bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain‐derived neurotrophic factor and autism: maternal and infant peripheral blood levels in the Early Markers for Autism (EMA) study
Authors: Croen Lisa A. , Goines Paula , Braunschweig Daniel , Yolken Robert , Yoshida Cathleen K. , Grether Judith K. , Fireman Bruce , Kharrazi Martin , Hansen Robin L. , Van de Water Judy
Published: May 2008

To investigate levels of brain‐derived neurotrophic factor (BDNF) in mid‐pregnancy and neonatal blood specimens as early biologic markers for autism, we conducted a population‐based case–control study nested within the cohort of infants born from July 2000 to September 2001 to women who participated in the prenatal screening program in Orange County, CA. Cases (n=84) were all children receiving services for autism at the Regional Center of Orange County. Two comparison groups from the same study population were included: children with mental retardation or developmental delay (n=49) receiving services at the same regional center, and children not receiving services for developmental disabilities, randomly sampled from the California birth certificate files (n=159), and frequency matched to autism cases on sex, birth year, and birth month. BDNF concentrations were measured in archived mid‐pregnancy and neonatal blood specimens drawn during routine prenatal and newborn screening using a highly sensitive bead‐based assay (Luminex, Biosource Human BDNF Antibody Bead Kit, Invitrogen‐Biosource, Carlsbad, CA). The concentration of BDNF in maternal mid‐pregnancy and neonatal specimens was similar across all three study groups. These data do not support previous findings of an association between BDNF and autism and suggest that the concentration of BDNF during critical periods of early neurodevelopment is not likely to be a useful biomarker for autism susceptibility.
Self–other relations in social development and autism: multiple roles for mirror neurons and other brain bases
Authors: Williams Justin H.G.
Published: May 2008

Mirror neuron system dysfunction may underlie a self–other matching impairment, which has previously been suggested to account for autism. Embodied Cognition Theory, which proposes that action provides a foundation for cognition has lent further credence to these ideas. The hypotheses of a self–other matching deficit and impaired mirror neuron function in autism have now been well supported by studies employing a range of methodologies. However, underlying mechanisms require further exploration to explain how mirror neurons may be involved in attentional and mentalizing processes. Impairments in self–other matching and mirror neuron function are not necessarily inextricably linked and it seems possible that different sub‐populations of mirror neurons, located in several regions, contribute differentially to social cognitive functions. It is hypothesized that mirror neuron coding for action–direction may be required for developing attentional sensitivity to self‐directed actions, and consequently for person‐oriented, stimulus‐driven attention. Mirror neuron networks may vary for different types of social learning such as “automatic” imitation and imitation learning. Imitation learning may be more reliant on self–other comparison processes (based on mirror neurons) that identify differences as well as similarities between actions. Differential connectivity with the amygdala–orbitofrontal system may also be important. This could have implications for developing “theory of mind,” with intentional self–other comparison being relevant to meta‐representational abilities, and “automatic” imitation being more relevant to empathy. While it seems clear that autism is associated with impaired development of embodied aspects of cognition, the ways that mirror neurons contribute to these brain–behavior links are likely to be complex.
Missing the big picture: impaired development of global shape processing in autism
Authors: Suzanne Scherf K. , Luna Beatriz , Kimchi Ruth , Minshew Nancy , Behrmann Marlene
Published: May 2008

Individuals with autism exhibit hypersensitivity to local elements of the input, which may interfere with the ability to group visual elements perceptually. We investigated the development of perceptual grouping abilities in high‐functioning individuals with autism (HFA) across a wide age range (8–30 years) using a classic compound letter global/local (GL) task and a more fine‐grained microgenetic prime paradigm (MPP), including both few‐ and many‐element hierarchical displays. In the GL task, contrary to the typically developing (TD) controls, HFA participants did not develop an increasing sensitivity to the global information with age. In the MPP, like the TD controls, individuals with autism at all three age groups evinced a bias to individuate the few‐element displays. However, contrary to the TD controls, the HFA group failed to show age‐related improvements in the ability to encode the global shape of the many‐element displays. In fact, across the age range, the HFA group was consistently faster than the TD controls at perceiving the local elements in these displays. These results indicate that in autism the full process of garnering shape information from perceptual grouping, which is essential for the ability to do fast and efficient object recognition and identification, never matures, and this is especially evident in adolescence when this ability begins to improve in TD individuals. The atypical development of these perceptual organizational abilities may disrupt processing of visually presented objects, which may, in turn, fundamentally impede the development of major aspects of the social and emotional behaviors in individuals with autism.
Gel formation and low‐temperature intramolecular conformation transition of a triple‐helical polysaccharide lentinan in water
Authors: Zhang Yangyang , Xu Xiaojuan , Zhang Lina
Published: May 2008

The gelation behavior of the triple‐helical polysaccharide lentinan fractions having different molecular weights in water at 25°C were studied by using a rheometer. The analysis of concentration and molecular weight dependence of shear stress and shear viscosity showed that aqueous lentinan is a typical shear‐thinning fluid, possessing potential as a viscosity control agent, and that a weak gel with entangled network structure formed. The dynamic oscillatory behavior of lentinan in the temperature range of 1–15°C was also investigated by rheologic method. The storage modulus G′ and complex viscosity η* increased first with decreasing temperature, and underwent a maximum centered at 7–9°C, and then decreased with further decreasing temperature. This abnormal phenomenon was ascribed to formation of rigid structure in the gel state, which was confirmed by the experimental results from micro‐DSC. The micro‐DSC curves showed that an endothermic peak appeared at 7–9°C for lentinan in water upon heating, which was attributable to the intramolecular order–disorder structure transition similar to triple‐helical polysaccharide schizophyllan. Namely, at lower temperature, the side glucose residues of lentinan (triplix II) formed a well‐organized triple‐helical structure (triplix I) through hydrogen‐bonding with the surrounding water molecules. Moreover, this conformation transition was proved to be thermally reversible. © 2008 Wiley Periodicals, Inc. Biopolymers 89: 852–861, 2008.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Incidence of perforated diverticulitis and risk factors for death in a UK population
Authors: Morris C R , Harvey I M , Stebbings W S L , Hart A R
Published: May 2008

Background

Perforated diverticulitis (PD) remains a serious acute abdominal condition. The aims of this study were to measure its incidence in a large UK population and to identify factors affecting outcomes.

Methods

Computerized searches of hospital coding databases for PD were performed in five hospitals in East Anglia, UK. Data were collected from hospital records over 5 years (1995–2000). Incidence was calculated using population data, and factors associated with mortality and morbidity were identified using univariable and multivariable testing.

Results

Some 202 patients with PD were identified, of whom 93·1 per cent underwent surgery and 24·3 per cent died. The age-adjusted adult incidence of perforation was 3·5 per 100 000 per annum, with a standardized female to male ratio of 1·3 (95 per cent confidence interval (c.i.) 1·1 to 1·5) to 1. Risk factors for death were increased age (odds ratio (OR) 3·5 (95 per cent c.i. 1·9 to 6·1)), pre-existing renal disease (OR 18·7 (1·6 to 211·4)) and pre-existing use of non-steroidal anti-inflammatory drugs (NSAIDs) (OR 3·1 (1·3 to 7·3)).

Conclusion

PD is uncommon, with the highest incidence in women over 65 years old. Mortality rates are high, particularly in those taking NSAIDs or with pre-existing renal impairment.
Analysis of Cibacron blue F3G‐A interaction with therapeutic proteins by MALDI‐TOF mass spectrometry
Authors: Sutkeviciute Ieva , Sereikaite Jolanta , Bumelis Vladas‐Algirdas
Published: May 2008

The formation of the complexes between Cibacron blue F3G‐A and two therapeutic proteins, recombinant human interferon‐α2b and recombinant human growth hormone, was investigated. The method of time‐resolved limited proteolysis coupled with MALDI‐TOF mass spectrometry was used. The analysis of peptide maps revealed that A17HR19 and L20HQLAFDTYQEFEEAYIPK38 of hGH, and R14TLMLLAQMR23 and D33RHDFGFPQEEFGNQFQK50 of hIFN‐α2b, exhibit affinity to Cibacron blue F3G‐A. Copyright © 2008 John Wiley & Sons, Ltd.
Using RNA interference to identify the different roles of SMAD2 and SMAD3 in NIH/3T3 fibroblast cells
Authors: Zheng Rong , Xiong Qi , Zuo Bo , Jiang SiWen , Li FengE , Lei MingGang , Deng ChangYan , Xiong YuanZhu
Published: May 2008

Smad proteins are principal intracellular signaling mediators of transforming growth factor β (TGF‐β) that regulate a wide range of biological processes. However, the identities of Smad partners mediating TGF‐β signaling are not fully understood. We firstly examined the expression of Smad2 and Smad3 induced by TGF‐β 1 in normal NIH/3T3 cells. The expression of Smad2 and Smad3 was assessed by RT‐PCR and Western blotting. The results showed that the expression of Smad2 was increased after treatment with TGF‐βI, but Smad3 was more sensitive to TGF‐βI than Smad2. RNA interference (RNAi) provides a new approach for elucidation of gene function. Use of hairpin siRNA expression vectors for RNAi has provided a rapid and versatile method for assessing gene function in mammalian cells. Here, we have constructed Smad2 and Smad3 hairpin siRNA expression plasmids, and then transfected them into mouse NIH/3T3 cells. Endogenous Smad2 and Smad3 proteins decreased significantly at 48 h after transfection. We found the expression of Smad3 in Smad2‐depleted cells was increased, however, the expression of Smad2 in Smad3‐depleted cells was not changed. Consistently, the expression of Smad4 mRNA was also attenuated in Smad3‐depleted cells. From these data, we suggest that Smad3, but not Smad2, may play a key role in TGF‐β signaling. Copyright © 2008 John Wiley & Sons, Ltd.
Synthesis of a Stabilized Version of the Imidazolone DNA Lesion
Authors: Mueller Heiko , Hopfinger Mathias , Carell Thomas
Published: May 2008

Imidazolone (dIz) is an abundant, highly mutagenic, and rather unstable DNA lesion that can cause dG→dC transversion mutations. dIz is generated in DNA by a variety of oxidative processes such as type I photooxidation. Herein we report the synthesis of a carbocyclic nucleoside analogue of dIz and of DNA containing this stabilized lesion analogue. The carbocyclic modification protects this lesion analogue from anomerization. As the repair of the lesion analogue by DNA glycosylases is not possible, this analogue should allow cocrystallization studies together with wild‐type repair enzymes. Characterization of the lesion analogue was performed by using spectroscopic methods and enzymatic digestion experiments of the oligonucleotides.
Ionic Liquids and Proteases: A Clean Alliance for Semisynthesis
Authors: Wehofsky Nicole , Wespe Christian , Cerovsky Vaclav , Pech Andreas , Hoess Eva , Rudolph Rainer , Bordusa Frank
Published: May 2008

Herein we present the first report on protease‐catalysed ligation of cleavage‐sensitive peptide and protein fragments in ionic‐liquid‐containing solvent systems. By applying the newly established [MMIM][Me2PO4]/buffer mixture as a reaction medium, significant advantages over purely aqueous or conventional organic solvent‐containing media could be identified, including in particular the use of active wild‐type proteases as biocatalysts, the suppression of any competitive proteolytic side reactions, the high turnover rates compared to classical organic solvents and the high stability of chemically labile reactants.
The Corrin Moiety of Coenzyme B12 is the Determinant for Switching the btuB Riboswitch of E. coli
Authors: Gallo Sofia , Oberhuber Michael , Sigel Roland K. O. , Kräutler Bernhard
Published: May 2008

Riboswitches are regulatory elements in the 5′‐untranslated region (5′‐UTR) of bacterial mRNAs that bind certain metabolites with high specificity and affinity. The 202 nucleotide (nt)‐long btuB riboswitch RNA of E. coli interacts specifically with coenzyme B12 and its derivatives thereby leading to changes in the RNA structure and hence to an altered expression of the downstream btuB gene. We report the investigations of the rearrangement of the three‐dimensional structure of the btuB riboswitch upon binding to four different B12 derivatives: coenzyme B12, vitamin B12, adenosyl factor A and adenosyl‐cobinamide. In‐line probing experiments have shown that the corrin ring plays the crucial role in switching the three‐dimensional riboswitch structure. Instead, the apical ligands influence only the binding affinity of the B12 derivative to the btuB riboswitch.
Self‐Assembly of Two Different Hierarchical Nanostructures on Either Side of an Organic Supramolecular Film in One Step
Authors: Shi Naien , Yin Gui , Han Min , Jiang Lei , Xu Zheng
Published: May 2008

We fabricated different hierarchical organic nanostructures on each side of a supramolecular film, by using hydrogen‐bonding interactions between tetrapyridylporphyrin and benzene‐1,3,5‐tricarboxylic acid at the H2O/CHCl3 interface. The surface of the film that faces water is composed of nanoprism arrays, whereas the surface facing CHCl3 is composed of three‐dimensional sunflower‐like hierarchical micro‐ and nanostructures. FTIR spectral evidence showed that all pyridyl groups of the tetrapyridylporphyrin hydrogen bonded to the carboxylic acid groups of 1,3,5‐benzene‐tricarboxylic acid. The aggregation modes of porphyrin presented in this supramolecular film were studied by UV/Vis and fluorescence spectroscopy. Moreover, each side of the film exhibits distinct soakage properties.
Supramolecular Tandem Enzyme Assays for Multiparameter Sensor Arrays and Enantiomeric Excess Determination of Amino Acids
Authors: Bailey David M. , Hennig Andreas , Uzunova Vanya D. , Nau Werner M.
Published: May 2008

The coupling of an enzymatic transformation with dynamic host‐guest exchange allows the unselective binding of macrocycles to be used for highly selective analyte sensing. The resulting supramolecular tandem enzyme assays require the enzymatic substrate and its corresponding product to differ significantly in their affinity for macrocycles, for example, cation receptors, and to show a differential propensity to displace a fluorescent dye from its host‐guest complex. The enzymatic transformation results in a concomitant dye displacement that can be accurately followed by optical spectroscopy, specifically fluorescence. By exploiting this label‐free continuous enzyme assay principle with the fluorescent dye Dapoxyl and the macrocyclic host cucurbit[7]uril, a multiparameter sensor array has been designed, which is capable of detecting the presence of amino acids (e.g. histidine, arginine, lysine, and tyrosine) and their decarboxylases. Only in the presence of both, the particular amino acid and the corresponding decarboxylase, is the amine or diamine product formed. These products are more highly positively charged than the substrate, have a higher affinity for the macrocycle and, therefore, displace the dye from the complex. The extension of the high selectivity and μM sensitivity of the tandem assay principle has also allowed for the accurate measurement of D‐lysine enantiomeric excesses of up to 99.98 %, as only the L‐enantiomer is accepted by the enzyme as a substrate and is converted to the product that is responsible for the observed fluorescence signal.
The Tandem Ring‐Closing Metathesis–Isomerization Approach to 6‐Deoxyglycals
Authors: Schmidt Bernd , Biernat Anne
Published: May 2008

Protected 3,6‐dideoxyglycals have been synthesized de novo as single isomers starting from ethyl lactate by using the tandem RCM–isomerization reaction as the key step. Different relative configurations become accessible by addition of vinyl‐ or allyl–metal compounds to protected lactaldehydes under Cram‐chelate or Felkin–Anh control. The concept is exemplified for glycals of L‐rhodinose and L‐amicetose, as well as for ring‐expanded non‐natural analogues thereof. This novel approach to glycals is also applicable to the synthesis of disaccharide glycals via a reiterative strategy, as exemplified for the dimer of L‐rhodinose and its non‐natural ring expanded analogue.
Vibrational circular dichroism and IR spectral analysis as a test of theoretical conformational modeling for a cyclic hexapeptide
Authors: Bour Petr , Kim Joohyun , Kapitan Josef , Hammer Robert P. , Huang Rong , Wu Ling , Keiderling Timothy A.
Published: May 2008

A model cyclohexapeptide, cyclo‐(Phe‐DPro‐Gly‐Arg‐Gly‐Asp) was synthesized and its IR and VCD spectra were used as a test of density functional theory (DFT) level predictions of spectral intensities for a peptide with a nonrepeating but partially constricted conformation. Peptide structure and flexibility was estimated by molecular dynamics (MD) simulations and the spectra were simulated using full quantum mechanical (QM) approaches for the complete peptide and for simplified models with truncated side chains. After simulated annealing, the backbone conformation of the ring structure is relatively stable, consisting of a normal β‐turn and a tight loop (no H‐bond) which does not vary over short trajectories. Only in quite long MD runs at high temperatures do other conformations appear. MD simulations were carried out for the cyclic peptide in water and in TFE, which match experimental solvents, as well as with and without protonation of the Asp carboxyl group. DFT spectral simulations were made using the annealed structure and were extended to include basis set variation, to determine an optimal computational approach, and solvent simulation with a polarized continuum model (PCM). Stepwise full DFT simulation of spectra was done for various sequences with the same backbone geometry but based on (1) solely Gly residues, (2) Ala substitution except Gly and Pro, and (3) complete sequences with side chains. Additionally, a selection of structures was used to compute IR and VCD spectra with the optimal method to determine structural variation effects. The side chains, especially the AspCOOH and ArgNH2 transitions, had an impact on the computed amide frequencies, IR intensities and VCD pattern. Since experimentally these groups would have little chirality, due to conformational variation, they do not impact the observed VCD spectra. Correcting for frequency shifts, the Ala model for the cyclopeptide gives the clearest representation of the amide VCD. The experimental sign pattern for the amide I' band in D2O and also the sharper, more intense amide I VCD band in TFE was seen to some degree in one conformer with Type II′ turns, but the data favor a mix of structures. Chirality, 2008. © 2008 Wiley‐Liss, Inc.
Use of large‐scale chromatography in the preparation of armodafinil
Authors: Hauck Willy , Adam Philippe , Bobier Christelle , Landmesser Nelson
Published: May 2008

Armodafinil, the (R)‐enantiomer of modafinil, is a medication used to treat the excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome, and shift work sleep disorder. We report here the chemical development of armodafinil and the investigations that led to a commercial route to prepare this pure enantiomer. Three synthetic approaches were used to provide the chiral sulfoxide. Resolution via preferential crystallization was used for phase I clinical trials and was subsequently replaced by chiral chromatography, enabling us to pursue a rapid filing and registration of the API. Finally, the commercial route was developed and employed asymmetric oxidation catalyzed by a titanium(IV) isopropoxide and diethyl tartrate system. The advantages of choosing a chromatographic development pathway to expedite registration while concurrently developing an economical chiral synthesis route is discussed in the context of armodafinil development. Chirality, 2008. © 2008 Wiley‐Liss, Inc.
Chiral phosphites derived from carboranes: Electronic effect in catalytic asymmetric hydrogenation
Authors: Lyubimov Sergey E. , Kalinin Valery N. , Tyutyunov Andrey A. , Olshevskaya Valentina A. , Dutikova Yulia V. , Cheong Chan Seong , Petrovskii Pavel V. , Safronov Anton S. , Davankov Vadim A.
Published: May 2008

A series of new fine‐tunable monodentate phosphite and phosphoramidite ligands based on carboranes have been synthesized and used for asymmetric Rh‐catalyzed hydrogenation of prochiral olefins with the result of up to 99.8% ee. Dependence of the enantioselectivity on the electron‐withdrawing or electron‐donating properties of the carboranyl substituent has been studied. Chirality, 2009. © 2008 Wiley‐Liss, Inc.
A new reference material for UV–visible circular dichroism spectroscopy
Authors: Damianoglou Angeliki , Crust Edward J. , Hicks Matthew R. , Howson Suzanne E. , Knight Alex E. , Ravi Jascindra , Scott Peter , Rodger Alison
Published: May 2008

To obtain accurate and consistent measurements from circular dichroism (CD) instruments over time and from different laboratories, it is important that they are properly calibrated. The characteristics of the available reference materials are not ideal to ensure proper calibration as they typically only give peaks in one or two spectral regions, and often have issues concerning purity and stability. Currently either camphor sulfonic acid or ammonium camphor sulfonate are used. The latter can be an unstable, slightly hygroscopic secondary standard compound with only one characterized CD band. The former is the very hygroscopic primary standard for which only one enantiomer is readily available. We have synthesized a new reference material for CD, Na[Co(EDDS)]·H2O (EDDS = N,N‐ethylenediaminedisuccinic acid) which addresses these problems. It is extremely stable and available in both enantiomeric forms. The CD spectrum of Na[Co(EDDS)]·H2O has nine distinct peaks between 180 and 599 nm. It thus fulfils the principal requirements for CD calibration chemical standards and has the potential to be used to ensure good practice in the measurement of CD data, providing two spectra of equal magnitude and opposite sign for a given concentration and path length. We have carried out an interlaboratory comparison using this material and show how it can be used to improve CD comparability between laboratories. A fitting algorithm has been developed to assess CD spectropolarimeter performance between 750 and 178 nm. This could be the basis of a formal quality control process once criteria for performance have been decided. Chirality, 2008. © 2008 Wiley‐Liss, Inc.
Highly enantioselective organocatalytic conjugate addition of nitromethane to benzylidene acetones
Authors: Szántó Gábor , Bombicz Petra , Grün Alajos , Kádas István
Published: May 2008

Six active 4‐aryl‐5‐nitro‐pentan‐2‐ones were synthesized enantioselectively from the corresponding 5‐aryl‐butenones by asymmetric Michael addition of nitromethane using an imidazolidine‐type enantioselective organocatalyst. The ee ratio of the products were between 67 and 100%, determined by HPLC with Chiracel OD. Molecular and crystal structure of 3,4‐methylenedioxy‐phenyl‐5‐nitro‐pentan‐2‐one has been studied by single crystal X‐ray diffraction. Chirality, 2008. © 2008 Wiley‐Liss, Inc.
Diamagnetic lanthanide tris β‐diketonates as organic‐soluble chiral NMR shift reagents
Authors: Wenzel Thomas J. , Wenzel Bradford T.
Published: May 2008

Diamagnetic lanthanium(III) and lutetium(III) tris β‐diketonate complexes of 3‐(trifluoroacetyl)‐d‐camphor, 3‐(heptafluorobutyryl)‐d‐camphor, and d,d‐dicampholylmethane are shown to be effective chiral NMR shift reagents for determining the enantiomeric purity of compounds with hard Lewis base functional groups. These include substrates with amine, alcohol, epoxide, sulfoxide, and oxaxolidine moieties. Enantiomeric discrimination is observed in the 1H NMR spectrum. Diamagnetic lanthanide complexes represent an alternative to paramagnetic varieties that often cause too much line broadening in the NMR spectra. The choice of which metal to use varies with substrate. Similarly, there is no consistent trend with ligand as not one of the complexes is consistently better than the others for all substrates. The enantiomeric discrimination also varies with solvent. Comparisons show that the chiral recognition was usually larger in benzene‐d6 than in chloroform‐d or cyclohexane‐d12. Chirality, 2009. © 2008 Wiley‐Liss, Inc.
Liquid chromatographic direct resolution of tocainide and its analogs on a (3,3′‐diphenyl‐1,1′‐binaphthyl)‐20‐crown‐6‐based chiral stationary phase containing residual silanol protecting n‐octyl groups
Authors: Choi Hee Jung , Jin Jong Sung , Hyun Myung Ho
Published: May 2008

Optically active (3,3′‐diphenyl‐1,1′‐binaphthyl)‐20‐crown‐6‐based chiral stationary phase (CSP) containing residual silanol protecting n‐octyl groups on silica surface was applied to the liquid chromatographic direct resolution of tocainide and its analogs. The chiral recognition ability of the CSP was excellent, the separation (α) and the resolution factors (RS) for 15 analytes including tocainide being in the range of 3.02–22.92 and 3.94–20.41, respectively. In addition, the chiral recognition ability of the CSP was much greater than that of (3,3′‐diphenyl‐1,1′‐binaphthyl)‐20‐crown‐6‐based CSP containing residual silanol groups on the silica surface. The chromatographic behaviors for the resolution of tocainide and its analogs were found to be dependent on the content and the type of organic and acidic modifiers and the ammonium acetate concentration in aqueous mobile phase. Chirality, 2009. © 2008 Wiley‐Liss, Inc.
Conformation and absolute configuration of 2‐naphthylalkylsulfoxides by combined use of dynamic NMR, ECD spectroscopy, DFT computations, and X‐ray diffraction
Authors: Casarini Daniele , Lunazzi Lodovico , Mancinelli Michele , Mazzanti Andrea , Scafato Patrizia
Published: May 2008

The E/Z conformer ratios of five 2‐naphtylalkylsulfoxides were determined by means of dynamic NMR spectroscopy at very low temperatures and this information was used to predict, by means of DFT calculations, the ECD spectra of the R and S enantiomers. The latter were separated by enantioselective HPLC technique and the comparison of theoretical and experimental ECD spectra allowed the absolute configurations to be determined. In the case of 2‐naphtyl tert‐butylsulfoxide (1), the assignment was independently confirmed by anomalous dispersion using single crystal X‐ray crystallography. Chirality, 2009. © 2008 Wiley‐Liss, Inc.
Current and Foreseeable Applications of Supercritical Water for Energy and the Environment
Authors: Loppinet‐Serani Anne , Aymonier Cyril , Cansell François
Published: May 2008

It is crucial to develop economical and energy‐efficient processes for the sustainable transformation of biomass into fuels and chemicals. In this context, supercritical water biomass valorization (SCBV) processes are an alternative way to produce biogas, biofuels, and valuable chemicals. Supercritical water technology has seen much progress over the last fifteen years and an industrial application has merged: the supercritical water oxidation of wastes. The evolution from lab‐scale to pilot‐scale facilities has provided data on reaction mechanisms, kinetics, modeling, and reactor technology as well as an important know‐how, which can now be exploited to use the reactivity in supercritical water to transform biomass into gases (CO, H2, CO2, CH4, and N2) or into liquids (liquid fuel and valuable chemicals) with the supercritical water biomass gasification and liquefaction processes, respectively. This Review highlights the potential of SCBV processes to transform biomass into gas and liquid energy sources and highlights the developments that are still necessary to push this technology onto the market.
Drug design: hiding in full view
Authors: Radin Norman S.
Published: May 2008

Compounds that can produce potent biological effects in cells encompass a variety of structural motifs. Many of these compounds share a structural feature that has rarely been noted. It is an allylic cluster of atoms, a 3‐carbon chain with a double bond between two of the atoms and an oxygen atom at the other end. The oxygen can be in a hydroxyl group, or in an ether or ketal or ester linkage, or simply a carbonyl form. In the latter case, the linkage is an allylic ketone (ene‐one) structure. Nitrogen is often seen in equivalent forms. Inclusion of at least one allylic moiety appears to be able to turn a modestly active or inert compound into an effective drug or toxin. Some compounds lack the allylic moiety but develop one by enzymatic action, usually via cytochrome P‐450 enzymes. These metabolites probably represent the active drug forms. The above concepts seem to be radically simplistic and improbable, but the evidence supporting them and the explanations for the biological activities are hidden “in plain view.” Comparisons with the pleiotropic activities of the allylic sphingolipid, ceramide, indicate that many allylic drugs operate by controlling the state of protein phosphorylation, by activating proteases, by generating reactive oxygen species, by slowing mitochondrial electron transport, or by lowering cellular glutathione concentrations. Drug Dev Res 69:15–25, 2008 © 2008 Wiley‐Liss, Inc.
Repeated neonatal separation stress alters the composition of neurochemically characterized interneuron subpopulations in the rodent dentate gyrus and basolateral amygdala
Authors: Seidel Katja , Helmeke Carina , Poeggel Gerd , Braun Katharina
Published: May 2008

Emotional experience during early life has been shown to interfere with the development of excitatory synaptic networks in the prefrontal cortex, hippocampus, and the amygdala of rodents and primates. The aim of the present study was to investigate a developmental “homoeostatic synaptic plasticity” hypothesis and to test whether stress‐induced changes of excitatory synaptic composition are counterbalanced by parallel changes of inhibitory synaptic networks. The impact of repeated early separation stress on the development of two GABAergic neuronal subpopulations was quantitatively analyzed in the brain of the semiprecocial rodent Octodon degus. Assuming that PARV‐ and CaBP‐D28k‐expression are negatively correlated to the level of inhibitory activity, the previously described reduced density of excitatory spine synapses in the dentate gyrus of stressed animals appears to be “amplified” by elevated GABAergic inhibition, reflected by reduced PARV‐ (down to 85%) and CaBP‐D28k‐immunoreactivity (down to 74%). In opposite direction, the previously observed elevated excitatory spine density in the CA1 region of stressed animals appears to be amplified by reduced inhibition, reflected by elevated CaPB‐D28k‐immunoreactivity (up to 149%). In the (baso)lateral amygdala, the previously described reduction of excitatory spine synapses appears to be “compensated” by reduced inhibitory activity, reflected by dramatically elevated PARV‐ (up to 395%) and CaPB‐D28k‐immunoreactivity (up to 327%). No significant differences were found in the central nucleus of the amygdala, the piriform, and somatosensory cortices and in the hypothalamic paraventricular nucleus. Thus during stress‐evoked neuronal and synaptic reorganization, a homeostatic balance between excitation and inhibition is not maintained in all regions of the juvenile brain. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008
Differential expression of connexins during histogenesis of the chick retina
Authors: Kihara A.H. , Paschon V. , Akamine P.S. , Saito K.C. , Leonelli M. , Jiang J.X. , Hamassaki D.E. , Britto L.R.G.
Published: May 2008

Gap junction (GJ) channels couple adjacent cells, allowing transfer of second messengers, ions, and molecules up to 1 kDa. These channels are composed by a multigene family of integral membrane proteins called connexins (Cx). In the retina, besides being essential circuit element in the visual processing, GJ channels also play important roles during its development. Herein, we analyzed Cx43, Cx45, Cx50, and Cx56 expression during chick retinal histogenesis. Cx exhibited distinct expression profiles during retinal development, except for Cx56, whose expression was not detected. Cx43 immunolabeling was observed at early development, in the transition of ventricular zone and pigmented epithelium. Later, Cx43 was seen in the outer plexiform and ganglion cell layers, and afterwards also in the inner plexiform layer. We observed remarkable changes in the phosphorylation status of this protein, which indicated modifications in functional properties of this Cx during retinal histogenesis. By contrast, Cx45 showed stable gene expression levels throughout development and ubiquitous immunoreactivity in progenitor cells. From later embryonic development, Cx45 was mainly observed in the inner retina, and it was expressed by glial cells and neurons. In turn, Cx50 was virtually absent in the chick retina at initial embryonic phases. Combination of PCR, immunohistochemistry and Western blot indicated that this Cx was present in differentiated cells, arising in parallel with the formation of the visual circuitry. Characterization of Cx expression in the developing chick retina indicated particular roles for these proteins and revealed similarities and differences when compared to other species. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008
CD4+ T cell help improves CD8+ T cell memory by retained CD27 expression
Authors: Matter Matthias S. , Claus Christina , Ochsenbein Adrian F.
Published: May 2008

CD4+ T cell help during the priming of CD8+ T lymphocytes imprints the capacity for optimal secondary expansion upon re‐encounter with antigen. Helped memory CD8+ T cells rapidly expand in response to a secondary antigen exposure, even in the absence of T cell help and, are most efficient in protection against a re‐infection. In contrast, helpless memory CTL can mediate effector function, but secondary expansion is reduced. How CD4+ T cells instruct CD8+ memory T cells during priming to undergo efficient secondary expansion has not been resolved in detail. Here, we show that memory CTL after infection with lymphocytic choriomeningitis virus are CD27high whereas memory CTL primed in the absence of CD4+ T cell have a reduced expression of CD27. Helpless memory CTL produced low amounts of IL‐2 and did not efficiently expand after restimulation with peptide in vitro. Blocking experiments with monoclonal antibodies and the use of CD27–/– memory CTL revealed that CD27 ligation during restimulation increased autocrine IL‐2 production and secondary expansion. Therefore, regulating CD27 expression on memory CTL is a novel mechanism how CD4+ T cells control CTL memory.
Generating functional CD8+ T cell memory response under transient CD4+ T cell deficiency: Implications for vaccination of immunocompromised individuals
Authors: Smith Corey , Martinez Michelle , Cooper Leanne , Rist Michael , Zhong Jie , Khanna Rajiv
Published: May 2008

Studies based on either MHC class II‐knockout or CD4+ T cell‐depleted murine models have demonstrated a critical role for CD4+ T cells in the generation of CD8+ T cell memory. However, it is difficult to extend these findings to immunocompromised humans where a complete loss of CD4+ T cells is rarely observed. Here, we have developed a model setting, which allows studies on the generation of CD8+ T cell memory responses in a transient CD4+ T cell‐deficient setting similar to that seen in immunocompromised patients. Immunisation with an adenoviral vaccine under transient helpless or help‐deficient conditions showed varying degrees of impact on the priming of CD8+ T cell responses. Antigen‐specific T cells generated under normal CD4+ T cell help and transient help‐deficient conditions showed similar effector phenotype and were capable of proliferation upon secondary antigen encounter. Most importantly, in spite of CD4+ T cell deficiency, the long‐term CD8+ T cell memory response remained functionally stable and showed comparable cytotoxic effector function as seen in CD8+ T cells generated with normal CD4+ T cell numbers. These findings provide evidence that in spite of partially impaired activation of a primary CD8+ T cell response, a fully functional and stable memory CTL response can be induced under conditions of severe transient CD4+ T cell deficiency.
Blood CD8+ T cell responses against myelin determinants in multiple sclerosis and healthy individuals
Authors: Berthelot Laureline , Laplaud David‐Axel , Pettré Ségolène , Ballet Caroline , Michel Laure , Hillion Sophie , Braudeau Cécile , Connan Francine , Lefrère Fabienne , Wiertlewski Sandrine , Guillet Jean‐Gérard , Brouard Sophie , Choppin Jeannine , Soulillou Jean‐Paul
Published: May 2008

Patients with multiple sclerosis (MS) display significant peripheral blood CD8+ T cell receptor biases, suggesting clonal selection. Our objective was to identify relevant myelin‐derived peptides capable of eliciting responses of fresh blood CD8+ T cells in MS patients. We focused our analysis on the HLA supertypes (HLA‐A3, ‐A2, ‐B7, ‐B27, ‐B44) predominant in a patient cohort. Three myelin protein (MBP, PLP and MOG) sequences were screened for HLA binding motifs and peptides were tested for their binding to HLA molecules. The cellular responses of 27 MS patients and 19 age‐ and sex‐matched healthy controls (HC) were tested in IFN‐γ ELISPOT assays only detecting pre‐committed CD8+ T cells. Sixty‐nine new epitopes elicited positive responses, with MOG‐derived peptides being the most immunogenic and peptides binding to HLA‐A3 being the most frequent. However, MS patients and HC displayed the same frequency of autoreactive cells. The epitopes inducing the strongest responses were not those with the highest HLA binding, suggesting an effective thymic selection in MS patients. Our data extend the concept that the frequency of myelin‐reactive T cells in MS patient blood is not increased compared to HC. The description of this set of myelin‐derived peptides (MHC class I restricted, recognized by CD8+ T cells) offers new tools to explore the CD8+ cell role in MS.
Interleukin 10 suppresses Th17 cytokines secreted by macrophages and T cells
Authors: Gu Yongpeng , Yang Jianfei , Ouyang Xinshou , Liu Weicheng , Li Hongxing , Yang Jianjun , Bromberg Jonathan , Chen Shu‐Hsia , Mayer Lloyd , Unkeless Jay C. , Xiong Huabao
Published: May 2008

IL‐17 and IL‐22 are typical cytokines produced by the Th17 T cell subset, but it is unclear if Th17 cytokines can be produced by other cell types. We demonstrate that IL‐10‐deficient and IL‐10R‐deficient macrophages stimulated with lipopolysaccharide produce high levels of IL‐17 and IL‐22. Addition of exogenous IL‐10 to IL‐10‐deficient macrophages abolished IL‐17 production. When IL‐10‐deficient and IL‐10R‐deficient splenocytes were cultured under Th17 polarizing conditions, the population of IL‐17‐producing cells was increased and the cultures produced significantly higher levels of IL‐17 and IL‐22. The addition of recombinant IL‐10 to IL‐10‐deficient splenocytes significantly decreased the percentage of IL‐17‐producing CD4+ T cells. Finally, the mRNA for the Th17 transcription factor retinoic acid‐related orphan receptor (ROR)γt was significantly elevated in IL‐10‐deficient spleen cells and macrophages. These data demonstrate that Th17 cytokines and RORγt are also expressed in macrophages and that IL‐10 negatively regulates the expression of Th17 cytokines and RORγt by both macrophages and T cells.
Solvent‐Mediated Ion Exchange and Structural Transformations of Cluster‐Based Coordination Polymers
Authors: Zhang Jian‐Jun , Zhao Yue , Gamboa Sergio Aarón , Muñoz Miguel , Lachgar Abdessadek
Published: May 2008

Reactions between [Nb6Cl12(CN)6]4– and [Mn(salen)]+ in MeOH/H2O solvent mixture led to the formation of {[Mn(salen)(H2O)]2[(Mn(salen))2(Nb6Cl12(CN)6)]}·0.66 MeOH·5.33 H2O (1) which has a 2D anionic 4,4′‐network built of [Nb6Cl12(CN)6]4– and [Mn(salen)]+ nodes linked by CN ligands. The layers in 1 stack perfectly on top of each other and generate channels where dimeric complexes [Mn(salen)(H2O)]22+ are located. Unusual cation‐induced solvent‐mediated structural transformations have been observed when 1 was exposed to solutions of different cations. In contact with (Me4N)Cl in MeOH, 1 is transformed to the 2D framework of the previously reported compound [Me4N]2[(Mn(salen))2(Nb6Cl12(CN)6)] (2). In the presence of (Et3BzN)+, 1 is transformed into a mixture of [Et3BzN]2[(Mn(salen)(MeOH))2(Nb6Cl12(CN)6)]·4 MeOH (3) and [Et3BzN]2[(Mn(salen))2 (Nb6Cl12(CN)6)]·3 H2O (4) which are formed as crystals suitable for single‐crystal X‐ray diffraction. Compound 3 consists of heterotrimeric supramolecular anions built of [Nb6Cl12(CN)6]4– linked to two [Mn(salen)(H2O)]+ through two CN ligands located in axial positions, while 4 features 2D anionic 4,4′‐net with the same connectivity as that observed for 1 and 2 but different layer stacking and interlayer spacing. In contact with methanolic solution of (Et4N)+, 1 is converted to [Et4N]2[(Mn(salen)(H2O))2(Nb6Cl12(CN)6)]·6 H2O (5) which is built of heterotrimeric structural motif similar to those found in 3. In the presence of M+ [M+ = Li+, Na+, K+, (Bu4N)+, or (PPh4)+], the 2D framework of 1 is transformed to heteropentamers built of [Nb6Cl12(CN)6]4– linked to four [Mn(salen)(MeOH)]+: [(Mn(salen)(MeOH))4(Nb6Cl12(CN)6)]·4 MeOH (6). The mechanism for these unusual solvent‐mediated phase‐to‐phase transformation is discussed.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Allylic Amination and Aziridination of Olefins by Aryl Azides Catalyzed by CoII(tpp): A Synthetic and Mechanistic Study
Authors: Caselli Alessandro , Gallo Emma , Fantauzzi Simone , Morlacchi Simona , Ragaini Fabio , Cenini Sergio
Published: May 2008

CoII(tpp) catalyzes the reaction of aromatic azides (ArN3) with nonactivated olefins to yield allylic amines or aziridines in moderate‐to‐good yields. The chemoselectivity of the catalytic reaction is particularly high. Depending on the substrate employed, allylic amines or aziridines can be obtained. The reaction mechanism was investigated, and the reaction proceeds through reversible coordination of the aryl azide to the CoII–porphyrin complex. The often postulated “nitrene” complex is not an intermediate in this reaction. The kinetics for the allylic amination is first order in azide, Co(tpp), and olefin. For the aziridination, the kinetics is again first order in azide and catalyst, but we observed a first‐order dependence of the rate on α‐methylstyrene only up to an olefin concentration of 6.9 M. An inhibiting role of the competitively formed 1‐(4‐nitrophenyl)‐5‐methyl‐5‐phenyl‐1,2,3‐triazoline was identified. The triazoline was shown to reversibly coordinate to Co(tpp), which blocks the free coordination site necessary for the catalytic reaction to proceed, and is it responsible for the catalyst deactivation in the aziridination reaction of α‐methylstyrene by 4‐nitrophenyl azide. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
An Atropo‐Stereogenic Diphosphane Ligand with a Proximal Cationic Charge: Specific Catalytic Properties of a Palladium Complex Thereof
Authors: Debono Nathalie , Canac Yves , Duhayon Carine , Chauvin Remi
Published: May 2008

A class of cationic diphosphane ligands combining phosphane and amidiniophosphane moieties is illustrated on the N‐methyl,N‐naphthylbenzimidazolium framework. The palladium(II) complex thereof is described and compared to the corresponding complex of the analogous neutral diphosphane. Contrary to first‐level expectations, the N2C–P and N2CP–Pd bonds in the cationic diphosphane complex are not longer than those occurring in its neutral counterpart. In the cationic ligand, the proximal positive charge is indeed conjugated to one phosphanyl group, and the coordination scheme is tentatively interpreted by resonance of the phosphane→metal dative bond (+N2C–P:→[Pd]) with a carbene→phosphenium dative bond (N2C:→[+P:→Pd]). Despite this peculiar structural feature, the electronic σ donation (vs. π acceptation) towards the palladium centre remains lowered in the cationic ligand. This specific property can be a priori valuable in a catalytic process where oxidative addition is not the limiting step. It is indeed shown that although the neutral complex is more active in Suzuki coupling reactions, the cationic complex is more active in Sonogashira‐type coupling reactions involving predissociated halide substrates, namely an acyl chloride. These likely atropo‐chiral ligands deserve to be resolved for application in asymmetric catalysis.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Crystal Structures of Ag2ZrF6·8NH3 and Ag2HfF6·8NH3 and Their Synthesis by the “Reactive Fluoride Route” in Liquid Ammonia
Authors: Meng Weizhe , Kraus Florian
Published: May 2008

Starting from the ternary transition‐metal fluorides Ag3M2F14 (M = Zr, Hf) and dry liquid ammonia, [Ag(NH3)4(μ‐NH3)Ag(NH3)3]ZrF6 (1) and [Ag(NH3)4(μ‐NH3)Ag(NH3)3]HfF6 (2) have been prepared as colorless single crystals crystallizing isotypically in the space group Pnma‐D2h16 (No. 62). The compounds feature weak Ag···Ag interactions known as argentophilicity, which is yet unknown in fluorides. It is also shown that ionic silver(II) fluorides are suitable starting materials for fluorine chemistry in liquid ammonia and are easily reduced to AgI by oxidizing ammonia. This driving force bypasses the generally high lattice energy of ionic fluorides, so that they can be dissolved easily. We would like to introduce the term “reactive fluoride route” for this method of dissolving reactive ionic fluorides in liquid ammonia. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
A Rare Thermally Induced Single Crystal to Single Crystal Transformation from a 2D Chiral Coordination Polymer to a 3D Chiral Coordination Polymer
Authors: Zhu Ping , Gu Wen , Zhang Li‐Zhi , Liu Xin , Tian Jin‐Lei , Yan Shi‐Ping
Published: May 2008

A rare single‐crystal to single crystal (SCSC) transformation assisted by hydrogen bonding was induced thermally. A2D homochiral coordination polymer {[Ni2(L‐tar)2(H2O)2](H2O)3}∞ was irreversibly converted into a 3D homochiral coordination polymer, and the structure was confirmed by X‐ray crystallography and XRD. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Lanthanide‐Hinged Calixarene Bicapsules: Discrete Hexanuclear LnIII/Phenanthroline/p‐Sulfonatocalix[4]arene Oligomers (Ln = Gd, Tb)
Authors: Liao Wuping , Bi Yanfeng , Gao Song , Li Deqian , Zhang Hongjie , Dronskowski Richard
Published: May 2008

The dumbbell‐like calixarene bicapsule in two novel LnIII–C4AS compounds was found to be a hexanuclear LnIII/phenanthroline/p‐sulfonatocalix[4]arene oligomer. The magnetic and luminescent properties of these compounds were examined. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)