bluuebunny/crossref_metadata_2025 huggingface dataset:
Crabtree Effect
Authors: Thierie Jacques , Penninckx Michel
Published: March 2010

The Crabtree effect is still little known and relates as well to prokaryotic cells (bacteria) as to eukaryotes (fungi and mammals). In this article we havetwo major aims: (i) to treat the Crabtree effect as exhaustively as possible (e.g. by not restricting ourselves toSaccharomyces cerevisiae) and (ii) to adopt a presentation tailored to the philosophy of the encyclopedia.

This means that the malignant cells Crabtree effect was treated in a more fundamental and biochemical way because these cells, as such, are less subject to industrial cultivation or production processes.

The other two categories (fungi and bacteria) were treated in a more physiological way, so as to provide a maximum of proposals for the optimization of a culture and/or production process.

In particular, for yeasts, we tried to make the point as precisely as possible and attempted to decide between the various assumptions explaining the metabolism involved. Indeed, a bad interpretation of this process can lead to an inadequate approach to research into practical solutions for a production problem. We are conscious of the slightly polemical aspect of this section, but that reflects the actual state of the art in this field.

Relating to bacteria, the literature is undeniably limited and the results remain basically experimental. The polemic on the possible mechanisms of the Crabtree effect is thus quasi non‐existent: either because it is not considered or because it is extrapolated starting from the yeast problems. We also adopted a novel, and perhaps promising approach by considering the use of association or consortia of microorganisms to produce high value products at low costs. Except in very exceptional cases, this approach will probably require numerous fundamental R&D efforts.

We came to the conclusion that we cannot put forward a “universal” and ultimate mechanism. Our discussion is then based on the main parameters that have to be taken into consideration to act in a practical way on the Crabtree effect (in a positive or negative way). It did not appear achievable, in the current state of our knowledge, to provide a simple “recipe” to resolve this kind of problems.
L‐Aspartic Acid, Production Processes
Authors: Yukawa Hideaki , Ookino Shohei , Inui Masayuki
Published: March 2010

L‐Aspartic acid is a four‐carbon amino acid that is used not only as a stand‐alone food additive, but also as a raw material for the food and pharmaceutical industries. It is conventionally produced in bioprocesses utilizing immobilized enzyme‐mediated or bacterial cell‐mediated bioconversion. Notably, processes that make use ofCorynebacteriumspecies under growth‐arrested conditions in a membrane reactor constitute attractive options for the industrial‐scale manufacture of this important amino acid.
Environmental neurotoxin‐induced progressive model of parkinsonism in rats
Authors: Shen Wei‐Bin , McDowell Kimberly A. , Siebert Aubrey A. , Clark Sarah M. , Dugger Natalie V. , Valentino Kimberly M. , Jinnah H. A. , Sztalryd Carole , Fishman Paul S. , Shaw Christopher A. , Jafri M. Samir , Yarowsky Paul J.
Published: March 2010

Objective

Exposure to a number of drugs, chemicals, or environmental factors can cause parkinsonism. Epidemiologic evidence supports a causal link between the consumption of flour made from the washed seeds of the plant Cycas micronesica by the Chamorro population of Guam and the development of amyotrophic lateral sclerosis/parkinsonism dementia complex.

Methods

We now report that consumption of washed cycad flour pellets by Sprague‐Dawley male rats induces progressive parkinsonism.

Results

Cycad‐fed rats displayed motor abnormalities after 2 to 3 months of feeding such as spontaneous unilateral rotation, shuffling gait, and stereotypy. Histological and biochemical examination of brains from cycad‐fed rats revealed an initial decrease in the levels of dopamine and its metabolites in the striatum (STR), followed by neurodegeneration of dopaminergic (DAergic) cell bodies in the substantia nigra (SN) pars compacta (SNc). α‐Synuclein (α‐syn; proteinase K‐resistant) and ubiquitin aggregates were found in the DAergic neurons of the SNc and neurites in the STR. In addition, we identified α‐syn aggregates in neurons of the locus coeruleus and cingulate cortex. No loss of motor neurons in the spinal cord was found after chronic consumption of cycad flour. In an organotypic slice culture of the rat SN and the striatum, an organic extract of cycad causes a selective loss of dopamine neurons and α‐syn aggregates in the SN.

Interpretation

Cycad‐fed rats exhibit progressive behavioral, biochemical, and histological hallmarks of parkinsonism, coupled with a lack of fatality. ANN NEUROL 2010;68:70–80
Levodopa, methylmalonic acid, and neuropathy in idiopathic Parkinson disease
Authors: Toth Cory , Breithaupt Kim , Ge Shaohua , Duan Yanjun , Terris Joan M. , Thiessen Anita , Wiebe Samuel , Zochodne Douglas W. , Suchowersky Oksana
Published: March 2010

Objective

Peripheral neuropathy (PN) is thought to be coincidental in patients with idiopathic Parkinson disease (IPD). We sought to examine the prevalence of PN in a population of IPD patients and a potential relationship to levodopa use and fasting methylmalonic acid (MMA) levels.

Methods

In a prospective cohort study, IPD patients randomly selected from a comprehensive database were compared to control subjects regarding the presence and severity of PN using clinical and electrophysiological measures. IPD severity was determined using the Unified Parkinson's Disease Rating Scale (UPDRS). We determined the relation of levodopa use with serum levels of cobalamin, MMA, and homocysteine (Hcy). We also explored the association between presence and severity of PN and age, duration of IPD, cumulative levodopa dosing, cobalamin, MMA, and Hcy levels.

Results

Fifty‐eight randomly selected IPD patients were compared to 58 age‐ and sex‐matched controls. PN was present in 55% of IPD patients and 9% of controls. Patients with IPD had greater prevalence of PN and fasting MMA/Hcy levels than controls. IPD patients with PN were older and exhibited higher UPDRS scores, fasting MMA/Hcy levels, and cumulative levodopa exposure. PN severity in IPD subjects positively correlated with both levodopa exposure and MMA levels.

Interpretation

IPD patients have a higher prevalence of PN than controls. Although causality is not established, levodopa exposure is associated with MMA elevation and sensorimotor neuropathy in IPD patients. Cobalamin replacement concurrent with levodopa therapy should be considered to protect against development of PN in IPD patients. ANN NEUROL 2010;67:28–36
Thieno[2,3‐d]pyrimidines in the Synthesis of Antitumor and Antioxidant Agents
Authors: Aly Ashraf A. , Brown Alan B. , Ramadan Mohamed , Gamal‐Eldeen Amira M. , Abdel‐Aziz Mohamed , Abuo‐Rahma Gamal El‐Din A. A. , Radwan Mohamed F.
Published: March 2010

Dimethyl acetylenedicarboxylate, ethyl propiolate, andE‐dibenzoylethylene react with thienopyrimidines (cyclo‐pentyl, ‐hexyl, and ‐heptyl) derivatives to form thiazolo[3,2‐a]thieno‐[2,3‐d]pyrimidin‐2‐ylidene) acetates, thieno[2,3‐d]pyrimidin‐2‐ylthioacrylates, and thieno[2′,3′:4,5]pyrimido[2,1‐b][1,3]thiazin‐6‐ones, respectively. Reactions proceedviacyclization and thio‐addition processes. Some derivatives of thienopyrimidines showed high inhibition of Hep‐G2 cell growth compared with the growth of untreated control cells. However, the fused heptyl of thienopyrimidothiazines indicates a promising specific antitumor agent against Hep‐G2 cells with IC50< 20 μM.
Antioxidant Activity of Newly Synthesized 2,7‐Diazaphenothiazines
Authors: Morak‐Młodawska Beata , Pluta Krystian , Matralis Alexios N. , Kourounakis Angeliki P.
Published: March 2010

A series of 19 derivatives of 2,7‐diazaphenothiazine was synthesized and evaluated for their antioxidant activity bearing in mind the structural similarity with “classical” phenothiazines several of which are considered powerful antioxidants. Among the new derivatives that inhibited in vitro Fe2+/ascorbate‐induced lipid peroxidation of rat liver microsomal membranes, several exhibited significant antioxidant activity with IC50 values in the range of 64–125 μM. Although N‐substitution led to a variable degree of antioxidant activity, the latter appears to correlate with the lipophilicity (expressed as clogP values) of the substituted derivatives. Reduced lipophilicity may also explain the relatively lower protection offered by these derivatives against lipid peroxidation when compared to their “classical” phenothiazine counterparts. Thus, modification of the phenothiazine structure by a substitution of two benzene rings with pyridine rings to form this new type of azaphenothiazines does not enhance antioxidant activity, although it retains it.
Healthy properties of proanthocyanidins
Authors: de la Iglesia Rocío , Milagro Fermín I. , Campión Javier , Boqué Noemí , Martínez J. Alfredo
Published: March 2010

Proanthocyanidins, also named condensed tannins, are the result of flavanols condensation. Oligomers and polymers of proanthocyanidins can widely be found in the plant kingdom, as in fruits and berries, seeds, flowers, and leafs. They have a putative role as antioxidants, and they affect the inflammatory process via calcium‐dependent release of nitric oxide and protect against H2O2‐induced lipid peroxidation. They also demonstrated a role in cardiovascular diseases via vessel relaxation and LDL oxidation inhibition. These condensed tannins have also shown activities that improve diabetic complications, such as neuropathy, retinopathy, or nephropathy, including a decrease in serum glucose and advanced glycation end products. Furthermore, proanthocyanidins have evidenced anticancer properties by mitigating tumor development through induction of apoptosis or inhibition of cell proliferation. Finally, they are able to produce antiadhesive actions against bacteria in urinary and dental infections, including Escherichia coli and Streptococcus mutans. Hence, proanthocyanidins are considered as beneficial molecules in preventing or treating many diseases and pathological conditions. Therefore, finding out more about condensed tannins bioavailability, and understanding the regulatory genes and pathways involved in their effects should be aimed in future research.
Characterization of uptake of folates by rat and human blood–brain barrier endothelial cells
Authors: Araújo João R. , Gonçalves Pedro , Martel Fátima
Published: March 2010

This study aimed to characterize 3H‐folic acid (3H‐FA) and 14C‐methyltetrahydrofolic acid (14C‐MTHF) uptake by rat (RBE4) and human (hCMEC/D3) blood–brain barrier (BBB) endothelial cell lines. Uptake of 3H‐FA and 14C‐MTHF by RBE4 cells was time dependent and linear for the first 2 min of incubation; uptake by hCMEC/D3 cells showed a less marked time‐dependency and a greater experimental variability. So, further experiments were performed in RBE4 cells only. Uptake of 3H‐FA was stimulated at acidic and alkaline pH, Na+ dependent, stimulated when F− substituted for Cl−, energy independent, inhibited by premetrexed, stimulated by cytochalasin D, and unaffected by MTHF, DIDS, SITS, methotrexate, monensin, and FA. Uptake of 14C‐MTHF was found to be pH‐, Na+‐, Cl−‐ and energy independent, inhibited by premetrexed and methotrexate, stimulated by cytochalasin D, and unaffected by FA, DIDS, SITS, monensin, and MTHF. RT‐PCR analysis showed mRNA expression of reduced folate transporter (RFC), but neither of FRα nor of proton‐coupled folate transporter (PCFT) in RBE4 cells, and mRNA expression of RFC and PCFT, but not of FRα, in hCMEC/D3 cells. In conclusion, both human and rat BBB endothelial cells show little capacity for 3H‐FA and 14C‐MTHF apical uptake. Hence, these cell lines do not appear to be a good model to study the transport of folates at the BBB.
Effect of adiponectin on apoptosis: Proapoptosis or antiapoptosis?
Authors: Sun Yiyi , Chen Xiuping
Published: March 2010

Adiponectin is a protein hormone mainly secreted by adipose tissue that regulates energy homeostasis and glucose and lipid metabolism. Compared with other adipose‐derived hormones, adiponectin is very abundant in plasma and is proposed to be a convenient biomarker for many diseases. A large number of in vitro and in vivo studies support the beneficial effects of adiponectin on metabolic syndrome, diabetes, and atherosclerosis. However, the protective actions were challenged occasionally by the controversies in its role in inflammation and in the specific functions of its different conformations. Recently, quite a few reports suggested that the antiapoptotic activity of adiponectin might contribute to its therapeutic potential during ischemia/reperfusion injury in vivo, whereas some studies demonstrated that adiponectin induced apoptosis both in vitro and in vivo. Herein, this review attempts to summarize the present consensus and divergence and to provide possible alternative and/or complementary explanations for this apparent paradox.
Regulatory mechanisms of intestinal iron absorption—Uncovering of a fast‐response mechanism based on DMT1 and ferroportin endocytosis
Authors: Núñez Marco T.
Published: March 2010

Knowledge on the intestinal iron transport process and the regulation of body iron stores has greatly increased during the last decade. The liver, through the sensing of circulating iron, is now recognized as the central organ in this regulation. High iron levels induce the synthesis of hepcidin, which in turn decreases circulating iron by inhibiting its recycling from macrophages and its absorption at the intestine. Another mechanism for the control of iron absorption by the enterocyte is an active Iron Responsive Element (IRE)/Iron Regulatory Protein (IRP) system. The IRE/IRP system regulates the expression of iron uptake and storage proteins thus regulating iron absorption. Similarly, increasing evidence points to the transcriptional regulation of both divalent metal transporter 1 (DMT1) and ferroportin expression. A new mechanism of regulation related to a phenomenon called the mucosal block is starting to be unveiled. The mucosal block describes the ability of an initial dose of ingested iron to block absorption of a second dose given 2–4 h later. Here, we review the mechanisms involved in the expression of DMT1 and ferroportin, and present recent evidence on the molecular components and cellular processes involved in the mucosal block response. Our studies indicate that mucosal block is a fast‐response endocytic mechanism destined to decrease intestinal iron absorption during a high ingest of iron.
Metabolism of Methoxychlor by the P450‐Monooxygenase CYP6G1 Involved in Insecticide Resistance of Drosophila melanogaster after Expression in Cell Cultures of Nicotiana tabacum
Authors: Joußen Nicole , Schuphan Ingolf , Schmidt Burkhard
Published: March 2010

Cytochrome P450 monooxygenase CYP6G1 of Drosophila melanogaster was heterologously expressed in a cell suspension culture of Nicotiana tabacum. This in vitro system was used to study the capability of CYP6G1 to metabolize the insecticide methoxychlor (=1,1,1‐trichloro‐2,2‐bis(4‐methoxyphenyl)ethane, 1) against the background of endogenous enzymes of the corresponding non‐transgenic culture. The Cyp6g1‐transgenic cell culture metabolized 96% of applied methoxychlor (45.8 μg per assay) within 24 h by demethylation and hydroxylation mainly to trishydroxy and catechol methoxychlor (16 and 17%, resp.). About 34% of the metabolism and the distinct formation of trishydroxy and catechol methoxychlor were due to foreign enzyme CYP6G1. Furthermore, methoxychlor metabolism was inhibited by 43% after simultaneous addition of piperonyl butoxide (458 μg), whereas inhibition in the non‐transgenic culture amounted to 92%. Additionally, the rate of glycosylation was reduced in both cultures. These results were supported by the inhibition of the metabolism of the insecticide imidacloprid (6; 20 μg, 24 h) in the Cyp6g1‐transgenic culture by 82% in the presence of piperonyl butoxide (200 μg). Due to CYP6G1 being responsible for imidacloprid resistance of Drosophila or being involved in DDT resistance, it is likely that CYP6G1 conveys resistance to methoxychlor (1). Furthermore, treating Drosophila with piperonyl butoxide could weaken the observed resistance phenomena.
Ioniols I and II, Tetracyclic Diterpenes with Antibacterial Activity, from Sphaerococcus coronopifolius
Authors: Smyrniotopoulos Vangelis , Vagias Constantinos , Rahman Mukhlesur M. , Gibbons Simon , Roussis Vassilios
Published: March 2010

Two naturally occurring diterpenes featuring unprecedented tetracyclic skeletons, ioniols I and II (1 and 2, resp.), along with two previously reported metabolites 3 and 4, were isolated from the organic extract of Sphaerococcus coronopifolius collected from the rocky coasts of Corfu island in the Ionian Sea. The structures of the new natural products, as well as their relative configuration, were elucidated on the basis of extensive spectral analysis, including 2D‐NMR experiments. The isolated metabolites were evaluated for their antibacterial activity against a panel of Staphylococcus aureus strains, which included multidrug‐resistant (MDR) and methicillin‐resistant Staphylococcus aureus (MRSA) strains.
Studies on the Redox Characteristics of Ferrioxamine E
Authors: Kazmi S. Arif , Shorter A. Lee , McArdle James V. , Ashiq Uzma , Jamal Rifat Ara
Published: March 2010

Thermodynamic parameters for the reduction of ferrioxamine E as calculated from redox potentials determined at four different temperatures were found to be ΔH≠=7.1±3.4 kJ mol−1 and ΔS≠=−146 J mol−1 K−1. The negative entropy value is large, because the decrease in the charge at the metal center and an increase in its ionic radius force the structure of the complex to become less rigid and resemble the desferrisiderophore. The hydrophilic groups of the system are now (relatively more) available for solvent interaction. Thus, a large negative entropy change accompanies the reduction of the complex. Kinetics of reduction of ferrioxamine by VII, CrII, EuII, and dithionite were measured at different temperatures and by dithionite at different pH values. The CrII and EuII reactions proceed by an inner‐sphere mechanism and have second‐order rate constants at 25° of 1.37×104 and 1.23×105 M−1 s−1, respectively. For the VII reduction, the corresponding rate constant was 1.89×103 M−1 s−1. The activation parameters for the VII reduction were ΔH≠ = 8.3 kJ mol−1; ΔS≠ =−154 J mol−1 K−1. These values are indicative of an outer‐sphere mechanism for VII reduction. The reduction by dithionite is half order in dithionite concentration indicating that SO$\rm{{_{2}^{-}}}$. is the sole reducing species. log of reduction rate constants of different trihydroxamates by this reductant were correlated with their respective redox potentials, and the variation was found to be in approximate correspondence with the expectations of Marcus relationship.
Fragrant Volatile Compounds in the Liverwort Drepanolejeunea madagascariensis (Steph.) Grolle: Approach by the HS‐SPME Technique
Authors: Gauvin‐Bialecki Anne , Ah‐Peng Claudine , Smadja Jacqueline , Strasberg Dominique
Published: March 2010

Three populations of the epiphyllous liverwort Drepanolejeunea madagascariensis collected in the cloud forests of Reunion Island (Mascarene Archipelago) were investigated for their volatile compounds, because of the pleasant, sweet, warm, woody‐spicy, and herbaceous fragrance, slightly reminiscent of dill, of this species. By applying the headspace solid‐phase microextraction (HS‐SPME) technique coupled to GC/MS analysis, 34 compounds were detected in total, with p‐menth‐1‐en‐9‐ol (28.8–43.5%), limonene (10.5–14.7%), β‐phellandrene (8.8–11.6%), and the so‐called dill ether (8.5–16.6%) as the main components. The presence of 1‐epi‐α‐pinguisene confirms the possible use of pinguisane‐type sesquiterpenoids as a characteristic chemical marker for the order Jungermanniales.
Cytotoxic Steroidal Saponins from the Rhizomes of Tacca integrifolia
Authors: Shwe Htay Htay , Aye Mye , Sein Myint Myint , Htay Khin Than , Kreitmeier Peter , Gertsch Jürg , Reiser Oliver , Heilmann Jörg
Published: March 2010

Three new steroid saponins (3β,25R)‐spirost‐5‐en‐3‐yl 6‐deoxy‐α‐L‐mannopyranosyl‐(1→2)‐[β‐D‐glucopyranosyl‐(1→4)‐6‐deoxy‐α‐L‐mannopyranosyl‐(1→3)]‐β‐D‐glucopyranoside (1), (3β,22R,25R)‐26‐(β‐D‐glucopyranosyloxy)‐22‐hydroxyfurost‐5‐en‐3‐yl 6‐deoxy‐α‐L‐mannopyranosyl‐(1→2)‐[6‐deoxy‐α‐L‐mannopyranosyl‐(1→3)]‐β‐D‐glucopyranoside (3), and (3β,22R,25R)‐26‐(β‐D‐glucopyranosyloxy)‐22‐hydroxyfurost‐5‐en‐3‐yl 6‐deoxy‐α‐L‐mannopyranosyl‐(1→2)‐[β‐D‐glucopyranosyl‐(1→4)‐6‐deoxy‐α‐L‐mannopyranosyl‐(1→3)]‐β‐D‐glucopyranoside (5), as well as the new pregnane glycoside (3β,16β)‐3‐{[6‐deoxy‐α‐L‐mannopyranosyl‐(1→2)‐[6‐deoxy‐α‐L‐mannopyranosyl‐(1→3)]‐β‐D‐glucopyranosyl]oxy}‐20‐oxopregn‐5‐en‐16‐yl (4R)‐5‐(β‐D‐glucopyranosyloxy)‐4‐methylpentanoate (6), were isolated from the rhizomes of Tacca integrifolia together with two known (25R) configurated steroid saponins (3β,25R)‐spirost‐5‐en‐3‐yl 6‐deoxy‐α‐L‐mannopyranosyl‐(1→2)‐[6‐deoxy‐α‐L‐mannopyranosyl‐(1→3)]‐β‐D‐glucopyranoside (2) and (3β,22R,25R)‐26‐(β‐D‐glucopyranosyloxy)‐22‐methoxyfurost‐5‐en‐3‐yl 6‐deoxy‐α‐L‐mannopyranosyl‐(1→2)‐[6‐deoxy‐α‐L‐mannopyranosyl‐(1→3)]‐β‐D‐glucopyranoside (4). The cytotoxic activity of the isolated compounds was evaluated in HeLa cells and showed the highest cytotoxicity value for compound 2 with an IC50 of 1.2±0.4 μM. Intriguingly, while compounds 1–5 exhibited similar cytotoxic properties between 1.2±0.4 (2) and 4.0±0.6 μM (5), only compound 2 showed a significant microtubule‐stabilizing activity in vitro.
A New Prenylated Flavanonol from Seseli annuum Roots Showing Protective Effect on Human Lymphocytes DNA
Authors: Vučković Ivan , Vajs Vlatka , Stanković Miroslava , Tešević Vele , Milosavljević Slobodan
Published: March 2010

A new prenylated flavanonol named seselinonol (1) was isolated from the roots of Seseli annuum, together with the well‐known biologically active polyacetylenes falcarinol (2) and falcarindiol (3), and the prenylated furanocoumarin phellopterin (4). Its structure was elucidated by extensive spectroscopic analysis, including HR‐ESI‐MS, 1D‐ and 2D‐NMR. Seselinonol and phellopterin were tested for in vitro protective effect on chromosome aberrations in peripheral human lymphocytes using cytochalasin‐B blocked micronucleus (CBMN) assay. The new compound exerted a beneficial effect by decreasing DNA damage of human lymphocytes.
Effect of Crossbreeding on the Chemical Composition and Biological Characteristics of Tunisian New Olive Progenies
Authors: Rjiba Imed , Dabbou Samia , Gazzah Nouredine , Hammami Mohamed
Published: March 2010

Olive fruit characteristics (weight, pulp/stone ratio, and oil and moisture content) and the iodine value (IV) of 31 new olive progenies (Olea europaea L.) were determined. To evaluate the effect of the genetic variability on these parameters, the new olive progenies, obtained through cross‐pollination between Tunisian and Mediterranean olive cultivars, were planted in a selected grove guaranteeing the homogeneity of the pedologic and climatic conditions. A strong genetic effect and significant differences between genotypes were obtained for the IV and the fruit characteristics evaluated. Discriminant analysis was used to classify the new progenies as distinct from each other, based on their IV, and their pulp and stone weight. An almost full discrimination of the olives from different genotypes was only achieved when the fruit characteristics (pulp and stone weight) and the IV data were analyzed together.
Oligonucleotide N3′→P5′ Phosphoramidates and Thio‐Phoshoramidates as Potential Therapeutic Agents
Authors: Gryaznov Sergei M.
Published: March 2010

Nucleic acids analogues, i.e., oligonucleotide N3′→P5′ phosphoramidates and N3′→P5′ thio‐phosphoramidates, containing 3′‐amino‐3′‐deoxy nucleosides with various 2′‐substituents were synthesized and extensively studied. These compounds resist nuclease hydrolysis and form stable duplexes with complementary native phosphodiester DNA and, particularly, RNA strands. An increase in duplexes' melting temperature, ΔTm, relative to their phosphodiester counterparts, reaches 2.2–4.0° per modified nucleoside. 2′‐OH‐ (RNA‐like), 2′‐O‐Me‐, and 2′‐ribo‐F‐nucleoside substitutions result in the highest degree of duplex stabilization. Moreover, under close to physiological salt and pH conditions, the 2′‐deoxy‐ and 2′‐fluoro‐phosphoramidate compounds form extremely stable triple‐stranded complexes with either single‐ or double‐stranded phosphodiester DNA oligonucleotides. Melting temperature, Tm, of these triplexes exceeds Tm values for the isosequential phosphodiester counterparts by up to 35°. 2′‐Deoxy‐N3′→P5′ phosphoramidates adopt RNA‐like C3′‐endo or N‐type nucleoside sugar‐ring conformations and hence can be used as stable RNA mimetics. Duplexes formed by 2′‐deoxy phosphoramidates with complementary RNA strands are not substrates for RNase H‐mediated cleavage in vitro. Oligonucleotide phosphoramidates and especially thio‐phosphoramidates conjugated with lipid groups are cell‐permeable and demonstrate high biological target specific activity in vitro. In vivo, these compounds show good bioavailability and efficient biodistribution to all major organs, while exerting acceptable toxicity at therapeutically relevant doses. Short oligonucleotide N3′→P5′ thio‐phosphoramidate conjugated to 5′‐palmitoyl group, designated as GRN163L (Imetelstat), was recently introduced as a potent human telomerase inhibitor. GRN163L is not an antisense agent; it is a direct competitive inhibitor of human telomerase, which directly binds to the active site of the enzyme and thus inhibits its activity. This compound is currently in multiple Phase‐I and Phase‐I/II clinical trials as potential broad‐spectrum anticancer agent.
Locked Nucleic Acids: Promising Nucleic Acid Analogs for Therapeutic Applications
Authors: Veedu Rakesh N. , Wengel Jesper
Published: March 2010

Locked Nucleic Acid (LNA) is a unique nucleic‐acid modification possessing very high binding affinity and excellent specificity toward complementary RNA or DNA oligonucleotides. The remarkable properties exhibited by LNA oligonucleotides have been employed in different nucleic acid‐based therapeutic strategies both in vitro and in vivo. Herein, we highlight the applications of LNA nucleotides for controlling gene expression.
Erythropoietin induces nuclear translocation of Nrf2 and heme oxygenase‐1 expression in SH‐SY5Y cells
Authors: Genc Kursad , Egrilmez Mehtap Y. , Genc Sermin
Published: March 2010

Erythropoietin (Epo) exerts neuroprotective, glioprotective, and vascular protective effects in the nervous system. However, the mechanisms of the cytoprotective effect of Epo have not been fully clarified. Here, we investigated whether Epo affects the transcription and activation of nuclear factor erythroid 2‐related factor 2 (Nrf2), which is a key transcription factor of the cellular anti‐oxidant defense system, and mRNA expression of its target genes including heme oxygenase‐1 (HO‐1). Epo was added to SH‐SY5Y cells at 1 U mL−1 and cultures were incubated for 24 h and then mRNA expression of Nrf2 target genes were analyzed with real‐time PCR. SH‐SY5Y cells were incubated with Epo at different time points and the nuclear and cytoplasmic levels of Nrf2 protein expression were examined by Western blotting and immunohistochemistry. Specific inhibitors of mitogen‐activated protein kinases (MAPKs) and phosphatidylinositol‐3 kinase (PI3K) were used to find out the possible signaling pathways that mediate the activating effect of Epo on Nrf2 activation. In cultured human SH‐SY5Y neuroblastoma cells, Western blotting, immunohistochemistry, and real‐time PCR analysis demonstrated that Epo‐induced nuclear translocation of Nrf2 and upregulates HO‐1 expression. Inhibitors of MAPKs and PI3K decreased Epo‐induced nuclear translocation of Nrf2 and HO‐1 mRNA expression. These results suggest that Epo induces neural HO‐1 expression through the activation of PI3K, MAPK, and Nrf2 pathways, and this may unveil a novel mechanism which mediates the cytoprotective responses elicited by Epo. Copyright © 2010 John Wiley & Sons, Ltd.
Bis(phosphinimino)methanide Borohydride Complexes of the Rare‐Earth Elements as Initiators for the Ring‐Opening Polymerization of ε‐Caprolactone: Combined Experimental and Computational Investigations
Authors: Jenter Jelena , Roesky Peter W. , Ajellal Noureddine , Guillaume Sophie M. , Susperregui Nicolas , Maron Laurent
Published: March 2010

Rare‐earth‐metal borohydrides are known to be efficient catalysts for the polymerization of apolar and polar monomers. The bis‐borohydrides [{CH(PPh2NSiMe3)2}La(BH4)2(THF)] and [{CH(PPh2NSiMe3)2}Ln(BH4)2] (Ln=Y, Lu) have been synthesized by two different synthetic routes. The lanthanum and the lutetium complexes were prepared from [Ln(BH4)3(THF)3] and K{CH(PPh2NSiMe3)2}, whereas the yttrium analogue was obtained from in situ prepared [{CH(PPh2NSiMe3)2}YCl2]2 and NaBH4. All new compounds were characterized by standard analytical/spectroscopic techniques, and the solid‐state structures were established by single‐crystal X‐ray diffraction. The ring‐opening polymerization (ROP) of ε‐caprolactone initiated by [{CH(PPh2NSiMe3)2}La(BH4)2(THF)] and [{CH(PPh2NSiMe3)2}Ln(BH4)2] (Ln=Y, Lu) was studied. At 0 °C the molar mass distributions determined were the narrowest values (M̄w/M̄n=1.06–1.11) ever obtained for the ROP of ε‐caprolactone initiated by rare‐earth‐metal borohydride species. DFT investigations of the reaction mechanism indicate that this type of complex reacts in an unprecedented manner with the first BH activation being achieved within two steps. This particularity has been attributed to the metallic fragment based on the natural bond order analysis.
Triazolyl Azabicyclo[3.1.0]hexanes: a Class of Potent and Selective Dopamine D3Receptor Antagonists
Authors: Bonanomi Giorgio , Braggio Simone , Capelli Anna Maria , Checchia Anna , Di Fabio Romano , Marchioro Carla , Tarsi Luca , Tedesco Giovanna , Terreni Silvia , Worby Angela , Heibreder Christian , Micheli Fabrizio
Published: March 2010

Herein we report a detailed description of the structure–activity relationships for a novel series of “C‐linked” 1,2,4‐triazolylazabicyclo[3.1.0]hexanes. These derivatives are endowed with very high in vitro affinity and selectivity for the dopamine D3receptor. An optimization with respect to undesired affinity toward the hERG potassium channel is also reported. Members of this compound series also show excellent in vitro and in vivo pharmacokinetic properties.
Fixation for distributed clustering processes
Authors: Hilário M. R. , Louidor O. , Newman C. M. , Rolla L. T. , Sheffield S. , Sidoravicius V.
Published: March 2010

We study a discrete‐time resource flow in
\input amssym ${\Bbb Z}^d $
where wealthier vertices attract the resources of their less rich neighbors. For any translation‐invariant probability distribution of initial resource quantities, we prove that the flow at each vertex terminates after finitely many steps. This answers (a generalized version of) a question posed by van den Berg and Meester in 1991. The proof uses the mass transport principle and extends to other graphs. © 2010 Wiley Periodicals, Inc.
Vortex energy and 360° Néel walls in thin‐film micromagnetics
Authors: Ignat Radu , Knüpfer Hans
Published: March 2010

We study the vortex pattern in ultrathin ferromagnetic films of circular crosssection. The model is based on the following energy functional:

for in‐plane magnetizations m: B2 → S1 in the unit disc
$\font\open=msbm10 at 10pt\def\R{\hbox{\open R}}B^2 \subset \R^2$. The avoidance of volume charges ▿ · m ≠ 0 in B2 and surface charges m · ν ≠ 0 on δB2 leads to the formation of a vortex in the limit ε → 0. At the level ε > 0 the vortex is regularized by the formation of a 360° Néel wall (a one‐dimensional transition layer with core of scale ε) concentrated along a radius of B2. We derive the limiting energy of the vortex by matching upper and lower bounds. Our analysis on the lower bound is based on a dynamical system argument and an interpolation inequality with sharp leading‐order constant, while the upper bound uses the leading‐order energy for 360° Néel walls. © 2010 Wiley Periodicals, Inc.
Communication via responsibility reporting and its effect on firm value in Finland
Authors: Schadewitz Hannu , Niskala Mikael
Published: March 2010

n this paper, we first analyzed the responsibility reporting literature with an emphasis on the linkage between responsibility reporting and a firm's performance and valuation. Based on the literature review, we developed a research question: How does communication via responsibility reporting affect firm value? We analyzed the market valuation of listed Finnish firms through a conventional valuation model combined with responsibility reporting. The starting point for our valuation was the Ohlson model. We expanded upon the conventional valuation by studying whether communication via responsibility reporting is related to firm valuation. Our research question is linked to the broader academic question of whether earnings worth as an information source has been erased over the last few years. In addition, we contribute to the literature that tries to understand the link between corporate social responsibility and firm performance/share performance. Specifically, we focused on responsibility reporting according to the Global Reporting Initiative (GRI) and especially on whether the existence of these reports provides a further explanation for firm value.

Our sample was a population type that covered all listed Finnish firms that have adopted GRI. No other responsibility reporting practice was used by listed firms in their responsibility reporting communication during the years 2002–2005. The other necessary information for valuation models was obtained from Thomson Financial Services (commercial database).

The applied model supported the conclusion that communication via GRI responsibility reporting is an important explanatory factor for a firm's market value. The result indicates that responsibility reporting is a part of a firm's communication tools in order to decrease information asymmetry between managers and investors. In other words, GRI responsibility reporting is called for in order to produce a more precise market valuation of a firm. Copyright © 2010 John Wiley & Sons, Ltd and ERP Environment.
miRNAs give worms the time of their lives: Small RNAs and temporal control in Caenorhabditis elegans
Authors: Resnick Tamar D. , McCulloch Katherine A. , Rougvie Ann E.
Published: March 2010

Alteration in the timing of particular developmental events can lead to major morphological changes that have profound effects on the life history of an organism. Insights into developmental timing mechanisms have been revealed in the model organism Caenorhabditis elegans, in which a regulatory network of heterochronic genes times events during larval development, ensuring that stage‐specific programs occur in the appropriate sequence and on schedule. Developmental timing studies in C. elegans led to the landmark discovery of miRNAs and continue to enhance our understanding of the regulation and activity of these small regulatory molecules. Current views of the heterochronic gene pathway are summarized here, with a focus on the ways in which miRNAs contribute to temporal control and how miRNAs themselves are regulated. Finally, the conservation of heterochronic genes and their functions in timing, as well as their related roles in stem cells and cancer, are highlighted. Developmental Dynamics 239:1477–1489, 2010. © 2010 Wiley‐Liss, Inc.
CH4 flux from peatlands: a new measurement method
Authors: Baird Andrew J. , Stamp Imelda , Heppell Catherine M. , Green Sophie M.
Published: March 2010

Peatlands are important sources of atmospheric CH4, a potent greenhouse gas. Identifying the controls on CH4 flux from peatlands requires detailed investigation of fluxes at small scales (the microform scale) where flux chambers are best deployed for measurement. Using chambers presents challenges, not least that of how the CH4 concentration in chamber gas should be measured. Current field approaches usually involve either (i) online measurement with a flow‐through laser absorption spectroscopy instrument or (ii) online or offline analysis of CH4 by gas chromatography–flame ionization detector (GC‐FID) analysis. Online measurement restricts the number of chambers that can be monitored to c. 10 and their spatial spread to a distance of 10–20 m from the CH4 analyser and is not suited to large‐scale studies. GC‐FID may present logistical difficulties when conducting research at remote sites because of the need for frequent calibration and, hence, calibration gases. Generally, it is not suited to non‐laboratory applications. An alternative is to analyse syringe samples of chamber gas near the field site using a modified laser spectroscopy instrument. We show how such a modification may be made. The theory of our modification is presented, as are the results obtained using it. It is shown that the instrument with the modification compares favourably with GC‐FID and can be used near remote field sites in the absence of laboratory facilities. We present flux data from a peatland in Wales, where the flux‐chamber CH4 concentrations were obtained using the modified instrument. Copyright © 2010 John Wiley & Sons, Ltd.
Immunodominant T‐cell epitopes of hnRNP‐A2 associated with disease activity in patients with rheumatoid arthritis
Authors: Trembleau Sylvie , Hoffmann Markus , Meyer Brigitte , Nell Valerie , Radner Helga , Zauner Wolfgang , Hammer Juergen , Aichinger Gerald , Fischer Gottfried , Smolen Josef , Steiner Günter
Published: March 2010

The heterogeneous nuclear ribonucleoprotein A2 (hnRNP‐A2) has been described as an important autoantigen in rheumatoid arthritis (RA) since it is targeted by autoantibodies, autoreactive T cells, and is aberrantly expressed in synovial cells in patients. To identify hnRNP‐A2‐specific T‐cell epitopes possibly associated with pathogenicity, we used an innovative approach. We first scanned 280 overlapping hnRNP‐A2 peptides for binding to the RA‐associated class II molecules HLA‐DR4 and HLA‐DR1, leading to a comprehensive selection of binders. The selected peptides were tested in IFN‐γ‐specific ELISPOT assay: PBMC from 18% of RA patients showed a significant IFN‐γ response to hnRNP‐A2 peptides, 15% to the overlapping sequences 117–133 and/or 120–133, whereas PBMC from healthy individuals tested negative. We measured proliferative responses to these two peptides in another cohort of patients with RA or osteoarthritis: positive responses were found in 28% of RA, but also in 11% of osteoarthritis patients and these responses could be blocked by anti‐MHC class II Ab. Remarkably, the presence of 117/120–133‐specific T cells was significantly associated with active disease in RA patients, and bone erosion appeared to be more common in T‐cell positive patients. These data suggest involvement of hnRNP‐A2 specific cellular autoimmune responses in RA pathogenesis.
Human peripheral blood and bone marrow Epstein–Barr virus‐specific T‐cell repertoire in latent infection reveals distinct memory T‐cell subsets
Authors: Guerreiro Manuel , Na Il‐Kang , Letsch Anne , Haase Doreen , Bauer Sandra , Meisel Christian , Roemhild Andy , Reinke Petra , Volk Hans‐Dieter , Scheibenbogen Carmen
Published: March 2010

EBV infection leads to life‐long viral persistence. Although EBV infection can result in chronic disease and malignant transformation, most carriers remain disease‐free as a result of effective control by T cells. EBV‐specific IFN‐γ‐producing T cells could be demonstrated in acute and chronic infection as well as during latency. Recent studies, however, provide evidence that assessing IFN‐γ alone is insufficient to assess the quantity and quality of a T‐cell response. Using overlapping peptide pools of latent EBV nuclear antigen 1 and lytic BZLF‐1 protein and multicolor flow cytometry, we demonstrate that the majority of ex vivo EBV‐reactive T cells in healthy virus carriers are indeed IL‐2‐ and/or TNF‐producing memory cells, the latter being significantly more frequent in BM. After in vitro expansion, a substantial number of EBV‐specific CD4+ and CD8+ T cells retained a CC‐chemokine receptor 7 (CCR7)‐positive memory phenotype. Based on their cytokine profiles, six different EBV‐specific T‐cell subsets could be distinguished with TNF‐single or TNF/IL‐2‐double producing cells expressing the highest CCR7 levels resembling early‐differentiated memory T cells. Our study delineates the memory T‐cell profile of a protective immune response and provides a basis for analyzing T‐cell responses in EBV‐associated diseases.
N‐Heterocyclic Carbenes: Useful Ligands for the Palladium‐Catalysed Direct C5 Arylation of Heteroaromatics with Aryl Bromides or Electron‐Deficient Aryl Chlorides
Authors: Ozdemir Ismail , Gök Yetkin , Özeroğlu Özlem , Kaloğlu Murat , Doucet Henri , Bruneau Christian
Published: March 2010

New Pd–N‐heterocyclic carbene complexes have been prepared and employed for palladium‐catalysed direct arylation of heteroaromatic derivatives by using aryl halides. These catalyst precursors promote the coupling of challenging aryl halides such as deactivated or congested aryl bromides and also activated aryl chlorides. This procedure employs only 1 mol‐% of an air‐stable palladium complex. This is a practical advantage over the procedures that employ palladium attached to air‐sensitive phosphane ligands, which are often used to promote the coupling of such aryl halides.
An Improved Synthesis of Borazine with Aluminum Chloride as Catalyst
Authors: Li Jun‐sheng , Zhang Chang‐rui , Li Bin , Cao Feng , Wang Si‐qing
Published: March 2010

Borazine is an excellent precursor for boron nitride. However the existing synthetic methods for the preparation of borazine have drawbacks such as relatively high reaction temperatures, side reactions, long reaction times, and low yields. An improved synthesis procedure was disclosed, which involved the use of aluminum chloride as a catalyst in the reaction of sodium borohydride with ammonium sulfate. The aluminum chloride catalyst brought the reaction temperature down from 120–140 °C to 45 °C. Improved yields of borazine were obtained in comparison to the reaction without a catalyst. In addition, the reaction process was investigated in detail by 11B NMR spectroscopy and Fourier transform infrared spectroscopy (FTIR). It was found that aluminum borohydride formed in very small quantity when aluminum chloride was introduced, which plays an important role in the reaction.
Oil quality characteristics of irradiated sunflower and maize seed
Authors: Yaqoob Nazia , Bhatti Ijaz Ahmed , Anwar Farooq , Asi Muhammad Rafique
Published: March 2010

The characteristics of oils extracted from gamma‐irradiated sunflower (Halianthus annuus) and maize (Zea mays) seeds at absorbed doses of 2, 4, 6, 8, and 10 kGy were investigated. Gamma irradiation did not affect the lipid, protein, fiber, and ash contents of neither sunflower nor maize seeds significantly (p>0.05). No significant changes were observed for the values of refractive index and density between the control and irradiated sunflower and maize oils. Peroxide value, acid value, para‐anisidine value, and conjugated dienes and trienes contents increased, while iodine values decreased in the irradiated oils as compared to those of control oils (p<0.05). A small decrease in the contents of α‐, γ‐, and δ‐tocopherols of both sunflower and maize oils was noted by radiation treatment up to 6 kGy, however, the decline was more pronounced at higher dosages. The effects of irradiation on the fatty acid composition of sunflower oil showed a significant (p<0.05) change in the amounts of stearic, oleic, and linoleic acids, while the concentration of palmitic acid was unaffected even at 10 kGy. Similar trends in the fatty acid profile were found for both the sunflower and maize oil.
Modification of the fat composition of the Iberian pig using Bacillus licheniformis and Bacillus subtilis
Authors: Parra Vita , Petrón María Jesús , Martín Lourdes , Broncano Julio Manuel , Timón María Luisa
Published: March 2010

The aim of this work was to study the influence of a diet with probiotic bacteria on the lipid composition of different tissues from Iberian pigs. Cholesterol and fatty acid profiles were measured in liver, subcutaneous fat, and Serratus ventralis muscle samples. Feeding Iberian pigs a mixture of probiotic microorganisms for 45 days prior to slaughter affected the tissue composition. The feeds of the control and probiotic groups were identical except for the added Bacillus licheniformis and Bacillus subtilis (1.28 × 109 cfu/kg feed) in the feed of the probiotic group. The diet with probiotics significantly affected the fatty acid profile of liver, subcutaneous fat and Serratus ventralis muscle samples, but no significant differences were found for the cholesterol content. The livers of the probiotic group contained lower levels of n‐6 fatty acids and higher levels of n‐3 fatty acids. The subcutaneous fat contained lower levels of n‐6 fatty acids. Serratus ventralis muscles from the probiotic group contained a significantly higher percentage of oleic acid than those of the control group.

Practical applications: This study deals with the effect of the addition of probiotic bacteria to the diet of pigs on both the cholesterol and fatty acid content. B. subtilis and B. licheniformis can be used in pig feed (Regulation EC no. 2148/2004), but there are no studies about their effects on fresh meat or other tissues, particularly regarding the fat composition. Thus, it is interesting to study how feeding these microorganisms affects the different tissues. Including these microorganisms in the basic diet could serve as a strategy to modify the fat composition and to obtain healthier products from pigs.
Effect of feeding and genotype on the lipid profile of organic chicken meat
Authors: Sirri Federico , Castellini Cesare , Roncarati Alessandra , Franchini Achille , Meluzzi Adele
Published: March 2010

The effects of partial substitution of soybean (SB) with faba bean (FB) and of genotypes [fast‐growing Cobb 700 (FG), medium‐growing naked‐neck Kabir (MG), slow‐growing Brown Classic Lohman (SG)] on the lipid composition as well as the meat quality attributes of chickens reared under organic conditions were evaluated. A total of 720 1‐day‐old male chicks were equally divided into three groups according to genotype and raised for 81 (MG and FG) or 96 days (SG): half birds of each genotype received either SB grower diet or FB grower diet. Meat from SG and MG birds exhibited a lower lipid content than that from FG birds. Both in breast and thigh meat, MUFA were significantly increased from SG to MG and FG. SG meat contained the highest amounts of either arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, or docosapentaenoic acid, but the lowest amounts of α‐linolenic acid. Total PUFA gradually decreased from SG to MG and FG birds (413, 358, and 324 g/kg of fat), as well as total n − 6 and total n − 3. The Δ5‐ plus Δ6‐desaturase index was 54.0, 34.4, and 23.6 for SG, MG, and FG birds, respectively. The n − 6/n − 3 ratio was lower in SG and MG than in FG birds. The partial replacement of SB with FB had a lesser effect than the genotype on the meat quality characteristics.