bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enantioselective Annulation Reactions of Bisenolates Prepared Through Dearomatization Reactions of Aromatic and Heteroaromatic Diesters
Authors: Pérez‐Vázquez Jaime , Veiga Alberte X. , Prado Gustavo , Sardina F. Javier , Paleo M. Rita 
Published: December 2011

AbstractA one‐pot, enantioselective strategy for the dearomatization–annulation of aromatic diesters to give a range of highly functionalized polycyclic molecules with excellent enantioselectivity is presented. This methodology is based on the reaction of bisenolates, prepared by treating aromatic diesters with trialkyltin lithium reagents, which involves a stanna‐Brook rearrangement, with 1,ω‐dihaloalkanes and other biselectrophiles. We have also developed experimental conditions for performing these reactions with substoichiometric amounts of the required tin reagent by in situ recycling of Me6Sn2 into Me3SnLi with excess lithium metal, and provide a study of the scope and limitations of this synthetic methodology.
Concerted functions of HDAC1 and microRNA‐574‐5p repress alternatively spliced ceramide synthase 1 expression in human cancer cells
Authors: Meyers‐Needham Marisa , Ponnusamy Suriyan , Gencer Salih , Jiang Wenhui , Thomas Raquela J. , Senkal Can E. , Ogretmen Besim 
Published: December 2011

AbstractHistone deacetylases (HDACs) and microRNAs (miRs) have pro‐survival roles, but the mechanism behind this is unclear. Repression of ceramide synthase 1 (CerS1), altering C18‐ceramide generation, was linked to drug resistance and metastasis. Here we report that the CerS1 promoter was repressed by HDAC1‐dependent inhibition of Sp1 recruitment to two specific GC‐boxes spanning the −177 and −139 region. Moreover, an alternatively spliced variant CerS1 mRNA (CerS1‐2) was detected mainly in cancer cells or primary tumour tissues compared to controls, which was targeted by miR‐574‐5p for degradation. A specific 3′UTR‐targeting site, localized within the retained intron between exons 6 and 7, was identified, and its mutation, or miR‐574‐5p knockdown prevented the degradation of CerS1‐2 mRNA. Interference with HDAC1 and miR‐574‐5p reconstituted CerS1‐2 expression and C18‐ceramide generation in multiple human cancer cell lines, which subsequently inhibited proliferation and anchorage‐independent growth. Accordingly, knockdown of CerS1 partially protected cancer cells from MS‐275/miR‐574‐5p siRNA‐mediated growth inhibition. Thus, these data suggest that the HDAC1/miR‐574‐5p axis might provide a novel therapeutic target to reconstitute tumour suppressor CerS1/ceramide signalling.
Wnt transmembrane signaling and long‐term spatial memory
Authors: Tabatadze Nino , Tomas Caroline , McGonigal Rhona , Lin Brian , Schook Andrew , Routtenberg Aryeh 
Published: December 2011

AbstractTransmembrane signaling mechanisms are critical for regulating the plasticity of neuronal connections underlying the establishment of long‐lasting memory (e.g., Linden and Routtenberg (1989) Brain Res Rev 14:279–296; Sossin (1996) Trends Neurosci 19:215–218; Mayr and Montminy (2001) Nat Rev Mol Cell Biol 2:599–609; Chen et al. (2011) Nature 469:491–497). One signaling mechanism that has received surprisingly little attention in this regard is the well‐known Wnt transmembrane signaling pathway even though this pathway in the adult plays a significant role, for example, in postsynaptic dendritic spine morphogenesis and presynaptic terminal neurotransmitter release (Inestrosa and Arenas (2010) Nat Rev Neurosci 11:77–86). The present report now provides the first evidence of Wnt signaling in spatial information storage processes. Importantly, this Wnt participation is specific and selective. Thus, spatial, but not cued, learning in a water maze selectively elevates the levels in hippocampus of Wnt 7 and Wnt 5a, but not the Wnt 3 isoform, indicating behavioral selectivity and isoform specificity. Wnt 7 elevation is subfield‐specific: granule cells show an increase with no detectable change in CA3 neurons. Wnt 7 elevation is temporally specific: increased Wnt signaling is not observed during training, but is seen 7 days and, unexpectedly, 30 days later. If the Wnt elevation after learning is activity‐dependent, then it may be possible to model this effect in primary hippocampal neurons in culture. Here, we evaluate the consequence of potassium or glutamate depolarization on Wnt signaling. This represents, to our knowledge, the first demonstration of an activation‐dependent elevation of Wnt levels and surprisingly an increased number of Wnt‐stained puncta in neurites suggestive of trafficking from the cell body to neuronal processes, probably dendrites. It is proposed that Wnt signaling pathways regulate long‐term information storage in a behavioral‐, cellular‐, and isoform‐specific manner. © 2011 Wiley Periodicals, Inc.
Dorsal versus ventral hippocampal contributions to trace and contextual conditioning: Differential effects of regionally selective nmda receptor antagonism on acquisition and expression
Authors: Czerniawski Jennifer , Ree Fredrick , Chia Chester , Otto Tim 
Published: December 2011

AbstractThe dorsal and ventral subregions of the hippocampus likely play dissociable roles in some forms of learning. For example, we have previously demonstrated that temporary inactivation of ventral, but not dorsal, hippocampus dramatically impaired the acquisition of trace fear conditioning, while temporary inactivation of dorsal, but not ventral, hippocampus impaired spatially guided reinforced alternation (Czerniawski et al. (2009) Hippocampus 19:20–32). Importantly, emerging data suggest that lesions, temporary inactivation, and NMDA receptor antagonism within these subregions can produce quite different patterns of behavioral effects when administered into the same region. Specifically, while neither lesions nor temporary inactivation of dorsal hippocampus impair the acquisition of trace fear conditioning, learning in this paradigm is severely impaired by pre‐training administration of the NMDA receptor antagonist dl‐2‐phosphonovaleric acid (APV) in dorsal hippocampus; the effect of NMDA receptor antagonism within ventral hippocampus on the acquisition and expression of trace conditioning, or on learning in general, has not yet been systematically explored. The present study extends our previous work examining the differential effect of lesions or inactivation of the dorsal and ventral hippocampal subregions by systematically examining the effect of regionally selective pre‐training or pre‐testing administration of APV on the acquisition and expression of trace and contextual fear conditioning. The results of these studies demonstrate that while pre‐training NMDA receptor antagonism within either the dorsal or ventral subregion of the hippocampus impaired the acquisition of both trace and contextual conditioning, pre‐testing NMDA receptor antagonism within ventral, but not dorsal, hippocampus impaired the expression of previously‐acquired trace and contextual fear conditioning. These data suggest that selectively manipulating the integrity of individual subregions may result in compensatory mechanisms that can support learning, and that NMDA‐dependent plasticity within both dorsal and ventral hippocampus is normally required for the acquisition and maintenance of memory in trace and contextual fear conditioning. © 2011 Wiley Periodicals, Inc.
Influence of heterogeneity on unsaturated hydraulic properties (2) – percentage and shape of heterogeneity
Authors: Wu Cheng‐Mau , Chen Pen‐Yuan , Chen Chu‐Hui , Hsu Nien‐Sheng , Wen Jet‐Chau 
Published: December 2011

AbstractIn subsurface porous media, the soil water retention curve (WRC) and unsaturated hydraulic conductivity curve (UHC) are two important soil hydraulic property curves. Spatial heterogeneity is ubiquitous in nature, which may significantly affect soil hydraulic property curves. The main theme of this paper is to investigate how spatial heterogeneities, including their arrangements and amounts in soil flumes, affect soil hydraulic property curves. This paper uses a two‐dimensional variably saturated flow and solute transport finite element model to simulate variations of pressure and moisture content in soil flumes under a constant head boundary condition. To investigate the behavior of soil hydraulic property curves owing to variations of heterogeneities and their arrangements as well, cases with different proportions of heterogeneities are carried out. A quantitative evaluation of parameter variations in the van Genuchten model (VG model) resulting from heterogeneity is presented. Results show that the soil hydraulic properties are strongly affected by variations of heterogeneities and their arrangements. If the pressure head remains at a specific value, the soil moisture increases when heterogeneities increase in the soil flumes. On the other hand, the unsaturated hydraulic conductivity decreases when heterogeneities increase in the soil flumes under a constant pressure head. Moreover, results reveal that parameters estimated from both WRC and UHC also are affected by shapes of heterogeneity; this indicates that the parameters obtained from the WRC are not suitable for predicting the UHC of different shapes in heterogeneous media. Copyright © 2011 John Wiley & Sons, Ltd.
Organ differences in the impact of p27kip1 deficiency on carcinogenesis induced by N‐methyl‐N‐nitrosourea
Authors: Ogawa Kumiko , Murasaki Toshiya , Sugiura Satoshi , Nakanishi Makoto , Shirai Tomoyuki 
Published: December 2011

ABSTRACTTo evaluate the impact of p27 on carcinogenesis in various organs, N‐methyl‐N‐nitrosourea (MNU), a direct‐acting alkylating agent, was given to p27 knock‐out mice. Groups of 20–40 male and female mice with null, hetero‐ or wild‐type p27 alleles were given drinking water containing 240 ppm MNU or distilled water every other week for five cycles. The incidence and multiplicity of the induced proliferative lesions were then histologically evaluated at weeks 14 and 20. MNU treatment induced various lesions including squamous hyperplasia and squamous cell carcinoma in the forestomach, atypical hyperplasia and adenocarcinomas in the fundic and pyloric glands, adenomas and adenocarcinomas in the duodenum, malignant lymphomas in the thymus, liver, kidney and spleen and alveolar hyperplasia, adenomas, adenocarcinomas and malignant lymphomas in the lung. Although the incidences of the lesions in the forestomach, fundic and pyloric glands did not differ among the p27 genotypes, those of alveolar hyperplasia of the lung and malignant lymphoma of the thymus were significantly increased in p27‐null males as compared with both wild‐ and hetero‐type animals. Moreover, in both p27+/+ and p27+/− cases, the rates for p27‐positive cells were obviously increased in proliferative lesions of the pyloric gland and the lung. However, an increased rate of p27‐positive cells was not observed in malignant lymphoma of the thymus. These findings suggest that p27 does not control the cell cycle equally in all organs affected by MNU‐induced carcinogenesis. Copyright © 2011 John Wiley & Sons, Ltd.
Chlorpyrifos exposure reduces reproductive capacity owing to a damaging effect on gametogenesis in the nematode Caenorhabditis elegans
Authors: Ruan Qin‐Li , Ju Jing‐Juan , Li Yun‐Hui , Li Xiao‐Bo , Liu Ran , Liang Ge‐Yu , Zhang Juan , Pu Yue‐Pu , Wang Da‐Yong , Yin Li‐Hong 
Published: December 2011

ABSTRACTPrevious studies have revealed that chlorpyrifos exposure adversely affects the reproductive capacity of male rodents. The present study investigated the reproductive toxicity of chlorpyrifos exposure and possible related mechanisms using the nematode Caenorhabditis elegans. L4 nematode larvae were exposed to chlorpyrifos at concentrations of 0.003, 0.03, 0.3 and 3.0 mg l−1 for different durations. In addition to decreased brood size, reduced spermatid size, increased percentage of abnormal spermatids, suppressed spermatid activation and motility of sperm, damaged oocyte morphology, increased numbers of apoptotic cells and unfertilized oocytes were observed in nematodes exposed to various concentrations of chlorpyrifos. Moreover, expression patterns of the genes spe‐10, spe‐15, fer‐1, prg‐1, glp‐1, mlh‐1, cyb‐3, ced‐3, ced‐4 and ced‐9 (which are associated with spermatid size, spermatid activation and morphology, oocyte morphology, oocyte function, and apoptosis) were altered after chlorpyrifos exposure. Therefore, chlorpyrifos exposure may adversely affect fertility in nematodes by influencing both spermatogenesis and oogenesis. Alterations in the expression patterns of genes involved in gametogenesis may explain the corresponding changes in gametogenesis in nematodes exposed to chlorpyrifos. Hence, the model organism Caenorhabditis elegans is recommended for assessment of reproductive toxicity relating to gametogenesis. Copyright © 2011 John Wiley & Sons, Ltd.
Rapid acquisition of Raman spectral maps through minimal sampling: applications in tissue imaging
Authors: Rowlands Christopher J. , Varma Sandeep , Perkins William , Leach Iain , Williams Hywel , Notingher Ioan 
Published: December 2011

AbstractA method is presented for acquiring high‐spatial‐resolution spectral maps, in particular for Raman micro‐spectroscopy (RMS), by selectively sampling the spatial features of interest and interpolating the results. This method achieves up to 30 times reduction in the sampling time compared to raster‐scanning, the resulting images have excellent correlation with conventional histopathological staining, and are achieved with sufficient spectral signal‐to‐noise ratio to identify individual tissue structures. The benefits of this selective sampling method are not limited to tissue imaging however; it is expected that the method may be applied to other techniques which employ point‐by‐point mapping of large substrates. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
On the effect of a variation of the force field, spatial boundary condition and size of the QM region in QM/MM MD simulations
Authors: Meier Katharina , Thiel Walter , van Gunsteren Wilfred F. 
Published: December 2011

AbstractDuring the past years, the use of combined quantum–classical, QM/MM, methods for the study of complex biomolecular processes, such as enzymatic reactions and photocycles, has increased considerably. The quality of the results obtained from QM/MM calculations is largely dependent on five aspects to be considered when setting up a molecular model: the QM Hamiltonian, the MM Hamiltonian or force field, the boundary and coupling between the QM and MM regions, the size of the QM region and the boundary condition for the MM region. In this study, we systematically investigate the influence of a variation of the molecular mechanics force field and the size of the QM region in QM/MM MD simulations on properties of the photoactive part of the blue light photoreceptor protein AppA. For comparison, we additionally performed classical MD simulations and studied the effect of a variation of the type of spatial boundary condition. The classical boundary conditions and the force field used in a QM/MM MD simulation are shown to have non‐neglegible effects upon the structural and energetic properties of the protein which makes it advisable to minimize computational artifacts in QM/MM MD simulations by application of periodic boundary conditions and a thermodynamically calibrated force field. A comparison of the structural and energetic properties of MD simulations starting from two alternative, different X‐ray structures for the blue light utilizing flavin protein in its dark state indicates a slight preference of the two force fields used for the so‐called Anderson structure over the Jung structure. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2012
Thermodynamics and kinetics of large‐time‐step molecular dynamics
Authors: Rao Francesco , Spichty Martin 
Published: December 2011

AbstractMolecular dynamics (MD) simulations provide essential information about the thermodynamics and kinetics of proteins. Technological advances in both hardware and algorithms have seen this method accessing timescales that used to be unreachable only few years ago. The quest to simulate slow, biologically relevant macromolecular conformational changes, is still open. Here, we present an approximate approach to increase the speed of MD simulations by a factor of ∼4.5. This is achieved by using a large integration time step of 7 fs, in combination with frozen covalent bonds and look‐up tables for nonbonded interactions of the solvent. Extensive atomistic MD simulations for a flexible peptide in water show that the approach reproduces the peptide's equilibrium conformational changes, preserving the essential properties of both thermodynamics and kinetics. Comparison of this approximate method with state‐of‐the‐art implicit solvation simulations indicates that the former provides a better description of the underlying free‐energy surface. Finally, simulations of a 33‐residue peptide show that these fast MD settings are readily applicable to investigate biologically relevant systems. © 2011 Wiley Periodicals, Inc.
A Novel and Efficient Synthesis of Dronedarone Hydrochloride, an Antiarrhythmic Drug Substance
Authors: Mohanarangam Saravanan , Satyanarayana Bollikonda , Elati Chandrashekar R. , Vijayabhaskar Bolugoddu , Pratap Reddy Padi 
Published: December 2011

AbstractA novel and efficient synthesis of dronedarone hydrochloride starting from 2‐n‐butyl‐5‐nitrobenzofuran by employing mild and selective reaction conditions is described. The synthetic approach is operationally simple and suitable for industrial application.
Predicting the Activity of Peptides Based on Amino Acid Information
Authors: Wang Xiao‐Yu , Wang Juan , Hu Yong , Lin Yong , Shu Mao , Wang Li , Cheng Xiao‐Ming , Lin Zhi‐Hua 
Published: December 2011

AbstractA set of amino acid descriptors including hydrophobic, stereo and electrical properties were applied to construct quantitative structure‐activity relationships (QSARs) models of three peptides datasets (angiotensin‐converting enzyme inhibitor dipeptides, bactericidal peptides and oxytocin peptides) with stepwise multiple regression combined partial least squares regression (SMR‐PLS). The results of QASRs models are very robust, with multiple correlation coefficients (R2), and cross validation (Q2) equal to 0.687, 0.671; 0.977, 0.890 and 0.950, 0.802 respectively. The robust models show the descriptors can be further expanded for polypeptides and serve as a useful quantitative tool for the rational drug design and discovery.
Ortho‐carboxylate Effects in Copper‐mediated Nucleophilic Substitution of Halothiophenecarboxylic Acids and Halobenzoic Acids with Sodium Bisulphite
Authors: Ramaswamy Govindarajan K. , Mohanasundaram Thanigaiarasu , Velayutham Murugesan , Kuppuswamy Balasubramanian K. 
Published: December 2011

AbstractOrtho‐carboxylate effects in Ullmann type nucleophilic substitution reactions were found to be much more pronounced as compared to those of other substituent and steric factors. In this study, we propose an ortho halogen assisted intramolecular oxidative addition‐reductive elimination mechanism that fits our experimental observations. Experimental data has been generated with halothiophenecarboxylic acids and halobenzoic acids by performing copper‐mediated nucleophilic substitution with scant referred sodium bisulphite as nucleophile under aqueous conditions. The novel mechanism was used to establish a new and improved process for preparation of monopotassium salts of 3‐sulphothiophene‐2‐carboxylic acid, 2‐sulphobenzoic acid, and 5‐sulphothiophene‐2‐carboxylic acid. These monopotassium salts are critical intermediates and building blocks in the preparation of several therapeutically valuable drugs. The differences in reactivity between the halogens, chlorine and bromine was utilized to prepare aryl ethers including 2‐acetyl‐3‐phenoxythiophene and 2‐acetyl‐3‐(m‐tolyloxy)thiophene that have not been reported in literature so far.
Sterols from the Stems of Momordica charantia
Authors: Liao Yun‐Wen , Chen Chiy‐Rong , Hsu Jue‐Liang , Cheng Hsueh‐Ling , Shih Wen‐Ling , Kuo Yueh‐Hsiung , Huang Tzou‐Chi , Chang Chi‐I 
Published: December 2011

AbstractA new sterol, 5α,6α‐epoxy‐3β‐hydroxy‐(22E,24R)‐ergosta‐8,22‐dien‐7‐one (1), together with eight known sterols, 5α,6α‐epoxy‐(22E,24R)‐ergosta‐8,22‐diene‐3β,7α‐diol (2), 5α,6α‐epoxy‐(22E,24R)‐ergosta‐8,22‐diene‐3β,7β‐diol (3), 5α,6α‐epoxy‐(22E,24R)‐ergosta‐8(14),22‐diene‐3β,7α‐diol (4), 3β‐hydroxy‐(22E,24R)‐ergosta‐5,8,22‐trien‐7‐one (5), ergosterol peroxide (6), clerosterol (7), decortinol (8), and decortinone (9), were isolated from the stems of Momordica charantia. Their structures were elucidated by mean of extensive spectroscopic methods, including 1H, 13C, 2D‐NMR and HR‐EI‐MS, as well as comparison with the literature data. Compounds 1, 4, 5, 8, and 91 were not cytotoxic against the SK‐Hep 1 cell line.
An Easy and Efficient Synthesis of Bisindolylmethanes and Tetraindolylmethane Tröger's Base Catatlyzed by AgBF4
Authors: Shaikh Ajam C. , Chen Chinpiao 
Published: December 2011

AbstractThis work presents a highly efficient and simple method for the synthesis of bisindolylmethanes, catalyzed by AgBF4, with excellent yields. Various substituted aldehydes and ketones with indole under this reaction condition is elucidated. This reaction occurs efficiently under mild reaction conditions, such as are applied with methoxy or furfural, which commonly undergoes cleavage under strongly acidic reaction conditions. The presented approach was suitable for the synthesis of complex systems, such as tetraindolylmethane Tröger's Base.
The Isolation and Determination of Sulforaphane from Broccoli Tissues by Reverse Phase‐High Performance Liquid Chromatography
Authors: Azizi Naser Seyed , Amiri‐Besheli Behnam , Sharifi‐Mehr Salman 
Published: December 2011

AbstractSulforaphane is a cognate isothiocyanate of glucoraphanin, released by degradation of glucosinolate through myrosinase enzyme, when Brassica tissues are crushed or chewed. C8 analytical column and mixture of water/acetonitrile 65/35 (ν/ν) as mobile phase were used to separate sulforaphane in broccoli tissues (e.g., 7‐day‐seedling, seed, floret and leave). Confirmation of sulforaphane in crude extract of broccoli tissues was monitored using gas chromatography‐mass spectroscopy (GC‐MS). The highest amount of sulforaphane (1216 μg/g dry weight) found in 7‐day‐seedling. This method is suitable for routine screening of plant materials and proposes a low cost and robust technique for the analysis of sulforaphane.
Direct Electrochemistry and Electrocatalysis of Myoglobin with Ionic Liquid through Multilayers Film on Carbon Ionic Liquid Electrode
Authors: Ruan Chengxiang , Lou Jin , Wang Yan , Guo Yaqing , Gao Weimin , Sun Wei 
Published: December 2011

AbstractMultilayers of myoglobin (Mb) with ionic liquid 1‐ethyl‐3‐methylimidazolium tetrafluoroborate ([EMIM]BF4) was assembled on carbon ionic liquid electrode (CILE) based on the electrostatic attraction between the negatively charged Mb and the positively charged imidazolium ion of IL. The CILE was fabricated with 1‐ethyl‐3‐methylimidazolium ethylsulfate ([EMIM]EtOSO3) as the modifier, which exhibited imidazolium ion on the electrode surface. Then Mb molecules were assembled on the surface of CILE step‐by‐step to get a {IL/Mb}n multilayer film modified electrode. UV‐Vis adsorption and FT‐IR spectra indicated that Mb remained its native structure in the IL matrix. In deaerated phosphate buffer solution (pH 7.0) a pair of well‐defined quasi‐reversible redox peaks appeared with the apparent formal potential (E0′) as ‐0.212 V (vs. SCE), which was the characteristic of Mb heme Fe(III)/Fe(II) redox couples. The results indicated that the direct electron transfer of Mb was realized on the modified electrode. The {IL/Mb}n/CILE displayed excellent electrocatalytic ability to the trichloroacetic acid reduction in the concentration range from 2.0 to 22.0 mmol/L with the detection limit of 0.6 mmol/L (3σ). The proposed method provides a new platform to fabricate the third generation biosensor based on the self‐assembly of redox protein with ILs.