bluuebunny/crossref_metadata_2025 huggingface dataset:
Endothelin-1 Signaling Promotes Fibrosis In Vitro in a Bronchopulmonary Dysplasia Model by Activating the Extrinsic Coagulation Cascade
Authors: Kambas Konstantinos , Chrysanthopoulou Akrivi , Kourtzelis Ioannis , Skordala Marianna , Mitroulis Ioannis , Rafail Stavros , Vradelis Stergios , Sigalas Ioannis , Wu You-Qiang , Speletas Matthaios , Kolios George , Ritis Konstantinos
Published: April 2011

Neonatal respiratory distress syndrome can progress to bronchopulmonary dysplasia (BPD), a serious pulmonary fibrotic disorder. Given the involvement of the extrinsic coagulation cascade in animal models of lung fibrosis, we examined its role in BPD. We observed a higher number of neutrophils expressing tissue factor (TF) in bronchoalveolar lavage fluid (BALF) from infants with BPD than from those with uncomplicated respiratory distress syndrome together with a parallel decrease in TF and connective tissue growth factor (CTGF) in BALF supernatants during the disease course. The involvement of coagulation in the fibrotic process associated with BPD was further evaluated by treating primary human colonic myofibroblasts with BALF supernatants from infants with BPD. These human colonic myofibroblasts demonstrated an enhanced C5a- and thrombin-dependent migration. Moreover, they expressed TF in an endothelin-1–dependent manner, with subsequent activation of the extrinsic coagulation cascade and CTGF production mediated by protease-activator receptor-1 signaling. These data provide a novel mechanism for the development of BPD and indicate that endothelin-1 signaling contributes to fibrosis by upregulating a TF/thrombin amplification loop responsible for CTGF production, and offer novel and specific therapeutic targets for pulmonary fibrotic disease.
Suppressive CD8+ T Cells Arise in the Absence of CD4 Help and Compromise Control of Persistent Virus
Authors: Molloy Michael J. , Zhang Weijun , Usherwood Edward J.
Published: April 2011

There is an urgent need to develop novel therapies for controlling chronic virus infections in immunocompromised patients. Disease associated with persistent γ-herpesvirus infection (EBV, human herpesvirus 8) is a significant problem in AIDS patients and transplant recipients, and clinical management of these conditions is difficult. Immune surveillance failure followed by γ-herpesvirus recrudescence can be modeled using murine γ-herpesvirus (MHV)-68 in mice lacking CD4+ T cells. In contrast with other chronic infections, no obvious defect in the functional capacity of the viral-specific CD8+ T cell response was detected. We show in this article that adoptive transfer of MHV-68–specific CD8+ T cells was ineffective at reducing the viral burden. Together, these indicate the potential presence of T cell extrinsic suppressive factors. Indeed, CD4-depleted mice infected with MHV-68 express increased levels of IL-10, a cytokine capable of suppressing the function of both APCs and T cells. CD4-depleted mice developed a population of CD8+ T cells capable of producing IL-10 that suppressed viral control. Although exhibiting cell surface markers indicative of activation, the IL-10–producing cells expressed increased levels of programmed death-1 but were not enriched in the MHV-68–specific compartment, nor were they uniformly CD44hi. Therapeutic administration of an IL-10R blocking Ab enhanced control of the recrudescent virus. These data implicate IL-10 as a promising target for the restoration of immune surveillance against chronic γ-herpesvirus infection in immunosuppressed individuals.
Papillomavirus-Specific CD4+ T Cells Exhibit Reduced STAT-5 Signaling and Altered Cytokine Profiles in Patients with Recurrent Respiratory Papillomatosis
Authors: James Eddie A. , DeVoti James A. , Rosenthal David W. , Hatam Lynda J. , Steinberg Bettie M. , Abramson Allan L. , Kwok William W. , Bonagura Vincent R.
Published: April 2011

Recurrent respiratory papillomatosis (RRP) is caused by human papillomavirus type 6 (HPV-6) or HPV-11. Specific HLA-DR haplotypes DRB1*01:02 and DRB1*03:01 are associated with the development of RRP, disease severity, and Th2-like responses to HPV early proteins. Th1-like responses to HPV proteins have been shown to be protective in animal models. Therefore, we investigated the hypothesis that RRP patients have dysfunctional Th1-like, HPV-specific T cell responses. Using MHC class II tetramers, we identified immunogenic peptides within HPV-11 early proteins. Two distinct peptides (E6113–132 and E21–20) contained DRB1*01:02- or DRB1*03:01-restricted epitopes, respectively. An additional peptide (E2281–300) contained an epitope presented by both alleles. Peptide binding, tetramer, and proliferation assays identified minimal epitopes within these peptides. These epitopes elicited E2/E6-specific CD4+ T cell responses in RRP patients and healthy control subjects, allowing the isolation of HPV-specific T cell lines using tetramers. The cytokine profiles and STAT signaling of these tetramer-positive T cells were measured to compare the polarization and responsiveness of HPV-specific T cells from patients with RRP and healthy subjects. HPV-specific IFN-γ secretion was substantially lower in T cells from RRP patients. HPV-specific IL-13 secretion was seen at modest levels in T cells from RRP patients and was absent in T cells from healthy control subjects. HPV-specific T cells from RRP patients exhibited reduced STAT-5 phosphorylation and reduced IL-2 secretion, suggesting anergy. Levels of STAT-5 phosphorylation and IFN-γ secretion could be improved through addition of IL-2 to HPV-specific T cell lines from RRP patients. Therapeutic vaccination or interventions aimed at restoring Th1-like cytokine responses to HPV proteins and reversing anergy could improve clinical outcomes for RRP patients.
Protein Kinase CK2/PTEN Pathway Plays a Key Role in Platelet-Activating Factor-Mediated Murine Anaphylactic Shock
Authors: Kang Nam-In , Yoon Ha-Yong , Kim Han-A , Kim Kyoung-Jin , Han Myung-Kwan , Lee Young-Rae , Hwang Pyoung-Han , Soh Byoung-Yul , Shin Sook-Jeong , Im Suhn-Young , Lee Hern-Ku
Published: April 2011

Platelet-activating factor (PAF) is a major mediator in the induction of fatal hypovolemic shock in murine anaphylaxis. This PAF-mediated effect has been reported to be associated with PI3K/Akt-dependent eNOS-derived NO. The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is phosphatidylinositol phosphate phosphatase, which negatively controls PI3K by dephosphorylating the signaling lipid, phosphatidylinositol 3,4,5-triphosphate. In this study, we examined the possible involvement of PTEN in PAF-mediated anaphylactic shock. Induction of anaphylaxis or PAF injection resulted in a rapid decrease in PTEN activity, followed by increases in PI3K activity and phosphorylation of Akt and eNOS. Systemic administration of adenoviruses carrying PTEN cDNA (adenoviral PTEN), but not the control AdLacZ, not only attenuated anaphylactic symptoms, but also reversed anaphylaxis- or PAF-induced changes in PTEN and PI3K activities, as well as phosphorylation of Akt and eNOS. We found that the decreased PTEN activity was associated with PTEN phosphorylation, the latter effect being prevented by the protein kinase CK2 inhibitor, DMAT. DMAT also inhibited anaphylactic symptoms as well as the anaphylaxis- or PAF-mediated PTEN/PI3K/Akt/eNOS signaling cascade. CK2 activity was increased by PAF. The present data provide, as the key mechanism underlying anaphylactic shock, PAF triggers the upstream pathway CK2/PTEN, which ultimately leads to the activation of PI3K/Akt/eNOS. Therefore, CK2/PTEN may be a potent target in the control of anaphylaxis and other many PAF-mediated pathologic conditions.
Small Cell Carcinoma of the Renal Pelvis: A Case Report and Review of the Literature
Authors: Patil Sachin , Kaza R. C. M. , Kakkar A. K. , Chamberlain Ronald S.
Published: April 2011

Extrapulmonary small cell carcinoma occurs in nearly all organs except the central nervous system and the liver. We are presenting a case of renal small cell carcinoma (SCC) with two unique characters. A 75-year-old patient was evaluated for back pain with no other complaints. Magnetic Resonance (MR) imaging of the abdomen revealed homogeneous tumor in the left renal pelvis extending beyond the kidney. Metastatic workup was negative. A left nephroureterectomy was performed. Histopathology and immunohistochemistry revealed a small cell carcinoma of the renal pelvis. The patient declined adjuvant therapy and died 2 months after surgery due to unrelated causes. After comprehensive worldwide literature search, we found 13 cases of SCC of the renal pelvis, including the current case. The mean age was 61.6 years (37–83), with a M : F ratio of 1 : 1.8. The average duration of symptoms was 71.4 days (21–168). Gross hematuria was the most common symptom (69.2%) followed by pain (61.5%). Adjuvant chemotherapy was provided to 4 patients (30.7%), and neoadjuvant to 1 patient. The median survival of patients who did and did not receive chemotherapy was 5.5 months (3–8) and 6 months (2–31), respectively, P<.50. In conclusion, renal SCC (both parenchymal and pelvic SCC) is a rapidly fatal disease with a median survival of ≤8 months.
Preparing Emergency Personnel in Dialysis: A Just-in-Time Training Program for Additional Staffing During Disasters
Authors: Stoler Genevieve B. , Johnston James R. , Stevenson Judy A. , Suyama Joe
Published: April 2011

Background

There are 341 000 patients in the United States who are dependent on routine dialysis for survival. Recent large-scale disasters have emphasized the importance of disaster preparedness, including supporting dialysis units, for people with chronic disease. Contingency plans for staffing are important for providing continuity of care for a technically challenging procedure such as dialysis. PReparing Emergency Personnel in Dialysis (PREP-D) is a just-in-time training program designed to train individuals having minimum familiarity with the basic steps of dialysis to support routine dialysis staff during a disaster.

Methods

A 5-module educational program was developed through a collaborative, multidisciplinary effort. A pilot study testing the program was performed using 20 nontechnician dialysis facility employees and 20 clinical-year medical students as subjects.

Results

When comparing pretest and posttest scores, the entire study population showed a mean improvement of 28.9%, with dialysis facility employees and medical students showing improvements of 21.8% and 36.4%, respectively (P < .05 for all comparisons).

Conclusions

PREP-D participants were able to demonstrate improved tests scores when taught in a just-in-time training format. The knowledge gained by using the PREP-D program during a staffing shortage may allow for continuity of care for critical services such as dialysis during a disaster. (Disaster Med Public Health Preparedness. 2013;7:272-277).
Templating Synthesis of SnO2 Nanotubes Loaded with Ag2O Nanoparticles and Their Enhanced Gas Sensing Properties
Authors: Chen Xing , Guo Zheng , Xu Wei‐Hong , Yao Hong‐Bin , Li Min‐Qiang , Liu Jin‐Huai , Huang Xing‐Jiu , Yu Shu‐Hong
Published: April 2011

A new kind of SnO2 nanotubes loaded with Ag2O nanoparticles can be synthesized by using Ag@C coaxial nanocables as sacrificial templates. The composition of silver in SnO2 nanotubes can be controlled by tuning the compositions of metallic Ag in Ag@C sacrificial templates, and the morphology of tubular structures can be changed by use of nanocables with different thicknesses of carbonaceous layer. This simple strategy is expected to be extended for the fabrication of similar metal‐oxide doped nanotubes using different nanocable templates. In contrast to SnO2@Ag@C nanocables as well as to other types of SnO2 reported previously, the Ag2O‐doped SnO2 nanotubes exhibit excellent gas sensing behaviors. The dynamic transients of the sensors demonstrated both their ultra‐fast response (1–2 s) and ultra‐fast recovery (2–4 s) towards ethanol, and response (1–4 s) and recovery (4–5 s) towards butanone. The combination of SnO2 tubular structure and catalytic activity of Ag2O dopants gives a very attractive sensing behavior for applications as real‐time monitoring gas sensors with ultra‐fast responding and recovering speed.
Silver Stars: Silver–Polymer Composite Stars: Synthesis and Applications (Adv. Funct. Mater. 9/2011)
Authors: Homan Kimberly A. , Chen Jeffrey , Schiano Adriane , Mohamed Mona , Willets Katherine A. , Murugesan Sankaran , Stevenson Keith J. , Emelianov Stanislav
Published: April 2011

Colloidal “silver stars” were synthesized upon poly(lactic‐co‐glycolic) acid nanosphere templates via a facile two‐step silver reduction method. Myriad dendrimer‐like Ag star morphologies were synthesized by varying the amount of poly(vinyl alcohol) and trisodium citrate used during silver reduction. Scanning electron microscopy studies revealed that star‐shaped silver–polymer composites possessing nanoscopic, fractal morphologies with diameters ranging from 500 nm to 7 μm were produced. These composites have broad applications from antibacterial agents to catalysis; two such applications were tested here. Surface‐enhanced Raman spectroscopy (SERS) studies showed multiple hot spots of SERS activity within a single star. Electrochemical catalysis experiments demonstrated the feasibility of using the silver stars instead of platinum for the oxygen reduction reaction in alkaline fuel cells.
Titania Nanotubes: Protein‐Enabled Layer‐by‐Layer Syntheses of Aligned, Porous‐Wall, High‐Aspect‐Ratio TiO2 Nanotube Arrays (Adv. Funct. Mater. 9/2011)
Authors: Berrigan John D. , Kang Tae‐Sik , Cai Ye , Deneault James R. , Durstock Michael F. , Sandhage Kenneth H.
Published: April 2011

An aqueous, protein‐enabled (biomimetic), layer‐by‐layer titania deposition process is developed, for the first time, to convert aligned‐nanochannel templates into high‐aspect‐ratio, aligned nanotube arrays with thin (34 nm) walls composed of co‐continuous networks of pores and titania nanocrystals (15 nm ave. size). Alumina templates with aligned open nanochannels are exposed in an alternating fashion to aqueous protamine‐bearing and titania precursor‐bearing (Ti(IV) bis‐ammonium‐lactato‐dihydroxide, TiBALDH) solutions. The ability of protamine to bind to alumina and titania, and to induce the formation of a Ti–O‐bearing coating upon exposure to the TiBALDH precursor, enables the layer‐by‐layer deposition of a conformal protamine/Ti–O‐bearing coating on the nanochannel surfaces within the porous alumina template. Subsequent protamine pyrolysis yields coatings composed of co‐continuous networks of pores and titania nanoparticles. Selective dissolution of the underlying alumina template through the porous coating then yields freestanding, aligned, porous‐wall titania nanotube arrays. The interconnected pores within the nanotube walls allow enhanced loading of functional molecules (such as a Ru‐based N719 dye), whereas the interconnected titania nanoparticles enable the high‐aspect‐ratio, aligned nanotube arrays to be used as electrodes (as demonstrated for dye‐sensitized solar cells with power conversion efficiencies of 5.2 ± 0.4%).
Charge‐Transfer Interactions: An Efficient Tool for Recycling Bis(oxazoline)‐Copper Complexes in Asymmetric Henry Reactions
Authors: Didier Dorian , Magnier‐Bouvier Caroline , Schulz Emmanuelle
Published: April 2011

An anthracenyl‐modified chiral bis(oxazoline) copper complex has been demonstrated to efficiently promote nitroaldol reactions between structurally varying aldehydes and nitromethane or nitroethane. The catalyst was recovered through formation of a charge transfer complex between the chiral ligand and trinitrofluorenone and its subsequent precipitation with pentane. The efficiency of this procedure was proved through several consecutive catalytic cycles that allowed the sturdy formation of the expected product with a high enantioselectivity. The catalyst′s stability was also put to the test in an original multi‐substrate procedure. Following the same recovery concept, a new heterogeneous procedure was tested for which trinitrofluorenone was covalently linked to a silica support. Asymmetric heterogeneous catalysis was performed under these conditions as one of the few examples demonstrating the potential catalyst recycling in nitroaldol reactions through reversible, non‐covalent interactions.
Organocatalytic Asymmetric Aldol Reaction of Ketones with β,γ‐Unsaturated α‐Keto Esters: An Efficient Access to Chiral Tertiary Alcohol Skeletons
Authors: Li Pengfei , Chan Sau Hing , Chan Albert S. C. , Kwong Fuk Yee
Published: April 2011

This update describes a highly efficient organocatalytic aldol reaction of ketones and β,γ‐unsaturated α‐keto esters for constructing the chiral tertiary alcohol motif. With the application of 9‐amino(9‐deoxy)epi‐Cinchona alkaloid and an acidic additive as catalysts, both acyclic and cyclic ketones react with β,γ‐unsaturated α‐keto esters smoothly to afford aldol adducts in good to excellent yields and asymmetric induction. This protocol offers a new pathway for the construction of adjacent chiral carbon centers and the synthesis of chiral β‐hydroxy carbonyl compounds.
Ligand‐Free Reusable Palladium‐Catalyzed Heck‐Type Coupling Reactions of Hypervalent Iodine Reagents under Mild Conditions
Authors: Qu Xiaoming , Sun Peng , Li Tingyi , Mao Jincheng
Published: April 2011

Highly effective palladium‐catalyzed Heck‐type couplings of hypervalent iodine reagents are reported for the first time. It is noteworthy that such reactions could be carried out in the absence of ligand at 40 °C and the catalytic system could be easily reused for five times.
Percolation transitions in the hard‐sphere fluid
Authors: Woodcock Leslie V.
Published: April 2011

The number densities (ν/V) above or below which “pockets” of additional‐sphere excluded volume (ρpe) and available volume (ρpa) begin to percolate the whole volume of the system, sometimes referred to as percolation thresholds, have been determined for the equilibrium hard‐sphere fluid of diameter σ using a Monte Carlo (MC) approach. Values obtained are ρpeσ3 = 0.0785 ± 0.01 and ρpaσ3 = 0.537 ± 0.005. The present value of ρpeσ3 agrees with an interpolation of previous data for the percolation diameter (σp) for various densities from Heyes et al. The available volume (Va) can be resolved as a “radial acceptance function” (u(r)), which is easily obtained from MC acceptance ratio statistics providing a direct route to the chemical potential up to liquid‐like densities. The closed‐virial equation‐of‐state of the hard‐sphere fluid is found to deviate slightly, but significantly from thermodynamic pressures at densities exceeding ρpa. Knowledge of the hard‐sphere fluid percolation transitions could lead to a more formal description of the critical point and origins of the liquid state, in the spirit of van der Waals. © 2011 American Institute of Chemical Engineers AIChE J, 2012
A combined complete pore blocking and cake filtration model for steady‐state electric field‐assisted ultrafiltration
Authors: Sarkar Biswajit , De Sirshendu
Published: April 2011

An analysis for the flux decline and identification of dominant fouling mechanism in electric field enhanced cross‐flow ultrafiltration (UF) is proposed. The model is developed based on the modification of Hérmia's approach for constant pressure dead‐end filtration laws. Electric field‐assisted cross‐flow UF experiments of synthetic juice (a mixture of pectin and sucrose) are performed in a rectangular flow channel. Using the flux decline data, the dominant fouling mechanism is identified by estimation of model parameters. The effect of various operating conditions such as electric field, feed solute concentration, cross‐flow velocity, and transmembrane pressure on the flux decline and the corresponding fouling mechanism are studied. Experimental results show that electric field has significant effect on the onset of cake formation as well as on the enhancement in permeate flux. Model‐predicted results are successfully compared with the experimental data. © 2011 American Institute of Chemical Engineers AIChE J, 2012
Identification of p.A684V missense mutation in the WFS1 gene as a frequent cause of autosomal dominant optic atrophy and hearing impairment
Authors: Rendtorff Nanna D. , Lodahl Marianne , Boulahbel Houda , Johansen Ida R. , Pandya Arti , Welch Katherine O. , Norris Virginia W. , Arnos Kathleen S. , Bitner‐Glindzicz Maria , Emery Sarah B. , Mets Marilyn B. , Fagerheim Toril , Eriksson Kristina , Hansen Lars , Bruhn Helene , Möller Claes , Lindholm Sture , Ensgaard Stefan , Lesperance Marci M. , Tranebjaerg Lisbeth
Published: April 2011

Optic atrophy (OA) and sensorineural hearing loss (SNHL) are key abnormalities in several syndromes, including the recessively inherited Wolfram syndrome, caused by mutations in WFS1. In contrast, the association of autosomal dominant OA and SNHL without other phenotypic abnormalities is rare, and almost exclusively attributed to mutations in the Optic Atrophy‐1 gene (OPA1), most commonly the p.R445H mutation. We present eight probands and their families from the US, Sweden, and UK with OA and SNHL, whom we analyzed for mutations in OPA1 and WFS1. Among these families, we found three heterozygous missense mutations in WFS1 segregating with OA and SNHL: p.A684V (six families), and two novel mutations, p.G780S and p.D797Y, all involving evolutionarily conserved amino acids and absent from 298 control chromosomes. Importantly, none of these families harbored the OPA1 p.R445H mutation. No mitochondrial DNA deletions were detected in muscle from one p.A684V patient analyzed. Finally, wolframin p.A684V mutant ectopically expressed in HEK cells showed reduced protein levels compared to wild‐type wolframin, strongly indicating that the mutation is disease‐causing. Our data support OA and SNHL as a phenotype caused by dominant mutations in WFS1 in these additional eight families. Importantly, our data provide the first evidence that a single, recurrent mutation in WFS1, p.A684V, may be a common cause of ADOA and SNHL, similar to the role played by the p.R445H mutation in OPA1. Our findings suggest that patients who are heterozygous for WFS1 missense mutations should be carefully clinically examined for OA and other manifestations of Wolfram syndrome. © 2011 Wiley‐Liss, Inc.
High patient satisfaction after secondary rhinoplasty in cleft lip patients
Authors: Hens Greet , Picavet Valerie A. , Poorten Vincent Vander , Schoenaers Joseph , Jorissen Mark , Hellings Peter W.
Published: April 2011

Objectives

We surveyed the subjective outcome of secondary rhinoplasty in cleft lip patients.

Methods

Questionnaires were sent to 38 patients who had undergone a secondary rhinoplasty. A total of 30 questionnaires were returned and analyzed. Patients were asked to score their preoperative and postoperative nasal function and form. The validated Rhinoplasty Outcome Evaluation (ROE) questionnaire was supplemented with questions on the subjective burden of the procedure and general satisfaction. In parallel, the objective aesthetic outcome was judged by 2 surgeons using preoperative and postoperative photographs.

Results

There was a significant subjective improvement in ROE scores (from 39.3 ± 3.1 to 73.1 ± 2.0, p < 0.001), and in specific scores for nasal aesthetical appearance (from 3.6 ± 0.3 to 7.9 ± 0.2, p < 0.0001) and breathing capacity (from 4.9 ± 0.4 to 6.8 ± 0.3, p < 0.01). Subjective improvement in nasal aesthetics was generally evaluated to be better than improvement in nasal breathing. In retrospect, all patients would undergo the procedure again. Patient satisfaction did not correlate with the surgeon's appreciation of the aesthetic outcome of the rhinoplasty.

Conclusion

Patient satisfaction after secondary rhinoplasty in cleft lip patients is high and comparable to that of non–cleft lip rhinoplasty patients. © 2011 ARS‐AAOA, LLC.
What is the origin of Staphylococcus aureus in the early postoperative sinonasal cavity?
Authors: Jervis‐Bardy Joshua , Foreman Andrew , Boase Samuel , Valentine Rowan , Wormald Peter‐John
Published: April 2011

Background:

Despite increasing evidence of a role for Staphylococcus aureus (S. aureus) biofilms in chronic rhinosinusitis (CRS), the origin of this organism in the postsurgical sinonasal cavity had been unclear. Recently, we suggested that the increased culture rate of S. aureus following endoscopic sinus surgery (ESS) may be related to biofilm activity. This study, therefore, was designed to evaluate the origin of early postoperative sinonasal S. aureus and assess the early postoperative outcomes in patients culture‐positive for this organism.

Methods:

Twenty‐nine patients undergoing ESS for medically‐recalcitrant CRS were prospectively enrolled. A comprehensive intraoperative S. aureus screening protocol was followed for all patients (including swabs for culture and tissue for fluorescence in situ hybridization [FISH] S. aureus biofilm analysis); early postoperative management included endoscopically‐guided swabs for culture in all patients.

Results:

Twenty of 29 (69.0%) patients cultured S. aureus postoperatively, of which 17 of 20 (85.0%) were screen‐positive at surgery. Seven of 11 (63.6%) intraoperatively biofilm‐positive but culture‐negative patients progressed to culture S. aureus post‐ESS. S. aureus culture was associated with selected poorer early post‐ESS outcomes.

Conclusion:

S. aureus persists in the sinonasal cavity despite ESS. The postoperative culture of sinonasal S. aureus in patients previously biofilm‐positive but culture‐negative may reflect the dynamic ability of S. aureus to adapt to the surgically‐altered microenvironment with subsequent biofilm dispersal and release of planktonic clones. © 2011 ARS‐AAOA, LLC.
Aromatische Ringe in chemischer und biologischer Erkennung: Energien und Strukturen
Authors: Salonen Laura M. , Ellermann Manuel , Diederich François
Published: April 2011

Dieser Aufsatz beschreibt Phänomene der molekularen Erkennung von aromatischen Ringen in chemischen und biologischen Systemen in einem multidimensionalen Ansatz. Neue Ergebnisse aus der Wirt‐Gast‐Chemie, biologischen Affinitätsassays und Biostrukturanalysen, Datenbanksuchen in der Cambridge Structural Database (CSD) und der Protein Data Bank (PDB) und hochentwickelten Rechnungen, die seit dem Erscheinen eines früheren Aufsatzes in 2003 veröffentlicht wurden, sind hier zusammengefasst. Die Themen Aren‐Aren‐, Perfluoraren‐Aren‐, Schwefel‐Aren‐, Kation‐π‐ und Anion‐π‐Wechselwirkungen sowie Wasserstoffbrücken zu aromatischen Systemen werden behandelt. Das gewonnene Wissen kommt besonders der strukturbasierten Hit‐zur‐Leitstruktur‐Entwicklung und der Leitstrukturoptimierung sowohl in der pharmazeutischen als auch in der Pflanzenschutzindustrie zugute. Zudem erleichtert es die Entwicklung neuer Materialien und supramolekularer Systeme und soll zu weiteren Anwendungen von Wechselwirkungen mit aromatischen Ringen zur Kontrolle des stereochemischen Verlaufs chemischer Umsetzungen inspirieren.
Nitroxides: Applications in Synthesis and in Polymer Chemistry
Authors: Tebben Ludger , Studer Armido
Published: April 2011

This Review describes the application of nitroxides to synthesis and polymer chemistry. The synthesis and physical properties of nitroxides are discussed first. The largest section focuses on their application as stoichiometric and catalytic oxidants in organic synthesis. The oxidation of alcohols and carbanions, as well as oxidative CC bond‐forming reactions are presented along with other typical oxidative transformations. A section is also dedicated to the extensive use of nitroxides as trapping reagents for C‐centered radicals in radical chemistry. Alkoxyamines derived from nitroxides are shown to be highly useful precursors of C‐centered radicals in synthesis and also in polymer chemistry. The last section discusses the basics of nitroxide‐mediated radical polymerization (NMP) and also highlights new developments in the synthesis of complex polymer architectures.
Modular amino acid amide chiral ligands for enantioselective addition of diethylzinc to aromatic aldehydes
Authors: Gou Shaohua , Ye Zhongbin , Chang Jing , Gou Guangjun , Feng Mingming
Published: April 2011

Enantioselective addition of diethylzinc to a series of aromatic aldehydes was developed using a modular amino acid amide chiral ligand (2S)‐3‐phenyl‐N‐((R)‐1‐phenyl‐ethyl)‐2‐(tosylamino)propanamide without using titanium complex. The catalytic system employing 10 mol% of 1g was found to promote the addition of diethylzinc (ZnEt2) to a wide range of aromatic aldehydes with electron‐donating and electron‐withdrawing substituents, giving up to 82% ee of the corresponding secondary alcohol under mild conditions. Copyright © 2011 John Wiley & Sons, Ltd.
Synthesis, spectroscopic, thermal and biological aspects of drug‐based copper(II) complexes
Authors: Patel Paresh N. , Patel Darshana J. , Patel Hasmukh S.
Published: April 2011

A series of novel complexes of the type Cu(II)(Ln)2(H2O)2]•xH2O [where Ln = L1–4, these ligands being described as: L1, 2‐({4‐[6,7‐dihydrothieno[3,2‐c]pyridin‐5(4H)‐ylsulfonyl]phenylimino}methyl)phenol, x = 1; L2, 2‐({4‐[6,7‐dihydrothieno[3,2‐c] pyridin‐5(4H)‐ylsulfonyl]phenylimino}methyl)‐5‐(methoxy)phenol, x = 2; L3, 5‐chloro‐2‐({4‐[6,7‐dihydrothieno[3,2‐c]pyridin‐5(4H)‐ylsulfonyl]phenylimino}methyl)phenol, x = 2; and L4, 5‐bromo‐4‐chloro‐2‐({4‐[6,7‐dihydrothieno[3,2‐c]pyridin‐5(4H)‐ylsulfonyl]phenylimino} methyl)phenol, x = 1] was investigated. They were characterized by elemental analysis, IR, 1H‐NMR, 13C‐NMR and electronic spectra, magnetic measurements and thermal studies. The FAB‐mass spectrum of [Cu(II)(L1)2(H2O)2]•H2O was determined. A magnetic moment and reflectance spectral study revealed that an octahedral geometry could be assigned to all the prepared complexes. Ligands (Ln) and their metal complexes were screened for their in vitro antibacterial activity against Bacillus subtillis, Pseudomonas aeruginosa, Escherichia coli and Serratia marcescens bacterial strains. Kinetic parameters such as order of reaction (n), the energy of activation (Ea), the pre‐exponential factor (A), the activation entropy (ΔS≠), the activation enthalpy (ΔH≠) and the free energy of activation (ΔG≠) are reported. Copyright © 2011 John Wiley & Sons, Ltd.
Two liquid‐phase bubble column bioreactors for the removal of volatile organic compounds from air streams
Authors: Hashemi Seyedeh Fatemeh , Goharrizi Ataallah Soltani , Fazaelipoor Mohammad Hassan
Published: April 2011

Two equal‐sized bubble column bioreactors were used to investigate the effect of silicone oil on the removal efficiency (RE) of a bubble column bioreactor for hydrophobic volatile organic compounds (VOCs). In the first stage, the performance of the two liquid‐phase bubble column bioreactors (in terms of hexane removal) containing 4 L mineral medium and 400 mL of silicone oil was compared to a control bioreactor (without silicone oil). With the airflow rate of 1.5 L min−1 and n‐hexane concentration of 1.6 g m−3, the hexane RE of oil‐added bioreactor was 27% compared to 16.3% for the control bioreactor. To obtain better removal efficiencies, in the second stage of the experiments, the airflow rate and the inlet n‐hexane concentration were reduced to 0.9 L min−1 and 1 g m−3, respectively. In this stage, 150 mL of fermentation medium was replaced with fresh medium daily to avoid possible nutrient limitation and build up of toxicants. As a result of this replacement, the hexane RE of the oil‐added bioreactor was 76% compared to 37% for the control bioreactor. In the third stage, the effect of silicone oil percentage on the bioreactor's hexane RE was investigated. The results showed that increasing silicone oil percentage from 5 to 15% had a significant positive effect on the hexane RE (for the hexane inlet concentration of 1.6 g m−3, the RE approximately doubled). However, the effect of oil percentage on the VOC RE was seen insignificant when silicone oil was above 15%. In the final stage of this work, the effect of adding expanded perlite particles to the liquid medium of two liquid‐phase bubble column bioreactors was investigated. The results showed that perlite had a significant positive effect on the hexane RE of the bioreactor. © 2011 Curtin University of Technology and John Wiley & Sons, Ltd.
Computer Three‐Dimensional Anatomical Reconstruction of the Human Sinus Node and a Novel Paranodal Area
Authors: Chandler Natalie , Aslanidi Oleg , Buckley David , Inada Shin , Birchall Steven , Atkinson Andrew , Kirk Danielle , Monfredi Oliver , Molenaar Peter , Anderson Robert , Sharma Vinod , Sigg Daniel , Zhang Henggui , Boyett Mark , Dobrzynski Halina
Published: April 2011

We have previously shown in rabbit that the pacemaker of the heart (the sinus node) is widespread and matches the wide distribution of the leading pacemaker site within the right atrium. There is, however, uncertainty about the precise location of the pacemaker in human heart, and its spatial relationships with the surrounding right atrial muscle. Therefore, the aim of the current study was to investigate the distribution of the sinus node tissue in a series of healthy human hearts and, for one of the hearts to construct a computer three‐dimensional anatomical model of the sinus node, including the likely orientation of myocytes. A combination of experimental techniques—diffusion tensor magnetic resonance imaging (DT‐MRI), histology, immunohistochemistry, image processing and computer modelling—was used. Our data show that the sinus node was larger than in previous studies and, most importantly, we identified a previously unknown area running alongside the sinus node (the “paranodal area”), which is even more extensive than the sinus node. This area possesses properties of both nodal and atrial tissues and may have a role in pacemaking. For example, it could explain the wide spread distribution of the leading pacemaker site in human right atrium, a phenomenon known as the wandering pacemaker observed in clinics. In summary, a novel 3D anatomical reconstruction presents a new picture of the distribution of nodal cells within the human right atrium. Anat Rec, , 2011. © 2011 Wiley‐Liss, Inc.
Reviewing the Morphology of the Jaw‐Closing Musculature in Squirrels, Rats, and Guinea Pigs with Contrast‐Enhanced MicroCt
Authors: Cox Philip G. , Jeffery Nathan
Published: April 2011

Rodents are defined by their unique masticatory apparatus and are frequently separated into three nonmonophyletic groups—sciuromorphs, hystricomorphs, and myomorphs—based on the morphology of their masticatory muscles. Despite several comprehensive dissections in previous work, inconsistencies persist as to the exact morphology of the rodent jaw‐closing musculature, particularly, the masseter. Here, we review the literature and document for the first time the muscle architecture noninvasively and in 3D by using iodine‐enhanced microCT. Observations and measurements were recorded with reference to images of three individuals, each belonging to one of the three muscle morphotypes (squirrel, guinea pig, and rat). Results revealed an enlarged superficial masseter muscle in the guinea pig compared with the rat and squirrel, but a reduced deep masseter (possibly indicating reduced efficiency at the incisors). The deep masseter had expanded forward to take an origin on the rostrum and was also separated into anterior and posterior parts in the rat and squirrel. The zygomaticomandibularis muscle was split into anterior and posterior parts in all the three specimens by the masseteric nerve, and in the rat and guinea pig had an additional rostral expansion through the infraorbital foramen. The temporalis muscle was found to be considerably larger in the rat, and its separation into anterior and posterior parts was only evident in the rat and squirrel. The pterygoid muscles were broadly similar in all three specimens, although the internal pterygoid was somewhat enlarged in the guinea pig implying greater lateral movement of the mandible during chewing in this species. Anat Rec,, 2011. © 2011 Wiley‐Liss, Inc.
Contribution of the Proinflammatory Cytokine IL‐18 in the Formation of Human Nasal Polyps
Authors: Zhang Guimin , JING XIANG , Wang Xinting , Shi Wenjie , Sun Peiyong , Su Chao , Zhu Mengyu , Yang Zhenxia , Yao Zhi , Yang Jie
Published: April 2011

Nasal polyposis is a chronic inflammatory disease of the nasal mucosa. The etiology and the mechanisms of formation of nasal polyps are still not clear. Interleukin (IL)‐18 is a novel proinflammatory cytokine that plays important roles in regulating immune inflammatory responses. However, the presence of IL‐18 in human nasal mucosa and its roles in the inflammatory process of nasal polyps has not been studied yet. In this study, it was the first time to investigate the expression of IL‐18 in human nasal mucosa and nasal polyps, and its potential function in the formation of nasal polyps. Surgical samples were analyzed by Western blot and immunohistochemistry to evaluate the expression and location of IL‐18, and its correlated cytokines, IL‐4, and IFN‐γ. Furthermore, the airway epithelial cell line, A549, was used to investigate the mutual regulation of IFN‐γ, IL‐4, and IL‐18. IFN‐γ, IL‐4, and IL‐18 were all highly expressed in the epithelial cells, submucosal glands, and infiltrating inflammatory cells in the nasal polyp tissues, comparing with the control samples. Especially, the expression of IL‐18 was upregulated significantly in nasal polyp tissues compared with control tissues. In addition, IL‐18 was expressed in A549 cells in response to lipopolysaccharide and IL‐4. Our data suggest that nasal epithelial cells are involved in the pathogenesis of nasal polyps formation and potentially via the secretion of IL‐18, which is likely to play important roles in the formation of nasal polyps. Anat Rec, , 2011. © 2011 Wiley‐Liss, Inc.
Protective Effect of Extract of Astragalus on Learning and Memory Impairments and Neurons Apoptosis Induced by Glucocorticoids in 12‐Month Male Mice
Authors: Li Wei‐Zu , Li Wei‐Ping , Zhang Wen , Yin Yan‐Yan , Sun Xiang‐Xiang , Zhou Su‐Su , Xu Xiao‐Qiong , Tao Chun‐Rong
Published: April 2011

Alzheimer's disease (AD) is a chronic neurodegenerative disorder marked by a progressive loss of memory and cognitive function. Stress‐level glucocorticoids are correlated with dementia progression in patients with AD. In this study, 12‐month male mice were chronically treated with stress‐level dexamethasone (DEX, 5 mg/kg) and extract of Astragalus (EA, 10, 20, and 40 mg/kg) or Ginsenoside Rg1 (Rg1, 6.5 mg/kg) for 21 days. We investigated the protective effect of EA against DEX injury in mice and its action mechanism. Our results indicate that DEX can induce learning and memory impairments and neuronal cell apoptosis. The mRNA levels of caspase‐3 are selectively increased after DEX administration. The results of immunohistochemistry demonstrate that caspase‐3 and cytochrome c in hippocampus (CA1, CA3) and neocortex are significantly increased. Furthermore, DEX treatment increased the activity of caspase‐9 and caspase‐3. Treatment groups with EA (20 and 40 mg/kg) or Rg1 (6.5 mg/kg) significantly improve learning and memory, downregulate the mRNA level of caspase‐3, decrease expression of caspase‐3 and cytochrome c in hippocampus (CA1, CA3) and neocortex, and inhibit activity of caspase‐9 and caspase‐3. The present findings highlight a possible mechanism by which stress level of DEX accelerates learning and memory impairments and increases neuronal apoptosis and the potential neuronal protection of EA. Anat Rec,, 2011. © 2011 Wiley‐Liss, Inc.
Early Fetal Development of the Human Cochlea
Authors: Kim Ji Hyun , Rodríguez‐Vázquez Jose Francisco , Verdugo‐López Samuel , Cho Kwang Ho , Murakami Gen , Cho Baik Hwan
Published: April 2011

The cochlear scalas are differentiated from a single tube with a lining by the tall epithelium, that is, the cochlear duct. However, we have no information about the mechanism involved in the formation of the scalas. We evaluated histological sections taken from 20 fetuses: eight each at 8–9 weeks [early stage; 28–45 mm crown–rump length (CRL)] and 11–12 weeks (middle stage; 52–74 mm CRL), and four at 14–15 weeks (late stage; 90–110 mm CRL) of gestation. In four of eight early‐stage and in all eight middle‐stage specimens, we observed irregular perilymphatic spaces and their fusion; these spaces tended to be larger in the future scala tympani than in the future scala vestibuli. The cochlear duct epithelium was positive for cytokeratin 19 in contrast to the other parts of the cochlea. The tectorial membrane appeared in two of eight middle‐stage and all four late‐stage specimens. After 16 weeks, mesothelial lining of the scala may follow the development of aquaporin‐positive thin blood vessels along the scala wall. Notably, gap formation of the cochlear duct epithelium at a site facing the scala tympani consistently occurred before the development of S100 protein‐negative organ of Corti. This gap is likely to correspond to a site occupied finally by Hensen's cells. All these steps likely started in the basal coil and extended to the apical side of the cochlea. These findings suggest that leakage through the epithelial gap of endolymph, with a high concentration of potassium ions, causes mesenchymal cell death, leading to the coalescence of vacuoles containing low potassium perilymph. Anat Rec, , 2011. © 2011 Wiley‐Liss, Inc.
Comparative Ultrastructural Analysis of Mitochondria in the CA1 and CA3 Hippocampal Pyramidal Cells Following Global Ischemia in Mongolian Gerbils
Authors: Radenovic Lidija , Korenic Andrej , Maleeva Galyna , Osadchenko Iryna , Kovalenko Tatyana , Skibo Galyna
Published: April 2011

Post‐ischemic injury of the hippocampus unrolls at different levels and has both functional and structural implications. The deficiency in neuron energy metabolism is an initiating factor. We performed transmission electron microscopic (TEM) comparative analysis of mitochondria in excitatory spine synapses in CA1 stratum radiatum and CA3 hippocampal areas after 5 min of global cerebral ischemia in Mongolian gerbils, 4 and 7 days after reperfusion. Electron microscopy and unbiased morphometric methods were used to evaluate synaptic plasticity, and the number and size of mitochondria in synaptic terminals. We compared the morphological organization of mitochondria in presynaptic terminals between CA1 and CA3 areas in control and post‐ischemic condition according to the following morphometric parameters: mitochondrial volume fraction, mitochondrial frequency in CA1 and CA3 terminals, mean number of mitochondria per presynaptic terminal, frequency of damaged mitochondria in terminals, and density of presynaptic terminals. Our ultrastructural study revealed statistically significant differences in morphometric parameters between CA1 and CA3 areas in control conditions, as well as in post‐ischemic conditions. Also, we found temporal differences in measured parameters obtained 4 and 7 days after reperfusion. This study showed significant morphological differences in the organization of mitochondria in excitatory spine synapses between CA1 and CA3 areas, which corresponded with already known differences in functionality and sensitivity to the ischemic insult. Our conclusion is that revealed post‐ischemic changes in mitochondrial distribution in presynaptic CA1 and CA3 terminals could be an indicator of hippocampal metabolic dysfunction and synaptic plasticity. Anat Rec,, 2011. © 2011 Wiley‐Liss, Inc.
A Morphological Analysis on the Osteocytic Lacunar Canalicular System in Bone Surrounding Dental Implants
Authors: Haga Maiko , Nozawa‐Inoue Kayoko , Li Minqi , Oda Kimimitsu , Yoshie Sumio , Amizuka Norio , Maeda Takeyasu
Published: April 2011

Osseointegration is the most preferable interface of dental implants and newly formed bone. However, the cavity preparation for dental implants often gives rise to empty lacunae or pyknotic osteocytes in bone surrounding the dental implant. This study aimed to examine the chronological alternation of osteocytes in the bone surrounding the titanium implants using a rat model. The distribution of the osteocytic lacunar canalicular system (OLCS) in bone around the titanium implants was examined by silver impregnation according to Bodian's staining. We also performed double staining for alkaline phosphatase (ALP) and tartrate‐resistant acid phosphatase (TRAP), as well as immunohistochemistry for fibroblast growth factor (FGF) 23—a regulator for the serum concentration of phosphorus—and sclerostin, which has been shown to inhibit osteoblastic activities. Newly formed bone and the injured bone at the early stage exhibited an irregularly distributed OLCS and a few osteocytes positive for sclerostin or FGF23, therefore indicating immature bone. Osteocytes in the surrounding bone from Day 20 to Month 2 came to reveal an intense immunoreactivity for sclerostin. Later on, the physiological bone remodeling gradually replaced such immature bone into a compact profile bearing a regularly arranged OLCS. As the bone was remodeled, FGF23 immunoreactivity became more intense, but sclerostin became less so in the well‐arranged OLCS. In summary, it seems likely that OLCS in the bone surrounding the dental implants is damaged by cavity formation, but later gradually recovers as bone remodeling takes place, ultimately inducing mature bone. Anat Rec,, 2011. © 2011 Wiley‐Liss, Inc.
Distribution of Nitrergic Neurons in the Dorsal Root Ganglia of the Bottlenose Dolphin (Tursiops truncatus)
Authors: Bombardi Cristiano , Cozzi Bruno , Nenzi Alice , Mazzariol Sandro , Grandis Annamaria
Published: April 2011

Dorsal root ganglia (DRGs) contain the cell bodies of primary afferent neurons that transmit sensory information from the periphery into the spinal cord. Distinct populations of DRG neurons have been characterized by a variety of different immunohistochemical markers. A subpopulation of ganglionic neurons containing neuronal nitric oxide synthase (nNOS), an enzyme known to generate nitric oxide, has been detected in a number of mammalian species. Despite previous studies, no information is known on the presence and exact distribution of nNOS‐immunoreactive neurons in the DRGs of the bottlenose dolphin. In this investigation, immunoperoxidase for nNOS was used to determine the distribution and the perikaryal size of nitrergic neurons in the DRGs of this species. Double immunofluorescence protocol was used to determine the percentage of nNOS‐immunoreactive (IR) neurons over the total primary afferent neurons. In addition, double immunostaining was used to verify whether there was colocalization of nNOS with substance P (SP). In all DRGs, a subpopulation of small‐ and medium‐sized neurons (about 9%) exhibited nNOS immunoreactivity. Data analysis revealed that the majority of nNOS‐IR neurons (81.3%) expressed SP. The density of nNOS‐immunoreactive and nNOS/SP‐double immunopositive cells was relatively constant throughout the ganglia. However, as observed in others mammals, the number of nitrergic neurons decreased in the caudalmost DRGs. Our results, in conjunction with previous observations, suggest that nNOS‐IR neurons may be involved in the afferent transmission of visceral and nociceptive information as well as in the regulation of the vascular tone. Anat Rec,, 2011. © 2011 Wiley‐Liss, Inc.
Vertebral Anomaly in Fossil Sea Cows (Mammalia, Sirenia)
Authors: Voss Manja , Asbach Patrick , Hilger André
Published: April 2011

Four incompletely preserved caudal vertebrae lacking the neural arches of two fossil sirenian individuals of Halitherium schinzii (Oligocene) from the Rhine area in Germany and northern Belgium reveal osteological alterations. The caudal vertebrae possess a transverse process with growth retardation. This asymmetry indicates that the affected transverse processes are less developed than their counterparts and, consequently, deviate from the norm. Computed tomography (CT) scans reveal osteosclerotic patterns, a morphological feature that characterizes sea cows and supports the nonpathological state of the vertebrae. Additionally, no indications of vertebral fractures or any other occurrences due to external factors are present. This is the oldest documentation of such an anomaly in any sirenian and is interpreted here as hypoplasia, the underdevelopment of an organ or parts of it that might cause a functional deficiency. Anat Rec, 2011. © 2011 Wiley‐Liss, Inc.