Protective Effect of Zinc: a Potent Heat Shock Protein Inducer in Cold Preservation of Rat Liver

Hepatobiliary & Pancreatic Diseases International : HBPD INT. May, 2002  |  Pubmed ID: 14612279

To study the synthesis of heat shock protein 70 (HSP70) by zinc (ZnSO4) and its protective effect during cold preservation in rat liver by establishment of a simple cold preservation model.

Regulation of Immune Recognition Molecules by Flavivirus, West Nile

Viral Immunology. 2002  |  Pubmed ID: 12081012

We have shown the flaviviruses can up-regulate the cell surface expression of the immune recognition molecules, major histocompatability complex class-I and class-II (MHC-I, MHC-II), ICAM-1, VCAM, and E-selectin, in an interferon-independent and tumor necrosis factor-independent manner. This up-regulation is associated with an increased transcription of the relevant genes and is due to activation of the transcription factor, nuclear factor-kappa B. The level of up-regulation is determined in part by the cell cycle position of the cell when infected with the flavivirus, as quiescent cells show a greater increase in the level of expression of the immune recognition molecules, MHC-I and ICAM-1, than cells in other phases of the cell cycle. The resultant increased cell surface expression is functional with the increased expression resulting in increased recognition by flavivirus-specific and allo-specific cytotoxic T cells.

Zinc is a Potent Heat Shock Protein Inducer During Liver Cold Preservation in Rats

Chinese Medical Journal. Dec, 2002  |  Pubmed ID: 12622922

A simple liver cold preservation model was established to study the synthesis of heat shock protein 70 (HSP70) induced by zinc (ZnSO(4), i.p.) and its protection during liver cold preservation in rat.

[Experimental Study on Effect of Astragalus Extractum on Canine Isolated Kidney During Hypothermia Perfusion and Preservation]

Zhongguo Zhong Xi Yi Jie He Za Zhi Zhongguo Zhongxiyi Jiehe Zazhi = Chinese Journal of Integrated Traditional and Western Medicine / Zhongguo Zhong Xi Yi Jie He Xue Hui, Zhongguo Zhong Yi Yan Jiu Yuan Zhu Ban. Apr, 2003  |  Pubmed ID: 12764915

To investigate the effect of Astragalus Extractum on canine isolated kidney during hypothermia perfusion and preservation.

Global Disruption of the Cerebellar Transcriptome in a Down Syndrome Mouse Model

Human Molecular Genetics. Aug, 2003  |  Pubmed ID: 12913072

Trisomy 21 (Down syndrome) results in cerebellar dysmorphology with direct parallels in the Ts65Dn mouse. Despite pronounced changes in morphology, cerebellar function is not markedly different. As a first test of whether those cerebellar cells that have survived to adulthood in trisomic mice are equivalent to euploid cells, we used microarrays to assess the trisomic and euploid cerebella. Trisomic and euploid transcriptomes were robustly distinguished. Changes in expression of individual genes were very subtle, but the differences in respective transcriptome phenotypes extended deeply into the set of nearly 7000 probes (genes) located throughout the genome. In contrast to deterministic models of gene action in trisomy, examination of the discriminating genes in two independent experiments suggests that the global perturbation includes a significant stochastic component. Thus, dosage imbalance of 124 genes in Ts65Dn mice alters the expression of thousands of genes to create a variable trisomic transcriptome. This global destabilization has important implications for approaches to ameliorative therapies in Down syndrome.

The Surprising Nucleophilic Addition of Aminochlorocarbenes to Diethyl Acetylenedicarboxylate and to Oxalyl Chloride: Quinolines and Benzo[1,4]diazepines from N-alkylformanilides and Oxalyl Chloride in the Presence of Hünig's Base

Organic & Biomolecular Chemistry. Oct, 2003  |  Pubmed ID: 14599025

Vilsmeier reagents derived from N-methylformanilides undergo ready deprotonation with Hünig's base. In xylene, the derived nucleophilic arylaminochlorocarbenes bearing 4-methyl- and 4-methoxy-substituents react with acetylenedicarboxylates to give 2-(2-chloro-1,2-bis(ethoxycarbonyl)vinyl)-3,4-bis(ethoxycarbonyl)-1-methyl-1,2-dihydroquinolines while most derivatives react with oxalyl chloride to give substituted 1-methyl-4 phenylbenzo[f][1,4]diazepine-2,3-dicarboxylic anhydrides.

The Unique Nucleophilic Reactivity of Arylaminochlorocarbenes

Chemical Communications (Cambridge, England). Jan, 2003  |  Pubmed ID: 12610980

4-Methyl and 4-methoxyphenylaminochlorocarbene (readily formed by deprotonation of the Vilsmeier reagent derived from the corresponding N-methylformanilide with Hünig's base) reacted with diethyl acetylenedicarboxylate to give 1:2 quinoline adducts, while p-halophenylaminochlorocarbenes yielded benzoazepine derivatives from 2:1 interaction of the carbene with oxalyl chloride under the same reaction conditions.

[Study of Antibody Enzyme with Acetylcholonesteraseactivity]

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi = Chinese Journal of Cellular and Molecular Immunology. May, 2003  |  Pubmed ID: 15155086

To study anti-idiotype antibody(AId Ab)directed at mAb 3F3 Fab idiotypic determinant with acetylcholinesteras(AchE) activity.

Oddi Sphincter Function After Canine Auto-pancreas Transplantation with Bladder Drainage

World Journal of Gastroenterology : WJG. Dec, 2003  |  Pubmed ID: 14669350

Several neural and hormonal factors are known to affect motility of sphincter of Oddi (SO). The major roles of SO are to regulate the flow of bile and pancreatic juice into the duodenum and to prevent the reflux of duodenal contents into the biliary and pancreatic duct. After pancreas transplantation, graft SO was denervated and graft pancreatitis might have relations to SO motility. The motility of SO after canine pancreas transplantation with bladder drainage was investigated.

Major Histocompatibility Complex Class I (MHC-I) Induction by West Nile Virus: Involvement of 2 Signaling Pathways in MHC-I Up-regulation

The Journal of Infectious Diseases. Feb, 2004  |  Pubmed ID: 14767820

Type 1 interferon (IFN) receptor gene knockout (IFNAR(-/-)) mouse embryo fibroblasts (MEFs) are more susceptible to and productive of West Nile virus (WNV) and produce less type 1 IFN than WNV-infected wild-type (wt) MEFs. WNV infection of IFNAR(-/-) MEFs induced activation of a p65/p50 heterodimer of nuclear factor (NF)- kappa B and up-regulation of cell-surface expression of major histocompatibility complex class I (MHC-I) molecules. WNV infection of wt MEFs resulted in a greater up-regulation of MHC-I than did infection of IFNAR(-/-) MEFs because of the action of endogenous type 1 IFN production. IFN- beta -treatment of wt MEFs did not activate NF- kappa B but did up-regulate cell-surface MHC-I expression. The WNV-induced NF- kappa B activation was partially abrogated by the serine protease inhibitor N-benzoyl-l-tosyl-l-phenylalanine, which also abrogated the up-regulation of MHC-I. Thus, we demonstrate 2 pathways for WNV-induced up-regulation of MHC-I, a WNV-induced NF- kappa B-dependent, IFN-independent pathway and an NF- kappa B-independent, IFN-dependent pathway.

Heterocycles Derived from Heteroatom-substituted Carbenes

Chemical Reviews. May, 2004  |  Pubmed ID: 15137798

[Metabolic Syndrome: a High-cardiovascular Risk]

Zhonghua Nei Ke Za Zhi [Chinese Journal of Internal Medicine]. Nov, 2004  |  Pubmed ID: 15634533

Telehealth Practice Recommendations for Diabetic Retinopathy

Telemedicine Journal and E-health : the Official Journal of the American Telemedicine Association. 2004  |  Pubmed ID: 15689653

Telehealth holds the promise of increased adherence to evidenced-based medicine and improved consistency of care. Goals for an ocular telehealth program include preserving vision, reducing vision loss, and providing better access to medicine. Establishing recommendations for an ocular telehealth program may improve clinical outcomes and promote informed and reasonable patient expectations. This document addresses current diabetic retinopathy telehealth clinical and administrative issues and provides recommendations for designing and implementing a diabetic retinopathy ocular telehealth care program. The recommendations also form the basis for evaluating diabetic retinopathy telehealth techniques and technologies. Recommendations in this document are based on careful reviews of current evidence, medical literature and clinical practice. They do not, however, replace sound medical judgment or traditional clinical decision-making. "Telehealth Practice Recommendations for Diabetic Retinopathy" will be annually reviewed and updated to reflect evolving technologies and clinical guidelines.

Evaluation of the Viability and Energy Metabolism of Canine Pancreas Graft Subjected to Significant Warm Ischemia Damage During Preservation by UW Solution Cold Storage Method

World Journal of Gastroenterology : WJG. Jun, 2004  |  Pubmed ID: 15188506

To evaluate the viability and energy metabolism of long warm ischemically damaged pancreas during preservation by the UW solution cold storage method.

Protective Effects of L-arginine on Reperfusion Injury After Pancreaticoduodenal Transplantation in Rats

Hepatobiliary & Pancreatic Diseases International : HBPD INT. Aug, 2004  |  Pubmed ID: 15313667

Post-transplantation pancreatitis and graft thrombosis are two major complications of pancreas transplantation that contribute to morbidity, mortality, and graft loss. Nitric oxide(NO) is a potent vasodilator agent formed when L-arginine (L-Arg) is converted to L-citrulline by the action of NO synthase (NOS), and plays a major role in microcirculatory changes. We therefore investigated the effect of L-Arg on reperfusion injury following pancreaticoduodenal transplantation in rats.

[The Changes of Oddi Sphincter Motility After Canine Pancreas Transplantation with Bladder Drainage]

Zhonghua Wai Ke Za Zhi [Chinese Journal of Surgery]. Aug, 2004  |  Pubmed ID: 15363256

To study the changes of canine Oddi sphincter (SO) function after pancreas transplantation with bladder drainage and the effect on the graft function.

Metallothionein I and II Mitigate Age-dependent Secondary Brain Injury

Journal of Neuroscience Research. Nov, 2004  |  Pubmed ID: 15389833

Both the immediate insult and delayed apoptosis contribute to functional deficits after brain injury. Secondary, delayed apoptotic death is more rapid in immature than in adult CNS neurons, suggesting the presence of age-dependent protective factors. To understand the molecular pathobiology of secondary injury in the context of brain development, we identified changes in expression of oxidative stress response genes during postnatal development and target deprivation-induced neurodegeneration. The antioxidants metallothionein I and II (MT I/II) were increased markedly in the thalamus of adult C57BL/6 mice compared to mice <15 days old. Target deprivation generates reactive oxygen species that mediate neuronal apoptosis in the central nervous system; thus the more rapid apoptosis observed in the immature brain might be due to lower levels of MT I/II. We tested this hypothesis by documenting neuronal loss after target-deprivation injury. MT I/II-deficient adult mice experienced greater thalamic neuron loss at 96 hr after cortical injury compared to that in controls (80 +/- 2% vs. 57 +/- 4%, P < 0.01), but not greater overall neuronal loss (84 +/- 4% vs. 79 +/- 3%, MT I/II-deficient vs. controls). Ten-day-old MT I/II-deficient mice, however, experienced both faster onset of secondary neuronal death (30 vs. 48 hr) and greater overall neuronal loss (88 +/- 2% vs. 69 +/- 4%, P = 0.02). MT I/II are thus inhibitors of age-dependent secondary brain injury, and the low levels of MT I/II in immature brains explains, in part, the enhanced susceptibility of the young brain to neuronal loss after injury. These findings have implications for the development of age-specific therapeutic strategies to enhance recovery after brain injury.

The Role of Tumor Necrosis Factor in Modulating Responses of Murine Embryo Fibroblasts by Flavivirus, West Nile

Virology. Nov, 2004  |  Pubmed ID: 15518815

Murine embryo fibroblasts (MEF) transcribe tumor necrosis factor (TNF) mRNA and secrete soluble TNF in response to infection by West Nile virus (WNV) and TNF was demonstrated to be protective against WNV infection in vitro. TNF is not required for the WNV-induced upregulation of MHC-I expression on MEF, as TNF deficiency did not affect the upregulation of major histocompatibility complex class I (MHC-I) by WNV. Furthermore, NF-kappaB was activated by WNV in TNF-deficient MEF, demonstrating that WNV induces NF-kappaB activation in a TNF-independent manner. The subunits of NF-kappaB activated by TNF and WNV differed, WNV-activated a p65/p50 NF-kappaB complex while TNF-activated NF-kappaB was composed of p65, p50, and c-Rel. Furthermore, TNF-induced activation of NF-kappaB occurred earlier than WNV-induced NF-kappaB activation. The data demonstrate that WNV infection of MEF is associated with TNF production, but the WNV-induced activation of NF-kappaB and subsequent upregulation of MHC-I by WNV is TNF-independent.

Activation of STAT3 Signaling in Human Stomach Adenocarcinoma Drug-resistant Cell Line and Its Relationship with Expression of Vascular Endothelial Growth Factor

World Journal of Gastroenterology : WJG. Feb, 2005  |  Pubmed ID: 15682485

To investigate the difference in activation of STAT3 signaling between two human stomach adenocarcinoma cell lines: 5-fluorouracil resistant cell line and its parental cell line, and to evaluate its relationship with the expression of vascular endothelial growth factor (VEGF).

Evaluation of CMU-1 Preservation Solutions Using an Isolated Perfused Rat Liver Model

World Journal of Gastroenterology : WJG. Apr, 2005  |  Pubmed ID: 15832430

CMU-1 is a new preservation solution with a low potassium concentration as well as low viscosity that is highly effective in reducing preservation injury. The purpose of this experiment is to compare the protective effect of CMU-1 solution with that of UW during cold preservation and normothermic reperfusion.

Interaction of Aryloxychlorocarbenes with Acetylenedicarboxylate: Novel Formation of Polyfunctional Butadienes and 8-oxatricyclo[3.2.1.0(2.4)]oct-6-enes

The Journal of Organic Chemistry. Jun, 2005  |  Pubmed ID: 15932326

The interaction of aryloxychlorocarbenes with dialkyl acetylenedicarboxylates has been examined. Thermolyses of 3-aryloxy-3-chlorodiazirines in the presence of acetylenedicarboxylate resulted in the formation of unexpected polyfunctional 1,3-butadienes and 8-oxatricyclo[3.2.1.0(2.4)]oct-6-enes or of 2-aryoxycarbonylmaleates dependent upon reaction conditions. This work confirmed the nucleophilicity of aryloxychlorocarbenes and underlined their synthetic potential.

Islet Transplantation for Diabetic Rats Through the Spleen

Hepatobiliary & Pancreatic Diseases International : HBPD INT. May, 2005  |  Pubmed ID: 15908316

Islet transplantation is considered a potentially curative treatment for diabetic mellitus. The aim of this study was to assess the feasibility of islet transplant through the spleen.

The Effect of Glycation of CD59 on Complement-mediated Cytolysis

Cellular & Molecular Immunology. Aug, 2005  |  Pubmed ID: 16274631

Vascular proliferation is one of the major causes for morbidity and mortality in diabetes. However, the cellular and molecular mechanisms that link hyperglycemia to this complication remain unclear. In present study, we demonstrated by site-directed mutagenesis that mutated CD59 was more susceptible to glycation-inactivation for hyperglycemia. Mutated and wild-type CD59s were stably expressed in Chinese hamster ovary cells using the pALTER-MAX mammalian expression vector. Western blot, FACS and immunological fluorescence were conducted to confirm that CD59s were tethered to the plasma membrane. Compared to wild-type CD59, human CD59 mutants led to a significant increase in dye release assay. These results indicate that there may be some mutations of CD59 in diabetes population and the mutated CD59, which is more likely to be of glycation than the wild-type, may help to explain the distinct propensity of diabetes subjects to develop vascular proliferation complications.

[Influence of Lidocaine on Systemic Inflammation in Perioperative Patients Undergoing Cardiopulmonary Bypass]

Beijing Da Xue Xue Bao. Yi Xue Ban = Journal of Peking University. Health Sciences. Dec, 2005  |  Pubmed ID: 16378115

To investigate the influence of lidocaine on systemic inflammation in the perioperative ventricular septal defect (VSD).

Daytime Orthokeratology Associated with Infectious Keratitis by Multiple Gram-negative Bacilli: Burkholderia Cepacia, Pseudomonas Putida, and Pseudomonas Aeruginosa

Eye & Contact Lens. Jan, 2006  |  Pubmed ID: 16415688

To report a case of a corneal ulcer in a patient who wore orthokeratology contact lenses during the day.

[Specific Coalescent Peptide of CD59 Screened by Phage Library]

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi = Chinese Journal of Cellular and Molecular Immunology. Mar, 2006  |  Pubmed ID: 16507249

To screen and identify the short-peptide which specifically bind to human CD59 so as to design short-peptide clamp with counteracting tumor escape activity.

A N-heterocyclic Carbene Derived Highly Regioselective Ambident C-C-S and C-C-N 1,3-dipolar System

Chemical Communications (Cambridge, England). Mar, 2006  |  Pubmed ID: 16518495

N-Heterocyclic carbene derived 2-phenylthiocarbamoyl benzimidazolium and imidazolinium inner salts are a unique ambident C-C-S and C-C-N 1,3-dipolar system able to undergo highly efficient and regioselective cycloaddition with dimethyl acetylenedicarboxylate and ethyl propiolate to furnish, respectively, spiro[imidazole-2,3'-thiophene] and spiro[imidazole-2,3'-pyrrole] derivatives in good to excellent yields.

Factors Associated with Work Satisfaction of Registered Nurses

Journal of Nursing Scholarship : an Official Publication of Sigma Theta Tau International Honor Society of Nursing / Sigma Theta Tau. 2006  |  Pubmed ID: 16579327

To examine the factors that influence the work satisfaction of a national sample of registered nurses in metropolitan statistical areas (MSAs).

[A Pilot Evaluation of the Diagnostic Value of Body Mass Index in Elderly Men with Metabolic Syndrome]

Zhonghua Nei Ke Za Zhi [Chinese Journal of Internal Medicine]. Feb, 2006  |  Pubmed ID: 16624114

The aim of the study is to determine the relationship between body mass index (BMI) and metabolic syndrome and to investigate the epidemiological characteristics of this syndrome in elderly men.

Use of Ecotilling As an Efficient SNP Discovery Tool to Survey Genetic Variation in Wild Populations of Populus Trichocarpa

Molecular Ecology. Apr, 2006  |  Pubmed ID: 16626459

Abstract Ecotilling was used as a simple nucleotide polymorphism (SNP) discovery tool to examine DNA variation in natural populations of the western black cottonwood, Populus trichocarpa, and was found to be more efficient than sequencing for large-scale studies of genetic variation in this tree. A publicly available, live reference collection of P. trichocarpa from the University of British Columbia Botanical Garden was used in this study to survey variation in nine different genes among individuals from 41 different populations. A large amount of genetic variation was detected, but the level of variation appears to be less than in the related species, Populus tremula, based on reported statistics for that tree. Genes examined varied considerably in their level of variation, from PoptrTB1 which had a single SNP, to PoptrLFY which had more than 23 in the 1000-bp region examined. Overall nucleotide diversity, measured as (Total), was relatively low at 0.00184. Linkage disequilibrium, on the other hand, was higher than reported for some woody plant species, with mean r2 equal to 0.34. This study reveals the potential of Ecotilling as a rapid genotype discovery method to explore and utilize the large pool of genetic variation in tree species.

[Upregulated Rho-kinase and Increased Phosphorylation of Myosin-binding Subunit of Myosin Phosphates Are Key Players in a Porcine Coronary Artery Spasm Model with Interleukin-1beta]

Zhonghua Xin Xue Guan Bing Za Zhi. Jan, 2006  |  Pubmed ID: 16626550

Phosphorylation of myosin light chain (MLC) is one of the most important steps for vascular smooth muscle contraction and Rho-kinase is involved in this process. We investigated the role of Rho-kinase in a porcine coronary artery spasm model with interleukin-1beta.

High Nucleophilicity of Cyclic Amidocarbene Toward Aryl Isocyanates, New Approach to Spiro[azetidinone-4,3'-indolinone] Derivatives

The Journal of Organic Chemistry. Jun, 2006  |  Pubmed ID: 16749769

The nucleophilic addition of beta-lactam-4-ylidenes 2, a type of ambiphilic cyclic amidocarbene, to aryl isocyanates has been studied and their application in organic synthesis has been demonstrated. Thermolysis of spiro[beta-lactam-4,2'-oxadiazolines] 1 in the presence of aryl isocyanates afforded both N-lactam and O-lactam substituted spiro[azetidine-2-one-4,3'-indole-2'-one] derivatives 5 and 6 in the total yield of 65-86%. Upon hydrolysis, products 5 and 6 were converted into spiro[azetidine-2-one-4,3'-indole-2'-one] 9 that was analogous to known biologically active compounds.

[Effects of Rapamycin on Rho-kinase and P27 MRNA Expressions in a Porcine Coronary Intimal Proliferation Model Induced by Interleukin-1beta]

Zhonghua Xin Xue Guan Bing Za Zhi. May, 2006  |  Pubmed ID: 16776964

To observe the effects of rapamycin on the expressions of Rho-kinase and p27 mRNA during vascular intimal proliferation in a porcine model of coronary stenosis induced by interleukin-1beta (IL-1beta).

Identification of Sox17 As a Transcription Factor That Regulates Oligodendrocyte Development

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Sep, 2006  |  Pubmed ID: 16988043

Microarray analysis of oligodendrocyte lineage cells purified by fluorescence-activated cell sorting (FACS) from 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP)-enhanced green fluorescent protein (EGFP) transgenic mice revealed Sox17 (SRY-box containing gene 17) gene expression to be coordinately regulated with that of four myelin genes during postnatal development. In CNP-EGFP-positive (CNP-EGFP+) cells, Sox17 mRNA and protein levels transiently increased between postnatal days 2 and 15, with white matter O4+ preoligodendrocytes expressing greater Sox17 levels than Nkx2.2+ (NK2 transcription factor related, locus 2) NG2+, or GalC+ (galactocerebroside) cells. In spinal cord, Sox17 protein expression was undetectable in the primary motor neuron domain between embryonic days 12.5 and 15.5 but was evident in Nkx2.2+ and CC1+ cells. In cultured oligodendrocyte progenitor cells (OPCs), Sox17 levels were maximal in O4+ cells and peaked during the phenotypic conversion from bipolar to multipolar. Parallel increases in Sox17 and p27 occurred before MBP protein expression, and Sox17 upregulation was prevented by conditions inhibiting differentiation. Sox17 downregulation with small interfering RNAs increased OPC proliferation and decreased lineage progression after mitogen withdrawal, whereas Sox17 overexpression in the presence of mitogen had opposite effects. Sox17 overexpression enhanced myelin gene expression in OPCs and directly stimulated MBP gene promoter activity. These findings support important roles for Sox17 in controlling both oligodendrocyte progenitor cell cycle exit and differentiation.

Basic Science; Metallothionein I and II Attenuate the Thalamic Microglial Response Following Traumatic Axotomy in the Immature Brain

Journal of Neurotrauma. Jan, 2007  |  Pubmed ID: 17263668

The clinical manifestations of inflicted traumatic brain injury in infancy most commonly result from intracranial hemorrhage, axonal stretch and disruption, and cerebral edema. Often hypoxia ischemia is superimposed, leading to early forebrain and later thalamic neurodegeneration. Such acute and delayed cellular injury activates microglia in the CNS. Although activated microglia provide important benefits in response to injury, microglial release of reactive oxygen species can be harmful to axotomized neurons. We have previously shown that the antioxidants metallothionein I and II (MT I & II) promote geniculocortical neuronal survival after visual cortex lesioning. The purpose of this investigation was to determine the influence of MT I & II on the density and rate of thalamic microglial activation and accumulation following in vivo axotomy. We ablated the visual cortex of 10-day-old and adult MT I & II knock out (MT(-/-)) and wild-type mice and then determined the density of microglia in the dorsal lateral geniculate nucleus (dLGN) over time. Compared to the wild-type strain, microglial activation occurred earlier in both young and adult MT(-/-) mice. Similarly, microglial density was significantly greater in young MT(-/-) mice 30, 36, and 48 hours after injury, and 3, 4, and 5 days after injury in MT(-/-) adults. In both younger and older mice, time and MT I & II deficiency each contributed significantly to greater microglial density. Only in younger mice did MT I & II expression significantly slow the rate (density x time) of microglial accumulation. These results suggest that augmentation of MT I & II expression may provide therapeutic benefits to infants with inflicted brain injury.

A Versatile Strategy for Divergent and Diastereoselective Synthesis of Natural Product-like Polyhydroxylated Indolizidines

The Journal of Organic Chemistry. Mar, 2007  |  Pubmed ID: 17298097

A general and versatile method for the divergent and diastereoselective synthesis of polyhydroxylated indolizidines has been established. The annulation reactions of a readily available enantiopure dihydroxylated cyclic secondary enamine with alpha,beta-unsaturated carboxylates including methyl acrylate, methyl crotonate, methyl 2-hexenoate, allenoate, and dimethyl acetylenedicarboxylate and with malonyl chloride produced hexahydro- or tetrahydro-5-indolizinone-8-carboxylates in high yields. The resulting 5-indolizinone derivatives were converted into diverse polyhydroxylated indolizidines in good yields through practical hydrogenation and reduction reactions.

Substrate-controlled and Site-selective [3+2] Cycloadditions of N-heterocyclic Carbene Derived Ambident Dipoles

Chemistry (Weinheim an Der Bergstrasse, Germany). 2007  |  Pubmed ID: 17323390

2-aryl thiocarbamoyl benzimidazolium and imidazolinium inner salts derived from benzimidazole and imidazoline carbenes are unique ambident C-C-S and C-C-N 1,3-dipolar systems, which undergo highly efficient and site-selective cycloaddition reactions with dimethyl acetylenedicarboxylate or dibenzoylacetylene to furnish spiro(imidazole-2,3'-thiophene) derivatives in excellent yields. When treated with ethyl propiolate, methyl acrylate or acrylonitrile, spiro(imidazole-2,3'-pyrrole) derivatives were formed in good yields. Theoretical studies revealed an asynchronous concerted mechanism for both the C-C-S and C-C-N 1,3-dipolar cycloaddition reactions. The site selectivity in the [3+2] cycloaddition reaction of ambident 1,3-dipoles was predictably regulated by both the electronic and steric effects of dipolarophiles.

Interaction of Beta-lactam Carbenes with Aryl Isonitriles: an Unprecedented Rearrangement of 2-azetidinonylidene Indoles to Delta-carbolinones

The Journal of Organic Chemistry. Mar, 2007  |  Pubmed ID: 17338577

The reaction of beta-lactam carbenes with aryl isonitriles proceeded in a novel [2 + 2] fashion to give high yields of 2-azetidinonylidene indoles 4, which underwent an unprecedented rearrangement to furnish 4-arylimino-delta-carbolin-2-ones 5 in almost quantitative yields. Acid catalyzed rearrangement and the subsequent hydrolysis of 2-azetidinonylidene indoles 4 produced two types of delta-carbolin-2,4-diones 10 and 11, respectively, in good to excellent yields. The photophysical study showed that both delta-carbolin-2,4-diones 10 and 11 are highly fluorescent with the fluorescent quantum yields being up to 0.43.

An Unprecedented Tandem 1,3-dipolar Cycloaddition-cheletropic Elimination: a Facial Approach to Novel Push-pull Olefins

Organic & Biomolecular Chemistry. Apr, 2007  |  Pubmed ID: 17406728

The interaction of 2-(phenylthiocarbamoyl) imidazolium inner salts with dimethyl acetylenedicarboxylate produced dimethyl 2-(imidazolin-2-ylidene)-3-thioxobutanedioates in moderate to good yields. The process involved a tandem reaction comprising a 1,3-dipolar cycloaddition and an unprecedented cheletropic elimination of the phenyl isonitrile from a 2-phenyliminodihydrothiophene moiety. NMR and X-ray diffraction studies confirmed that the 2-(imidazolin-2-ylidene)-3-thioxobutanedioates are novel push-pull olefins and have potential applications in nonlinear optical materials.

[Improved the Solubility of Maize Uroporphyrinogen III Methyltransferase As the Red Fluorescent Indicator by Site-directed Mutagenesis]

Sheng Wu Gong Cheng Xue Bao = Chinese Journal of Biotechnology. Mar, 2007  |  Pubmed ID: 17460889

S-adenosylmethionine-dependent uroporphyrinogen III methyltransferase (SUMT) is a novel red fluorescence indicator. However, the production of SUMT in Escherichia coli is restricted by its relatively low solubility, and little is known about the red fluorescent materials that are associate with SUMT. Two individual SUMT mutations, L166A and L88R/L89G double mutant were produced by site-directed mutagenesis. Both mutants were overexpressed in E. coli and purified by Ni-NTA chromatography. The reddish mixtures isolated from the purified L88R/L89G double mutant were analyzed by UV-visible spectra scanning and mass analysis(MS). The L88R/L89G double mutant has enzymatic activity in vivo, whereas L166A mutant loses the activity. Trimethylpyrrocorphin is identified as the main constituent in the isolated pigments. The purified L88R/L89G mutant increases protein solubility, which is applied potentially as the fluorescent indicator denoting the solubility of protein fusion partner.

Dendritic Cells Modified with 6Ckine/IFNgamma Fusion Gene Induce Specific Cytotoxic T Lymphocytes in Vitro

Cancer Immunology, Immunotherapy : CII. Nov, 2007  |  Pubmed ID: 17503043

[corrected] Dendritic cells play an important role in initiation and regulation of immune responses. Previous studies demonstrated that intratumoral administration of 6Ckine-modified DCs enhanced local and systemic antitumor effects. Herein we report the investigation of the specific CTL responses elicited by adenoviral 6Ckine/IFNgamma fusion gene-modified DCs in vitro.

Elevation of Vascular Endothelial Growth Factor Production and Its Effect on Revascularization and Function of Graft Islets in Diabetic Rats

World Journal of Gastroenterology : WJG. May, 2007  |  Pubmed ID: 17569125

To determine whether the elevated vascular endothelial growth factor (VEGF) expression produced by the transfected vascular endothelial cells (VECs) could stimulate angiogenesis of the graft islets and exert its effect on the graft function.

[Purification and Production of the Extracellular 5-aminolevulinate from Recombiniant Escherichia Coli Expressing Yeast ALAS]

Sheng Wu Gong Cheng Xue Bao = Chinese Journal of Biotechnology. May, 2007  |  Pubmed ID: 17578005

Aminolevulinic acid (ALA) is biosynthesized by the enzyme ALA synthase (ALAS). The ALA production has been studied using the overproducing ALAS from several bacteria in Escherchia coil, respectively. However, ALAS from eucaryote expressed in E. coli for producing ALA in the culture is not known. The extracellular ALA production and cell growth were investageted respectively using the recombinant E. coli overproducing Saccharomyces cerevisiae ALAS in shake-flask fermentations. The ALAS activity from the cell extract was assayed. The extracellular ALA was purified by the national-made large-dimension resins and confirmed by the capillary electrophoresis measurements. At 12h after induction at 37 degrees C, the extracellular ALA production was up to 162mg per liter LB culture at initial pH 6.5 with exogenous levulinate, succinate and and glycine at the concentration of 20 mmol/L respectively. The purity of ALA after purification is up to 90%.

Highly Efficient and Site-selective [3 + 2] Cycloaddition of Carbene-derived Ambident Dipoles with Ketenes for a Straightforward Synthesis of Spiro-pyrrolidones

The Journal of Organic Chemistry. Aug, 2007  |  Pubmed ID: 17629341

The [3 + 2] cycloaddition reaction of 2-arylthiocarbamoyl benzimidazolium, -imidazolinium, and -triazolium inner salts (the ambident C-C-N and C-C-S 1,3-dipoles derived from carbenes) with ketenes proceeded efficiently in a highly site-selective manner to produce the C-C-N cycloaddition products benzimidazoline-, imidazolidine-, or triazoline spiro-pyrrolidones in 58-93% yields. Theoretical calculation suggests a stepwise mechanism for the reaction and indicates that the C-C-N cycloaddition of the dipoles with ketenes is both a dynamically and thermodynamically favored reaction pathway. Their easy availability, high reactivity, and reaction selectivity render the benzimidazolium, -imidazolinium, and -triazolium inner salts powerful and versatile 1,3-dipoles in the construction of novel spiro heterocyclic systems, which are not easily accessible by other methods.

Work Attitudes of Older RNs

Policy, Politics & Nursing Practice. May, 2007  |  Pubmed ID: 17652628

Using data collected from 1,906 RNs from Metropolitan Statistical Areas in 29 states, the purpose of this study was to examine the characteristics and work attitudes of older RNs compared to RNs less than age 50 at two time periods, and compare among the older RNs those who are working in nursing, working outside nursing, and not working. Older RNs reported more distributive justice (fairness of rewards), work group cohesion, and supervisory support and less organizational constraint, and quantitative workload than younger RNs. Overall, older RNs were more satisfied, had greater organizational commitment, and had less desire to quit than younger RNs. There were no significant differences between older and younger RNs for autonomy, mentor support, or variety. Strategic efforts by employers and government could be used to retain older workers, attract RNs working in nonnursing settings back into nursing, and recruit retired RNs into the nursing workforce.

Absence of Serotype-specific Surface Antigen in Laboratory Variants of Epidemic-associated Listeria Monocytogenes Strains

Applied and Environmental Microbiology. Oct, 2007  |  Pubmed ID: 17675434

Variants that lacked reactivity with the serotype 4b-specific monoclonal antibody c74.22 and that lost susceptibility to certain Listeria- or serotype 4b-specific phages were identified in the course of genetic studies with serotype 4b Listeria monocytogenes strains H7550 and F2381L (epidemic clones I and II, respectively). Our findings suggest that such variants can become inadvertently established under laboratory conditions and suggest caution in work involving serotype 4b strains and genetic constructs thereof.

The Unprecedented Ring Transformation from Thiazoline-spiro-thiophene to Thieno[2,3-b]pyrazine Involved in the Reaction of 2-thiocarbamoyl Thiazolium Salts with Dimethyl Acetylenedicarboxylate

Chemical Communications (Cambridge, England). Dec, 2007  |  Pubmed ID: 18049762

Reaction of 2-thiocarbamoyl thiazolium salts with dimethyl acetylenedicarboxylate proceeded via a tandem [3+2] cycloaddition and a unprecedented ring transformation to produce functionalized thieno[2,3-b]pyrazine derivatives in good to excellent yields.

[Effects of Blocking the CXC Chemokine Receptor 3 Pathway on Acute Rejection of Islet Allograft]

Zhonghua Wai Ke Za Zhi [Chinese Journal of Surgery]. Feb, 2007  |  Pubmed ID: 17498386

To identify the effect of PNA CXCR3 on acute rejection of islet allograft.

Protective Effect of Inducible Nitric Oxide Synthase Inhibitor on Pancreas Transplantation in Rats

World Journal of Gastroenterology : WJG. Dec, 2007  |  Pubmed ID: 18023101

To investigate the effect of inducible nitric oxide synthase inhibitor, aminoguanidine, on pancreas transplantation in rats.

Endovascular Treatment of Giant Intracranial Aneurysms with Willis Covered Stents: Technical Case Report

Neurosurgery. May, 2008  |  Pubmed ID: 18580791

To evaluate the efficacy of endovascular treatment of giant intracranial aneurysms with Willis covered stents (Micro-Port, Shanghai, China).

Efficient Removal of Cr(VI) from Aqueous Solution with Fe@Fe2O3 Core-shell Nanowires

Environmental Science & Technology. Sep, 2008  |  Pubmed ID: 18853815

The batch removal of Cr(VI) from simulated wastewater with Fe@Fe2O3 core-shell nanowires (FCSNs) was investigated in this study. Itwas found that each gram of the FCSNs could remove 7.78 mg of Cr(VI) from simulated wastewater containing 8.0 mg L(-1) of Cr(VI) with an initial pH of 6.5 at room temperature. The Freundlich adsorption isotherm was applicable to describe the removal processes. Kinetics of the Cr(VI) removal was found to follow pseudo-second-order rate equation. Furthermore, the as-prepared and Cr(VI)-adsorbed FCSNs were carefully examined by scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), Fourier transform infrared spectroscopy (FT-IR), and X-ray photoelectron spectroscopic analysis (XPS). The characterization results suggested that the adsorbed Cr(VI) was partially reduced to Cr(lll) in Cr2O3/Cr(OH)3 on the FCSNs. The possible mechanism of removal of Cr(VI) on FCSNs was proposed, which involved the dominant Cr(VI) adsorption, followed by the partial reduction of Cr(VI) to Cr(III) (chromium(III) oxyhydroides) on the surface of FCSNs. These Fe@Fe2O3 core-shell nanowires with high specific surface area and strong magnetic property are very attractive for the removal of Cr(VI) from wastewater.

Teichoic Acid Glycosylation Mediated by GtcA is Required for Phage Adsorption and Susceptibility of Listeria Monocytogenes Serotype 4b

Applied and Environmental Microbiology. Mar, 2008  |  Pubmed ID: 18192405

An insertion mutant of gtcA, responsible for serotype-specific glycosylation of the cell wall teichoic acid in serotype 4b strains of Listeria monocytogenes, was also resistant to both Listeria genus- and serotype 4b-specific phages. The sugar substituents on teichoic acid appeared essential for the adsorption of phages A500 (serotype 4b specific) and A511 (Listeria genus specific) to serotype 4b L. monocytogenes.

[Wx Sequence Analysis of a Autotetraploid Indica Mutant Rice and Establishment of Molecular Marker for Identifying]

Yi Chuan = Hereditas / Zhongguo Yi Chuan Xue Hui Bian Ji. Feb, 2008  |  Pubmed ID: 18244928

The amylose content of the mutant of autotetraploid indica rice D4063-1 is 5.23% anout, which was half of its origin diploid rice Minghui 63. The whole sequence of Waxy gene of D4063-1 was amplified and sequenced. A base was absent on the Wx of D4063-1 in exon sequence, which resulted in frameshift mutation and terminating codon occurred ahead in the 9 exon. The mutation of Wx also led to the change of some mutation in the 9 exon and terminating codon occurred early. The change of Wx also led to changes of the sites of common restriction endonuclease. The results showed that D4063-1 added two sph sites compared to indica and japonica rice; Compared to japonica rice, D4063-1decreased six Acc sites, and added 4 Xba, a Pst and a Sal restriction sites. Phylogenic analysis showed that the DNA sequence of Waxy gene of D4063-1 was closer to indica rice. We supposed that the Waxy gene of D4063-1 originated from genotype of Wxa. According to the differences of Wx in D4063-1, we deduced the absent base led to RNA splicing obstacle, which was the main cause of low amylose content and it might be related to the soft rice phenotype. Based on analysis of Wx of D4063-1, indica and japonica and according to the special sites of the three species, primers as markers-AUT4063-I were designed to distinguish D4063-1 from other rice. Combining with primer pair F5, dominant and codominant ways were established for discriminating them, and rapid and correct identification of D4063-1 from other rice could be done.

[Prevention and Treatment of Biliary Complications Following Orthotopic Liver Transplantation]

Zhonghua Wai Ke Za Zhi [Chinese Journal of Surgery]. Jun, 2008  |  Pubmed ID: 19035148

To study the prevention and treatment of biliary complications after orthotopic liver transplantation.

[Diagnostic Values of Double-balloon Enteroscopy and Abdominal Computed Tomography in Small Bowel Disease]

Zhonghua Yi Xue Za Zhi. Dec, 2008  |  Pubmed ID: 19159561

To evaluate the diagnostic values of double-balloon enteroscopy (DBE) and abdominal computed tomography (CT) in small bowel disease.

[Capecitabine Combined with Cisplatin As First-line Therapy in Chinese Patients with Advanced Gastric Carcinoma-a Phase II Clinical Study]

Zhonghua Zhong Liu Za Zhi [Chinese Journal of Oncology]. Dec, 2008  |  Pubmed ID: 19173999

To evaluate the effectiveness and safety of the combination chemotherapy of capecitabine (X) with fractionated administration of cisplatin (C) in Chinese patients with advanced gastric cancer (AGC).

17beta-estradiol Activates Estrogen Receptor Beta-signalling and Inhibits Transient Receptor Potential Vanilloid Receptor 1 Activation by Capsaicin in Adult Rat Nociceptor Neurons

Endocrinology. Nov, 2008  |  Pubmed ID: 18617618

There is mounting evidence that estrogens act directly on the nervous system to affect the severity of pain. Estrogen receptors (ERs) are expressed by sensory neurons, and in trigeminal ganglia, 17beta-estradiol can indirectly enhance nociception by stimulating expression and release of prolactin, which increases phosphorylation of the nociceptor transducer transient receptor potential vanilloid receptor 1 (TRPV1). Here, we show that 17beta-estradiol acts directly on dorsal root ganglion (DRG) sensory neurons to reduce TRPV1 activation by capsaicin. Capsaicin-induced cobalt uptake and the maximum TRPV1 current induced by capsaicin were inhibited when isolated cultured DRGs neurons from adult female rats were exposed to 17beta-estradiol (10-100 nm) overnight. There was no effect of 17beta-estradiol on capsaicin potency, TRPV1 activation by protons (pH 6-4), and P2X currents induced by alpha,beta-methylene-ATP. Diarylpropionitrile (ERbeta agonist) also inhibited capsaicin-induced TRPV1 currents, whereas propylpyrazole triol (ERalpha agonist) and 17alpha-estradiol (inactive analog) were inactive, and 17beta-estradiol conjugated to BSA (membrane-impermeable agonist) caused a small increase. TRPV1 inhibition was antagonized by tamoxifen (1 microm), but ICI182870 (10 microm) was a potent agonist and mimicked 17beta-estradiol. We conclude that TRPV1 in DRG sensory neurons can be inhibited by a nonclassical estrogen-signalling pathway that is downstream of intracellular ERbeta. This affects the vanilloid binding site targeted by capsaicin but not the TRPV1 activation site targeted by protons. These actions could curtail the nociceptive transducer functions of TRPV1 and limit chemically induced nociceptor sensitization during inflammation. They are consistent with clinical reports that female pelvic pain can increase after reductions in circulating estrogens.

Chlamydia Pneumoniae Infection and Hyperlipidaemia-induced Expression of P50 and C-Fos in the Heart of C57BL6J Mice

Acta Cardiologica. Apr, 2008  |  Pubmed ID: 18468197

The objective of this study was to investigate infection by Chlamydia pneumoniae (C. pneumoniae) and the combined effects of an atherogenic diet on the expression of AP-1 or the subunit of AP-1 (c-Fos) and NF-kappaB or the subunit of NF-kappaB (P50) in myocardial cells of C57BL/6J mice.

The Maximum Priority Index Method for Severely Constrained Item Selection in Computerized Adaptive Testing

The British Journal of Mathematical and Statistical Psychology. May, 2009  |  Pubmed ID: 18534047

This paper introduces a new heuristic approach, the maximum priority index (MPI) method, for severely constrained item selection in computerized adaptive testing. Our simulation study shows that it is able to accommodate various non-statistical constraints simultaneously, such as content balancing, exposure control, answer key balancing, and so on. Compared with the weighted deviation modelling method, it leads to fewer constraint violations and better exposure control while maintaining the same level of measurement precision.

[The Effect of INOS Gene Expression Inhibited by RNA Inference on the Pancreas Islet Apoptosis and Function in Rats]

Zhonghua Wai Ke Za Zhi [Chinese Journal of Surgery]. Sep, 2009  |  Pubmed ID: 20092778

To investigate the effect of iNOS gene on cell apoptosis and insulin secretion of pancreas islet in rats by RNA inference (RNAi).

Effects of Estrogens and Bladder Inflammation on Mitogen-activated Protein Kinases in Lumbosacral Dorsal Root Ganglia from Adult Female Rats

BMC Neuroscience. 2009  |  Pubmed ID: 20035635

Interstitial cystitis is a chronic condition associated with bladder inflammation and, like a number of other chronic pain states, symptoms associated with interstitial cystitis are more common in females and fluctuate during the menstrual cycle. The aim of this study was to determine if estrogens could directly modulate signalling pathways within bladder sensory neurons, such as extracellular signal-related kinase (ERK) and p38 mitogen-activated protein (MAP) kinases. These signalling pathways have been implicated in neuronal plasticity underlying development of inflammatory somatic pain but have not been as extensively investigated in visceral nociceptors. We have focused on lumbosacral dorsal root ganglion (DRG) neurons projecting to pelvic viscera (L1, L2, L6, S1) of adult female Sprague-Dawley rats and performed both in vitro and in vivo manipulations to compare the effects of short- and long-term changes in estrogen levels on MAPK expression and activation. We have also investigated if prolonged estrogen deprivation influences the effects of lower urinary tract inflammation on MAPK signalling.

An Experimental and Theoretical Study on the Interaction of N-heterocyclic Carbene-derived 1,3-dipoles with Methoxycarbonylallenes: Highly Regio- and Stereoselective [3+2]-cycloadditions Controlled by the Structures of N-heterocycles of 1,3-dipoles

The Journal of Organic Chemistry. Mar, 2009  |  Pubmed ID: 19231834

The reactions of N-heterocyclic carbene-derived 1,3-dipoles with methoxycarbonylallenes were studied systematically by means of experimental and theoretical approach. The regioselectivity of [3+2]-cycloaddition of 1,3-dipoles toward the ester-substituted (activated) or alkyl-substituted (less activated) carbon-carbon double bond of methoxycarbonylallenes was strongly governed by the structures of N-heterocycles of 1,3-dipoles. In addition, the reaction temperature played an important part in regulating the regioselectivity of [3+2]-cycloaddition in some cases. While the reaction between benzimidazole carbene-derived 2-thiocarbamoyl benzimidazolium inner salts 5 and methoxycarbonylallenes 6 with or without heating gave predominantly adducts of C(+)-C-S(-) moiety to the alkyl-substituted double bond of methoxycarbonylallenes, triazole carbene-derived triazolium salts 14 underwent mainly its [3+2]-cycloaddition of C(+)-C-S(-) dipoles to the ester-substituted double bond of methoxycarbonylallenes. In the case of imidazoline carbene-derived 1,3-dipoles 10, the cycloaddition occurred between the C(+)-C-S(-) fragment and the activated double bond at room temperature, while in refluxing benzene, however, the same reaction yielded cycloadducts from the addition of 10 to the less activated double bond of methoxycarbonylallenes. DFT calculation revealed asynchronous cycloaddition mechanisms for the reactions of benzimidazole and imidazoline carbene-derived 1,3-dipoles with methoxycarbonylallenes, and a concerted mechanism for the reaction of triazole carbene-derived dipoles. The different regioselectivity of the reaction originated from the combination of electronic and steric effects of the reactants and the stability of the final products.

The [3 + 2] Cycloaddition Reaction of Thiazole Carbene-derived C-C-Se 1,3-dipoles: a Concise and Highly Efficient Strategy for the Construction of Multifunctional Dihydroselenophenes and Selenopheno[2,3-b]pyrazines

Organic & Biomolecular Chemistry. Aug, 2009  |  Pubmed ID: 19641784

The first study on the reaction of C(+)-C-Se(-) 1,3-dipoles with electron-deficient alkenes and alkyne is reported. 2-Arylselenocarbamoylthiazolium inner salts, the unique thiazole carbene-derived C(+)-C-Se(-) 1,3-dipoles, reacted efficiently with methoxycarbonylallenes or dimethyl acetylenedicarboxylate to produce dihydroselenophenes or selenopheno[2,3-b]pyrazines, respectively, in high yields. Both reactions probably proceeded via a [3 + 2] cycloaddition of C(+)-C-Se(-) 1,3-dipoles with alkenes or alkyne followed by different transformations of the thiazole-spiro-selenophene intermediates. This work provides a concise and efficient strategy for the construction of multifunctional dihydroselenophenes and selenopheno[2,3-b]pyrazines, which are not easy accessible by other methods.

Inhibition of Soluble Epoxide Hydrolase Attenuated Atherosclerosis, Abdominal Aortic Aneurysm Formation, and Dyslipidemia

Arteriosclerosis, Thrombosis, and Vascular Biology. Sep, 2009  |  Pubmed ID: 19667112

Epoxyeicosatrienoic acids (EETs) have been shown to have antiinflammatory effects and therefore may play a role in preventing vascular inflammatory and atherosclerotic diseases. Soluble epoxide hydrolase (s-EH) converts EETs into less bioactive dihydroxyeicosatrienoic acids. Thus, inhibition of s-EH can prevent degradation of EETs and prolong their effects. The present study aimed to test the hypothesis that inhibition of s-EH has vascular protective effects.

[Clinical Evaluation of the Application of Gene Chip for Identifying Pathogens in Blood Cultures]

Nan Fang Yi Ke Da Xue Xue Bao = Journal of Southern Medical University. Oct, 2009  |  Pubmed ID: 19861269

To explore the feasibility of using gene chip method to identify pathogens in blood cultures.

Synthesis of Novel Synthetic Intermediates from the Reaction of Benzimidazole and Triazole Carbenes with Ketenimines and Their Application in the Construction of Spiro-pyrroles

Organic & Biomolecular Chemistry. Dec, 2009  |  Pubmed ID: 19907793

2-(2-Alkoxycarbonyl-1-arylamino-1-propenyl)benzimidazolium and 5-(2-alkoxycarbonyl-1-arylamino-1-propenyl)triazolium salts were synthesized in good yields from the reaction of benzimidazole and triazole carbenes with ketenimines. Upon treatment with a base, both salts were converted into novel 1,3-dipoles which underwent [3+2] cycloaddition reactions with electron-deficient alkynes and allenes to produce benzimidazole-spiro-pyrroles or triazole-spiro-pyrroles. This work provides novel synthons for the construction of multifunctional spiro-pyrrole derivatives that are not easy accessible by other synthetic methods and are potentially amenable to further transformations.

Deleterious Effects of Minocycline After in Vivo Target Deprivation of Thalamocortical Neurons in the Immature, Metallothionein-deficient Mouse Brain

Journal of Neuroscience Research. May, 2009  |  Pubmed ID: 19115404

Compared with adults, immature metallothionein I and II knockout (MT(-/-)) mice incur greater neuronal loss and a more rapid rate of microglia accumulation after target deprivation-induced injury. Because minocycline has been proposed to inhibit microglial activation and associated production of neuroinflammatory factors, we investigated its ability to promote neuronal survival in the immature, metallothionein-deficient brain. After ablation of the visual cortex, 10-day-old MT(-/-) mice were treated with minocycline or saline and killed 24 or 48 hr after injury. By means of stereological methods, the number of microglia and neurons were estimated in the ipsilateral dorsal lateral geniculate nucleus (dLGN) by an investigator blinded to the treatment. No effect on neuronal survival was observed at 24 hr, but 48 hr after injury, an unanticipated but significant minocycline-mediated increase in neuronal loss was detected. Further, while failing to inhibit microglial accumulation, minocycline treatment increased the proportion of amoeboid microglia in the ipsilateral dLGN. To understand the molecular mechanisms underlying this neurotoxic response, we identified minocycline-mediated changes in the expression of three potentially proapoptotic/inflammatory genes: growth arrest- and DNA damage-inducible gene 45gamma (GADD45gamma); interferon-inducible protein 1 (IFI1), and cytokine-induced growth factor. We also observed increased mitogen-activated protein kinase p38 phosphorylation with minocycline treatment. Although minocycline inhibited calpain activity at 12 hr after injury, this effect was not sustained at 24 hr. Together, these results help to explain how minocycline has a deleterious effect on neuronal survival in this injury model.

Predictors of RNs' Intent to Work and Work Decisions 1 Year Later in a U.S. National Sample

International Journal of Nursing Studies. Jul, 2009  |  Pubmed ID: 18377910

Many studies have examined predictors of nurses' intention to work in their job, including desire to quit. Intent has been a good predictor of actual turnover. Few longitudinal studies exist that consider regional variables.

The Role of L. Monocytogenes Serotype 4b GtcA in Gastrointestinal Listeriosis in A/J Mice

Foodborne Pathogens and Disease. Jan-Feb, 2009  |  Pubmed ID: 18991548

Serotype 4b strains of Listeria monocytogenes have been responsible for most large outbreaks of listeriosis. In L. monocytogenes serotype 4b, gtcA and gltA have been implicated in serotype-specific glycosylation of the teichoic acid of the cell wall with galactose and glucose. In this study, we investigated the impact of mutations in gltA (resulting in absence of glucose on teichoic acid) and gtcA (resulting in absence of galactose, and markedly reduced glucose on teichoic acid) on virulence following intragastric infection of anesthetized A/J mice. The gltA mutant was not impaired in virulence in this model. In contrast, testing of gtcA mutants constructed in two different strains showed that the mutants were recovered in lower numbers than their respective parent strains from the spleen, liver, ceca, and gall bladders of intragastrically inoculated mice. Genetic complementation of the gtcA mutation partially restored gastrointestinal virulence. When mice were inoculated intravenously, the gtcA mutants were also recovered in lower numbers from the liver (for both mutant strains) and the spleen (for one mutant strain) than their respective parental strains. The mutants were also evaluated for invasion and intracellular multiplication in the Caco-2 human intestinal epithelial cell line. Inactivation of gltA did not affect invasion or intracellular growth of the bacteria. In contrast, gtcA mutants showed decreased invasion, but normal multiplication in Caco-2 cells. Overall, these data demonstrate a role for gtcA in the pathogenesis of gastrointestinal listeriosis in mice, and suggest that diminished ability of gtcA mutants to invade intestinal epithelial cells may be partly responsible for decreased gastrointestinal virulence.

An Unprecedented Chemospecific and Stereoselective Tandem Nucleophilic Addition/cycloaddition Reaction of Nucleophilic Carbenes with Ketenimines

The Journal of Organic Chemistry. Jan, 2009  |  Pubmed ID: 19032113

The first study of the reaction between nucleophilic carbenes and ketenimines is reported. The interaction of thiazole and benzothiazole carbenes with ketenimines proceeded in a chemospecific and stereoselective manner to produce thiazole- and benzothiazole-spiro-pyrrole derivatives generally in good yields. The reaction was proposed to proceed via a tandem nucleophilic addition of carbene to the C=N bond of ketenimine followed by a stepwise [3+2] cycloaddition of the 1,3-dipolar intermediate with the C=C bond of ketenimine. This reaction provides a powerful protocol for the construction of novel polyfunctional thiazole-spiro-pyrrole or benzothiazole-spiro-pyrrole compounds that are not readily accessible by other methods.

[Assessment of Mitochondrial Metabolic Oxidative State in Living Cardiomyocytes with Spectrally-resolved Fluorescence Lifetime Spectroscopy of NAD(P)H]

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi = Journal of Biomedical Engineering = Shengwu Yixue Gongchengxue Zazhi. Dec, 2009  |  Pubmed ID: 20095467

The primary function of cardiac mitochondria is the production of ATP to support heart contraction. Examination of the mitochondrial redox state is therefore crucially important to sensitively detect early signs of mitochondrial function in pathophysiological conditions, such as ischemia, diabetes and heart failure. We study fingerprinting of mitochondrial metabolic oxidative state in living cardiomyocytes with spectrally-resolved fluorescence lifetime spectroscopy of NAD(P)H, the principal electron donor in mitochondrial respiration responsible for vital ATP supply. Here NAD(P)H is studied as a marker for non-invasive fluorescent probing of the mitochondrial function. NAD(P) H fluorescence is recorded in cardiac cells following excitation with 375nm UV-light and detection by spectrally-resolved time-correlated single photon counting (TCSPC), based on the simultaneous measurement of the fluorescence spectra and fluorescence lifetimes. Modulation of NADH production and/or mitochondrial respiration is tested to study dynamic characteristics of NAD(P) H fluorescence decay. Our results show that at least a 3-exponential decay model, with 0.4-0.7ns, 1.2-1.9ns and 8.0-13. Ons lifetime pools is necessary to describe cardiomyocyte autofluorescence (AF) within 420-560nm spectral range. Increased mitochondrial NADH production by ketone bodies enhanced the fluorescence intensity, without significant change in fluorescent lifetimes. Rotenone, the inhibitor of Complex I of the mitochondrial respiratory chain, increased AF intensity and shortened the average fluorescence lifetime. Dinitrophenol (DNP), an uncoupling agent of the mitochondrial oxidative phosphorylation, lowered AF intensity, broadened the spectral shoulder at 520 nm and increased the average fluorescence lifetime. These effects are comparable to the study of NADH fluorescence decay in vitro. In the present contribution we demonstrated that spectrally-resolved fluorescence lifetime technique provides promising new tool for analysis of mitochondrial NAD(P) H fluorescence with good reproducibility in living cardiomyocytes. This approach will enhance our knowledge about cardiomyocyte oxidative metabolism and/or its dysfunction at a cellular level. In the future, this approach can prove helpful in the clinical diagnosis and treatment of mitochondrial disorder.

Orthogonal Synthesis of Densely Functionalized Pyrroles and Thiophenes from the Reactions of Imidazo[1,5-a]pyridine Carbene-derived Zwitterions with Electron-deficient Alkynes

The Journal of Organic Chemistry. Apr, 2010  |  Pubmed ID: 20210328

1-Thiocarbamoyl imidazo[1,5-a]pyridinium inner salts, which were obtained readily from the addition of C,N-substituted heterocyclic carbenes imidazo[1,5-a]pyridine-1-ylidenes to isothiocyanates, are powerful ambident nucleophilic zwitterions. They acted as nitrogen nucleophiles toward ethyl propiolate to produce polyfunctionalized pyrrole derivatives in high yields. When treated with dimethyl acetylenedicarboxylate, they behaved exclusively as sulfur nucleophiles to afford fully substituted thiophenes in excellent yields. This work provides highly efficient orthogonal synthesis of polyfunctionalized pyrroles and thiophenes that were not easily obtained by other chemical means.

DNA Probes for Unambiguous Identification of Listeria Monocytogenes Epidemic Clone II Strains

Applied and Environmental Microbiology. May, 2010  |  Pubmed ID: 20305032

Listeria monocytogenes epidemic clone II (ECII) strains have been responsible for two major multistate outbreaks of food-borne listeriosis in the United States, but their prevalence and ecology remain poorly understood. In this study, we describe DNA probes that unambiguously identify this clonal group. These probes were able to differentiate ECII strains of outbreak, sporadic, or environmental origin from other L. monocytogenes strains of the same serotype (4b).

Double-balloon Enteroscopy for Obscure Gastrointestinal Bleeding: a Single Center Experience in China

World Journal of Gastroenterology : WJG. Apr, 2010  |  Pubmed ID: 20355245

To evaluate the diagnostic value of double-balloon enteroscopy (DBE) for obscure gastrointestinal bleeding (OGIB).

Rejection of Transplanted Hearts in Patients Evaluated by the Component Analysis of Multi-wavelength NAD(P)H Fluorescence Lifetime Spectroscopy

Journal of Biophotonics. Oct, 2010  |  Pubmed ID: 20635425

Rejection of transplanted hearts remains one of the principal reasons for death of paediatric patients, but an appropriate diagnostic tool for the mild rejection in early stages is still missing. Tissue autofluorescence (AF) is one of the most versatile non-invasive tools for mapping the metabolic state in living tissues. Increasing interest in the imaging and diagnosis of living cells and tissues based on their intrinsic fluorescence rather than fluorescence labelling is closely connected to the latest developments in high-performance spectroscopy and microscopy techniques. In this contribution, we investigate individual components in spectrally- and time-resolved NAD(P)H fluorescence, revealed by linear unmixing, responsible for increased fluorescence in patients presenting mild rejection of transplanted hearts. Application of such approach has the potential to improve the diagnostics of the cardiac transplant rejection by helping currently used histological analysis.

Mechanisms of Regulation of Oligodendrocyte Development by P38 Mitogen-activated Protein Kinase

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Aug, 2010  |  Pubmed ID: 20720108

Many extracellular and intrinsic factors regulate oligodendrocyte development, but their signaling pathways remain poorly understood. Although the p38 mitogen-activated protein kinase (MAPK)-dependent pathway is implicated in oligodendrocyte progenitor cell (OPC) lineage progression, its molecular targets involved in myelinogenesis are mostly unidentified. We have analyzed mechanisms by which p38MAPK regulates oligodendrocyte development and demonstrate that p38MAPK inhibition prevents OPC lineage progression and inhibits MBP (myelin basic protein) promoter activity and Sox10 function. In white-matter tissue, differential levels of MAPK phosphorylation are observed in oligodendrocyte lineage cells. Phosphorylated p38MAPK was found in CC1- and CNP-expressing differentiated oligodendrocytes of the adult brain and was temporally associated with a decline in the levels of phosphorylated extracellular signal-regulated kinase (ERK) in cells of this lineage. PDGF stimulates the phosphorylation of ERK, p38MAPK, and c-Jun N-terminal kinase (JNK), and p38MAPK inhibition was associated with increased ERK, JNK, and c-Jun phosphorylation. In the presence of PDGF, simultaneous inhibition of p38MAPK and either MAPK kinase (MEK) or JNK significantly alleviates the repression of myelin gene expression and lineage progression induced by p38MAPK inhibition alone. Dominant-negative c-Jun reverses the inhibition of myelin promoter activity by active MEK1 or dominant-negative p38MAPKalpha mutants, and phosphorylated c-Jun was detected at the MBP promoter after p38MAPK inhibition, indicating c-Jun as a negative mediator of p38MAPK action. Our findings indicate that p38MAPK activity in the brain supports myelin gene expression through distinct mechanisms via positive and negative regulatory targets. We show that oligodendrocyte differentiation involves p38-mediated Sox10 regulation and cross talk with parallel ERK and JNK pathways to repress c-Jun activity.

Multicomponent Reaction of Imidazo[1,5-a]pyridine Carbenes with Aldehydes and Dimethyl Acetylenedicarboxylate or Allenoates: a Straightforward Approach to Fully Substituted Furans

The Journal of Organic Chemistry. Oct, 2010  |  Pubmed ID: 20831236

The facile three-component reactions of N,N-substituted imidazo[1,5-a]pyridine carbenes, namely imidazo[1,5-a]pyridin-3-ylidenes, with aldehydes and DMAD or allenoates were disclosed. Both reactions proceeded via tandem nucleophilic addition, [3 + 2]-cycloaddition, and ring transformation to produce different 4-[(2-pyridyl)methyl]aminofuran derivatives generally in moderate yields. This work not only provided the first example of the application of imidazo[1,5-a]pyridin-3-ylidenes in organic synthesis but also developed a straightforward approach to fully substituted furans that are not easily accessible by other methods.

Tuning Electronic and Steric Effects: Highly Enantioselective [4+1] Pyrroline Annulation of Sulfur Ylides with Alpha,beta-unsaturated Imines

Angewandte Chemie (International Ed. in English). Jun, 2010  |  Pubmed ID: 20458720

Inflammation Inhibitory Effects of Sirolimus and Paclitaxel-eluting Stents on Interleukin-1β-induced Coronary Artery In-stent Restenosis in Pigs

Chinese Medical Journal. Sep, 2010  |  Pubmed ID: 21034557

Coronary artery in-stent restenosis (ISR) and late stent thrombosis remain as important complications of stenting. The inflammation reactions to sirolimus and paclitaxel-eluting stents were investigated in a swine stenosis model induced by interleukin (IL)-1β.

THE IMPACT OF FALLIBLE ITEM PARAMETER ESTIMATES ON LATENT TRAIT RECOVERY

Psychometrika. Jun, 2010  |  Pubmed ID: 21076651

In this paper we propose an upward correction to the standard error (SE) estimation of θ̂(ML), the maximum likelihood (ML) estimate of the latent trait in item response theory (IRT). More specifically, the upward correction is provided for the SE of θ̂(ML) when item parameter estimates obtained from an independent pretest sample are used in IRT scoring. When item parameter estimates are employed, the resulting latent trait estimate is called pseudo maximum likelihood (PML) estimate. Traditionally the SE of θ̂(ML) is obtained on the basis of test information only, as if the item parameters are known. The upward correction takes into account the error that is carried over from the estimation of item parameters, in addition to the error in latent trait recovery itself. Our simulation study shows that both types of SE estimates are very good when θ is in the middle range of the latent trait distribution, but the upward-corrected SEs are more accurate than the traditional ones when θ takes more extreme values.

Yuzurimine from of Daphniphyllum Macropodum Miq

Acta Crystallographica. Section E, Structure Reports Online. 2010  |  Pubmed ID: 21589172

The title compound, C(27)H(37)NO(7), is a Daphniphyllum alkaloid isolated from a branch of Daphniphyllum macropodum Miq. All of the five-membered rings adopt envelope conformations while the six- and seven-membered ring adopt chair conformations. Classical inter-molecular O-H⋯O and weak C-H⋯N hydrogen bonds are present in the crystal structure.

Does Adenosine Triphosphate Released into Voided Urodynamic Fluid Contribute to Urgency Signaling in Women with Bladder Dysfunction?

The Journal of Urology. Mar, 2010  |  Pubmed ID: 20092837

Adenosine triphosphate released from urothelium during stretch stimulates afferent nerves and conveys information on bladder fullness. We measured adenosine triphosphate released during cystometric bladder filling in women with idiopathic detrusor overactivity and stress incontinence (controls), and assessed whether the level of released adenosine triphosphate is related to cystometric parameters.

Experimental and Theoretical Study of a New Carbazole Derivative Having Terminal Benzimidazole Rings

Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy. Feb, 2010  |  Pubmed ID: 20015681

A novel intramolecular donor-acceptor compound has been synthesized and characterized. This compound was a symmetrical A-pi-D-pi-A type molecule containing two benzimidazole rings as two electron acceptors (A) and an N-ethylcarbazole group as electron donors (D). The absorption and emission spectra of the compound were determined by experimental methods in solution and were computed by using the density functional theory (DFT) and the time-dependent density functional theory (TDDFT) in gas phase and in chloroform solution. The calculated absorption and emission wavelengths were in good agreement with the experimental ones. The fluorescence quantum yields and fluorescence lifetimes of the compound in several solvents have been studied by means of steady state and time resolved fluorescence. The results showed the compound had high quantum yield. The cross-section of two-photon absorption (TPA) of the compound was measured by using femtosecond laser in dichloromethane solution. The result indicated the cross-section maximum of two-photon absorption was 430 GM at 600 nm. These results made the compound of great interest as a new fluorescent probe and photoluminescence material.

Improvements to Services at the European Nucleotide Archive

Nucleic Acids Research. Jan, 2010  |  Pubmed ID: 19906712

The European Nucleotide Archive (ENA; http://www.ebi.ac.uk/ena) is Europe's primary nucleotide sequence archival resource, safeguarding open nucleotide data access, engaging in worldwide collaborative data exchange and integrating with the scientific publication process. ENA has made significant contributions to the collaborative nucleotide archival arena as an active proponent of extending the traditional collaboration to cover capillary and next-generation sequencing information. We have continued to co-develop data and metadata representation formats with our collaborators for both data exchange and public data dissemination. In addition to the DDBJ/EMBL/GenBank feature table format, we share metadata formats for capillary and next-generation sequencing traces and are using and contributing to the NCBI SRA Toolkit for the long-term storage of the next-generation sequence traces. During the course of 2009, ENA has significantly improved sequence submission, search and access functionalities provided at EMBL-EBI. In this article, we briefly describe the content and scope of our archive and introduce major improvements to our services.

Leucine Deprivation Decreases Fat Mass by Stimulation of Lipolysis in White Adipose Tissue and Upregulation of Uncoupling Protein 1 (UCP1) in Brown Adipose Tissue

Diabetes. Jan, 2010  |  Pubmed ID: 19833890

White adipose tissue (WAT) and brown adipose tissue (BAT) play distinct roles in adaptation to changes in nutrient availability, with WAT serving as an energy store and BAT regulating thermogenesis. We previously showed that mice maintained on a leucine-deficient diet unexpectedly experienced a dramatic reduction in abdominal fat mass. The cellular mechanisms responsible for this loss, however, are unclear. The goal of current study is to investigate possible mechanisms.

Silencing Inducible Nitric Oxide Synthase Protects Rat Pancreatic Islet

Diabetes Research and Clinical Practice. Sep, 2010  |  Pubmed ID: 20541824

To investigate the effect of inducible nitric oxide synthase (iNOS) RNA interference on cytokine-induced injury of pancreatic islet in rats.

Organocatalytic Asymmetric Sulfa-michael/michael Addition Reactions: a Strategy for the Synthesis of Highly Substituted Chromans with a Quaternary Stereocenter

Angewandte Chemie (International Ed. in English). Nov, 2010  |  Pubmed ID: 20931588

[A Pilot Study of Weekly Versus 3-week Docetaxel in Combination with Capecitabine in Patients with Anthracycline-pretreated Metastatic Breast Cancer]

Zhonghua Yi Xue Za Zhi. Jul, 2010  |  Pubmed ID: 20979824

To evaluate the efficacy and safety of weekly or 3-week docetaxel in combination with capecitabine.

[Effect of Inducible Nitric Oxide Synthase on Pancreas Islet Apoptosis in Rats]

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi = Chinese Journal of Cellular and Molecular Immunology. Jan, 2010  |  Pubmed ID: 20056078

To investigate the effect and mechanism of cytokine and inducible nitric oxide synthase on apoptosis and function of rat pancreas islets cultured in vitro.

ATF4 Regulates Lipid Metabolism and Thermogenesis

Cell Research. Feb, 2010  |  Pubmed ID: 20066008

Activating transcription factor 4 (ATF4) has been shown to play key roles in many physiological processes. There are no reports, however, demonstrating a direct link between ATF4 and lipid metabolism. We noticed that Atf4-deficient mice are lean, suggesting a possible role for ATF4 in regulating lipid metabolism. The goal of our current study is to investigate the involvement of ATF4 in lipid metabolism and elucidate the underlying mechanisms. Studies using Atf4-deficient mice revealed increased energy expenditure, as measured by oxygen consumption. These mice also showed increases in lipolysis, expression of uncoupling protein 2 (UCP2) and beta-oxidation genes and decreases in expression of lipogenic genes in white adipose tissue (WAT), suggesting increased utilization and decreased synthesis of fatty acids, respectively. Expression of UCP1, 2 and 3 was also increased in brown adipose tissue (BAT), suggesting increased thermogenesis. The effect of ATF4 deletion on expression of UCPs in BAT suggests that increased thermogenesis may underlie increased energy expenditure. Thus, our study identifies a possible new function for ATF4 in regulating lipid metabolism and thermogenesis.

Quantification of Voriconazole in Human Plasma by High-performance Liquid Chromatography-electrospray Ionization Mass Spectrometry: Application to a Bioequivalence Study

Arzneimittel-Forschung. 2011  |  Pubmed ID: 21428249

A sensitive and specific liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) method was developed and validated for the identification and quantification of voriconazole (VRC, CAS 137234-62-9) in human plasma. Following liquid-liquid extraction, VRC and loratadine (internal standard, CAS 79794-75-5) were separated using a mobile phase comprised of methanol: water (0.1% formic acid) = 75:25 v/v on a Shimadzu Shim-pack VP-ODS C18 (150 x 2.0 mm ID, 5 microm) column and analyzed by electrospray ionization mass spectrometry. The chromatographic separation was achieved in less than 6 min. The standard curves were linear (r = 0.9994) over the concentration range of 2-2000 ng/mL for VRC and had good accuracy and precision. Both intra- and inter-batch standard deviations were less than 15%. The method was successfully applied to study the comparative bioavailability of VRC tablets test vs. reference in healthy Chinese volunteers through the statistical comparison of pharmacokinetic parameters obtained with the two formulations.

Toxin A-negative, Toxin B-positive Clostridium Difficile Infection Diagnosed by Polymerase Chain Reaction

Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. May, 2011  |  Pubmed ID: 21515990

The GUDMAP Database--an Online Resource for Genitourinary Research

Development (Cambridge, England). Jul, 2011  |  Pubmed ID: 21652655

The GenitoUrinary Development Molecular Anatomy Project (GUDMAP) is an international consortium working to generate gene expression data and transgenic mice. GUDMAP includes data from large-scale in situ hybridisation screens (wholemount and section) and microarray gene expression data of microdissected, laser-captured and FACS-sorted components of the developing mouse genitourinary (GU) system. These expression data are annotated using a high-resolution anatomy ontology specific to the developing murine GU system. GUDMAP data are freely accessible at www.gudmap.org via easy-to-use interfaces. This curated, high-resolution dataset serves as a powerful resource for biologists, clinicians and bioinformaticians interested in the developing urogenital system. This paper gives examples of how the data have been used to address problems in developmental biology and provides a primer for those wishing to use the database in their own research.

Visible Light-induced Intramolecular Cyclization Reactions of Diamines: a New Strategy to Construct Tetrahydroimidazoles

Chemical Communications (Cambridge, England). Aug, 2011  |  Pubmed ID: 21698332

A new and efficient synthesis of highly substituted tetrahydroimidazole derivatives by means of visible light-induced intramolecular cyclization reactions has been described. This photoredox catalytic reaction exhibited high diastereoselectivity and afforded the desired products in good yields.

Leucine Deprivation Stimulates Fat Loss Via Increasing CRH Expression in the Hypothalamus and Activating the Sympathetic Nervous System

Molecular Endocrinology (Baltimore, Md.). Sep, 2011  |  Pubmed ID: 21719534

We previously showed that leucine deprivation decreases abdominal fat mass largely by increasing energy expenditure, as demonstrated by increased lipolysis in white adipose tissue (WAT) and uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT). The goal of the present study was to investigate the possible involvement of central nervous system (CNS) in this regulation and elucidate underlying molecular mechanisms. For this purpose, levels of genes and proteins related to lipolysis in WAT and UCP1 expression in BAT were analyzed in wild-type mice after intracerebroventricular administration of leucine or corticotrophin-releasing hormone antibodies, or in mice deleted for three β-adrenergic receptors, after being maintained on a leucine-deficient diet for 7 d. Here, we show that intracerebroventricular administration of leucine significantly attenuates abdominal fat loss and blocks activation of hormone sensitive lipase in WAT and induction of UCP1 in BAT in leucine-deprived mice. Furthermore, we provide evidence that leucine deprivation stimulates fat loss by increasing expression of corticotrophin-releasing hormone in the hypothalamus via activation of stimulatory G protein/cAMP/protein kinase A/cAMP response element-binding protein pathway. Finally, we show that the effect of leucine deprivation on fat loss is mediated by activation of the sympathetic nervous system. These results suggest that CNS plays an important role in regulating fat loss under leucine deprivation and thereby provide novel and important insights concerning the importance of CNS leucine in the regulation of energy homeostasis.

The Effect of Damaged Skin Barrier Induced by Subclinical Irritation on the Sequential Irritant Contact Dermatitis

Cutaneous and Ocular Toxicology. Dec, 2011  |  Pubmed ID: 21774626

Skin damage caused by a single specific stimulus has been extensively studied. However, many additional mild skin irritants are experienced every day before obvious irritant contact dermatitis (ICD) appears. The effect that these previously experienced mild irritations have on the incidence and severity of sequential ICD remains undefined. The purpose of this work was to explore whether the effects of skin barrier damage induced by either the open patch test with 1% sodium lauryl sulfate (SLS), tape stripping test (TAP) (10×), or irradiation with 0.75 median erythemal dose UVB (MED) will affect the severity of sequential irritant dermatitis induced by a 0.5% SLS occlusive patch test (PT). Nine treatments were applied to nine different locations of the ventral forearm of each subject at random. The nine treatment types were as follows: open patch test with 1% SLS; 10× TAP; UVB irradiation with 0.75 MED; open patch test with 1% SLS + PT with 0.5% SLS (SLSPT); 10× TAP + PT with 0.5% SLS (TAPPT); UVB irradiation with 0.75 MED + PT with 0.5% SLS (UVPT); PT with distilled water (DISPT); PT with 0.5% SLS (PT); and the CONTROL (no treatment). After 5 days of subclinical irritation, the PT was applied on day 6. Transepidermal water loss (TEWL), capacitance (CAP), and skin color (a*) were measured at baseline and on days 6, 7, and 8. After the PT, indices of irritancy of PT, UVPT, SLSPT, and TAPPT were 60, 80, 87 and 100%, respectively. The index of irritancy of TAPPT and SLSPT were significantly higher than that of PT (p < 0.05). Clinical scores of SLSPT and TAPPT were also significantly higher than PT (p < 0.05). After 5 days of irritation, TEWL of SLS, TAP, SLSPT, and TAPPT were increased significantly compared to that of baseline. After the PT, D-value of TEWL between day 8 and day 6 ((≥6-8)TEWL) of SLSPT and TAPPT were greater than that of PT, and D-value of TEWL between day 8 and day 7 ((≥7-8)TEWL) of SLSPT and TAPPT were less than that of PT values. After the PT, a* values of SLSPT, TAPPT and PT all increased. The D-value of a* between day 8 and day 6 ((≥6-8)a*) of SLSPT and TAPPT were significantly greater than that of PT. After the PT, D-value of CAP between day 8 and day 6 ((≥6-8)CAP) of SLSPT was significantly different as compared to PT. The open patch test with 1% SLS and 10× TAP destroys the skin barrier and is able to significantly increase the irritancy and severity of sequential ICD by 0.5% SLS PT, and therefore influences the recovery speed of inflammation. The open patch test with 1% SLS, 10× TAP, and UVB irradiation with 0.75 MED affects the skin barrier to different degrees. TEWL is a sensitive biophysical parameter that can reflect mild damage to the skin barrier induced by subclinical irritation.

Experimental and Theoretical Study of Three New Benzothiazole-fused Carbazole Derivatives

Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy. Oct, 2011  |  Pubmed ID: 21795100

Three new D-π-A type compounds, each containing one benzothiazole ring as an electron acceptor and one N-ethylcarbazole group as electron donor, were synthesized and characterized by elemental analysis, NMR, MS and thermogravimetric analysis. The absorption and emission spectra of three compounds were experimentally determined in several solvents and were simultaneously computed using density functional theory (DFT) and time-dependent density functional theory (TDDFT). The calculated reorganization energy for hole and electron indicates that three compounds are in favor of hole transport than electron transport. The calculated absorption and emission wavelengths are well coincident with the measured data. The calculated lowest-lying absorption spectra can be mainly attributed to intramolecular charge transfer (ICT). And the calculated fluorescence spectra can be mainly described as originating from an excited state with intramolecular charge transfer (ICT) character. The results show that three compounds exhibited excellent thermal stability and high fluorescence quantum yields, indicating their potential applications as excellent optoelectronic material in optical field.

Reaction of β-lactam Carbenes with 2-pyridyl Isonitriles: a One-pot Synthesis of 2-carbonyl-3-(pyridylamino)imidazo[1,2-a]pyridines Useful As Fluorescent Probes for Mercury Ion

The Journal of Organic Chemistry. Sep, 2011  |  Pubmed ID: 21823590

The one-pot reaction of β-lactam carbenes with 2-pyridyl isonitriles followed by an acidic hydrolysis was reported, which produced 2-carbonyl-3-(pyridylamino)imidazo[1,2-a]pyridines in moderate to good yields. Among the resulting novel imidazo[1,2-a]pyridine derivatives, 1-(6-chloro-3-(5-chloropyridin-2-ylamino)imidazo[1,2-a]pyridin-2-yl)-2-ethylbutan-1-one was demonstrated to be an efficient fluorescent probe for mercury ion both in acetonitrile and in buffered aqueous solution.

SRY-box Containing Gene 17 Regulates the Wnt/β-catenin Signaling Pathway in Oligodendrocyte Progenitor Cells

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Sep, 2011  |  Pubmed ID: 21957254

The SRY-box (Sox) transcription factors regulate oligodendrocyte differentiation, but their signaling targets are largely unknown. We have identified a major signal transduction pathway regulated by Sox containing gene 17 (Sox17) in the oligodendrocyte lineage. Microarray analysis in oligodendrocyte progenitor cells (OPCs) after Sox17 attenuation revealed upregulated genes associated with cell cycle control and activation of the Wingless and integration site (Wnt)/β-catenin pathway. Sox17 knockdown also increases the levels of cyclin D1, Axin2, and activated β-catenin. In OPCs, the expression pattern of Sox17, cyclin D1, and secreted Frizzled-related protein-1 in the presence of platelet-derived growth factor (PDGF) was coordinately accelerated by addition of thyroid hormone, indicating differentiation-induced regulation of Sox17 targets. In developing white matter, decreased total β-catenin, activated β-catenin, and cyclin D1 levels coincided with the peak of Sox17 expression, and immunoprecipitates showed a developmentally regulated interaction among Sox17, T-cell transcription factor 4, and β-catenin proteins. In OPCs, PDGF stimulated phosphorylation of glycogen synthase 3β and the Wnt coreceptor LRP6, and enhanced β-catenin-dependent gene expression. Sox17 overexpression inhibited PDGF-induced TOPFLASH and cyclin D1 promoter activity, and decreased endogenous cyclin D1, activated β-catenin, as well as total β-catenin levels. Recombinant Sox17 prevented Wnt3a from repressing myelin protein expression, and inhibition of Sox17-mediated proteasomal degradation of β-catenin blocked myelin protein induction. These results indicate that Sox17 suppresses cyclin D1 expression and cell proliferation by directly antagonizing β-catenin, whose activity in OPCs is stimulated not only by Wnt3a, but also by PDGF. Our identification of downstream targets of Sox17 thus defines signaling pathways and molecular mechanisms in OPCs that are regulated by Sox17 during cell cycle exit and the onset of differentiation in oligodendrocyte development.

Asymmetric Cyclopropanation of β,γ-unsaturated α-ketoesters with Stabilized Sulfur Ylides Catalyzed by C2-symmetric Ureas

The Journal of Organic Chemistry. Jan, 2011  |  Pubmed ID: 21141872

A novel organocatalytic asymmetric cyclopropanation of β,γ-unsaturated α-ketoesters with stabilized sulfur ylides using C(2)-symmetric urea as a hydrogen-bond catalyst has been described. This reaction allows an efficient access to 1,2,3-trisubstituted cyclopropane derivatives in moderate to good yields with up to 16:1 dr and 90:10 er under mild reaction conditions. The mechanism study proved that the high stereoinduction originated from the cooperative effect of the hydrogen-bond catalyst.

1-(1-acetyl-piperidin-4-yl)-3-adamantan-1-yl-urea (AR9281) As a Potent, Selective, and Orally Available Soluble Epoxide Hydrolase Inhibitor with Efficacy in Rodent Models of Hypertension and Dysglycemia

Bioorganic & Medicinal Chemistry Letters. Feb, 2011  |  Pubmed ID: 21211973

1-(1-Acetyl-piperidin-4-yl)-3-adamantan-1-yl-urea 14a (AR9281), a potent and selective soluble epoxide hydrolase inhibitor, was recently tested in a phase 2a clinical setting for its effectiveness in reducing blood pressure and improving insulin resistance in pre-diabetic patients. In a mouse model of diet induced obesity, AR9281 attenuated the enhanced glucose excursion following an intraperitoneal glucose tolerance test. AR9281 also attenuated the increase in blood pressure in angiotensin-II-induced hypertension in rats. These effects were dose-dependent and well correlated with inhibition of the sEH activity in whole blood, consistent with a role of sEH in the observed pharmacology in rodents.

The Impact of Transgenic Papaya (TPY10-4) Fruit Supplementation on Immune Responses in Ovalbumin-sensitised Mice

Journal of the Science of Food and Agriculture. Feb, 2011  |  Pubmed ID: 21218490

A transgenic papaya line (TPY10-4) that is resistant to both papaya ringspot virus (PRSV) and papaya leaf distortion mosaic virus (PLDMV) has been developed in Taiwan. This study investigated the immunomodulatory properties of transgenic TPY10-4 and its native (TCK) papaya fruits using an ovalbumin (OVA)-sensitised mouse model. Both green and ripe papaya fruits at low (0.2 g powder kg(-1) body weight (BW)) and high (1.6 g powder kg(-1) BW) doses were administered to experimental mice by intragastric gavage for 5 weeks. Changes in serum total immunoglobulin A (IgA), IgE, IgG and IgM levels, OVA-specific IgE, IgG1 and IgG2a titres and Th1/Th2 cytokine secretions using splenocytes were determined.

RNA Interference Induces Effective Inhibition of MRNA Accumulation and Protein Expression of SHEV ORF3 Gene in Vitro

Current Microbiology. May, 2011  |  Pubmed ID: 21225263

RNA interference (RNAi) provides a powerful promising approach to inhibit viral infection specifically. To explore the possibility of using RNAi as a strategy against HEV infection, which is a serious public health problem in developing countries of Asia, Middle East, Africa, and in Mexico, after the fusion protein expression plasmids pEGFP-ORF3 which contain the EGFP reporter gene and SHEV ORF3 as silencing target, were constructed; EGFP-ORF3 fusion protein expressing HEK 293 cell lines were established; and four siRNAs targeting ORF3 gene were designed, synthesized, and used to transfect the stable cell lines. At 24, 48, and 72 h after transfection, flow cytometry, real-time quantitative PCR, and Western blot were used to assess the expression level of ORF3. The results demonstrated that specific siRNAs which are sequence dependant effectively inhibited mRNA accumulation and protein expression of SHEV ORF3 in HEK 293 cells. These findings provide useful information for the development of RNAi-based prophylaxis and therapy for SHEV infection.

Leucine Deprivation Increases Hepatic Insulin Sensitivity Via GCN2/mTOR/S6K1 and AMPK Pathways

Diabetes. Mar, 2011  |  Pubmed ID: 21282364

We have previously shown that serum insulin levels decrease threefold and blood glucose levels remain normal in mice fed a leucine-deficient diet, suggesting increased insulin sensitivity. The goal of the current study is to investigate this possibility and elucidate the underlying cellular mechanisms.

SiRNA Targeting MCD14 Inhibits TNF-α, MIP-2, and IL-6 Secretion and NO Production from LPS-induced RAW264.7 Cells

Applied Microbiology and Biotechnology. Oct, 2011  |  Pubmed ID: 21701985

Innate immunity plays a key role in protecting a host against invading microorganism, including Gram-negative bacteria. Cluster of differentiation antigen 14 (CD14) is an important innate immunity molecule, existing as a soluble (sCD14) and membrane-associated (mCD14) protein. Endotoxin [lipopolysaccharide (LPS)] is recognized as a key molecule in the pathogenesis of sepsis and septic shock caused by Gram negative bacteria. Emerging evidences indicate that upstream inhibition of bacterial LPS/Toll-like receptor 4(TLR4)/CD14-mediated inflammation pathway is an effective therapeutic approach for attenuating damaging immune activation. RNA interference (RNAi) provides a promising approach to down-regulate gene expression specifically. To explore the possibility of using RNAi against mCD14 as a strategy for inhibiting the secretion of cytokines and the nitric oxide (NO) production from LPS-activated RAW264.7 cells, four different short interfering RNA (siRNA) molecules corresponding to the sequence of mCD14 gene were designed and synthesized. We then tested the inhibition effects of these siRNA molecules on mCD14 expression by real-time quantitative RT-PCR and Western blot. After effective siRNA molecule (mCD14-siRNA-224), which is capable of reducing messenger RNA (mRNA) accumulation and protein expression of mCD14 specifically, was identified, RAW264.7 cells pretreated with mCD14-siRNA-224 were stimulated with LPS, and the secretion of tumor necrosis factor alpha (TNF-α), macrophage inflammatory protein-2 (MIP-2) and interleukin-6 (IL-6) and the NO production were evaluated. The results indicated that mCD14-siRNA-224 effectively inhibited TNF-α, MIP-2, and IL-6 release and NO production from LPS-stimulated RAW 264.7 cells by down-regulating mRNA accumulation and protein expression of mCD14 specifically. These findings provide useful information for the development of RNAi-based prophylaxis and therapy for endotoxin-related diseases.

Porcine Bladder Urothelial, Myofibroblast, and Detrusor Muscle Cells: Characterization and ATP Release

Frontiers in Pharmacology. 2011  |  Pubmed ID: 21713125

ATP is released from the bladder mucosa in response to stretch, but the cell types responsible are unclear. Our aim was to isolate and characterize individual populations of urothelial, myofibroblast, and detrusor muscle cells in culture, and to examine agonist-stimulated ATP release. Using female pig bladders, urothelial cells were isolated from bladder mucosa following trypsin-digestion of the luminal surface. The underlying myofibroblast layer was dissected, minced, digested, and cultured until confluent (10-14 days). A similar protocol was used for muscle cells. Cultures were used for immunocytochemical staining and/or ATP release investigations. In urothelial cultures, immunoreactivity was present for the cytokeratin marker AE1/AE3 but not the contractile protein α-smooth muscle actin (α-SMA) or the cytoskeletal filament vimentin. Neither myofibroblast nor muscle cell cultures stained for AE1/AE3. Myofibroblast cultures partially stained for α-SMA, whereas muscle cultures were 100% stained. Both myofibroblast and muscle stained for vimentin, however, they were morphologically distinct. Ultrastructural studies verified that the suburothelial layer of pig bladder contained abundant myofibroblasts, characterized by high densities of rough endoplasmic reticulum. Baseline ATP release was higher in urothelial and myofibroblast cultures, compared with muscle. ATP release was significantly stimulated by stretch in all three cell populations. Only urothelial cells released ATP in response to acid, and only muscle cells were stimulated by capsaicin. Tachykinins had no effect on ATP release. In conclusion, we have established a method for culture of three cell populations from porcine bladder, a well-known human bladder model, and shown that these are distinct morphologically, immunologically, and pharmacologically.

The European Nucleotide Archive

Nucleic Acids Research. Jan, 2011  |  Pubmed ID: 20972220

The European Nucleotide Archive (ENA; http://www.ebi.ac.uk/ena) is Europe's primary nucleotide-sequence repository. The ENA consists of three main databases: the Sequence Read Archive (SRA), the Trace Archive and EMBL-Bank. The objective of ENA is to support and promote the use of nucleotide sequencing as an experimental research platform by providing data submission, archive, search and download services. In this article, we outline these services and describe major changes and improvements introduced during 2010. These include extended EMBL-Bank and SRA-data submission services, extended ENA Browser functionality, support for submitting data to the European Genome-phenome Archive (EGA) through SRA, and the launch of a new sequence similarity search service.

[Molecular Typing Methods on Clostridium Difficile and Their Application]

Zhonghua Liu Xing Bing Xue Za Zhi = Zhonghua Liuxingbingxue Zazhi. Oct, 2011  |  Pubmed ID: 22333093

The Multicomponent Reaction of Imidazo[1,5-a]pyridine Carbenes with Phthalaldehydes and Dimethyl Acetylenedicarboxylate: a Facile Construction of Benzo[d]furo[3,2-b]azepines

Organic & Biomolecular Chemistry. Apr, 2011  |  Pubmed ID: 21293814

A study on the multicomponent reaction comprising both N-heterocyclic carbenes and substituted phthalaldehydes is reported. The imidazo[1,5-a]pyridine carbenes, namely imidazo[1,5-a]pyridine-3-ylidenes, reacted with phthalaldehydes and DMAD under very mild conditions to produce novel fused tricyclic benzo[d]furo[3,2-b]azepine derivatives. The resulting fused heterocyclic compounds are fluorescent and they give an emission around 500 nm with quantum yields (Φ(F)) being up to 0.81. This study provides not only a unique approach to fused azepine derivatives that are not easily accessible by other methods, but also opens a new avenue to complicated molecular skeletons. The fluorescence properties of long emission wavelength and high fluorescence quantum yields of some products predict their potential applications as optical sensors.

N-heterocyclic Carbene Catalyzed Reaction of Phthalaldehydes: Controllable Stereoselective Synthesis of Polyhydroxylated Spiro- and Fused Indenones Dictated by the Structure of NHC Catalysts

The Journal of Organic Chemistry. Mar, 2011  |  Pubmed ID: 21341805

The N-heterocyclic carbene catalyzed stereoselective dimerization reactions of phthalaldehydes produced polyhydroxylated spiro- or fused indenones. The reaction pathways were dictated by the structures of NHC catalysts. Under the catalysis of a imidazole carbene, phthalaldehydes produced dihydroxylspiro[indene-2,1'-isobenzofuran]-3-ones in good to excellent yields, whereas a triazole carbene catalyzed reaction of phthalaldehydes afforded fully cis-trihydroxylindeno[2,1-a]inden-5-ones in high yields. This work not only provides a highly efficient method for the construction of valuable polyhydroxyl substituted indene derivatives that are not easily assembled by other synthetic means but also reflects the versatility of organocatalysis using N-heterocyclic carbenes.

The Mechanism for the Ameliorative Effect of CpG-oligodeoxynucleotides on Bone Marrow Hemopoiesis Radiation Injury

Basic & Clinical Pharmacology & Toxicology. Jul, 2011  |  Pubmed ID: 21385323

Bone marrow is a major site of radiation injury. The extreme sensitivity of bone marrow cells to genotoxic stress largely determines the adverse side effects of radiation. CpG-oligodeoxynucleotide (ODN) is known to be radioprotective in extramedullary hemopoiesis, but its effect on bone marrow hemopoiesis remains unknown. In this study, we investigated whether CpG-ODN ameliorated hemopoiesis radiation injury when administered after total-body irradiation (TBI). Mice were treated with 50 μg of CpG-ODN via intraperitoneal injection (i.p) 30 min., 24 and 48 hr after TBI. Our results show that CpG-ODN was able to mediate the activation of nuclear factor κB (NF-κB) via degradation of inhibitor NF-κB (IκB-α), and some oxidative stress parameters (malondialdehyde, glutathione and superoxide dismutase) showed significant differences between the radiation control group and the radiation and administration of CpG-ODN group. White blood cell count, bone marrow cell count and bone marrow histological examination indicated that CpG-ODN minimized bone marrow damage induced by radiation. Exogenous colony-forming unit-spleen count indicated that CpG-ODN reduced primitive hemopoietic stem cell damage and reconstituted the hemopoietic system after TBI. The survival of mice was also enhanced after various levels of TBI. The calculated dose reduction factor was 1.2. Thus, we conclude that CpG-ODN may contribute to the amelioration of hemopoiesis radiation injury.

Identification and Characterization of Dicer-like, Argonaute and RNA-dependent RNA Polymerase Gene Families in Maize

Plant Cell Reports. Jul, 2011  |  Pubmed ID: 21404010

Eukaryotic gene expression is regulated at least by two processes, RNA interference at the post-transcriptional level and chromatin modification at the transcriptional level. Distinct small RNAs (approximately 21-24 nucleotides; sRNAs) were demonstrated to play vital roles in facilitating gene silencing. In plants, the generation of these sRNAs mainly depends on some proteins encoded by respective Dicer-like (DCL), Argonaute (AGO) and RNA-dependent RNA polymerases (RDR) gene families. Here, we analyzed the DCL, AGO and RDR gene families in maize, including gene structure, phylogenetic relationships, protein conserved motifs and genomic localization among gene family members. A total of 5 Zmdcl, 18 Zmago and 5 Zmrdr genes were identified in maize. Phylogenetic analyses clustered each of these genes families into four subfamilies. In addition, gene chromosomal localization revealed that five pairs of Zmago genes resulted from tandem or segmental duplication, respectively. EST expression data mining revealed that these newly identified genes had temporal and spatial expression pattern. Furthermore, the transcripts of these genes were detected in the leaves by two different abiotic stress treatments using semi-quantitative RT-PCR. The data demonstrated that these genes exhibited different expression levels in stress treatments. The results of this study provided basic genomic information for these gene families and insights into the probable roles of these genes in plant growth and development. This will further provide a solid foundation for future functional genomics studies of Dicer-like, Argonaute and RDR gene families in maize.

MiR-21 Plays an Important Role in Radiation Induced Carcinogenesis in BALB/c Mice by Directly Targeting the Tumor Suppressor Gene Big-h3

International Journal of Biological Sciences. 2011  |  Pubmed ID: 21494432

Dysregulation of certain microRNAs (miRNAs) in cancer can promote tumorigenesis, metastasis and invasion. However, the functions and targets of only a few mammalian miRNAs are known. In particular, the miRNAs that participates in radiation induced carcinogenesis and the miRNAs that target the tumor suppressor gene Big-h3 remain undefined. Here in this study, using a radiation induced thymic lymphoma model in BALB/c mice, we found that the tumor suppressor gene Big-h3 is down-regulated and miR-21 is up-regulated in radiation induced thymic lymphoma tissue samples. We also found inverse correlations between Big-h3 protein and miR-21 expression level among different tissue samples. Furthermore, our data indicated that miR-21 could directly target Big-h3 in a 3'UTR dependent manner. Finally, we found that miR-21 could be induced by TGFβ, and miR-21 has both positive and negative effects in regulating TGFβ signaling. We conclude that miR-21 participates in radiation induced carcinogenesis and it regulates TGFβ signaling.

Partially Hydrolyzed Cow's Milk Formula Has a Therapeutic Effect on the Infants with Mild to Moderate Atopic Dermatitis: a Randomized, Double-blind Study

Pediatric Allergy and Immunology : Official Publication of the European Society of Pediatric Allergy and Immunology. Nov, 2011  |  Pubmed ID: 21539614

The allergy-preventing effect of partially hydrolyzed cow's milk formula (phCMF) in infants at high risk of atopic dermatitis (AD) has been demonstrated in many studies. However, the therapeutic potential of phCMF in treating the infants with AD has not been reported. We sought to assess such therapeutic efficacy of phCMF in infants with mild to moderate AD.

Interaction of β-lactam Carbenes with 3,6-diphenyltetrazines: a Five-step Cascade Reaction for the Direct Construction of Indeno[2,1-b]pyrrol-2-ones

The Journal of Organic Chemistry. Jun, 2011  |  Pubmed ID: 21548593

A study of the nucleophilic addition of β-lactam carbenes to 3,6-diphenyltetrazines is reported. Instead of the formation of pyrazole derivatives like most reactions between nucleophilic or ambiphilic carbenes and 3,6-disubstituted tetrazines, β-lactam carbenes reacted with 3,6-diphenyltetrazines to produce indeno[2,1-b]pyrrol-2-ones in good yields. The reaction proceeds most probably through a five-step cascade process. This work has not only provided a one-pot operation for the efficient construction of mutisubstituted indeno[2,1-b]pyrrol-2-ones but also revealed the nucleophilicity of β-lactam carbenes.

Chinese Guidelines on the Diagnosis and Treatment of Primary Lung Cancer (2011)

Journal of Thoracic Disease. Feb, 2012  |  Pubmed ID: 22295172

Measuring T2 in Vivo with J-difference Editing: Application to GABA at 3 Tesla

Journal of Magnetic Resonance Imaging : JMRI. Jan, 2012  |  Pubmed ID: 22045601

To develop an experimental approach for determining in vivo transverse relaxation rates (T(2)) of metabolites that are detected by spectral editing without using simulations, and to demonstrate this approach to measure the T(2) of γ-aminobutyric acid (GABA).

Major Submissions Tool Developments at the European Nucleotide Archive

Nucleic Acids Research. Jan, 2012  |  Pubmed ID: 22080548

The European Nucleotide Archive (ENA; http://www.ebi.ac.uk/ena), Europe's primary nucleotide sequence resource, captures and presents globally comprehensive nucleic acid sequence and associated information. Covering the spectrum from raw data to assembled and functionally annotated genomes, the ENA has witnessed a dramatic growth resulting from advances in sequencing technology and ever broadening application of the methodology. During 2011, we have continued to operate and extend the broad range of ENA services. In particular, we have released major new functionality in our interactive web submission system, Webin, through developments in template-based submissions for annotated sequences and support for raw next-generation sequence read submissions.

Disruption of the Phospholipase D Gene Attenuates the Virulence of Aspergillus Fumigatus

Infection and Immunity. Jan, 2012  |  Pubmed ID: 22083709

Aspergillus fumigatus is the most prevalent airborne fungal pathogen that induces serious infections in immunocompromised patients. Phospholipases are key enzymes in pathogenic fungi that cleave host phospholipids, resulting in membrane destabilization and host cell penetration. However, knowledge of the impact of phospholipases on A. fumigatus virulence is rather limited. In this study, disruption of the pld gene encoding phospholipase D (PLD), an important member of the phospholipase protein family in A. fumigatus, was confirmed to significantly decrease both intracellular and extracellular PLD activity of A. fumigatus. The pld gene disruption did not alter conidial morphological characteristics, germination, growth, and biofilm formation but significantly suppressed the internalization of A. fumigatus into A549 epithelial cells without affecting conidial adhesion to epithelial cells. Importantly, the suppressed internalization was fully rescued in the presence of 100 μM phosphatidic acid, the PLD product. Indeed, complementation of pld restored the PLD activity and internalization capacity of A. fumigatus. Phagocytosis of A. fumigatus conidia by J774 macrophages was not affected by the absence of the pld gene. Pretreatment of conidia with 1-butanol and a specific PLD inhibitor decreased the internalization of A. fumigatus into A549 epithelial cells but had no effect on phagocytosis by J774 macrophages. Finally, loss of the pld gene attenuated the virulence of A. fumigatus in mice immunosuppressed with hydrocortisone acetate but not with cyclophosphamide. These data suggest that PLD of A. fumigatus regulates its internalization into lung epithelial cells and may represent an important virulence factor for A. fumigatus infection.

The Reaction of β-lactam Carbenes with 3,6-dipyridyltetrazines: Switch of Reaction Pathways by 2-pyridyl and 4-pyridyl Substituents of Tetrazines

Organic & Biomolecular Chemistry. Feb, 2012  |  Pubmed ID: 22134414

The reactions of β-lactam carbenes with both 3,6-di(2-pyridyl)tetrazine and 3,6-di(4-pyridyl)tetrazine were studied. It was found that β-lactam carbenes reacted with 3,6-di(2-pyridyl)tetrazine to produce 5-triazolo[1,5-a]pyridylpyrrol-2-ones in good yields, while with 3,6-di(4-pyridyl)tetrazine, they afforded pyrido[c]cyclopenta[b]pyrrol-2-ones in moderate yields. Both reactions were proposed to follow cascade mechanisms containing a 3,6a-dipyridylpyrrolo[3,2-c]pyrazol-5-one intermediate. The different pathways of the transformation of pyrrolo[3,2-c]pyrazol-5-ones were switched by the 2- and 4-pyridyl substituents. This work not only provided a simple and efficient strategy for the construction of novel triazolo[1,5-a]pyridine and pyrido[c]cyclopenta[b]pyrrole derivatives, respectively, but also revealed two different thermal transformation patterns of 3H-pyrazole compounds.

Effect of 40 Mg Versus 10 Mg of Atorvastatin on Oxidized Low-Density Lipoprotein, High-Sensitivity C-Reactive Protein, Circulating Endothelial-Derived Microparticles, and Endothelial Progenitor Cells in Patients With Ischemic Cardiomyopathy

Clinical Cardiology. Feb, 2012  |  Pubmed ID: 22271072

There are few recent data to delineate the beyond lipids-decreased effect of statins and the effect of different doses of statins on endothelial-derived microparticles (EMPs) and circulating endothelial progenitor cells (EPCs) in patients with ischemic cardiomyopathy (ICM).