bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and clinical correlates of bronchoreversibility in severe emphysema
Authors: Han M. K. , Wise R. , Mumford J. , Sciurba F. , Criner G. J. , Curtis J. L. , Murray S. , Sternberg A. , Weinman G. , Kazerooni E. , Fishman A. P. , Make B. , Hoffman E. A. , Mosenifar Z. , Martinez F. J.
Published: November 2009

Chronic obstructive pulmonary disease (COPD) exhibits airflow obstruction that is not fully reversible. The importance of bronchoreversibility remains controversial.

We hypothesised that an emphysematous phenotype of COPD would be associated with decreased bronchoreversibility.

544 patients randomised to the medical arm of the National Emphysema Treatment Trial formed the study group. Participants underwent multiple measurements of bronchoreversibility on a mean of four sessions over 1.91 yrs. They were also characterised by measures of symptoms, quality of life and quantitative measures of emphysema by computed tomography.

Mean baseline forced expiratory volume in 1 s (FEV1) in this patient population is 24% predicted. 22.2% of patients demonstrated bronchoreversibility on one or more occasions using American Thoracic Society/European Respiratory Society criteria. Few patients (0.37%) had bronchoreversibility on all completed tests. Patients who demonstrated bronchoreversibility were more likely to be male, and have better lung function and less emphysema. 64% of patients demonstrated large (≥400 mL) changes in forced vital capacity (FVC).

In a severe emphysema population, bronchoreversibility as defined by change in FEV1is infrequent, varies over time, and is more common in males and those with less severe emphysema. Improvements in FVC, however, were demonstrated in the majority of patients.
Prevalence and outcome of pulmonary fibrosis in microscopic polyangiitis
Authors: Tzelepis G.E. , Kokosi M. , Tzioufas A. , Toya S.P. , Boki K.A. , Zormpala A. , Moutsopoulos H.M.
Published: November 2009

We sought to determine the type of pulmonary involvement in microscopic polyangiitis (MPA), primarily focusing on pulmonary fibrosis (PF), its prevalence, temporal relationship with other disease manifestations and outcome.

33 patients (16 males) with biopsy proven perinuclear anti-neutrophilic cytoplasmic antibody-positive MPA (age 63.5 yrs) participated in the study. Pulmonary involvement was assessed using standard methods, including radiographic imaging (chest radiographs and high-resolution computed tomography), pulmonary function testing, bronchoscopy and bronchoalveolar lavage, and, if indicated, lung biopsy. All-cause mortality was analysed by the Kaplan–Meier method and was compared between MPA patients with and without PF.

At the time of diagnosis, renal involvement was detected in all patients, with renal biopsies being consistent with segmental necrotising glomerulonephritis in all patients. The most common respiratory symptom was haemoptysis, which was found in nine (27%) patients. PF was present in 12 (36%) patients at the time of diagnosis, whereas one patient developed PF while on therapy ∼10 yrs after disease diagnosis. In seven patients with PF, respiratory symptoms related to fibrosis preceded other disease manifestations by a median (range) period of 13 (5–120) months. Patients were followed up for a period of 38±30 months. Presence of PF was associated with increased mortality (p = 0.02), with six deaths occurring in the fibrotic group and one in the nonfibrotic group. In the fibrotic group most deaths were related to PF.

PF occurs frequently in MPA, may precede other disease manifestations by a variable length of time and has a poor prognosis.
Effects of formoterol and salmeterol on cytokine release from monocyte-derived macrophages
Authors: Donnelly L.E. , Tudhope S.J. , Fenwick P.S. , Barnes P.J.
Published: November 2009

Pulmonary macrophages are a target for inhaled therapies. Combinations of long-acting β2-agonists (LABA) and glucocorticosteroids have been developed for asthma and chronic obstructive pulmonary disease (COPD). This study examined two LABA, salmeterol and formoterol, and the glucocorticosteroid, budesonide, on cytokine release from monocyte-derived macrophages (MDM) to determine whether anti-inflammatory effects observed in patients are due to inhibition of macrophages.

MDM were incubated in the absence or presence of LABA or budesonide prior to stimulation with lipopolysaccharide (LPS). Tumour necrosis factor (TNF)-α, granulocyte macrophage-colony stimulating factor (GM-CSF) and CXC chemokine ligand (CXCL)8 were measured by ELISA.

Formoterol and salmeterol inhibited LPS-stimulated release of TNF-α (mean effective concentration (EC50) 2.4±1.8 and 3.5±2.7 nM, respectively; n = 11–16), GM-CSF (EC5024.6±2.1 and 52.4±40.8 nM, respectively, n = 11–12) but not CXCL8 from LPS-stimulated MDM. Budesonide inhibited release of all three cytokines (EC50TNF-α: 1.2±0.4 nM; GM-CSF: 0.4±0.2 nM; CXCL8: 0.4±0.1 nM; n = 3–4). Formoterol but not salmeterol elevated cAMP in these cells. These effects were attenuated by β-adrenoceptor antagonists, propranolol and ICI118551. Salmeterol (10−7M) also inhibited formoterol-induced cAMP and formoterol-mediated attenuation of cytokine release. Combining budesonide (0.3 nM) with formoterol, inhibited TNF-α release additively.

LABA may inhibit inflammatory cytokine release from macrophages in a cAMP-independent manner and act additively with budesonide.
Topical recombinant thrombin at a concentration of 1000 IU/mL reliably shortens in vivo TTH and delivers durable hemostasis in the presence of heparin anticoagulation and clopidogrel platelet inhibition in a rabbit model of vascular bleeding
Authors: Hughes Steven D , Bishop Paul D , Garcia Richard , Zhang Tracy , Alexander W Allan
Published: November 2009

Background

This study was designed to evaluate the effect of recombinant human thrombin (rThrombin) concentration on time to hemostasis (TTH), clot durability, and clot strength in settings that replicate the heparinization and platelet inhibition often found in surgical populations.

Methods

A modified, anticoagulated rabbit arteriovenous shunt preparation was selected to model vascular anastomotic bleeding. Rabbits were treated with heparin or heparin + clopidogrel and TTH was measured after applying a range of topical rThrombin concentrations or placebo, in combination with absorbable gelatin sponge, USP. Treatments (placebo, rThrombin) were randomly assigned and the investigator was blinded to treatment. TTH was evaluated with the Kaplan-Meier method. After hemostasis was achieved, clot burst assessment was performed for heparin + clopidogrel treated animals. Clot viscoelastic strength and kinetics were measured in ex-vivo samples using thromboelastography (TEG) methods.

Results

TTH decreased with increasing concentrations of rThrombin in heparin-treated animals and was shorter after treatment with 1000 IU/mL rThrombin (73 seconds) than with 125 IU/mL rThrombin (78 seconds; p = 0.007). TTH also decreased with increasing concentrations of rThrombin in heparin + clopidogrel treated animals; again it was significantly shorter after treatment with 1000 IU/mL rThrombin (71 seconds) than with 125 IU/mL rThrombin (177 seconds; p < 0.001). Variability in TTH was significantly smaller after treatment with 1000 IU/mL rThrombin than after 125 IU/mL rThrombin, indicating greater reliability of clot formation (p < 0.001 for heparin or heparin + clopidogrel treatments). Clot durability was examined in heparin + clopidogrel treated animals. Clots formed in the presence of 1000 IU/mL rThrombin were significantly less likely to rupture during clot burst assessment than those formed in the presence of 125 IU/mL rThrombin (0% versus 79%, p < 0.001). In vitro clot strength and clot kinetics, as determined by TEG in heparin + clopidogrel samples, were positively associated with the amount of rThrombin activity added for clot initiation.

Conclusion

In an animal model designed to replicate the anti-coagulation regimens encountered in clinical settings, topical rThrombin at 1000 IU/mL more reliably controlled the pharmacological effects of heparin or heparin + clopidogrel on hemostasis than rThrombin at 125 IU/mL. Results from in vitro assessments confirmed a positive relationship between the amount of rThrombin activity and both the rate of clot formation and clot strength.
CBP/p300 is a cell type-specific modulator of CLOCK/BMAL1-mediated transcription
Authors: Hosoda Hiroshi , kato Kenichi , Asano Hidenori , Ito Motonori , Kato Haruno , Iwamoto Taku , Suzuki Akinobu , Masushige Shoichi , Kida Satoshi
Published: November 2009

Background

Previous studies have demonstrated tissue-specific regulation of the rhythm of circadian transcription, suggesting that transcription factor complex CLOCK/BMAL1, essential for maintaining circadian rhythm, regulates transcription in a tissue-specific manner. To further elucidate the mechanism of the cell type-specific regulation of transcription by CLOCK/BMAL1 at the molecular level, we investigated roles of CBP/p300 and tissue-specific cofactors in CLOCK/BMAL1-mediated transcription.

Results

As shown previously, CBP/p300 stimulates CLOCK/BMAL1-mediated transcription in COS-1 cells. However, CBP/p300 repressed CLOCK/BMAL1-mediated transcription in NIH3T3 cells and knockdown of CBP or p300 expression by siRNA enhanced this transcription. Studies using GAL4-fusion proteins suggested that CBP represses CLOCK/BMAL1-mediated transcription by targeting CLOCK. We further investigated mechanisms of this cell type-specific modulation of CLOCK/BMAL1-mediated transcription by CBP by examining roles of co-repressor HDAC3 and co-activator pCAF, which are highly expressed in NIH3T3 and COS cells, respectively. CBP repressed CLOCK/BMAL1-mediated transcription in COS-1 cells when HDAC3 was overexpressed, but activated it in NIH3T3 cells when pCAF was overexpressed. CBP forms a complex with CLOCK by interacting with HDAC3 or pCAF; however, direct interaction of CBP with CLOCK was not observed.

Conclusion

Our findings indicate possible mechanisms by which CBP/p300 tissue-specifically acts cooperatively with pCAF and HDAC3 either as a co-activator or co-repressor, respectively, for CLOCK/BMAL1.
Abnormalities in brain structure and behavior in GSK-3alpha mutant mice
Authors: Kaidanovich-Beilin Oksana , Lipina Tatiana V , Takao Keizo , van Eede Matthijs , Hattori Satoko , Laliberté Christine , Khan Mustafa , Okamoto Kenichi , Chambers John W , Fletcher Paul J , MacAulay Katrina , Doble Bradley W , Henkelman Mark , Miyakawa Tsuyoshi , Roder John , Woodgett James R
Published: November 2009

Background

Glycogen synthase kinase-3 (GSK-3) is a widely expressed and highly conserved serine/threonine protein kinase encoded by two genes that generate two related proteins: GSK-3α and GSK-3β. Mice lacking a functional GSK-3α gene were engineered in our laboratory; they are viable and display insulin sensitivity. In this study, we have characterized brain functions of GSK-3α KO mice by using a well-established battery of behavioral tests together with neurochemical and neuroanatomical analysis.

Results

Similar to the previously described behaviours of GSK-3β+/-mice, GSK-3α mutants display decreased exploratory activity, decreased immobility time and reduced aggressive behavior. However, genetic inactivation of the GSK-3α gene was associated with: decreased locomotion and impaired motor coordination, increased grooming activity, loss of social motivation and novelty; enhanced sensorimotor gating and impaired associated memory and coordination. GSK-3α KO mice exhibited a deficit in fear conditioning, however memory formation as assessed by a passive avoidance test was normal, suggesting that the animals are sensitized for active avoidance of a highly aversive stimulus in the fear-conditioning paradigm. Changes in cerebellar structure and function were observed in mutant mice along with a significant decrease of the number and size of Purkinje cells.

Conclusion

Taken together, these data support a role for the GSK-3α gene in CNS functioning and possible involvement in the development of psychiatric disorders.
The modified two-by-one fixed orthodontic appliance for bodily movement of canine: a case report
Authors: Tsui Vicky WK , Alkhal Hessa A , Hou Huie M , Wong Ricky WK , Rabie A Bakr M
Published: November 2009

Background

Orthodontic management of an ectopically erupted canine requires substantial amount of bodily movement which is difficult to perform and often results in root resorption.

Case presentation

A 9 year old girl presented with Class I malocclusion with crowding and ectopically positioned upper left canine (23). Treatment involved extraction of all first premolars. The alignment of the upper left canine was achieved by the modified 2 by 1 appliance.

Conclusion

The design of this modified 2 by 1 appliance allows individualized bodily tooth movement of canine, it provides light and continuous force for physiological orthodontic movement with minimal root resorption.
Poly(A) signal-dependent degradation of unprocessed nascent transcripts accompanies poly(A) signal-dependent transcriptional pausing in vitro
Authors: Kazerouninia Amir , Ngo Benson , Martinson Harold G.
Published: November 2009

The poly(A) signal has long been known for its role in directing the cleavage and polyadenylation of eukaryotic mRNA. In recent years its additional coordinating role in multiple related aspects of gene expression has also become increasingly clear. Here we use HeLa nuclear extracts to study two of these activities, poly(A) signal-dependent transcriptional pausing, which was originally proposed as a surveillance checkpoint, and poly(A) signal-dependent degradation (PDD) of unprocessed transcripts from weak poly(A) signals. We confirm directly, by measuring the length of RNA within isolated transcription elongation complexes, that a newly transcribed poly(A) signal reduces the rate of elongation by RNA polymerase II and causes the accumulation of elongation complexes downstream from the poly(A) signal. We then show that if the RNA in these elongation complexes contains a functional but unprocessed poly(A) signal, degradation of the transcripts ensues. The degradation depends on the unprocessed poly(A) signal being functional, and does not occur if a mutant poly(A) signal is used. We suggest that during normal 3′-end processing the uncleaved poly(A) signal continuously samples competing reaction pathways for processing and for degradation, and that in the case of weak poly(A) signals, where poly(A) site cleavage is slow, the default pathway to degradation predominates.
hnRNP A1 and hnRNP H can collaborate to modulate 5′ splice site selection
Authors: Fisette Jean-François , Toutant Johanne , Dugré-Brisson Samuel , Desgroseillers Luc , Chabot Benoit
Published: November 2009

The mammalian proteins hnRNP A1 and hnRNP H control many splicing decisions in viral and cellular primary transcripts. To explain some of these activities, we have proposed that self-interactions between bound proteins create an RNA loop that represses internal splice sites while simultaneously activating the external sites that are brought in closer proximity. Here we show that a variety of hnRNP H binding sites can affect 5′ splice site selection. The addition of two sets of hnRNP H sites in a model pre-mRNA modulates 5′ splice site selection cooperatively, consistent with the looping model. Notably, binding sites for hnRNP A1 and H on the same pre-mRNA can similarly collaborate to modulate 5′ splice site selection. The C-terminal portion of hnRNP H that contains the glycine-rich domains (GRD) is essential for splicing activity, and it can be functionally replaced by the GRD of hnRNP A1. Finally, we used the bioluminescence resonance energy transfer (BRET) technology to document the existence of homotypic and heterotypic interactions between hnRNP H and hnRNP A1 in live cells. Overall, our study suggests that interactions between different hnRNP proteins bound to distinct locations on a pre-mRNA can change its conformation to affect splicing decisions.
Pathwise Estimation of Probability Sensitivities Through Terminating or Steady-State Simulations
Authors: Hong L. Jeff , Liu Guangwu
Published: November 2009

A probability is the expectation of an indicator function. However, the standard pathwise sensitivity estimation approach, which interchanges the differentiation and expectation, cannot be directly applied because the indicator function is discontinuous. In this paper, we design a pathwise sensitivity estimator for probability functions based on a result of Hong [Hong, L. J. 2009. Estimating quantile sensitivities. Oper. Res. 57(1) 118–130]. We show that the estimator is consistent and follows a central limit theorem for simulation outputs from both terminating and steady-state simulations, and the optimal rate of convergence of the estimator is n-2/5 where n is the sample size. We further demonstrate how to use importance sampling to accelerate the rate of convergence of the estimator to n-1/2, which is the typical rate of convergence for statistical estimation. We illustrate the performances of our estimators and compare them to other well-known estimators through several examples.
Reviews
Authors: Hind Claire
Published: November 2009

York/NEW YORK A performance installation featured at the Writing Encounters symposium at York St John University, September 2008
Differential expression of microRNAs in human parathyroid carcinomas compared with normal parathyroid tissue
Authors: Corbetta S , Vaira V , Guarnieri V , Scillitani A , Eller-Vainicher C , Ferrero S , Vicentini L , Chiodini I , Bisceglia M , Beck-Peccoz P , Bosari S , Spada A
Published: November 2009

Parathyroid carcinoma (PaC) is a rare cause of primary hyperparathyroidism. Though the loss of the oncosuppressor CDC73/HRPT2 gene product, parafibromin, has been involved in the hyperparathyroidism–jaw tumor syndrome and in a consistent set of sporadic PaCs, parathyroid carcinogenesis remains obscure. MicroRNAs are a new class of small, non-coding RNAs implicated in development of cancer, since their deregulation can induce aberrant expression of several target genes. The aim of the present study was to identify differentially expressed microRNAs in parathyroid cancers compared with normal tissues. We performed a TaqMan low-density array profiling of four parathyroid cancers harboring CDC73 inactivating mutations and negative for parafibromin immunostaining. Their microRNA profiling was compared with that of two normal parathyroid biopsies. Out of 362 human microRNAs assayed, 279 (77%) were successfully amplified. Fourteen and three microRNAs were significantly down- and over-expressed in parathyroid cancers respectively. Of these, miR-296 and miR-139 were down-regulated, and miR-503 and miR-222 were over-expressed with a null false discovery rate. Carcinomas could be discriminated from parathyroid adenomas by a computed score based on the expression levels of miR-296, miR-222, and miR-503 as miR-139 was similarly down-regulated in both cancers and adenomas. Finally, miR-296 and miR-222 levels negatively correlated with mRNA levels of the hepatocyte growth factor receptor-regulated tyrosine kinase substrate and p27/kip1 levels respectively. These results suggest the existence of an altered microRNA expression pattern in PaCs together with a potential role of miR-296 as novel oncosuppressor gene in these neoplasia.
The antioxidant properties of carnitine in vitro
Authors: Solarska Katarzyna , Lewińska Anna , Karowicz-Bilińska Agata , Bartosz Grzegorz
Published: November 2009

Many of the effects of carnitine are ascribed to its antioxidant properties. The aim of this study was to evaluate the antioxidant properties of carnitine in vitro. Carnitine was found to decolorize ABTS•+, and to protect fluorescein against bleaching induced by AAPH-derived peroxyl radicals and peroxynitrite, thiol groups against oxidation induced by hydrogen peroxide, peroxyl radicals, hypochlorite and peroxynitrite, and erythrocytes against hemolysis induced by peroxyl radicals and hypochlorite. These results show that carnitine has a direct antioxidant action against physiologically relevant oxidants.
The interaction of PVP complexes of gossypol and its derivatives with an artificial membrane lipid matrix
Authors: Ionov Maksim , Tukfatullina Ilnora , Salakhutdinov Bakhtiyar , Baram Nina , Bryszewska Maria , Aripov Takhir
Published: November 2009

In this paper, we present the results of a study on the membrane-active properties of gossypol, its derivatives and their polyvinylpyrrolidone complexes as assessed by differential scanning calorimetry and by the fluorescent probe method. The latter revealed the change in polarization of the incident radiation caused by the action of the polyphenol on the artificial membrane lipid matrix.
Novice and Experienced Physical Therapist Clinicians: A Comparison of How Reflection Is Used to Inform the Clinical Decision-Making Process
Authors: Wainwright Susan Flannery , Shepard Katherine F. , Harman Laurinda B. , Stephens James
Published: November 2009

Background

Prior experience informs clinical decision making and shapes how reflection is used by novice and experienced physical therapist clinicians.

Objectives

The aims of this research were: (1) to determine the types and extent of reflection that informs the clinical decision-making process and (2) to compare the use of reflection to direct and assess clinical decisions made by novice and experienced physical therapists.

Design

Qualitative research methods using grounded theory were used to gain insight into how physical therapists use reflection to inform clinical decision making.

Methods

Three participant pairs (each pair consisting of one novice and one experienced physical therapist) were purposively selected from 3 inpatient rehabilitation settings. Case summaries of each participant provided the basis for within- and across-case analysis. Credibility of these results was established through member check of the case summaries, presentation of low-inference data, and triangulation across multiple data sources and within and across the participant groups.

Results

Although all participants engaged in reflection-on-action, the experienced participants did so with greater frequency. The experienced participants were distinguished by their use of reflection-in-action and self-assessment during therapist-patient interactions. An intermediate effect beyond novice practice was observed.

Conclusions

The results of this study may be used by educators and employers to develop and structure learning experiences and mentoring opportunities to facilitate clinical decision-making abilities and the development of the skills necessary for reflection in students and novice practitioners.
Proliferation of vascular smooth muscle cells in glioblastoma multiforme
Authors: Takeuchi Hiroaki , Hashimoto Norichika , Kitai Ryuhei , Kubota Toshihiko , Kikuta Ken-ichiro
Published: November 2009

Object

Glioblastomas multiforme (GBM) contain a higher number of α-smooth muscle actin (SMA)–positive vascular smooth muscle cells (VSMCs) than those in the respective normal neuronal tissue. The role of VSMCs during angiogenesis is unclear, and it is also uncertain whether and to what extent angiogenic factors might be involved in GBM VSMCs. In GBMs, the contribution of VSMCs in angiogenesis accompanying endothelial proliferation and the correlation of VSMC proliferation with vascular endothelial growth factor (VEGF) expression were examined using an immunohistochemical method.

Methods

The examined material, including surrounding brain tissue, came from 12 cases (6 men and 6 women) with classic GBM. Microvessel densities (MVDs) of CD31-immunoreactive vessels (CD31-MVD) and SMA-immunoreactive vessels (SMA-MVD) were obtained in areas selected from white matter, boundary, tumor (concentrated area of tumor cells), and perinecrosis. Subsequently, the SMA-MVD/CD31-MVD (SMA/CD31) rate, representing the percentage of vessels with VSMCs in the region, was calculated in each area. The VEGF immunoreactivity of tumor cells was examined, and cases were divided into 2 groups: < 30% VEGF expression of tumor cells (low VEGF group) and > 30% VEGF expression of tumor cells (high VEGF group).

Results

The SMA/CD31 rate of the boundary was significantly lower than that of the tumor (p < 0.005) and perinecrosis (p < 0.001). The SMA/CD31 rate of the high VEGF group was significantly higher than that of the low VEGF group (p < 0.05) in the tumor.

Conclusions

In GBMs, the transformation and proliferation of VSMCs may accompany neovascularization and may also be induced by angiogenic factors.
Tissue Response to Subcutaneously Implanted Recombinant Spider Silk: An in Vivo Study
Authors: Fredriksson Camilla , Hedhammar My , Feinstein Ricardo , Nordling Kerstin , Kratz Gunnar , Johansson Jan , Huss Fredrik , Rising Anna
Published: November 2009

Spider silk is an interesting biomaterial for medical applications. Recently, a method for production of recombinant spider silk protein (4RepCT) that forms macroscopic fibres in physiological solution was developed. Herein, 4RepCT and MersilkTM (control) fibres were implanted subcutaneously in rats for seven days, without any negative systemic or local reactions. The tissue response, characterised by infiltration of macrophages and multinucleated cells, was similar with both fibres, while only the 4RepCT-fibres supported ingrowth of fibroblasts and newly formed capillaries. This in vivo study indicates that 4RepCT-fibres are well tolerated and could be used for medical applications, e.g., tissue engineering.
Variations in Hole Injection due to Fast and Slow Interfacial Traps in Polymer Light‐Emitting Diodes with Interlayers
Authors: Harding M. James , Poplavskyy Dmitry , Choong Vi‐En , So Franky , Campbell Alasdair J.
Published: November 2009

Detailed studies on the effect of placing a thin (10 nm) solution‐processable interlayer between a light‐emitting polymer (LEP) layer and a poly(3,4‐ethylenedioxythiophene)/poly(styrenesulfonic)‐acid‐coated indium tin oxide anode is reported; particular attention is directed at the effects on the hole injection into three different LEPs. All three different interlayer polymers have low ionization potentials, which are similar to those of the LEPs, so the observed changes in hole injection are not due to variations in injection barrier height. It is instead shown that changes are due to variations in hole trapping at the injecting interface, which is responsible for varying the hole current by up to two orders of magnitude. Transient measurements show the presence of very fast interfacial traps, which fill the moment charge is injected from the anode. These can be considered as injection pathway dead‐ends, effectively reducing the active contact surface area. This is followed by slower interfacial traps, which fill on timescales longer than the carrier transit time across the device, further reducing the total current. The interlayers may increase or decrease the trap densities depending on the particular LEP involved, indicating the dominant role of interfacial chain morphology in injection. Penetration of the interlayer into the LEP layer can also occur, resulting in additional changes in the bulk LEP transport properties.
Photochromic Polymers Based on the Photoinduced Opening and Thermal Closing of [1,3]Oxazine Rings
Authors: Tomasulo Massimiliano , Deniz Erhan , Benelli Tiziana , Sortino Salvatore , Raymo Françisco M.
Published: November 2009

Two macromolecular constructs incorporating a single polymer backbone with multiple photochromic side chains are developed. Both systems are prepared from preformed photochromic [1,3]oxazines after the ring‐opening polymerization of their norbornene appendages. In solution, UV illumination of these polymers opens the [1,3]oxazine rings in their side chains in less than 6 ns and with a quantum yield of 0.09 in both instances. The photogenerated species incorporate a 4‐nitrophenolate chromophore, and hence, their formation is accompanied by the appearance of an intense band in the visible region of the absorption spectrum. The photoproducts revert spontaneously to the original state with first‐order kinetics in microseconds. Furthermore, both photochromic polymers tolerate hundreds of switching cycles with no sign of degradation, even in the presence of molecular oxygen. Thus, this design logic and choice of functional building blocks can translate into the realization of innovative photoresponsive materials with excellent photochromic performance.
Designer Biomaterials for Nanomedicine
Authors: Doshi Nishit , Mitragotri Samir
Published: November 2009

Nanotechnology has had tremendous impact on medical science and has resulted in phenomenal progress in the field of drug delivery and diagnostics. A wide spectrum of novel nanomaterials including polymeric particles, liposomes, quantum dots, and iron oxide particles have been developed for applications in therapeutic delivery and diagnostics. This has resulted in control over the rate and period of delivery and targeting of drugs to specific organs in the human body. This feature article focuses on the delivery of drugs using polymeric particles. The size, choice of polymer, surface chemistry, shape, and mechanical properties of the particles are parameters that critically affect particle function. Numerous biomaterials and fabrication techniques have been developed in the last decade that focus on novel design parameters, such as shape and mechanical properties and the interplay of these parameters with the size and surface chemistry of particles. Recent advances with particular focus on the importance of particle shape are highlighted, and the challenges that are yet to be fulfilled are underscored.
Red‐Emitting Polyfluorenes Grafted with Quinoline‐Based Iridium Complex: “Simple Polymeric Chain, Unexpected High Efficiency”
Authors: Ma Zhihua , Ding Junqiao , Zhang Baohua , Mei Chongyu , Cheng Yanxiang , Xie Zhiyuan , Wang Lixiang , Jing Xiabin , Wang Fosong
Published: November 2009

A series of red‐light emitting electrophosphorescent polyfluorenes (PFs) with varying content of a quinoline‐based iridium complex, (PPQ)2Ir(acac) (bis(2,4‐diphenylquinolyl‐N,C2′) iridium(acetylacetonate)), in the side chain are synthesized by Suzuki polycondensation. Because of the efficient Förster energy transfer from the PF main chain to (PPQ)2Ir(acac) and direct charge trapping on the complex, the electroluminescent emission from PF is nearly completely quenched, even though the amount of iridium complex incorporated into the polymers is as low as 1 mol %. Based on a single‐layer device configuration, a luminous efficiency of up to 5.0 cd A−1 with a luminance of 2000 cd m−2 and Commission Internationale de L'Eclairage coordinates of (0.63, 0.35) (x, y) is realized, which is far superior to that of previously reported red‐light emitting PFs containing benzothiazole‐ and isoquinoline‐based iridium complexes. This result is beyond expectations, especially when considering that the simple polymeric chain involved has no additional charge‐transporting moieties. Noticeably, the device efficiency remains as high as 4.2 cd A−1 with a luminance of 4000 cd m−2 even at current densities of 100 mA cm−2. Further optimization of the device configuration by incorporating an additional electron‐injection layer leads to improved efficiencies of 8.3 and 7.5 cd A−1 at luminances of 100 and 1000 cd m−2, respectively. This state‐of‐the‐art performance indicates that covalently attaching quinoline‐based iridium complexes to a PF backbone is a simple and effective strategy to develop high‐efficiency red‐light emitting electrophosphorescent polymers.
Barrier and mechanical properties of nanocomposites based on polymer blends and organoclays
Authors: Ophir A. , Dotan A. , Belinsky I. , Kenig S.
Published: November 2009

Nanoclays (NCs) impart highly effective barrier properties to polymers due to their platelet structure, provided that the NCs are exfoliated and form a parallel array relative to the product surface. High barrier films with enhanced mechanical properties were developed and studied using blends of polyamide (PA) or ethylene vinyl alcohol (EVOH) with polyethylene (PE) and compatibilizing copolymer, and with incorporated NC. Permeability measurements indicated that by increasing the active polymers concentration up to 30%, however, reducing the barrier layer thickness comprising the active polymers (PA or EVOH), resulting in reduction of the oxygen transmission rate (OTR) by more than 7‐ to 8‐folds. When NC was incorporated in the concentrated active polymer layer, the barrier to oxygen was further increased. This resulting in equal or even better barrier properties compared to the case where the active polymers are at 95% concentration. The increase in barrier properties was attributed to the laminar structure of the incompatible active polymer in addition to the orientation of the NC with its additional effects due to nucleation and enhancement of the amorphous phase barrier. The mechanical properties of the concentrated active layer (CAL) films were better or comparable with respect to the high barrier reference films. Furthermore, a nucleation effect, leading to increased crystallinity, was identified in the cases where PA compositions contained NC, whereas selective nucleation was obtained in the case where EVOH compositions contained NC. These observations, on oxygen barrier and mechanical properties, were further supported by the results obtained from thermal analysis (differential scanning calorimetry [DSC]), X‐ray diffraction (XRD) measurements, and transmission electron microscopy (TEM) imaging studies carried out on the hybrid films. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Hypercrosslinked polystyrene microspheres with bimodal pore size distribution and controllable macroporosity
Authors: Liu Qingquan , Wang Li , Yu Weiting , Xiao Anguo , Yu Haojie , Huo Jia
Published: November 2009

A combination of suspension polymerization and postcrosslinking was used to prepare hypercrosslinked polystyrene (H‐PS) microspheres with controllably bimodal pore size distribution in the presence of toluene and polypropylene (PP) as a coporogen. The proportion of PP in the coporogen was changed to investigate the influence of the coporogen composition on the pore structure of the H‐PS microspheres. The addition of a small amount of PP achieved the aim of a clearly bimodal pore size distribution and the control of the macroporosity of the H‐PS microspheres, which have potential application in the preparation of catalyst supports. The specific surface area of the H‐PS microspheres could be adjusted in the range 380–790 m2/g by changes in the concentration of PP in the coporogen. Moreover, the H‐PS microspheres displayed all the characteristics of Davankov‐type resins by their ability to be swollen in both thermodynamically poor solvents such as water and good solvents such as toluene. Finally, the possible mechanism of porosity formation during polymerization and postcrosslinking was also examined by a combination of pore structure data and the appearance of the microspheres before and after postcrosslinking. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Synthesis of Glycocinnasperimicin D
Authors: Nishiyama Taihei , Kusumoto Yoshifumi , Okumura Ken , Hara Kanako , Kusaba Shohei , Hirata Keiko , Kamiya Yukihiro , Isobe Minoru , Nakano Keiji , Kotsuki Hiyoshizo , Ichikawa Yoshiyasu
Published: November 2009

The first total synthesis of amino sugar antibiotic glycocinnasperimicin D (1) has been achieved by a convergent, three‐component coupling strategy. The key steps involve the Heck–Mizoroki reaction by using the iodophenyl glycoside 50 and acryl amide 32 to furnish the right core structure of 1, and the construction of the urea glycoside employing the reaction of glycosyl isocyanate 8 with amino sugar 9. Glycosyl isocyanate 8 was prepared by the oxidation of isonitrile 10, which displayed excellent reactivity in the coupling event. Synthetic roadblocks, encountered during this synthetic effort, have led to the development of the α‐selective, Lewis acid catalyzed phenyl glycosylation process with 2‐amino‐hexopyranose and a procedure for acetonide deprotection without affecting the silyl ethers.
Bisnaphthalimidopropyl Derivatives as Inhibitors ofLeishmaniaSIR2 Related Protein 1
Authors: Tavares Joana , Ouaissi Ali , Kong Thoo Lin Paul , Loureiro Inês , Kaur Simranjeet , Roy Nilanjan , Cordeiro‐da‐Silva Anabela
Published: November 2009

The NAD+‐dependent deacetylases, namely sirtuins, are involved in the regulation of a variety of biological processes such as gene silencing, DNA repair, longevity, metabolism, apoptosis, and development. An enzyme from the parasiteLeishmania infantumthat belongs to this family, LiSIR2RP1, is a NAD+‐dependent tubulin deacetylase and an ADP‐ribosyltransferase. This enzyme's involvement inL. infantumvirulence and survival underscores its potential as a drug target. Our search for selective inhibitors of LiSIR2RP1 has led, for the first time, to the identification of the antiparasitic and anticancer bisnaphthalimidopropyl (BNIP) alkyl di‐ and triamines (IC50values in the single‐digit micromolar range for the most potent compounds). Structure–activity studies were conducted with 12 BNIP derivatives that differ in the length of the central alkyl chain, which links the two naphthalimidopropyl moieties. The most active and selective compound is the BNIP diaminononane (BNIPDanon), with IC50values of 5.7 and 97.4 μMagainst the parasite and human forms (SIRT1) of the enzyme, respectively. Furthermore, this compound is an NAD+‐competitive inhibitor that interacts differently with the parasite and human enzymes, as determined by docking analysis, which might explain its selectivity toward the parasitic enzyme.
Targeted three‐dimensional immunohistochemistry reveals localization of presynaptic proteins Bassoon and Piccolo in the rat calyx of Held before and after the onset of hearing
Authors: Dondzillo Anna , Sätzler Kurt , Horstmann Heinz , Altrock Wilko D. , Gundelfinger Eckart D. , Kuner Thomas
Published: November 2009

Bassoon and Piccolo contribute to the cytomatrix of active zones (AZ), the sites of neurotransmitter release in nerve terminals. Here, we examined the 3D localization of Bassoon and Piccolo in the rat calyx of Held between postnatal days 9 and 21, the period of hearing onset characterized by pronounced structural and functional changes. Bassoon and Piccolo were identified by immunohistochemistry (IHC) on slices of the brainstem harboring calyces labeled with membrane‐anchored green fluorescent protein (mGFP). By using confocal microscopy and 3D reconstructions, we examined the distribution of Bassoon and Piccolo in calyces delineated by mGFP. This allowed us to discriminate calyceal IHC signals from noncalyceal signals located in the spaces between the calyceal stalks, which could mimic a calyx‐like distribution. We found that both proteins were arranged in clusters resembling the size of AZs. These clusters were located along the presynaptic membrane facing the principal cell, close to or overlapping with synaptic vesicle (SV) clusters. Only about 60% of Bassoon and Piccolo clusters overlapped, whereas the remaining clusters contained predominantly Bassoon or Piccolo, suggesting differential targeting of these proteins within a single nerve terminal and potentially heterogeneous AZs functional properties. The total number of Bassoon and Piccolo clusters, which may approximate the number of AZs, was 405 ± 35 at P9 and 601 ± 45 at P21 (mean ± SEM, n = 12). Normalized to calyx volume at P9 and P21, the density of clusters was similar, suggesting that the absolute number of clusters, not density, may contribute to the functional maturation associated with hearing onset. J. Comp. Neurol. 518:1008–1029, 2010. © 2009 Wiley‐Liss, Inc.
Comparative analyses of the neuron numbers and volumes of the amygdaloid complex in old and new world primates
Authors: Carlo C.N. , Stefanacci L. , Semendeferi K. , Stevens C.F.
Published: November 2009

The amygdaloid complex (AC), a key component of the limbic system, is a brain region critical for the detection and interpretation of emotionally salient information. Therefore, changes in its structure and function are likely to provide correlates of mood and emotion disorders, diseases that afflict a large portion of the human population. Previous gross comparisons of the AC in control and diseased individuals have, however, mainly failed to discover these expected correlations with diseases. We have characterized AC nuclei in different nonhuman primate species to establish a baseline for more refined comparisons between the normal and the diseased amygdala. AC nuclei volume and neuron number in 19 subdivisions are reported from 13 Old and New World primate brains, spanning five primate species, and compared with corresponding data from humans. Analysis of the four largest AC nuclei revealed that volume and neuron number of one component, the central nucleus, has a negative allometric relationship with total amygdala volume and neuron number, which is in contrast with the isometric relationship found in the other AC nuclei (for both neuron number and volume). Neuron density decreases across all four nuclei according to a single power law with an exponent of about minus one‐half. Because we have included quantitative comparisons with great apes and humans, our conclusions apply to human brains, and our scaling laws can potentially be used to study the anatomical correlates of the amygdala in disorders involving pathological emotion processing. J. Comp. Neurol. 518:1176–1198, 2010. © 2009 Wiley‐Liss, Inc.
Postnatal changes in tryptophan hydroxylase and serotonin transporter immunoreactivity in multiple brainstem nuclei of the rat: Implications for a sensitive period
Authors: Liu Qiuli , Wong‐Riley Margaret T.T.
Published: November 2009

Previously, we found that the brainstem neuronal network in normal rats undergoes abrupt neurochemical, metabolic, and physiological changes around postnatal days (P) 12–13, a critical period when the animal's response to hypoxia is also the weakest. This has special implications for sudden infant death syndrome (SIDS), insofar as seemingly normal infants succumb to SIDS when exposed to respiratory stressors (e.g., hypoxia) during a narrow postnatal window. Because an abnormal serotonergic system has recently been implicated in SIDS, we conducted a large‐scale investigation of the 5‐HT‐synthesizing enzyme tryptophan hydroxylase (TPH) and serotonin transporter (SERT) with semiquantitative immunohistochemistry in multiple brainstem nuclei of normal rats aged P2–21. We found that 1) TPH and SERT immunoreactivity in neurons of raphé magnus, obscurus, and pallidus and SERT in the neuropil of the pre‐Bötzinger complex, nucleus ambiguus, and retrotrapezoid nucleus were high at P2–11 but decreased markedly at P12 and plateaued thereafter until P21; 2) SERT labeling in neurons of the lateral paragigantocellular nucleus (LPGi) and parapyramidal region (pPy) was high at P2–9 but fell significantly at P10, followed by a gradual decline until P21; 3) TPH labeling in neurons of the ventrolateral medullary surface was stable except for a significant fall at P12; and 4) TPH and SERT immunoreactivity in a number of other nuclei was relatively stable from P2 to P21. Thus, multiple brainstem nuclei exhibited a significant decline in TPH and SERT immunoreactivity during the critical period, suggesting that such normal development can contribute to a narrow window of vulnerability in postnatal animals. J. Comp. Neurol. 518:1082–1097, 2010. © 2009 Wiley‐Liss, Inc.
Differential distribution of tight junction proteins suggests a role for tanycytes in blood‐hypothalamus barrier regulation in the adult mouse brain
Authors: Mullier Amandine , Bouret Sebastien G. , Prevot Vincent , Dehouck Bénédicte
Published: November 2009

The median eminence is one of the seven so‐called circumventricular organs. It is located in the basal hypothalamus, ventral to the third ventricle and adjacent to the arcuate nucleus. This structure characteristically contains a rich capillary plexus and features a fenestrated endothelium, making it a direct target of blood‐borne molecules. The median eminence also contains highly specialized ependymal cells called tanycytes, which line the floor of the third ventricle. It has been hypothesized that one of the functions of these cells is to create a barrier that prevents substances in the portal capillary spaces from entering the brain. In this paper, we utilize immunohistochemistry to study the expression of tight junction proteins in the cells that compose the median eminence in adult mice. Our results indicate that tanycytes of the median eminence express occludin, ZO‐1, and claudin 1 and 5, but not claudin 3. Remarkably, these molecules are organized as a continuous belt around the cell bodies of the tanycytes that line the ventral part of the third ventricle. In contrast, the tanycytes at the periphery of the arcuate nucleus do not express claudin 1 and instead exhibit a disorganized expression pattern of occludin, ZO‐1, and claudin 5. Consistent with these observations, permeability studies using peripheral or central injections of Evans blue dye show that only the tanycytes of the median eminence are joined at their apices by functional tight junctions, whereas tanycytes located at the level of the arcuate nucleus form a permeable layer. In conclusion, this study reveals a unique expression pattern of tight junction proteins in hypothalamic tanycytes, which yields new insights into their barrier properties. J. Comp. Neurol. 518:943–962, 2010. © 2009 Wiley‐Liss, Inc.
Building the central complex in Drosophila: The generation and development of distinct neural subsets
Authors: Young J.M. , Armstrong J.D.
Published: November 2009

The distinctive midline neuropil, the central complex (CX), is one of the most prominent features of the insect brain. We investigated the development of the four CX structures and several sets of CX neurons in the Drosophila brain using immunostaining for two cell adhesion molecules, DN‐cadherin and Echinoid, and a set of seven enhancer trap lines. Our results showed that the CX is first identifiable in the third instar larva and that it elaborates over the first 48 hours of metamorphosis. The first identifiable structures to appear in their immature form are the protocerebral bridge and fan‐shaped body, which are present in the brain of the third instar larva, followed by the noduli (from P12h), and finally the ellipsoid body (from P24h). We observed that neurons are added incrementally to the developing CX structure, with sets of small‐field neurons projecting to the CX prior to the large‐field neurons. The small‐field neurons first project to the developing fan‐shaped body, before arborizing or extending to the other structures. We found evidence to suggest that small‐field neurons exist in sets of 16 and that they originate from eight common clusters of perikarya in the cortex, suggesting a common origin. We also identified a novel set of pontine neurons that connect contralateral segments in the fan‐shaped body. J. Comp. Neurol. 518:1525–1541, 2010. © 2009 Wiley‐Liss, Inc.
Raman and Neutron Scattering Study of Partially Deuterated L‐Alanine: Evidence of a Solid‐Solid Phase Transition
Authors: de Souza Joelma M. , Freire Paulo T. C. , Argyriou Dimitri N. , Stride John A. , Barthès Mariette , Kalceff Walter , Bordallo Heloisa N.
Published: November 2009

Raman and neutron experiments using specific isotope labeling were combined in order to study the dynamics and structure of L‐alanine. Inelastic neutron and Raman scattering data of C2H4(ND2)CO2D are discussed in relation to the doubling of the lattice parameter a observed by means of neutron powder diffraction in C2D4 (NH2)CO2H. The major changes accompanying the phase transition are found in the vibrational frequencies involving the torsional vibration τ(CO2−), which is clearly affected by the hydrogen bonds between the protons of the ammonium group and the oxygen atoms of the carboxylate group. At lower temperatures the rearrangement of identifiable hydrogen bonds induces changes in the bending vibration δ(ND3), confirming some orientational disorder.