bluuebunny/crossref_metadata_2025 huggingface dataset:
Determination of Three Tanshinones from Radix Salvia Miltiorrhiza by Molecularly Imprinted Solid‐phase Extraction
Authors: Yan Hongyuan , Tian Minglei , Row Kyung Ho
Published: November 2009

A selective molecularly imprinted solid‐phase extraction procedure was developed for the selective separation of tanshinone I, tanshinone IIA, and cryptotanshinone from Radix Salvia Miltiorrhiza samples. Tanshinone IIA imprinted polymers (MIP) synthesized in ethanol‐dodecanol system show high affinity to tanshinone IIA and its structure analogs in aqueous environment and the affinity can be controlled by adjusting the intensity of the eluents. By using 60% water‐40% methanol (volume ratio) and 99.5% methanol‐0.5% trifluoroacetic acid (volume ratio) as washing and eluting solvents, most interferences originating from the salvia matrix were eliminated. The extracts were sufficiently clean enough to be directly injected into HPLC for further chromatographic analysis. Good linearity was obtained from 0.4 to 500.0 mg·L−1 (r2=0.999) with the relative standard deviations less than 4.2%. The mean recoveries of tanshinone IIA in Radix Salvia Miltiorrhiza were more than 85.6% at three different concentrations and the limits of detection were 0.06–0.09 mg·L−1. This method is a viable alternative tool to the existing HPLC methods for analyzing the content of the three tanshinones in Radix Salvia Miltiorrhiza samples.
Preparation and Characterization of Temperature‐responsive Porous Monoliths
Authors: Zhang Rongyue , Qi Li , Xiao Qin , Xin Peiyong , Yang Gengliang
Published: November 2009

A new temperature‐responsive porous monolith has been prepared by surface‐initiated activators generated by electron transfer atom transfer radical polymerization (AGET ATRP) grafting poly(N‐isopropylacrylamide) (PNIPAAm) within the pores of the porous polymer monolith. The grafting copolymerization was carried out by a method based on a continuous flow‐through technique without special deoxygenation procedure needed in the general ATRP. The addition of ascorbic acid could counteract the oxidation effect of oxygen diffusing into the reaction system. The resulting grafted monolith was characterized by a mercury intrusion method and the size of macropore was 3.65 µm, which was suitable for flow through the monolith for HPLC. The thermally responsive property of the grafted monolith was evaluated by HPLC using steroids with various hydrophobicities as probes. Through determination of retention factor of each steroid on the grafted monolith at different temperatures using water as mobile phase, it was found that the slope of the plot of retention factor of each steroid versus the temperature changed around the low critical solution temperature (LCST, 32°C) of PNIPAAm in water. It was relative to the grafted PNIPAAm temperature sensitivity that a hydrophobic and hydrophilic alternation would take place around its LCST. Based on this thermally responsive property, the grafted monolith was used as stationary phase for HPLC and to separate the steroids using water as mobile phase by changing the column temperature. As a mobile phase, water is much better than organic solvents concerning the environment.
Experimental Study on Demercurization Performance of Wet Flue Gas Desulfurization System
Authors: Bao Jingjing , Yang Linjun , Yan Jinpei
Published: November 2009

The demercurization performance of wet flue gas desulfurization (WFGD) system was investigated by measuring mercury concentrations at the inlet and outlet of WFGD system with a QM201H mercury analyzer. The selected desulfurizer included NH3·H2O, NaOH, Na2CO3, Ca(OH)2 and CaCO3. The influences of adding oxidant and coagulant such as KMnO4, Fenton reagent, K2S2O8/CuSO4 and Na2S into desulfurization solutions were also studied. The results show that elemental mercury is the main component of gaseous mercury in coal‐fired flue gas, and the proportion of oxidized mercury is less than 36%. Oxidized mercury could be removed by WFGD system efficiently, and the removal efficiency could amount to 81.1%–92.6%. However, the concentration of elemental mercury slightly increased at the outlet of WFGD as a result of its insolubility and re‐emission. Therefore, the removal efficiency of gaseous mercury is only 13.3%–18.3%. The mercury removal efficiency of WFGD system increased with increasing the liquid‐gas ratio. In addition, adding KMnO4, Fenton reagent, K2S2O8/CuSO4 and Na2S into desulfurization solutions could increase the mercury removal efficiency obviously. Various additives have different effects, and Na2S is demonstrated to be the most efficient, in which a mercury removal efficiency of 67.2% can be reached.
Perfluorocyclobutyl‐containing Amphiphilic Block Copolymers Synthesized by RAFT Polymerization
Authors: Chen Yongjun , Zhang Sen , Feng Chun , Zhang Yaqin , Li Qingnuan , Li Wenxin , Huang Xiaoyu
Published: November 2009

Amphiphilic block copolymers containing hydrophobic perfluorocyclobutyl‐based (PFCB) polyacrylate and hydrophilic poly(ethylene glycol) (PEG) segments were prepared via reversible addition‐fragmentation chain transfer (RAFT) polymerization. The PFCB‐containing acrylate monomer, p‐(2‐(p‐tolyloxy)perfluorocyclobutoxy)‐phenyl acrylate, was first synthesized from commercially available compounds in good yields, and this kind of acrylate monomer can be homopolymerized by free radical polymerization or RAFT polymerization. Kinetic study showed the 2,2′‐azobis(isobutyronitrile) (AIBN) initiated and cumyl dithiobenzoate (CDB) mediated RAFT polymerization was in a living fashion, as suggested by the fact that the number‐average molecular weights (Mn) increased linearly with the conversions of the monomer, while the polydispersity indices kept less than 1.10. The block polymers with narrow molecular weight distributions (Mw/Mn≦1.21) were prepared through RAFT polymerization using PEG monomethyl ether capped with 4‐cyanopentanoic acid dithiobenzoate end group as the macro chain transfer agent (mPEG‐CTA). The length of the hydrophobic segment can be tuned by the feed ratio of the PFCB‐based acrylate monomer and the extending of the polymerization time. The micellization behavior of the block copolymers in aqueous media was investigated by the fluorescence probe technique.
Non‐covalent Interaction of Perfluorooctanoic Acid with DNA
Authors: Zhang Xian , Shen Rong , Chen Ling
Published: November 2009

Health risk from exposure of perfluorochemicals to wildlife and human has been a subject of concern in many fields such as environmental ecology, toxicology, pathology and life sciences. The interactions of perfluorooctanoic acid (PFOA) with DNA were investigated by equilibrium dialysis, circular dichroism and isothermal titration calorimetry techniques under normal physiological conditions in vitro. The binding of PFOA to DNA was a non‐covalent interaction and corresponded to the Langmuir adsorption isotherm in a two‐step binding model, in which PFOA climbed along the backbones of DNA and then interacted with the homolateral bases via hydrophobic interactions. The saturation number of PFOA was calculated to be 0.64 per base‐pair of DNA. Such an interaction caused the enhancement of circular dichroism spectra of DNA at both 245 and 275 nm, indicating the change of DNA conformation. The acidic media, low electrolyte and temperature ≦35°C are comparatively more favorable for PFOA binding to DNA. This work provides a useful experimental strategy for studying the interactions of perfluorochemicals with biomacromolecules, aiming at a better understanding of the gene toxicity mechanism of perfluorochemicals.
Hydrogen‐bonded Supramolecular Hydrogels Derived from 3,3′,4,4′‐Benzophenonetetracarboxylic Acid and Hydroxylpyridines
Authors: Wang Yujiang , Tang Liming , Wang Li , Yu Jian
Published: November 2009

In this paper, four gelators (defined as G1–G4) were prepared from 3,3′,4,4′‐benzophenonetetracarboxylic acid (BPTA) and para‐hydroxylpyridine or meta‐hydroxylpyridine at molar ratios 1:2 and 1:4 respectively, and characterized by 1H NMR, IR, UV‐Vis spectra and elemental analysis. Due to the amphiphilic features, all the gelators were able to gel water via cooling their aqueous solution under different stimulations. The structure of the assembling fibers and the macroscopic properties of the gels were investigated by multiple techniques. The results indicated that the minimum gelator concentration (MGC) increased by the order of G1, G2, G3 and G4, while the gel‐to‐sol dissociation temperature (Tgel) decreased by the same order, which were explained from the assembling structures of the gels.
Triflic Acid‐Promoted Formylation of Ceramide in Dimethylformamide
Authors: CHIANG Liwu , Pan Sider , Lo Jemmau , Yu Chungshan
Published: November 2009

The protected ceramide: N‐((2S,3S,4R)‐3,4‐bis(benzyloxy)‐1‐hydroxyoctadecan‐2‐yl)tetracosanamide, was attempted to introduce a triflate as a leaving group followed by a nucleophilic substitution with azido group in one‐pot manner. Unexpectedly, the oxazole ring formed via a thermodynamically favored intramolecular cyclization was opened to generate the original ceramide by triflic acid. In addition, the residual acid promoted a formylation of the primary hydroxy group in DMF.
Extracapsular lymph node spread
Authors: Alakus Hakan , Hölscher Arnulf H. , Grass Guido , Hartmann Eva , Schulte Christian , Drebber Uta , Baldus Stephan E. , Bollschweiler Elfriede , Metzger Ralf , Mönig Stefan P.
Published: November 2009

BACKGROUND:

Lymphatic spread is 1 of the most relevant prognostic factors for gastric carcinoma. The current International Union Against Cancer (UICC) pN staging system is based on the number of metastatic lymph nodes and does not take into consideration the characteristics of the metastatic lymph nodes itself. The aim of the current study was to examine the prognostic value of extracapsular lymph node involvement in gastric cancer and to find correlations with clinicopathological parameters.

METHODS:

Tissue samples were obtained from 159 gastric cancer patients who underwent gastrectomy with D2‐lymphadenectomy in 142 (89.3%) cases and subtotal gastrectomy with D2‐lymphadenectomy in 17 (10.7%) cases. The number of resected lymph nodes, number of metastatic lymph nodes, and number of metastatic lymph nodes with extracapsular lymph node involvement were determined. Extracapsular spread was defined as infiltration of cancer cells beyond the capsule of the metastatic lymph node.

RESULTS:

Ninety‐six (60.4%) patients had lymph node metastasis. In 57 (35.8%) cases, extracapsular lymph node involvement was also detected. Extracapsular lymph node involvement was significantly associated with higher pN‐category (P < .001), higher pM category (P = .048), and higher UICC stages (P = .001). According to the Kaplan‐Meier log‐rank statistical method, extracapsular lymph node involvement was significantly associated with poor survival (P = .001). In the multivariate analysis besides pT (P < .001) and R‐category (P = .009), extracapsular lymph node involvement also remained as an independent prognostic factor (P = .003), whereas the UICC pN‐category (P = .822) lost its prognostic value.

CONCLUSIONS:

Extracapsular lymph node involvement is associated with higher tumor stages and is an independent negative prognostic factor in gastric cancer. In future staging systems for gastric cancer, extracapsular lymph node involvement should be considered. Cancer 2010. © 2010 American Cancer Society.
Depth of invasion determines the postresectional prognosis for patients with T1 extrahepatic cholangiocarcinoma
Authors: Nagahashi Masayuki , Shirai Yoshio , Wakai Toshifumi , Sakata Jun , Ajioka Yoichi , Nomura Tatsuya , Tsuchiya Yoshiaki , Hatakeyama Katsuyoshi
Published: November 2009

BACKGROUND:

We tested the hypothesis that in patients with T1 extrahepatic cholangiocarcinoma (EHC), prognosis postresection is significantly different for those with tumors that are limited to the mucosa than for those with tumors that have invaded (but not penetrated) the fibromuscular layer.

METHODS:

A retrospective analysis was conducted of 33 consecutive patients with pathologic T1 (pT1) EHC tumors. According to the depth of invasion, the pT1 tumors were divided into 2 groups: Group 1, tumors that were limited to the mucosa (mucosal tumors); and Group 2, tumors that had invaded (but not penetrated) the fibromuscular layer (fibromuscular layer‐invasive tumors). Long‐term outcomes after resection were compared between the 2 groups for a median follow‐up time of 175 months.

RESULTS:

Eighteen patients had mucosal tumors and 15 patients had tumors that had invaded the fibromuscular layer. None of the patients with mucosal tumors had lymphovascular invasion, whereas 3 of the patients with fibromuscular layer‐invasive tumors had lymphovascular invasion (P = .083). Overall survival after resection was better in Group 1 than in Group 2 (cumulative 10‐year survival rate, 100% vs 52%; P = .024). The rate of disease‐free survival after resection was higher in Group 1 than in Group 2 (cumulative disease‐free 10‐year survival rate, 100% vs 56%; P = .022).

CONCLUSIONS:

The long‐term outcome after resection for EHC is significantly better for patients with mucosal tumors than for patients with fibromuscular layer‐invasive tumors. This suggests that the depth of tumor invasion affects the postresection prognosis for patients with pT1 EHC. Cancer 2010. © 2010 American Cancer Society.
Rapid and reliable confirmation of acute promyelocytic leukemia by immunofluorescence staining with an antipromyelocytic leukemia antibody
Authors: Dimov Nikolay D. , Medeiros L. Jeffrey , Kantarjian Hagop M. , Cortes Jorge E. , Chang Kun‐Sang , Bueso‐Ramos Carlos E. , Ravandi Farhad
Published: November 2009

BACKGROUND:

The authors evaluated the utility of immunofluorescence staining with an antipromyelocytic leukemia (anti‐PML) antibody for patients with a suspected diagnosis of new or relapsed acute promyelocytic leukemia (APL) and correlated the findings with the results of other established diagnostic modalities.

METHODS:

Bone marrow (BM) and/or peripheral blood (PB) smears from 349 patients in whom the diagnosis of APL was considered were assessed with the anti‐PML antibody using immunofluorescence. The study group included 199 patients with confirmed APL and 150 with other conditions. The results of conventional cytogenetics, reverse transcription polymerase chain reaction (RT‐PCR), and fluorescence in situ hybridization (FISH) performed on these patients were correlated with the PML results.

RESULTS:

Among patients with confirmed APL, anti‐PML antibody was positive in 182 of 184 BM and 32 of 33 PB smears. Conventional cytogenetics demonstrated t(15;17)(q22;q12) in 166 of 182 (91%) patients; 10 had a normal karyotype, 4 had insufficient mitoses to grow in culture, 1 was inconclusive, and 1 was 48, XX, +8, +8. Anti‐PML staining was positive in 9 of 10 with a normal karyotype and in all 4 cases with insufficient mitoses. RT‐PCR and FISH were positive for PML–retinoic acid receptor‐α in 169 of 172 (98%) and 90 of 94 (96%) cases, respectively. Among the patients without APL, 148 of 150 (98.6%) were negative with anti‐PML antibody. The sensitivity and specificity of the test were 98.9% and 98.7%, respectively.

CONCLUSIONS:

PML immunofluorescence staining is a rapid (<4 hours turnaround time) and reliable frontline diagnostic approach that can facilitate initiation of targeted therapy, particularly in clinical settings where cytogenetic and molecular testing are not readily available. Cancer 2010. © 2010 American Cancer Society.
D2 receptors receive paracrine neurotransmission and are consistently targeted to a subset of synaptic structures in an identified neuron of the crustacean stomatogastric nervous system
Authors: Oginsky Max F. , Rodgers Edmund W. , Clark Merry C. , Simmons Robert , Krenz Wulf‐Dieter C. , Baro Deborah J.
Published: November 2009

Dopamine (DA) modulates motor systems in phyla as diverse as nematodes and arthropods up through chordates. A comparison of dopaminergic systems across a broad phylogenetic range should reveal shared organizing principles. The pyloric network, located in the stomatogastric ganglion (STG), is an important model for neuromodulation of motor networks. The effects of DA on this network have been well characterized at the circuit and cellular levels in the spiny lobster, Panulirus interruptus. Here we provide the first data about the physical organization of the DA signaling system in the STG and the function of D2 receptors in pyloric neurons. Previous studies showed that DA altered intrinsic firing properties and synaptic output in the pyloric dilator (PD) neuron, in part by reducing calcium currents and increasing outward potassium currents. We performed single cell reverse transcriptase‐polymerase chain reaction (RT‐PCR) experiments to show that PD neurons exclusively expressed a type 2 (D2αPan) DA receptor. This was confirmed by using confocal microscopy in conjunction with immunohistochemistry (IHC) on STG wholemount preparations containing dye‐filled PD neurons. Immunogold electron microscopy showed that surface receptors were concentrated in fine neurites/terminal swellings and vesicle‐laden varicosities in the synaptic neuropil. Double‐label IHC experiments with tyrosine hydroxylase antiserum suggested that the D2αPan receptors received volume neurotransmissions. Receptors were further mapped onto three‐dimensional models of PD neurons built from Neurolucida tracings of confocal stacks from the IHC experiments. The data showed that D2αPan receptors were selectively targeted to approximately 40% of synaptic structures in any given PD neuron, and were nonuniformly distributed among neurites. J. Comp. Neurol. 518:255–276, 2010. © 2009 Wiley‐Liss, Inc.
The therapist–client relationship, computerized self‐help and active therapy ingredients
Authors: Peck David F.
Published: November 2009

There is strong evidence that a good relationship between therapist and client is associated with positive outcomes after all types of psychological therapy. There is also strong evidence that computer‐guided cognitive behaviour therapy (CCBT), in which there may be little or no face‐to‐face contact, is associated with outcomes that are as good as outcomes after conventional therapy. These two sets of findings can be reconciled by reference to the common factors debate, in that common factors may be as important in CCBT as in conventional therapy; and by reconstruing the therapist–client relationship as a channel through which common and specific factors are brought into play. Copyright © 2009 John Wiley & Sons, Ltd.

Key Practitioner Message:

• Computer‐guided CBT may benefit from a more explicit inclusion of common factors.

• A greater focus on methods of improving the transmission of active therapy ingredients through the therapist‐to‐client channel may be helpful in research and training.
Acid Hydrolysis of Cellulose as the Entry Point into Biorefinery Schemes
Authors: Rinaldi Roberto , Schüth Ferdi
Published: November 2009

Cellulose is a major source of glucose because it is readily available, renewable, and does not compete with the food supply. Hydrolysis of cellulose is experiencing a new research and development cycle in which this reaction is carried out over solid catalysts and coupled to other reactions for increased efficiency. Cellulose is typically not soluble in conventional solvents and very resistant to chemical and biological transformations. This Review focuses on aspects related to the hydrolysis of cellulose as this process is a significant entry point into the biorefinery scheme based on carbohydrates for the production of biofuels and biochemicals. Structural features of cellulose, conventional acid‐catalyzed reactions, and the use of solid acid catalysts for hydrolysis are discussed. The longterm success of the biorefinery concept depends on the development of energetically efficient processes to convert cellulose directly or indirectly into biofuels and chemicals.
Epigenetic control of translation regulation: Alterations in histone H3 lysine 9 post‐translation modifications are correlated with the expression of the translation initiation factor 2B (Eif2b5) during thermal control establishment
Authors: Kisliouk Tatiana , Ziv Maor , Meiri Noam
Published: November 2009

Thermal control set point is regulated by thermosensitive neurons of the preoptic anterior hypothalamus (PO/AH) and completes its development during postnatal critical sensory period. External stimuli, like increase in environmental temperature, influence the neuronal protein repertoire and, ultimately, cell properties via activation or silencing of gene transcription, both of which are regulated by the “histone code.''” Here, we demonstrated an increase in global histone H3 lysine 9 (H3K9) acetylation as well as H3K9 dimethylation in chick PO/AH during heat conditioning at the critical period of sensory development. In contrast to the global profile of H3K9 modifications, acetylation and dimethylation patterns of H3K9 at the promoter of the catalytic subunit of eukaryotic translation initiation factor 2B (Eif2b5) were opposite to each other. During heat conditioning, there was an increase in H3K9 acetylation at the Eif2b5 promoter, simultaneously with decrease in H3K9 dimethylation. These alterations coincided with Eif2b5 mRNA induction. Moreover, exposure to excessive heat during the critical period resulted in long‐term effect on both H3K9 tagging at the Eif2b5 promoter and Eif2b5 mRNA expression. These data suggest a role for dynamic H3K9 post‐translational modifications in global translation regulation during the thermal control establishment. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2010
Body checking induces an attentional bias for body‐related cues
Authors: Smeets Elke , Tiggemann Marika , Kemps Eva , Mills Jennifer S. , Hollitt Sarah , Roefs Anne , Jansen Anita
Published: November 2009

Objective:

Theoretical models suggest that body checking is linked to biased cognitive processing. However, this link has not been investigated in any systematic way. The present study examined the influence of body checking on attentional bias for body‐related cues by manipulating body checking behaviors in nonclinical participants.

Method:

66 women were randomly assigned to one of three conditions: body checking, body exposure, or control. A body visual search task was used to measure attentional bias.

Results:

Participants in the body checking condition showed speeded detection of body‐related information compared to participants in the exposure and control conditions. No evidence was found for increased distraction by body‐related information. Furthermore, participants in the body checking condition reported more body dissatisfaction after the manipulation than participants in the body exposure and control conditions.

Discussion:

These results are the first to experimentally establish the link between body checking and attentional bias toward body‐related cues. © 2010 by Wiley Periodicals, Inc. (Int J Eat Disord 2011; 44:50–57)
Digestive complication in severe malnourished anorexia nervosa patient: A case report of necrotizing colitis
Authors: Diamanti Antonella , Basso Maria Sole , Cecchetti Claudio , Monti Lidia , Noto Cristian , De Maria Francesco , Castro Massimo
Published: November 2009

Background:

Necrotizing colitis (NC) represents a severe, although rare, complication in patients with anorexia nervosa.

Objective:

We report the only case of NC with good prognosis in a severely malnourished AN patient.

Method:

Available patient records, imaging, and biochemical data were evaluated.

Discussion:

This case represents an unusual gastrointestinal complication and underlines the important clinical role that Parentera Nutrition (PN) has for some selected very malnourished AN patients. The severe starvation may compromise the normal function of gastrointestinal tract and it can also lead to an incomplete tolerance of enteral refeeding thus making PN required to reach the nutritional rehabilitation. © 2010 by Wiley Periodicals, Inc. (Int J Eat Disord 2011; 44:91–93)
Binge eating is not associated with elevated eating, weight, or shape concerns in the absence of the desire to lose weight in men
Authors: De Young Kyle P. , Lavender Jason M. , Anderson Drew A.
Published: November 2009

Objective

To investigate whether the desire to lose weight moderates the association between objective binge eating episodes (OBEs) and eating and body image‐related psychopathology in men.

Method

Participants (N = 404) completed questionnaires assessing eating and body image psychopathology and were grouped based on the presence of OBEs and the desire to lose weight.

Results

The desire to lose weight was found to moderate the relationships between the presence of OBEs and restraint, eating concerns, shape concerns, and weight concerns but not the presence of fasting, purging, driven exercise, or body image dissatisfaction. In fact, men who experienced OBEs engaged in similar rates of purging regardless of whether they desired to lose weight.

Discussion

The results of this study suggest that disordered eating behaviors may be manifested differently in some men compared to what is typically observed in women, with over one‐quarter of men who reported binge eating following this unusual pattern. © 2009 by Wiley Periodicals, Inc. Int J Eat Disord 2010; 43:732–736
Anorexia nervosa and Wernicke Korsakoff's syndrome: Atypical presentation by acute psychosis
Authors: Altinyazar Vesile , Kiylioglu Nefati , Salkin Gokhan
Published: November 2009

A 16‐year‐old girl was admitted to the emergency department because of acute changes in mental state such as paranoid and nihilistic delusions, confabulations, and distortions of body schema perception. Her history was compatible with anorexia nervosa in that she had lost more than 17 kg in weight over one and a half years. Her body mass index was 14. She was diagnosed with Wernicke Korsakoff's syndrome and was given intravenous thiamine at 250 mg/day. Response was dramatic for nystagmus and gait incoordination but not for other symptoms. After dosage was increased to 750 mg/day all symptoms including psychosis improved. With her increase in food consumption, secondary deterioration was observed and diagnosed as refeeding syndrome. After proper replacements she was completely normal in the 9th month, and her weight was 55 kg. This patient was interesting for the presenting symptoms (psychosis), and improvement by high doses of thiamine replacement, and also for refeeding syndrome during this period. © 2009 by Wiley Periodicals, Inc. Int J Eat Disord 2010; 43:766–769
Marked enhancement of antigen‐specific T‐cell responses by IL‐7‐fused nonlytic, but not lytic, Fc as a genetic adjuvant
Authors: Nam Hyo Jung , Song Mi‐Young , Choi Dong‐Hoon , Yang Se‐Hwan , Jin Hyun‐Tak , Sung Young‐Chul
Published: November 2009

IL‐7 plays a crucial role in the homeostatic proliferation, differentiation and survival of T cells, as well as in the survival and proliferation of precursor B cells. Here, we demonstrated that utilizing nonlytic Fc‐fused IL‐7 (IL‐7‐Fcm) as a genetic adjuvant significantly enhanced not only CD4+ but also CD8+ T‐cell responses by E7 DNA immunization, in addition to improving protection against TC‐1‐induced tumors in comparison to IL‐7 alone. Similar results were obtained in OT‐1 adoptive transfer experiments with OVA DNA injection, suggesting independence from antigenic nature and experimental conditions. In particular, the increased frequency of CD8+ T cells was mainly due to enhanced T‐cell proliferation in T‐cell priming, and not to decreased cellular apoptosis. Interestingly, the enhanced adjuvant effect was not seen in the co‐delivery of lytic Fc‐fused IL‐7 (IL‐7‐Fc) which increases T‐cell apoptosis as well as T‐cell proliferation, suggesting that the T‐cell proliferative effect may be neutralized by T‐cell apoptosis. Thus, our findings suggest that nonlytic Fc, in contrast to lytic Fc, fusion to cytokines may provide an insight in designing a potent genetic adjuvant for inducing CD4+ and CD8+ T‐cell responses.
Direct antigen presentation by DC shapes the functional CD8+ T‐cell repertoire against the nuclear self‐antigen La‐SSB
Authors: Keech Catherine L. , Pang Ken C. , McCluskey James , Chen Weisan
Published: November 2009

Controversy still surrounds the importance of cross‐presentation versus endogenous or direct presentation of MHC‐I restricted Ag in CD8+ T‐cell (TCD8+) immunity. It is even less clear what relative role these pathways play in shaping the T‐cell repertoire specific for ubiquitous self‐antigens, especially in cases where both Ag presentation pathways could potentially be involved. Here we provide evidence that a TCD8+ repertoire specific for a determinant from the nuclear autoantigen La‐SSB is largely shaped by direct presentation. In this system, mouse TCD8+ reactive to a xenogeneic human La (hLa51–58) Kb peptide did not recognize directly presented peptide on either spleen cells from hLa‐Tg mice or hLa transfected syngeneic cells. Interestingly, the same TCD8+ were activated by in vivo challenge with allogeneic APC expressing either the Tg hLa or loaded with intact recombinant hLa protein, indicating functional cross‐presentation of the hLa51–58. However, in irradiated bone marrow chimeric mice, DC expressing Tg hLa, but not WT DC that matured in hLa‐Tg mice, constitutively presented the hLa51–58 to TCD8+. These data demonstrate that although both the direct‐ and cross‐presentation pathways are potentially operative in revealing hLa51–58 to TCD8+, the TCD8+ repertoire to this determinant is shaped quantitatively according to the efficiency of Ag presentation.
A role for IL‐18 in protective immunity against Mycobacterium tuberculosis
Authors: Schneider Bianca E. , Korbel Daniel , Hagens Kristine , Koch Markus , Raupach Bärbel , Enders Jana , Kaufmann Stefan H. E. , Mittrücker Hans‐Willi , Schaible Ulrich E.
Published: November 2009

Tuberculosis remains the most hazardous bacterial infection worldwide. The causative agent, Mycobacterium tuberculosis, is a facultative intracellular pathogen of resting MΦ. IFN‐γ secreted by natural killer, CD4 Th 1 and CD8 T cells upon instruction by IL‐12 and ‐18 activates MΦ to restrict mycobacterial growth. Production of both cytokines is induced by TLR signalling in DC and MΦ. Mice deficient for the TLR adaptor, MyD88, are highly susceptible to M. tuberculosis infection. Shared usage of MyD88 by signalling cascades for TLR and receptors for IL‐1 and IL‐18 prompted us to revisit the role of IL‐18 during experimental infection with M. tuberculosis. We show that mice deficient for IL‐18 and MyD88 but not for IL‐18 receptor promptly succumbed to M. tuberculosis infection in contrast to WT or TLR‐2/‐4 double KO mice indicating that lack of IL‐18 contributes to the high susceptibility of MyD88 KO mice to M. tuberculosis. Without IL‐18, the protective Th1 response was decreased and hence, mycobacterial propagation was favoured. Neutrophil‐driven lung immunopathology concomitant with unrestrained growth of tubercle bacilli are most likely responsible for the premature death of IL‐18 KO mice. Thus, IL‐18 plays a decisive role in protective immunity against tuberculosis.
Adenosine mediated desensitization of cAMP signaling enhances T‐cell responses
Authors: Yang Ailian , Mucsi Ashley D. , Desrosiers Melanie D. , Chen Jiang‐Fan , Schnermann Jürgen B. , Blackburn Michael R. , Shi Yan
Published: November 2009

Adenosine has long been regarded as a crucial anti‐inflammatory agent that protects the host from excessive damage. It has been reported to play an important role in suppressing immune activation, particularly that of T cells. However, it is a general observation that induction of T‐cell activation is an efficient event despite the high adenosine levels that are often present in the affected host due to injury or stress. We report here that prior to antigenic stimulationviaTCR/CD3, exposure of T cells to adenosine desensitizes adenosine receptors, so as to create a window of time where the T cells are insensitive to this ubiquitous suppressor. T cells from mice that were pre‐exposed to this manipulation showed stronger responses to antigenic stimulation; therefore, the P1 adenosine receptor desensitization demonstrated an adjuvant‐like effect. Our results suggest that adenosine receptor desensitization may be a mechanism for T cells to escape the general suppression during early points of T‐cell activation and may emerge as a potential alternative for vaccine adjuvants.
An active CD8α/pMHCI interaction is required for CD8 single positive thymocyte differentiation
Authors: Kang Yoon‐Joong , Wang Xiaosong , Lin Sue‐Jane , Hsu Yen‐Ming , Chang Hsiu‐Ching
Published: November 2009

Recognition of viral antigenic peptides bound to major histocompatibility complex class I molecules (MHCI) by TCR is critical for initiating the responses of CD8+ T cells that ultimately lead to elimination of virus‐infected cells. This antigen recognition is enhanced by the CD8 coreceptor through its interaction with the peptide‐MHCI complexes (pMHCI). Mouse CD8αβ can form two different complexes with pMHCI via either the CD8α‐ or CD8β‐dominated interaction. To understand the functional significance of these complexes in vivo, we generated Tg mice carrying a variant CD8αβ (CD8αm3β) capable of forming only the CD8β‐dominated CD8αβ/pMHCI complex. These mice show sub‐optimal thymic differentiation with reduced populations of CD8+ single‐positive thymocytes. Tg CD8+ T cells exhibit a compromised developmental capacity when competing with CD8+ T cells from B6 mice in mixed bone marrow chimera experiments. However, once these CD8+ T cells have emigrated to the peripheral lymphoid organs, they exhibit normal effector function against viral infection. Our observations indicate that, in addition to the CD8 activity conferred by CD8β‐dominated CD8αβ/pMHCI complexes, full thymocyte differentiation requires additional coreceptor activities conferred by CD8αα and/or CD8αβ with CD8α‐dominated CD8/pMHCI complexes.
TLR2‐independent induction and regulation of chronic intestinal inflammation
Authors: Boulard Olivier , Asquith Mark J. , Powrie Fiona , Maloy Kevin J.
Published: November 2009

Interactions between the intestinal microflora and host innate immune receptors play a critical role in intestinal homeostasis. Several studies have shown that TLR2 can modulate inflammatory responses in the gut. TLR2 signals enhance tight junction formation and fortify the epithelial barrier, and may play a crucial role in driving acute inflammatory responses towards intestinal bacterial pathogens. In addition, TLR2 agonists can have direct effects on both Th1 cells and Treg. To define the role of TLR2 in the induction and regulation of chronic intestinal inflammation we examined the effects of TLR2 deletion on several complementary models of inflammatory bowel disease. Our results show that TLR2 signals are not required for the induction of chronic intestinal inflammation by either innate or adaptive immune responses. We further show that TLR2−/− mice harbor normal numbers of Foxp3+ Treg that are able to suppress intestinal inflammation as effectively as their WT counterparts. We also did not find any intrinsic role for TLR2 for pathogenic effector T‐cell responses in the gut. Thus, in contrast to their role in acute intestinal inflammation and repair, TLR2 signals may have a limited impact on the induction and regulation of chronic intestinal inflammation.
Splenic stromal cells mediate IL‐7 independent adult lymphoid tissue inducer cell survival
Authors: Hou Tie Zheng , Mustafa Mohammad Z. , Flavell Sarah J. , Barrington Fern , Jenkinson Eric J. , Anderson Graham , Lane Peter J. L. , Withers David R. , Buckley Christopher D.
Published: November 2009

Lymphoid tissue inducer cells (LTi) play an important role in the development of lymphoid tissue in embryos. Adult CD4+CD3− LTi‐like cells present a similar phenotype and gene expression to their embryonic counterpart and have important roles in CD4+ T‐cell memory and lymphoid tissue recovery following viral infection. However, adult LTi‐like cells are heterogeneous populations and the factors that regulate their survival and accumulation within secondary lymphoid organs remain unclear, in particular whether the T‐zone stroma is involved. Here we report the identification and characterization of a distinct subset of podoplanin+ murine splenic stromal cells that support adult LTi‐like cell survival. We have identified and isolated CD45−podoplanin+ stromal cell populations which have a similar but distinct phenotype to T‐zone reticular cells in LN. CD45−podoplanin+ fibroblast‐like cells mediate LTi‐like cell survival in vitro; surprisingly this was not dependent upon IL‐7 as revealed through blocking Ab experiments and studies using LTi‐like cells unable to respond to γ chain cytokines. Our findings show that adult LTi‐like cells require extrinsic signals from podoplanin+ splenic stromal cells to survive and suggest that IL‐7 is not necessary to mediate their survival in the adult spleen.
Diversity and clonotypic composition of influenza‐specific CD8+ TCR repertoires remain unaltered in the absence of Aire
Authors: Kedzierska Katherine , Valkenburg Sophie A. , Guillonneau Carole , Hubert Francois‐Xavier , Cukalac Tania , Curtis Joan M. , Stambas John , Scott Hamish S. , Kedzierski Lukasz , Venturi Vanessa , Davenport Miles P.
Published: November 2009

TCR repertoire diversity is important for the protective efficacy of CD8+ T cells, limiting viral escape and cross‐reactivity between unrelated epitopes. The exact mechanism for selection of restricted versus diverse TCR repertoires is far from clear, although one thought is that the epitopes resembling self‐peptides might select a limited array of TCR due to the deletion of autoreactive TCR. The molecule Aire promotes the expression of tissue‐specific Ag on thymic medullary epithelial cells and the deletion of autoreactive cells, and in the absence of Aire autoreactive cells persist. However, the contribution of Aire‐dependent peptides to the selection of the Ag‐specific TCR repertoire remains unknown. In this study, we dissect restricted (DbNP366%+CD8+) and diverse (DbPA224%+CD8+, KdNP147%+CD8+) TCR repertoires responding to three influenza‐derived peptides in Aire‐deficient mice on both B6 and BALB/c backgrounds. Our study shows that the number, qualitative characteristics and TCR repertoires of all influenza‐specific, DbNP366%+CD8+, DbPA224%+CD8+ and KdNP147%+CD8+ T cells are not significantly altered in the absence of Aire. This provides the first demonstration that the selection of an Ag‐specific T‐cell repertoire is not significantly perturbed in the absence of Aire.
Requirements for control of B‐cell lymphoma by NK cells
Authors: Brenner Christoph D. , King Susan , Przewoznik Margarethe , Wolters Imke , Adam Christian , Bornkamm Georg W. , Busch Dirk H. , Röcken Martin , Mocikat Ralph
Published: November 2009

The role of NK cells in the control of endogenously arising tumors is still unclear. We monitored activation and effector functions of NK cells in a c‐myc‐transgenic mouse model of spontaneously arising lymphoma. At early stages, tumors demonstrated reduced MHC class I expression and increased expression of natural killer group 2D ligands (NKG2D‐L). NK cells in these tumors showed an activated phenotype that correlated with the loss of tumor MHC class I. With increasing tumor load however, NK‐cell effector functions became progressively paralyzed or exhausted. In later stages of disease, tumors re‐expressed MHC class I and lost NKG2D‐L, suggesting a role of these two signals for NK cell‐mediated tumor control. Testing a panel of lymphoma cell lines expressing various MHC class I and NKG2D‐L levels suggested that NK cell‐dependent tumor control required a priming and a triggering signal that were provided by MHC class I down‐regulation and by NKG2D‐L, respectively. Deleting either of the “two signals” resulted in tumor escape. At early disease stages, immune stimulation through TLR‐ligands in vivo efficiently delayed lymphoma growth in a strictly NK cell‐dependent manner. Thus, NK‐receptor coengagement is crucial for NK‐cell functions in vivo and especially for NK cell‐mediated tumor surveillance.
Tartatric Acid and L‐Cysteine Synergistic‐Assisted Synthesis of Antimony Trisulfide Hierarchical Structures in Aqueous Solution
Authors: Pan Jun , Xiong Shenglin , Xi Baojuan , Li Jiangfa , Li Jiangying , Zhou Hongyang , Qian Yitai
Published: November 2009

Alveolate amorphous Sb2S3 microspheres about 2 μm in diameter were hydrothermally synthesized in aqueous solution without the use of a surfactant at 180 °C by using SbCl3, L‐cysteine, and tartaric acid as starting materials. After annealing at 250 °C for 3 h under a nitrogen atmosphere, polycrystalline Sb2S3 hollow spheres were obtained. The morphology, structure, and phase composition of alveolate Sb2S3 microspheres were characterized by X‐ray diffraction, field‐emission scanning electron microscopy, energy dispersive X‐ray analysis, and X‐ray photoelectron spectroscopy. It was demonstrated that tartaric acid and L‐cysteine play a key role in the formation of such hierarchical structures. In addition, the possible aggregation mechanism was proposed to illustrate the formation of Sb2S3 microspheres on the basis of the experimental results and analyses.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Observation and Interpretation of Structural Variety in Alkaline Earth Metal Derivatives of Diphosphanyldisiloxane
Authors: Kopecky Peter , von Hänisch Carsten , Weigend Florian , Kracke Andreas
Published: November 2009

Alkaline earth metal derivatives of the diphosphanyldisiloxane O(SiiPr2PH2)2 (1) were obtained by reactions of 1 with MgBu2 and M{N(SiMe3)2}2 (M = Ca, Sr, Ba), respectively. The metal complexes formed were characterised by elemental analysis, NMR spectroscopy, and IR spectroscopy as well as by single‐crystal structure analysis. The solid‐state structures depend on the metal ion involved. The magnesium derivative crystallizes from thf as a trimer and exhibits a six‐membered Mg3P3 ring. In contrast, the Ca und Sr derivatives show a dimeric structure via formation of M2P2 rings (M = Ca, Sr). Eventually, the Ba derivative forms a dimeric structure with an octahedral P4Ba2 moiety. Quantum chemical investigations indicate that the structural variety is a consequence of accessibility and spatial extent of the d‐orbitals of the alkaline earth metal atoms.
Synthesis and Characterisation of 2,2‐Bis(hydroxymethyl)‐1,3‐diselenolato Metal(II) Complexes Bearing Various Phosphanes
Authors: Niksch Tobias , Görls Helmar , Friedrich Manfred , Oilunkaniemi Raija , Laitinen Risto , Weigand Wolfgang
Published: November 2009

An improved synthesis of 4,4‐bis(hydroxymethyl)‐1,2‐diselenolane and the complexation properties of the corresponding diselenolato dianion to group‐10 metals are reported. We describe an efficient and straightforward procedure that bypasses the isolation of the malodorous and air‐sensitive diselenol and starts with the diselenide and an appropriate group‐10 metal complex bearing phosphane and chlorido ligands. A series of complexes with various mono‐ and bidentate phosphanes is prepared and characterised by multinuclear NMR spectroscopy, mass spectrometry, and elemental analysis. Furthermore, the structure of most complexes is studied by single‐crystal X‐ray diffraction to establish their supramolecular arrangement in the solid state. Consequently, several group‐10 metal complexes with P–M–P angles (bite angles) in the range from 71–108° are investigated. The use of the sterically demanding bridging phosphane 4,5‐bis(diphenylphosphanyl)‐9,9‐dimethylxanthene, which exhibits a large bite angle yields a mixture of a di‐ and trinuclear complex. While the platinum‐containing complexes are proven to be rather stable, the palladium and nickel analogues tend to decompose. Especially, the nickel complexes were found to be sensitive against oxidation. This circumstance leads to the formation of the so far unknown 1,8‐bis(diphenylphosphanyl)naphthalene monooxide, the formation and structure of which could be confirmed from NMR spectroscopic data and single‐crystal X‐ray diffraction.
Mechanistic Studies on the Copper‐Catalyzed Hydrosilylation of Ketones
Authors: Issenhuth Jean‐Thomas , Notter François‐Paul , Dagorne Samuel , Dedieu Alain , Bellemin‐Laponnaz Stéphane
Published: November 2009

The copper‐catalyzed asymmetric hydrosilylation of ketones is an efficient method for the synthesis of chiral enantiopure secondary alcohols. Herein, we present a detailed computational study (DFT/B3LYP) of the copper(I)‐catalyzed reaction. In particular, the two transition states involved in the catalytic cycle have been determined. The insertion of the ketone into the Cu–H bond was found to have a lower activation barrier than the reaction of the copper alkoxy intermediate with the silane, which regenerates Cu–H along with the silyl ether product. Our findings also reveal the importance of the copper hydride dimer in controlling the reactivity toward the ketone. The conclusions are supported by experimental mechanistic investigations including kinetic studies, kinetic isotope effect, and isotope labeling measurements.
Cristatomentin, a Green Pigment of Mixed Biogenetic Origin from Albatrellus cristatus (Basidiomycetes)
Authors: Koch Barbara , Kilpert Claus , Steglich Wolfgang
Published: November 2009

The structure of cristatomentin (5), the green pigment of the toadstool Albatrellus cristatus, has been elucidated by MS studies and a comparison of the NMR spectrum of 5 with the data for cristatic acid (1) and albatrellin (6). The furylbenzoquinone chromophore of 5 may be derived from 1 and 2‐O‐acetylatromentin (4), which co‐occur with cristatomentin in the fungus.
Synthesis of Bicyclic Ethers by a Gold/Palladium/Gold‐Catalyzed Cyclization/Cross Coupling Sequence
Authors: Gockel Birgit , Krause Norbert
Published: November 2009

The stereoselective gold‐catalyzed 6‐endo cyclization ofvarious β‐hydroxyallenes in the presence of N‐iodosuccinimide affords iodinated dihydropyrans in good yield. Subsequent functionalization by palladium‐catalyzed cross coupling opens an access to α‐hydroxyallenes that are converted in a second gold‐catalyzed cyclization into furopyrans which occur in various natural products.
Physicochemical Studies of New Anthocyano‐Ellagitannin Hybrid Pigments: About the Origin of the Influence of Oak C‐Glycosidic Ellagitannins on Wine Color
Authors: Chassaing Stefan , Lefeuvre Dorothée , Jacquet Rémi , Jourdes Michael , Ducasse Laurent , Galland Stéphanie , Grelard Axelle , Saucier Cédric , Teissedre Pierre‐Louis , Dangles Olivier , Quideau Stéphane
Published: November 2009

Kinetic and thermodynamic UV/Vis and structural NMR spectroscopic investigations on the anthocyano‐ellagitannin hybrid 1‐deoxyvescalagin‐(1β→8)‐oenin revealed that its enhanced color stability relative to that of the red‐colored pigment oenin and resulting bathochromism can be rationalized in terms of an intramolecular π‐stacking between the grape‐derived oenin chromophore and the oak‐derived vescalagin 4,6‐hexahydroxydiphenoyl moiety. The results led us to suggest that this bathochromism‐inducing molecular association could be the first ellagitannin‐based molecular‐level explanation of the red‐to‐purple color change that takes place during the aging of wine in oak barrels.