R-PKA). As the level of cAMP increases, it binds to R-PKA, displacing and thereby activating the C-PKA. Here we report that, in the presence of Shh, inactive C-PKA accumulates at the cilium base of proliferative CGNPs whereas removal of Shh triggers the activation of PKA at this particular location. Furthermore, we demonstrate that the anchoring of the PKA holoenzyme to the cilium base is mediated by the specific binding of the type II PKA regulatory subunit (RII-PKA) to the A-kinase anchoring proteins (AKAPs). Disruption of the interaction between RII-PKA and AKAPs inhibits Shh activity and, therefore, blocks proliferation of CGNP cultures. Collectively, these results demonstrate that the pool of PKA localized to the cilium base of CGNP plays an essential role in the integration of Shh signal transduction.
Direct demonstration of discrete Ca2+ microdomains associated with different isoforms of adenylyl cyclase
Authors: Willoughby Debbie , Wachten Sebastian , Masada Nanako , Cooper Dermot M. F.
Published: December 2009

Ca2+-sensitive adenylyl cyclases (ACs) orchestrate dynamic interplay between Ca2+ and cAMP that is a crucial feature of cellular homeostasis. Significantly, these ACs are highly selective for capacitative Ca2+ entry (CCE) over other modes of Ca2+ increase. To directly address the possibility that these ACs reside in discrete Ca2+ microdomains, we tethered a Ca2+ sensor, GCaMP2, to the N-terminus of Ca2+-stimulated AC8. GCaMP2-AC8 measurements were compared with global, plasma membrane (PM)-targeted or Ca2+-insensitive AC2-targeted GCaMP2. In intact cells, GCaMP2-AC8 responded rapidly to CCE, but was largely unresponsive to other types of Ca2+ rise. The global GCaMP2, PM-targeted GCaMP2 and GCaMP2-AC2 sensors reported large Ca2+ fluxes during Ca2+ mobilization and non-specific Ca2+ entry, but were less responsive to CCE than GCaMP2-AC8. Our data reveal that different AC isoforms localize to distinct Ca2+-microdomains within the plasma membrane. AC2, which is regulated via protein kinase C, resides in a microdomain that is exposed to a range of widespread Ca2+ signals seen throughout the cytosol. By contrast, a unique Ca2+ microdomain surrounds AC8 that promotes selectivity for Ca2+ signals arising from CCE, and optimizes CCE-mediated cAMP synthesis. This direct demonstration of discrete compartmentalized Ca2+ signals associated with specific signalling proteins provides a remarkable insight into the functional organization of signalling microdomains.
Cyclosporine Versus Tacrolimus in Immunosuppressive Maintenance Regimens in Renal Transplants in Brazil: Survival Analysis from 2000 to 2004
Authors: Guerra Augusto Afonso , Cesar Cibele Comini , Cherchiglia Mariângela Leal , Andrade Eli lola Gurgel , de Queiroz Odilon Vanni , Silva Grazielle D , de Assis Acurcio Francisco
Published: December 2009

BACKGROUND

In Brazil, the National Health System (SUS) is responsible for almost all renal transplants. SUS protocols recommend using cyclosporine, in association with azathioprine and corticosteroids, to maintain the immunosuppression that is essential for successful renal transplant. Alternatively, cyclosporine can be replaced by tacrolimus.

OBJECTIVE

To evaluate the effectiveness of therapeutic schema involving cyclosporine or tacrolimus after renal transplant during a 60-month follow-up period.

METHODS

A historical cohort study, from 2000 to 2004, was conducted using 5686 patients who underwent renal transplant and received cyclosporine or tacrolimus. Uni - and multivariate analyses were performed using the Cox model to examine factors associated with progression to treatment failure.

RESULTS

Most of the patients were male, aged 38 years or older, for whom the most frequent primary diagnosis of chronic renal failure (CRF) was glomerulonephritis/nephritis. Higher risk of treatment failure was associated with: therapeutic regimen (tacrolimus, HR 1.38, 95% CI 1.14 to 1.67), patient age at transplantation (additional year, HR 1.01, 95% CI 1.00 to 1.02), donor type (deceased, HR 1.60, 95% CI 1.35 to 1.89), median time of dialysis prior to transplantation (>24 mo, HR 1.29, 95% CI 1.09 to 1.52), and primary CRF diagnosis (diabetes, HR 1.54, 95% CI 1.09 to 2.17).

CONCLUSIONS

The risk of treatment failure of patients receiving tacrolimus was observed to be 1.38 times that of those receiving cyclosporine, after adjusting the model for possible confounding factors such as patient sex, patient age, graft origin, prior time of dialysis, and cause of CRF. Our results were obtained from an observational study, and further studies are necessary to evaluate whether compliance with SUS clinical protocols could result in more effective care for renal transplant recipients.
Cooperative and Competitive Interactions Facilitate Stereo Computations in Macaque Primary Visual Cortex
Authors: Samonds Jason M. , Potetz Brian R. , Lee Tai Sing
Published: December 2009

Inferring depth from binocular disparities is a difficult problem for the visual system because local features in the left- and right-eye images must be matched correctly to solve this “stereo correspondence problem.” Cortical architecture and computational studies suggest that lateral interactions among neurons could help resolve local uncertainty about disparity encoded in individual neurons by incorporating contextual constraints. We found that correlated activity among pairs of neurons in primary visual cortex depended both on disparity-tuning relationships and the stimuli displayed within the receptive fields of the neurons. Nearby pairs of neurons with distinct disparity tuning exhibited a decrease in spike correlation at competing disparities soon after response onset. Distant neuronal pairs of similar disparity tuning exhibited an increase in spike correlation at mutually preferred disparities. The observed correlated activity and response dynamics suggests that local competitive and distant cooperative interactions improve disparity tuning of individual neurons over time. Such interactions could represent a neural substrate for the principal constraints underlying cooperative stereo algorithms.
Endolymphatic Sodium Homeostasis by Extramacular Epithelium of the Saccule
Authors: Kim Sung Huhn , Marcus Daniel C.
Published: December 2009

The saccule is a vestibular sensory organ that depends upon regulation of its luminal fluid, endolymph, for normal transduction of linear acceleration into afferent neural transmission. Previous studies suggested that endolymph in the saccule was merely derived from cochlear endolymph. We developed and used a preparation of isolated mouse saccule to measure transepithelial currents from the extramacular epithelium with a current density probe. The direction and pharmacology of transepithelial current was consistent with Na+absorption by the epithelial Na+channel (ENaC) and was blocked by the ENaC-specific inhibitors benzamil and amiloride. Involvement of Na+,K+-ATPase and K+channels was demonstrated by reduction of the current by ouabain and the K+channel blockers Ba2+, XE991, and 4-AP. Glucocorticoids upregulated the current via glucocorticoid receptors. Dexamethasone stimulated the current after 24 h and the stimulation was blocked by mifepristone but not spironolactone. No acute response was observed to elevated cAMP in the presence of amiloride nor to bumetanide, a blocker of Na+,K+,2Cl−cotransporter. The results are consistent with a canonical model of corticosteroid-regulated Na+absorption that includes entry of luminal Na+through apical membrane Na+channels and active basolateral exit of Na+via a Na+pump, with recycling of K+at the basolateral membrane via K+-permeable channels. These observations provide our first understanding of the active role played by saccular epithelium in the local regulation of the [Na+] of endolymph for maintenance of our sense of balance.
Sustained Morphine-Induced Sensitization and Loss of Diffuse Noxious Inhibitory Controls in Dura-Sensitive Medullary Dorsal Horn Neurons
Authors: Okada-Ogawa Akiko , Porreca Frank , Meng Ian D.
Published: December 2009

Overuse of medications used to treat migraine headache can produce a chronic daily headache, termed medication overuse headache (MOH). Although “overuse” of opioids, triptans, and over-the-counter analgesics can all produce MOH, the neuronal mechanisms remain unknown. Headache pain is likely to be produced by stimulation of primary afferent neurons that innervate the intracranial vasculature and the resulting activation of medullary dorsal horn (MDH) neurons. The present study compared the receptive field properties of MDH dura-sensitive neurons in rats treated with morphine to those given vehicle. Animals were implanted with osmotic minipumps or pellets for sustained subcutaneous administration of morphine or vehicle 6–7 d before recording from dura-sensitive neurons. Electrical and mechanical activation thresholds from the dura were significantly lower in chronic morphine-treated animals when compared to vehicle controls. In addition, sustained morphine increased the cutaneous receptive field sizes. The presence of diffuse noxious inhibitory controls (DNICs) was examined by placing the tail in 55°C water during concomitant noxious thermal stimulation of the cutaneous receptive field, usually located in the ophthalmic region. The DNIC stimulus produced significant inhibition of heat-evoked activity in vehicle- but not chronic morphine-treated animals. Inactivation of the rostral ventromedial medulla with 4% lidocaine reinstated DNICs in chronic morphine-treated animals. These results are consistent with studies demonstrating a loss of DNICs in patients that suffer from chronic daily headache and may partially explain why overuse of medication used to treat migraine can induce headaches.
Neuroprotective Role of Haptoglobin after Intracerebral Hemorrhage
Authors: Zhao Xiurong , Song Shen , Sun Guanghua , Strong Roger , Zhang Jie , Grotta James C. , Aronowski Jaroslaw
Published: December 2009

After intracerebral hemorrhage (ICH), the brain parenchyma is exposed to blood containing red blood cells (RBCs) and consequently to its lysis products. Iron-rich hemoglobin (Hb) is the most abundant protein in RBCs. When released into the brain parenchyma during hemolysis, Hb becomes a central mediator of cytotoxicity. Our study indicates that haptoglobin (Hp), an acute-phase response protein primarily synthesized in the liver and known to bind and neutralize Hb in the bloodstream, is also expressed in brain in which it plays an important role in defending neurons from damage induced by hemolytic products after ICH. We demonstrate that the Hb-induced hypohaptoglobinemia aggravates ICH-induced brain damage while pharmacologic intervention with sulforaphane to induce brain Hp is linked to a reduction in brain damage. In agreement with these findings, Hp deficiency worsens whereas Hp overexpression alleviates ICH-mediated brain injury. We also identified that oligodendroglia are the primary source of brain-derived Hp among brain cells and that oligodendroglia-released Hp plays protective roles against Hb-mediated toxicity to neurons and oligodendrocytes. We conclude that Hp, particularly the brain-derived Hp, plays cytoprotective roles and represents a potential therapeutic target for ICH treatment.
Novel Mediators of Amyloid Precursor Protein Signaling
Authors: Swistowski Andrzej , Zhang Qiang , Orcholski Mark E. , Crippen Danielle , Vitelli Cathy , Kurakin Alexei , Bredesen Dale E.
Published: December 2009

Multiple recent reports implicate amyloid precursor protein (APP) signaling in the pathogenesis of Alzheimer's disease, but the APP-dependent signaling network involved has not been defined. Here, we report a novel consensus sequence for interaction with the PDZ-1 and PDZ-2 domains of the APP-interacting proteins Mint1, Mint2, and Mint3 (X11α, X11β, and X11γ), and multiple novel interactors for these proteins, with the finding that transcriptional coactivators are highly represented among these interactors. Furthermore, we show that Mint3 interaction with a set of the transcriptional coactivators leads to nuclear localization and transactivation, whereas interaction of the same set with Mint1 or Mint2 prevents nuclear localization and transactivation. These results define new mediators of the signal transduction network mediated by APP.
GABA Transporter-1 Activity Modulates Hippocampal Theta Oscillation and Theta Burst Stimulation-Induced Long-Term Potentiation
Authors: Gong Neng , Li Yong , Cai Guo-Qiang , Niu Rui-Fang , Fang Qi , Wu Kun , Chen Zhong , Lin Long-Nian , Xu Lin , Fei Jian , Xu Tian-Le
Published: December 2009

The network oscillation and synaptic plasticity are known to be regulated by GABAergic inhibition, but how they are affected by changes in the GABA transporter activity remains unclear. Here we show that in the CA1 region of mouse hippocampus, pharmacological blockade or genetic deletion of GABA transporter-1 (GAT1) specifically impaired long-term potentiation (LTP) induced by theta burst stimulation, but had no effect on LTP induced by high-frequency stimulation or long-term depression induced by low-frequency stimulation. The extent of LTP impairment depended on the precise burst frequency, with significant impairment at 3–7 Hz that correlated with the time course of elevated GABAergic inhibition caused by GAT1 disruption. Furthermore,in vivoelectrophysiological recordings showed that GAT1 gene deletion reduced the frequency of hippocampal theta oscillation. Moreover, behavioral studies showed that GAT1 knock-out mice also exhibited impaired hippocampus-dependent learning and memory. Together, these results have highlighted the important link between GABAergic inhibition and hippocampal theta oscillation, both of which are critical for synaptic plasticity and learning behaviors.
Frontal Feedback-Related Potentials in Nonhuman Primates: Modulation during Learning and under Haloperidol
Authors: Vezoli Julien , Procyk Emmanuel
Published: December 2009

Feedback monitoring and adaptation of performance involve a medial reward system including medial frontal cortical areas, the medial striatum, and the dopaminergic system. A considerable amount of data has been obtained on frontal surface feedback-related potentials (FRPs) in humans and on the correlate of outcome monitoring with single unit activity in monkeys. However, work is needed to bridge knowledge obtained in the two species. The present work describes FRPs in monkeys, using chronic recordings, during a trial and error task. We show that frontal FRPs are differentially sensitive to successes and failures and can be observed over long-term periods. In addition, using the dopamine antagonist haloperidol we observe a selective effect on FRP amplitude that is absent for pure sensory-related potentials. These results describe frontal dopaminergic-dependent FRPs in monkeys and corroborate a human-monkey homology for performance monitoring signals.
Augmentation of Antioxidant Defense System by Tinospora cordifolia: Implications in Radiation Protection
Authors: Tyagi Sonia , Singh Lakshman , Devi Mayamglambam Memita , Goel Harish Chandra , Rizvi Moshahid Alam
Published: December 2009

Objective: In this study, the antioxidant and radioprotective efficacy of a semi-purified aqua-alcoholic extract of T. cordifolia (RTp) was evaluated in the murine model system.Methods: Free radical scavenging ability was evaluated in chemical system. Radioprotective efficacy of RTp was then evaluated at in vivo level in terms of survival and dose reduction factor. The effect of RTp administration on endogenous defense system in irradiated mice was evaluated in small intestine.Results: RTp contained 47.5 ± 1.09 mg gallic acid equivalent polyphenols and 17.45 ± 1.89 µg quercetin equivalent flavonoids per gram of extract. RTp scavenged both Fenton reaction (IC50 0.48 mg/ml) and radiation generated (IC50 0.50 mg/ml) hydroxyl radicals; superoxide anions (IC50 0.49 mg/ml) and DPPH radicals (IC500.67 mg/ml). RTp (250 mg/kg body weight, i.p., -1 h) rendered 83.3% survival in lethally irradiated mice (DRF = 1.43). It accelerated recovery of radiation-induced decrease in body weight of mice. RTp administration on one hand improved the endogenous defense system by augmenting levels of total thiols, superoxide dismutase (SOD) and catalase and concomitantly decreased lipid peroxidation in mouse small intestine.Conclusion: These results imply that RTp treatment augmented antioxidant defense system which afforded an important mechanism of radioprotection. The bio-molecules present in RTp acting in this direction need to be investigated further.
An approach to fuzzy database querying, analysis and realization
Authors: Hudec Miroslav
Published: December 2009

Although the Structured Query Language (SQL) is a very powerful tool, it is unable to satisfy needs for data selection based on linguistic expressions and degrees of truth. The goal of the research whose results are presented in the paper is to capture these expressions and make them suitable for queries. For this purpose the fuzzy generalized logical condition for the WHERE part of SQL was developed. In this way, queries based on linguistic expressions are supported and are accessing relational databases in the same way as with the SQL. Fuzzy query is not only a querying tool; it improves the meaning of a query and extracts additional valuable information. Statistical data about districts of the Slovak Republic are used in the case study. Fuzzy approach has some limitations that would appear in a querying process. These limitations and ideas how to solve them are outlined in this paper.
Microarray missing values imputation methods: Critical analysis review
Authors: Hourani Mou'ath , El Emary
Published: December 2009

Gene expression data often contain missing expression values. For the purpose of conducting an effective clustering analysis and since many algorithms for gene expression data analysis require a complete matrix of gene array values, choosing the most effective missing value estimation method is necessary. In this paper, the most commonly used imputation methods from literature are critically reviewed and analyzed to explain the proper use, weakness and point the observations on each published method. From the conducted analysis, we conclude that the Local Least Square (LLS) and Support Vector Regression (SVR) algorithms have achieved the best performances. SVR can be considered as a complement algorithm for LLS especially when applied to noisy data. However, both algorithms suffer from some deficiencies presented in choosing the value of Number of Selected Genes (K) and the appropriate kernel function. To overcome these drawbacks, the need for new method that automatically chooses the parameters of the function and it also has an appropriate computational complexity is imperative.
Applications GeoGebra into teaching some topics of mathematics at the college level
Authors: Dikovic Ljubica
Published: December 2009

This paper presents new trends in technology and learning through GeoGebra, which could be especially important for the future development of e-learning for College mathematics. Also, contribution of this paper is presentation of methodological frames on several specifics examples for teaching mathematics at the college level on interactive and creative way. Discussed in this paper are the findings of a didactic experiment where some number of undergraduate students were exposed to an innovative (to the departments) method of teaching and learning a part of calculus supported by GeoGebra. Statistical analysis confirmed the fact that the use of the applets created with the help of GeoGebra and used in differential calculus teaching had a positive effect on the understanding and knowledge of the students.
Effect of Rimonabant on Glycemic Control in Insulin-Treated Type 2 Diabetes: The ARPEGGIO Trial
Authors: Hollander Priscilla A. , Amod Aslam , Litwak León E. , Chaudhari Umesh ,   for the ARPEGGIO Study Group
Published: December 2009

OBJECTIVE

To examine the efficacy and safety of rimonabant, a selective cannabinoid receptor type-1 antagonist, in patients with type 2 diabetes receiving insulin monotherapy.

RESEARCH DESIGN AND METHODS

Patients (n = 368; A1C ≥7%) were randomized to 20 mg/day rimonabant or placebo in this 48-week, double-blind, placebo-controlled multicenter trial. Change in baseline A1C to week 48 (primary outcome) and changes in body weight, waist circumference, and lipid levels (secondary outcomes) were assessed.

RESULTS

Rimonabant significantly reduced baseline A1C versus placebo (−0.89 vs. −0.24%; P < 0.0001), and significantly greater improvements were observed in cardiometabolic risk factors. More rimonabant patients achieved >10% reduction in mean total daily insulin dose versus placebo (P = 0.0012), and fewer required rescue medication (P < 0.0001). Hypoglycemia, nausea, dizziness, anxiety, and depression were more frequent with rimonabant.

CONCLUSIONS

Rimonabant improved glycemic control and cardiometabolic risk factors in patients with type 2 diabetes receiving insulin.
Patient Race/Ethnicity and Patient-Physician Race/Ethnicity Concordance in the Management of Cardiovascular Disease Risk Factors for Patients With Diabetes
Authors: Traylor Ana H. , Subramanian Usha , Uratsu Connie S. , Mangione Carol M. , Selby Joe V. , Schmittdiel Julie A.
Published: December 2009

OBJECTIVE

Patient-physician race/ethnicity concordance can improve care for minority patients. However, its effect on cardiovascular disease (CVD) care and prevention is unknown. We examined associations of patient race/ethnicity and patient-physician race/ethnicity concordance on CVD risk factor levels and appropriate modification of treatment in response to high risk factor values (treatment intensification) in a large cohort of diabetic patients.

RESEARCH DESIGN AND METHODS

The study population included 108,555 adult diabetic patients in Kaiser Permanente Northern California in 2005. Probit models assessed the effect of patient race/ethnicity on risk factor control and treatment intensification after adjusting for patient and physician-level characteristics.

RESULTS

African American patients were less likely than whites to have A1C <8.0% (64 vs. 69%, P < 0.0001), LDL cholesterol <100 mg/dl (40 vs. 47%, P < 0.0001), and systolic blood pressure (SBP) <140 mmHg (70 vs. 78%, P < 0.0001). Hispanic patients were less likely than whites to have A1C <8% (62 vs. 69%, P < 0.0001). African American patients were less likely than whites to have A1C treatment intensification (73 vs. 77%, P < 0.0001; odds ratio [OR] 0.8 [95% CI 0.7–0.9]) but more likely to receive treatment intensification for SBP (78 vs. 71%, P < 0.0001; 1.5 [1.3–1.7]). Hispanic patients were more likely to have LDL cholesterol treatment intensification (47 vs. 45%, P < 0.05; 1.1 [1.0–1.2]). Patient-physician race/ethnicity concordance was not significantly associated with risk factor control or treatment intensification.

CONCLUSIONS

Patient race/ethnicity is associated with risk factor control and treatment intensification, but patient-physician race/ethnicity concordance was not. Further research should investigate other potential drivers of disparities in CVD care.
Rapid Identification of Myocardial Infarction Risk Associated With Diabetes Medications Using Electronic Medical Records
Authors: Brownstein John S. , Murphy Shawn N. , Goldfine Allison B. , Grant Richard W. , Sordo Margarita , Gainer Vivian , Colecchi Judith A. , Dubey Anil , Nathan David M. , Glaser John P. , Kohane Isaac S.
Published: December 2009

OBJECTIVE

To assess the ability to identify potential association(s) of diabetes medications with myocardial infarction using usual care clinical data obtained from the electronic medical record.

RESEARCH DESIGN AND METHODS

We defined a retrospective cohort of patients (n = 34,253) treated with a sulfonylurea, metformin, rosiglitazone, or pioglitazone in a single academic health care network. All patients were aged >18 years with at least one prescription for one of the medications between 1 January 2000 and 31 December 2006. The study outcome was acute myocardial infarction requiring hospitalization. We used a cumulative temporal approach to ascertain the calendar date for earliest identifiable risk associated with rosiglitazone compared with that for other therapies.

RESULTS

Sulfonylurea, metformin, rosiglitazone, or pioglitazone therapy was prescribed for 11,200, 12,490, 1,879, and 806 patients, respectively. A total of 1,343 myocardial infarctions were identified. After adjustment for potential myocardial infarction risk factors, the relative risk for myocardial infarction with rosiglitazone was 1.3 (95% CI 1.1–1.6) compared with sulfonylurea, 2.2 (1.6–3.1) compared with metformin, and 2.2 (1.5–3.4) compared with pioglitazone. Prospective surveillance using these data would have identified increased risk for myocardial infarction with rosiglitazone compared with metformin within 18 months of its introduction with a risk ratio of 2.1 (95% CI 1.2–3.8).

CONCLUSIONS

Our results are consistent with a relative adverse cardiovascular risk profile for rosiglitazone. Our use of usual care electronic data sources from a large hospital network represents an innovative approach to rapid safety signal detection that may enable more effective postmarketing drug surveillance.
Carboxylation of Osteocalcin Affects Its Association With Metabolic Parameters in Healthy Children
Authors: Prats-Puig Anna , Mas-Parareda Marta , Riera-Pérez Elena , González-Forcadell Dolors , Mier Concepció , Mallol-Guisset Montserrat , Díaz Marta , Bassols Judit , de Zegher Francis , Ibáñez Lourdes , López-Bermejo Abel
Published: December 2009

OBJECTIVE

Osteocalcin (OC), a bone-derived protein, was recently shown to regulate metabolic pathways in mice. Undercarboxylated OC (ucOC), but not carboxylated OC (cOC), increases adiponectin and insulin secretion. It is unclear if carboxylation of OC affects its association with metabolic parameters in humans.

RESEARCH DESIGN AND METHODS

The associations between ucOC, cOC, total and high-molecular-weight (HMW) adiponectin, and insulin secretion (homeostasis model assessment [HOMA]-β) were investigated in a population-based sample of healthy prepubertal children (n = 103; 49 boys and 54 girls).

RESULTS

Weight-dependent associations were observed between the different forms of OC and metabolic parameters. Higher cOC was related to lower HMW adiponectin (with a stronger association in leaner children; P < 0.001). Higher ucOC-to-cOC ratio was associated with higher HOMA-β (P < 0.01) in leaner children and associated with higher HMW adiponectin (P < 0.001) in heavier children.

CONCLUSIONS

In a weight-dependent manner, cOC and the proportion of ucOC are differentially related to HMW adiponectin and insulin secretion in healthy children.
Approximation and asymptotics of eigenvalues of unbounded self-adjoint Jacobi matrices acting in l
2 by the use of finite submatrices
Authors: Malejki Maria
Published: December 2009

We consider the problem of approximation of eigenvalues of a self-adjoint operator J defined by a Jacobi matrix in the Hilbert space l
2(ℕ) by eigenvalues of principal finite submatrices of an infinite Jacobi matrix that defines this operator. We assume the operator J is bounded from below with compact resolvent. In our research we estimate the asymptotics (with n → ∞) of the joint error of approximation for the eigenvalues, numbered from 1 to N; of J by the eigenvalues of the finite submatrix J
n of order n × n; where N = max{k ∈ ℕ: k ≤ rn} and r ∈ (0; 1) is arbitrary chosen. We apply this result to obtain an asymptotics for the eigenvalues of J. The method applied in this research is based on Volkmer’s results included in [23].
Reactivity of ω-hydroxyalkylphosphinic Anilides in Cyclisation by Intramolecular Displacement of the Aniline Moiety
Authors: Collison Shaun , Harger Martin J. P.
Published: December 2009

A cyclic phosphinate 2 is formed when HO(CH2) n+3P(O)(NHPh)Ph ( n = 0 or 1) is treated with acid (P–N bond cleavage); five-membered ring formation ( n= 0) is 70 times faster than six in CHCI3 and 50 times faster in MeOH.
On the Correlation between ΔH‡ vs ΔS‡ in the thermal cis-to-trans isomerization of azobenzenes
Authors: Bunce Nigel J. , Forber Christine L.
Published: December 2009

Variable-temperature kinetics allow the determination of Δ H‡ vs Δ S‡ in a single experiment. Multiple variable-temperature data sets for the thermal isomerization of cis-azobenzene show an apparent isokinetic relationship, but this is due only to the mathematical correlation between Δ H‡ vs Δ S‡; the magnitude of the effect is almost identical to that observed for the thermal isomerization of a series of ortho-alkylated azobenzenes.
3-Carboxypyridinium Chlorochromate (CPCC): An Inexpensive and Convenient Reagent for Efficient Oxidation of Hantzsch 1,4-dihydropyridines
Authors: Mohammadpoor-Baltork Iraj , Sadeghi Majid M. M. , Memarian Hamid Reza , Pairow Raihaneh
Published: December 2009

A variety of Hantzsch 1,4-dihydropyridines are oxidized to their corresponding pyridines in excellent yields by 3-carboxypyridinium chlorochromate.
Oligomerization of Acrylic Acid Derivatives by a Reaction with the Alkylcopper(I)-Phosphine Complex
Authors: Mitani Michiharu , Pakjamsai Chitsakon , Tsuchida Teruko , Kudoh Hidekazu
Published: December 2009

Reaction of alkylcopper(I)phosphine complexes with electron-deficient olefins affected preferentially the products based on oligomerization, e.g. the product obtained by sequential conjugated addition, trimerization and cyclization from methyl methacrylate and the dimerization product from butyl acrylate.
A Facile and Efficient Method for Synthesis of the Aryloxyimidoyl Azides
Authors: Dabbagh Abdoul Hossein , Modarresi-Alam Ali Reza
Published: December 2009

A facile and efficient synthesis is introduced for the new aryloxyimidoyl azides in a quantitative yield.
Enaminonitriles in Heterocyclic Synthesis: New Routes for the Synthesis of Some Novel Azolo[1,5-a]pyrimidine, Pyrimido[1,2-a]benzimidazole, Pyrido[1,2-a]benimdazole, Pyrazolo[3,4-b]pyridine, Pyrazole and Pyrimidine Derivatives
Authors: Al-Zaydi Khadijah Mohamed , Al-Shiekh Mariam Abd Alha , Hafez Ebtisam Abdel-Aziz
Published: December 2009

The synthesis of several new azolo[1,5- a]pyrimidines, pyrimido[1,2- a]benzimidazoles, pyrazolo[3,4- b]pyridines, pyrido[1,2- a]benzimidazoles, pyrazoles and pyrimidines is reported.
Cryptolide, a New Brassinolide Catabolite with a 23-oxo group from Japanese cedar pollen/anther and its synthesis
Authors: Watanabe Tsuyoshi , Yokota Takao , Shibata Kyomi , Nomura Takahito , Seto Hideharu , Takatsuto Suguru
Published: December 2009

Based on the GC-MS direct comparison with synthetic candidates, a new brassinolide-related steroidal lactone detected in the pollen and anthers of Japanese cedar (Cryptomeria japonica) was identified as (22 R,24 S)-2α, 3α, 22-trihydroxy-24-methyl- B-homo-7-oxa-5α-cholestan-6,23-dione, being the first brassinolide catabolite with 23-oxo function in the side chain and termed as cryptolide, and furthermore, the first occurrence of 28-homobrassinolide in plants was also demonstrated by this work.
Hypervalent Iodine in Synthesis 67: A Convenient Method for the Synthesis of Diaryl Sulfones by Palladium-catalysed Arylation of Sodium Arenesulfinates with Diaryliodonium Salts
Authors: Zhou Tao , Chen Zhen-Chu
Published: December 2009

In the presence of Ph(PPh3)4, diaryliodonium salts react with sodium arenesulfinates to produce diaryl sulfones in reasonable yields under mild reaction conditions.
Synthesis of new benzo-fused macrocycle diamides
Authors: Girgis Adel S. , Abbas Ashraf A.
Published: December 2009

A facile synthetic approach was adopted towards the synthesis of 26–28 membered benzo-fused macrocycle diamides 6a–d via the base-catalyzed condensation reaction of 2,2′-[alkylbis(oxy)]bisbenzaldehydes 5 with bis-cyanoacetanilides 2 which had been obtained by the reaction of cyanoacetic acid with 2,2′-[alkylbis(oxy)]bisben-zenamines 1.
Reactions with hydrazonoyl halides XXIX: Synthesis of some new 1,2,4-triazolo[4,3-a]benzimidazole, thiazolo[3,2-a]benzimidazole, and unsymmetrical azine derivatives
Authors: Abdelhamid Abdou O. , Metwally Nadia H. , Bishai Nasr S.
Published: December 2009

Triazolo[4,3-a]benzimidazole, thiazolo[3,2-a]benzimidazole, and unsymmetrical azines, were synthesized via reactions of C-thiazol-5-oyl-N-phenylhydrazonoyl bromide with each of 2-(methylthio)benzimidazole, benzimidazoline-2-thione, and alkyl carbodithioate, respectively.
Synthesis of 3,4-bis(fluorenylidene)-5-(4-fluorophenyl-cyanomethylene)tetrahydrofuran-2-one and the X-ray structure of its cyclised form
Authors: Al-Shihry Shar S.
Published: December 2009

The title compound (4) cyclizes photochemically or thermally, via an unexpected [1,7] hydrogen shift, to a new stable adduct (7), the structure of which was confirmed by X-ray crystallographic analysis.
High-yield calix[4]pyrroles as αβαβ isomers and X-ray structure analysis
Authors: Su Xun-Cheng , Zhou Zhi-Fen , Zhu Shou-Rong , Lin Hua-Kuan , Leng Xue-Bing , Weng Lin-Hong , Chen Yun-Ti
Published: December 2009

Two calix[4]pyrroles as aβaβ isomers were prepared by the reactions of pyrrole with asymmetry ketones in high yields. In addition, two single crystals of calix[4]pyrrole 2 and 2·MeOH were solved by X-ray analysis, which further proved that either in free form or inclusion complex calix[4]pyrrole 2 is aβaβ isomer and adopts 1,3-alternate conformation.
Kinetics and mechanism of the reaction of substituted 4-pyrimidine carboxylic acids with diazodiphenylmethane in dimethylformamide
Authors: Jovanović Bratislav , Juranić Ivan , Mišić-Vuković Milica , Brkić Dominik , Vitnik Željko
Published: December 2009

Correlation of the data for the reaction of 11 substituted 4-pyrimidine carboxylic acids with diazodiphenylmethane (DDM) in dimethylformamide (DMF) with calculated atomic charges on the carboxylic group showed that the reaction in this solvent may proceed via a concerted transition state.
Strained Heterocyclic Systems. Part 21.1 the Menschutkin Reaction
Authors: Markgraf J. Hodge , Sangani Poorab K. , Manalansan Ryan J. , Snyder Scott A. , Thummel Randolph P.
Published: December 2009

Rate constants are determined for methyl iodide quaternisations of a series of 2-substituted quinolines and pyridines. Relative rates are interpreted in terms of steric effects, electronic effects and calculated geometries.
Reactions of 1-benzoselenopyrylium salts with nucleophiles: Formation of functionalised selenochromenes1
Authors: Sashida Haruki , Minamida Hiroshi , Yamamoto Kenji
Published: December 2009

Reactions of the stable 1-benzoselenopyrylium salts 1 with several nucleophiles (methoxide ion, isopropoxide ion, tert-butoxide ion, diethylamine and n-butylamine) and also LiAlH4 reduction are described; comparison of the behaviour of 1-benzotelluropyrylium salts is made.
Reactions of a chiral metal cluster containing a functionally substituted cyclopentadienyl ligand with hydrazines
Authors: Zhang Yu-Hua , Yin Yuan-Qi
Published: December 2009

Reaction of hydrazines with SFeCoMo(CO)8[η5-C5H4C(O)CH3] (1), gave four novel cluster hydrazones.
Heteroaromatization with ketene dithioacetals: Part I. Synthesis of some novel 5-amino-1-(1,3,4-thiadiazol-2-yl) and 1-(1,3,4-thiadiazin-2-yl)pyrazole-4-carbonitriles
Authors: Hassan Saber M. , Emam Hussein A. , Abdelall Mahmoud M.
Published: December 2009

5-Amino-3-methylthio-1-(1,3,4-thiadiazol-2-yl) and 1-(1,3,4-thiadiazin-2-yl)pyrazole-4-carbonitriles have been prepared from 5-aminopyrazoles using ketene dithioacetals as starting materials.
A novel and convenient approach to 5-aryltetrahydro-2-furanols
Authors: Selvamurugan V. , Aidhen Indrapal Singh
Published: December 2009

Various aryl and heteroarylterahydrofuranols (2a–h) have been conveniently prepared in good yields by reaction of synthetic equivalents of an acyl anion and a β-electrophilic propionaldehyde.
Synthetic utility of 4-acetyl-3-arylsydnones: Synthesis, spectral characterisation and antimicrobial activity of 3-aryl-4-[(2′,3′-dihydrospiro-1′,4′-benzodiazepine-5′,[3″-3″H]-2″-oxindol]-(1″H))-7′-yl] sydnones
Authors: Kavali Jyoti R. , Badami Bharati V.
Published: December 2009

3-Aryl-4-[3′-hydroxy-2'oxo)-3′-indol]acetylsydnones IIa–n have been synthesised from 4-acetyl-3-arylsdnones Ia–n and isatin. These β-hydroxy derivatives were readily converted into the corresponding α, β-unsaturated ketones IIIa–n which were further condensed with 1,2-phenylenediamine to give the 3-aryl-4-[2′,3′-dihydrospiro-1′,4′-benzodiazepine-5′,3″-[3″H]-2″-oxindol-)1″H))-7′-yl]sydnones IVa–n. All the compounds have been evaluated for their in vitro growth inhibitory activity against few microbes.
Microwave assisted regioselective opening reaction of epoxides with diphenyl diselenides
Authors: Wang Jin-Xian , Xi Yunsheng , Hu Yulai
Published: December 2009

A simple, rapid, preparation of reactive benzeneselenolate ion and its highly regioselective opening reaction with epoxides under microwave irradiation is described. The reaction of diphenyl diselenides with NaBH4/NaOH give phenylselenolate ion which reacts in turn with epoxypropoxyphenols to afford the substituted glycerol selenide ethers in good to excellent isolated yields.
Structural Studies on Bioactive Compounds. Part 31. Interaction of 9-azidoacridine and 1-morpholinocyclohexene: Formation, Decomposition and Rearrangement of the Intermediate 1,2,3-triazoline
Authors: Julino Markus , Lowe Philip R. , Stevens Malcolm F. G.
Published: December 2009

9-Azidoacridine 1 and the cyclic enamine 2 undergo a selective 1,3-dipolar cycloaddition reaction to give the 1,2,3-triazoline 3 with the expected regiochemistry. Exposure of the triazoline 3 to methanol induces the extrusion of nitrogen accompanied by a ring contraction to furnish the amidino-acridine 5 in high yield.
Facile Preparation of 1,1-Diacetates from Aldehydes with Acetic Anhydride Catalysed by TiO2/SO42- solid superacid
Authors: Jin Tong-Shou , Ma Yan-Ran , Sun Xu , Liang Dan , Li Tong-Shuang
Published: December 2009

A facile and efficient synthesis of 1,1-diacetates in excellent yields from aldehydes with acetic anhydride catalysed by TiO2/SO42- solid superacid.
Formation of an imidosuccinimide by cyclisation of a sterically hindered β-cyanoester with the lithium salt of a primary amine
Authors: Ros Francisco
Published: December 2009

The reaction of β-cyanoester 1 with a two-fold excess of the lithium salt of homoveratrylamine in THF at 0 °C to room temperature affords the imidosuccinimide 3, which undergoes derivation to the succinimide monooxime 4 by treatment with m-chloroperoxybenzoic acid.
Structural studies on bioactive compounds. Part 33. Synthesis of 9-arylacridines by palladium-mediated couplings
Authors: Palát Karel , Stevens Malcolm F. G.
Published: December 2009

9-Halogenoacridines undergo Suzuki cross-coupling reactions with a range of arylboronic and thienyl-3-boronic acids to yield substituted 9-arylacridines and 9-(thien-3-yl)acridines.
An Unusual Product in the Condensation of 3-t-butyl-2-hydroxy-5-methoxybenzaldehyde with acetylacetone
Authors: Venkateswarlu Somepalli , Ramachandra Marellapudi S. , Rambabu Madabattula , Subbaraju Gottumukkala V.
Published: December 2009

The reaction of 3- t-butyl-2-hydroxy-5-methoxybenzaldehyde 6 with acetylacetone resulted in the formation of an unusual product, 1-[8-( t-butyl)-6-methoxy-2H-chromem-2-ylidene] acetone 4.
A Convenient Synthesis of (E)-α-cyano and (E)-α-ethoxycarbonyl vinylphosphonates
Authors: Shen Yanchang , Jiang Guo-Fang
Published: December 2009

A new olefination catalysed by a base (KOBut) and its application to the stereoselective synthesis of substituted ( E)-α-cyano and ( E)-α-ethoxycarbonyl vinylphosphonates is described.
Solvent-free Cyclotrimerization of Isocyanates Catalysed by Sodium or Potassium Piperidinedithiocarbamate or Nitrite under Conventional or Microwave Heating: Preparation of Aryl or Alkyl Isocyanurates
Authors: Khajavi Mohammad S. , Dakamin Mohammad G. , Hazarkhani Hassan
Published: December 2009

A solvent-free method for the efficient preparation of symmetrically trisubstituted aryl or alkyl isocyanurates from isocyanates catalysed by sodium or potassium piperidinedithiocarbamate or the readily available sodium or potassium nitrite under conventional or microwave heating is described.
Vinylic substitution by DBN and DBU with ethyl (E)- and (Z)-3-aryl-3-chloro-2-cyanopropenoates
Authors: Lönnqvist Jan-Erik S. , Jalander Lars F.
Published: December 2009

Some new 6-aryl-7-cyano-1,5-diazatricyclo[7,4,11,9,05,14]tetradeca-6,9-dien-8-ones (4a–c) and 6-aryl-7-cyano-1,5-diazatricyclo[7,1,21,9,05,12]dodeca-6,9-dien-8-ones (5a–c) have been prepared in moderate to good yields by reacting ethyl ( E)- and ( Z)-3-aryl-3-chloro-2-cyanopropenoates (1a–c) with DBU (1,8-diazabicyclo[5,4,0]undec-7-ene) and DBN (1,5-diazabicyclo[4,3,0]non-5-ene).
The dichotomy between nitration of substituted 1,4-dimethoxybenzenes and formation of corresponding 1,4-benzoquinones by using nitric and sulfuric acid
Authors: Waterlot C. , Haskiak B. , Couturier D.
Published: December 2009

Various alkyl-substituted p-dimethoxybenzenes (ArH) react readily with nitric acid and sulfuric to form nitro-products (ArNO2). When the nitric acid is used in excess, the nitro-product react via either nitration to dinitro-compound (Ar(NO2)2) or via oxidative demethylation to nitro- p-quinone (Q). As such, the competition between the nitration, polynitration and oxidative dealkylation is effectively modulated by the added nitric acid and the alkyl-substituted p-dimethoxybenzenes.
Synthesis of Chiral Polyfunctionalised Cyclopentanes from the Diels–Alder Adduct of Furan and Maleic Anhydride
Authors: Brown Richard T. , Jameson Simon B. , Ouali Dehimi , Tattersall Peter I.
Published: December 2009

Chiral polyfunctionalised cyclopentanes have been readily obtained in ~65% enantiomeric excess via a stereo-specific Wagner–Meerwein rearrangement induced by bromination of derivatives of the exo-cis Diels–Alder adduct of furan and maleic anhydride, combined with desymmetrisation of a meso intermediate by pig liver esterase.