bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemical Synthesis of Asparagine‐Linked Archaeal N‐Glycan from Methanothermus fervidus
Authors: Sanapala Someswara Rao , Kulkarni Suvarn S. 
Published: March 2014

AbstractSeveral N‐linked glycoproteins have been identified in archaea and there is growing evidence that the N‐glycan is involved in survival and functioning of archaea in extreme conditions. Chemical synthesis of the archaeal N‐glycans represents a crucial step towards understanding the putative function of protein glycosylation in archaea. Herein the first total synthesis of the archaeal L‐asparagine linked hexasaccharide from Methanothermus fervidus is reported using a highly convergent [3+3] glycosylation approach in high overall yields. The synthesis relies on efficient preparation of regioselectively protected thioglycoside building blocks for orthogonal glycosylations and late stage N‐aspartylation.
On the Role of Pre‐ and Post‐Electron‐Transfer Steps in the SmI2/Amine/H2O‐Mediated Reduction of Esters: New Mechanistic Insights and Kinetic Studies
Authors: Szostak Michal , Spain Malcolm , Procter David J. 
Published: March 2014

AbstractThe mechanism of the SmI2‐mediated reduction of unactivated esters has been studied using a combination of kinetic, radical clocks and reactivity experiments. The kinetic data indicate that all reaction components (SmI2, amine, H2O) are involved in the rate equation and that electron transfer is facilitated by Brønsted base assisted deprotonation of water in the transition state. The use of validated cyclopropyl‐containing radical clocks demonstrates that the reaction occurs via fast, reversible first electron transfer, and that the electron transfer from simple Sm(II) complexes to aliphatic esters is rapid. Notably, the mechanistic details presented herein indicate that complexation between SmI2, H2O and amines affords a new class of structurally diverse, thermodynamically powerful reductants for efficient electron transfer to carboxylic acid derivatives as an attractive alternative to the classical hydride‐mediated reductions and as a source of acyl‐radical equivalents for CC bond forming processes.
Chirality in the Absence of Rigid Stereogenic Elements: Steric and Electronic Effects on the Configurational Stability of C3 Symmetric Residual Tris‐Aryl Phosphanes
Authors: Rizzo Simona , Cirilli Roberto , Pierini Marco 
Published: March 2014

ABSTRACTResidual stereoisomers result whenever closed subsets of appropriately substituted interconverting isomers (the residual stereoisomers) are generated from a full set of stereoisomers under the operation of a favored stereomerization mechanism. In the case of the three‐bladed propellers, differentiation of the edges of the blades and strict correlation in the motion of the rings are the prerequisites for the existence of residual stereoisomers. In these systems, the two‐ring flip mechanism is the lowest energy process. It does not interconvert all possible conformational stereoisomers generated by helicity and the three‐blade‐hub rotors. In the case of C3 symmetric systems, two noninterconverting subgroups (the residual stereoisomers) are generated, each one constituted of quickly interconverting diastereoisomers. A series of tris‐aryl phosphanes, structurally designed for existing as residual enantiomers or diastereoisomers, bearing substituents differing in size and electronic properties on the aryl rings, were synthesized and characterized. The configurational stability of residual phosphanes, evaluated by dynamic 1H‐ and 31P‐NMR analysis and by dynamic enantioselective high‐performance liquid chromatography (HPLC), was found 10 kcal mol‐1 lower than that shown by the corresponding phosphane‐oxides. In accordance with the calculations, an unexpectedly low barrier for phosphorus pyramidal inversion was invoked as responsible for the scarce configurational stability of the residual tris‐arylphosphanes. Chirality 26:601–606, 2014. © 2014 Wiley Periodicals, Inc.
Comprehensive Chiroptical Study of Proline‐Containing Diamide Compounds
Authors: Knapp Krisztina , Górecki Marcin , Frelek Jadwiga , Luboradzki Roman , Hollósi Miklós , Majer Zsuzsa , Vass Elemér 
Published: March 2014

ABSTRACTThe continuously growing interest in the understanding of peptide folding led to the conformational investigation of methylamides of N‐acetyl‐amino acids as diamide models. Here we report the results of detailed conformational analysis on Ac‐Pro‐NHMe and Ac‐β‐HPro‐NHMe diamides. These compounds were analyzed by experimental and computational methods, the conformational distributions obtained by Density Functional Theory (DFT) calculations for isolated and solvated diamide compounds are discussed. The conformational preference of proline‐containing diamide compounds as a function of the ambience was observed by a number of chiroptical spectroscopic techniques, such as vibrational circular dichroism (VCD), electronic circular dichroism (ECD), Raman optical activity (ROA) spectroscopy, and additionally by single crystal X‐ray diffraction analyses. Based on a comparison between Ac‐Pro‐NHMe and Ac‐β‐HPro‐NHMe, one can conclude that due to the greater conformational freedom of the β‐HPro derivative, Ac‐β‐HPro‐NHMe shows different behavior in solid‐ and solution‐phase, as well. Ac‐β‐HPro‐NHMe tends to form cis Ac‐β‐HPro amide conformation in water, dichloromethane, and acetonitrile in contrast to its α‐Pro analog. On the other hand, the crystal structure of the β‐HPro compound cannot be related to any of the conformers obtained in vacuum and solution while the X‐ray structure of Ac‐Pro‐NHMe was identified as tαL–, which is a trans Ac‐Pro amide containing conformer also predominant in polar solvents. Chirality 26:228–242, 2014. © 2014 Wiley Periodicals, Inc.
N‐H Stretching Modes Around 3300 Wavenumber From Peptide Backbones Observed by Chiral Sum Frequency Generation Vibrational Spectroscopy
Authors: Fu Li , Wang Zhuguang , Yan Elsa C. Y. 
Published: March 2014

ABSTRACTWe present a detailed analysis of the molecular origin of the chiral sum frequency generation (SFG) signals of proteins and peptides at interfaces in the N‐H stretching vibrational region. The N‐H stretching can be a probe for investigating structural and functional properties of proteins, but remains technically difficult to analyze due to the overlapping with the O‐H stretching of water molecules. Chiral SFG spectroscopy offers unique tools to study the N‐H stretching from proteins at interfaces without interference from the water background. However, the molecular origin of the N‐H stretching signals of proteins is still unclear. This work provides a justification of the origin of chiral N‐H signals by analyzing the vibrational frequencies, examining chiral SFG theory, studying proton (hydrogen/deuterium) exchange kinetics, and performing optical control experiments. The results demonstrate that the chiral N‐H stretching signals at ~3300 cm‐1 originate from the amide group of the protein backbones. This chiral N‐H stretching signal offers an in situ, real‐time, and background‐free probe for interrogating the protein structures and dynamics at interfaces at the molecular level. Chirality 26:521–524, 2014. © 2014 Wiley Periodicals, Inc.
Targeting Cystalysin, a Virulence Factor of Treponema denticola‐Supported Periodontitis
Authors: Spyrakis Francesca , Cellini Barbara , Bruno Stefano , Benedetti Paolo , Carosati Emanuele , Cruciani Gabriele , Micheli Fabrizio , Felici Antonio , Cozzini Pietro , Kellogg Glen E. , Voltattorni Carla Borri , Mozzarelli Andrea 
Published: March 2014

AbstractCystalysin from Treponema denticola is a pyridoxal 5′‐phosphate dependent lyase that catalyzes the formation of pyruvate, ammonia, and sulfide from cysteine. It is a virulence factor in adult periodontitis because its reaction contributes to hemolysis, which sustains the pathogen. Therefore, it was proposed as a potential antimicrobial target. To identify specific inhibitors by structure‐based in silico methods, we first validated the crystal structure of cystalysin as a reliable starting point for the design of ligands. By using single‐crystal absorption microspectrophotometry, we found that the enzyme in the crystalline state, with respect to that in solution, exhibits: 1) the same absorption spectra for the catalytic intermediates, 2) a close pKa value for the residue controlling the keto enamine ionization, and 3) similar reactivity with glycine, L‐serine, L‐methionine, and the nonspecific irreversible inhibitor aminoethoxyvinylglycine. Next, we screened in silico a library of 9357 compounds with the Fingerprints for Ligands and Proteins (FLAP) software, by using the three‐dimensional structure of cystalysin as a template. From the library, 17 compounds were selected and experimentally evaluated by enzyme assays and spectroscopic methods. Two compounds were found to competitively inhibit recombinant T. denticola cystalysin, with inhibition constant (Ki) values of 25 and 37 μM. One of them exhibited a minimum inhibitory concentration (MIC) value of 64 μg mL−1 on Moraxella catarrhalis ATCC 23246, which proves its ability to cross bacterial membranes.
Pig models of neurodegenerative disorders: Utilization in cell replacement‐based preclinical safety and efficacy studies
Authors: Dolezalova Dasa , Hruska‐Plochan Marian , Bjarkam Carsten R. , Sørensen Jens Christian H. , Cunningham Miles , Weingarten David , Ciacci Joseph D. , Juhas Stefan , Juhasova Jana , Motlik Jan , Hefferan Michael P. , Hazel Tom , Johe Karl , Carromeu Cassiano , Muotri Alysson , Bui Jack , Strnadel Jan , Marsala Martin 
Published: March 2014

ABSTRACTAn important component for successful translation of cell replacement‐based therapies into clinical practice is the utilization of large animal models to conduct efficacy and/or safety cell dosing studies. Over the past few decades, several large animal models (dog, cat, nonhuman primate) were developed and employed in cell replacement studies; however, none of these models appears to provide a readily available platform to conduct effective and large‐scale preclinical studies. In recent years, numerous pig models of neurodegenerative disorders were developed using both a transgenic approach as well as invasive surgical techniques. The pig model (naïve noninjured animals) was recently used successfully to define the safety and optimal dosing of human spinal stem cells after grafting into the central nervous system (CNS) in immunosuppressed animals. The data from these studies were used in the design of a human clinical protocol used in amyotrophic lateral sclerosis (ALS) patients in a Phase I clinical trial. In addition, a highly inbred (complete major histocompatibility complex [MHC] match) strain of miniature pigs is available which permits the design of comparable MHC combinations between the donor cells and the graft recipient as used in human patients. Jointly, these studies show that the pig model can represent an effective large animal model to be used in preclinical cell replacement modeling. This review summarizes the available pig models of neurodegenerative disorders and the use of some of these models in cell replacement studies. The challenges and potential future directions in more effective use of the pig neurodegenerative models are also discussed. J. Comp. Neurol. 522:2784–2801, 2014. © 2014 Wiley Periodicals, Inc.
Established monolayer differentiation of mouse embryonic stem cells generates heterogeneous neocortical‐like neurons stalled at a stage equivalent to midcorticogenesis
Authors: Sadegh Cameron , Macklis Jeffrey D. 
Published: March 2014

ABSTRACTTwo existing and widely applied protocols of embryonic stem (ES) cell differentiation have been developed to enable in vitro generation of neurons resembling neocortical projection neurons in monolayer culture and from embryoid bodies. The monolayer approach offers advantages for detailed in vitro characterizations and potential mechanistic and therapeutic screening. We investigated whether mouse ES cells undergoing largely undirected neocortical differentiation in monolayer culture recapitulate progressive developmental programs of in vivo progenitor and postmitotic differentiation and whether they develop into specific neocortical subtypes. We find that ES‐derived mitotic cells that have been dorsalized by the sonic hedgehog antagonist cyclopamine, and that express, as a total population, cardinal markers of telencephalic progenitors, are, in fact, molecularly heterogeneous. We next show that these progenitors subsequently generate small numbers of heterogeneous neocortical‐like neurons that are “stalled” at an immature stage of differentiation, based on multiple developmental criteria. Although some aspects of neocortical development are recapitulated by existing protocols of ES cell differentiation, these data indicate that mouse ES‐derived neocortical progenitors both are more heterogeneous than their in vivo counterparts and seemingly include many incorrectly specified progenitors. Furthermore, these ES‐derived progenitors spontaneously differentiate into sparse, and incompletely and largely imprecisely differentiated, neocortical‐like neurons that fail to adopt specific neuronal identities in vitro. These results provide both foundation and motivation for refining and enhancing directed differentiation of clinically important neocortical projection neuron subtypes. J. Comp. Neurol. 522:2691–2706, 2014. © 2014 Wiley Periodicals, Inc.
Treating Parkinson's disease in the 21st century: Can stem cell transplantation compete?
Authors: Buttery Philip C. , Barker Roger A. 
Published: March 2014

ABSTRACTThe characteristic and selective degeneration of a unique population of cells—the nigrostriatal dopamine (DA) neurons—that occurs in Parkinson's disease (PD) has made the condition an iconic target for cell replacement therapies. Indeed, transplantation of fetal ventral mesencephalic cells into the DA‐deficient striatum was first trialled nearly 30 years ago, at a time when other treatments for the disease were less well developed. Over recent decades standard treatments for PD have advanced, and newer biological therapies are now emerging. In the 21st century, stem cell technology will have to compete alongside other sophisticated treatments, including deep brain stimulation and gene therapies. In this review we examine how stem cell–based transplantation therapies compare with these novel and emerging treatments in the management of this common condition. J. Comp. Neurol. 522:2802–2816, 2014. © 2014 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.
Human induced pluripotent stem cells are a novel source of neural progenitor cells (iNPCs) that migrate and integrate in the rodent spinal cord
Authors: Sareen Dhruv , Gowing Geneviève , Sahabian Anais , Staggenborg Kevin , Paradis Renée , Avalos Pablo , Latter Jessica , Ornelas Loren , Garcia Leslie , Svendsen Clive N. 
Published: March 2014

ABSTRACTTransplantation of human neural progenitor cells (NPCs) into the brain or spinal cord to replace lost cells, modulate the injury environment, or create a permissive milieu to protect and regenerate host neurons is a promising therapeutic strategy for neurological diseases. Deriving NPCs from human fetal tissue is feasible, although problematic issues include limited sources and ethical concerns. Here we describe a new and abundant source of NPCs derived from human induced pluripotent stem cells (iPSCs). A novel chopping technique was used to transform adherent iPSCs into free‐floating spheres that were easy to maintain and were expandable (EZ spheres) (Ebert et al. [2013] Stem Cell Res 10:417–427). These EZ spheres could be differentiated towards NPC spheres with a spinal cord phenotype using a combination of all‐trans retinoic acid (RA) and epidermal growth factor (EGF) and fibroblast growth factor‐2 (FGF‐2) mitogens. Suspension cultures of NPCs derived from human iPSCs or fetal tissue have similar characteristics, although they were not similar when grown as adherent cells. In addition, iPSC‐derived NPCs (iNPCs) survived grafting into the spinal cord of athymic nude rats with no signs of overgrowth and with a very similar profile to human fetal‐derived NPCs (fNPCs). These results suggest that human iNPCs behave like fNPCs and could thus be a valuable alternative for cellular regenerative therapies of neurological diseases. J. Comp. Neurol. 522:2707–2728, 2014. © 2014 Wiley Periodicals, Inc.
PTEN inhibition enhances neurite outgrowth in human embryonic stem cell–derived neuronal progenitor cells
Authors: Wyatt Lindsey A. , Filbin Marie T. , Keirstead Hans S. 
Published: March 2014

ABSTRACTWe investigated the role of PTEN (phosphatase and tensin homolog deleted on chromosome 10) during neurite outgrowth of human embryonic stem cell (hESC)‐derived neuronal progenitors. PTEN inhibits phosphoinositide 3‐kinase (PI3K)/Akt signaling, a common and central outgrowth and survival pathway downstream of neuronal growth factors. It is known that PTEN inhibition, by either polymorphic mutation or gene deletion, can lead to the development of tumorigenesis (Stambolic et al., ; Tamura et al., ). However, temporary inhibition of PTEN, through pharmacological manipulation, could regulate signaling events such as the PI3K/Akt signaling pathway, leading to enhanced recovery of central nervous system (CNS) injury and disease. We demonstrate that pharmacological inhibition of PTEN in hESC‐derived neuronal progenitors significantly increased neurite outgrowth in vitro in a dose‐ and time‐dependent manner. Our results indicate that inhibition of PTEN augments neurite outgrowth beyond that of traditional methods such as elevation of intracellular cyclic adenosine monophosphate (cAMP) levels, and depends on upregulation of the PI3K/Akt signaling pathway and its downstream effectors, such as mammalian target of rapamycin (mTOR). PTEN inhibition also rescued neurite outgrowth over an inhibitory substrate in vitro. These findings indicate a remarkable impact on hESC‐derived neuronal progenitor plasticity through PTEN inhibition. Overall, these findings identify a novel therapeutic strategy for neurite outgrowth in CNS injury and disease. J. Comp. Neurol. 522:2741–2755, 2014. © 2014 Wiley Periodicals, Inc.
Compromised blood–brain barrier competence in remote brain areas in ischemic stroke rats at the chronic stage
Authors: Garbuzova‐Davis Svitlana , Haller Edward , Williams Stephanie N. , Haim Eithan D. , Tajiri Naoki , Hernandez‐Ontiveros Diana G. , Frisina‐Deyo Aric , Boffeli Sean M. , Sanberg Paul R. , Borlongan Cesario V. 
Published: March 2014

ABSTRACTStroke is a life‐threatening disease leading to long‐term disability in stroke survivors. Cerebral functional insufficiency in chronic stroke might be due to pathological changes in brain areas remote from the initial ischemic lesion, i.e., diaschisis. Previously, we showed that the damaged blood–brain barrier (BBB) was involved in subacute diaschisis. The present study investigated BBB competence in chronic diaschisis by using a transient middle cerebral artery occlusion (tMCAO) rat model. Our results demonstrated significant BBB damage mostly in the ipsilateral striatum and motor cortex in rats at 30 days after tMCAO. The BBB alterations were also determined in the contralateral hemisphere via ultrastructural and immunohistochemical analyses. Major BBB pathological changes in contralateral remote striatum and motor cortex areas included 1) vacuolated endothelial cells containing large autophagosomes, 2) degenerated pericytes displaying mitochondria with cristae disruption, 3) degenerated astrocytes and perivascular edema, 4) Evans blue extravasation, and 5) appearance of parenchymal astrogliosis. Discrete analyses of striatal and motor cortex areas revealed significantly higher autophagosome accumulation in capillaries of ventral striatum and astrogliosis in dorsal striatum in both cerebral hemispheres. These widespread microvascular alterations in ipsilateral and contralateral brain hemispheres suggest persistent and/or continued BBB damage in chronic ischemia. The pathological changes in remote brain areas likely indicate chronic ischemic diaschisis, which should be considered in the development of treatment strategies for stroke. J. Comp. Neurol. 522:3120–3137, 2014. © 2014 Wiley Periodicals, Inc.
Titanium(IV)‐Immobilized Hydrophilic Hierarchically Ordered Macro‐/Mesoporous Silica for Fast Enrichment of Phosphopeptides
Authors: Yan Yinghua , Zheng Zhifang , Li Yan , Deng Chunhui , Zhang Xiangmin 
Published: March 2014

AbstractFeasible design is essential to achieve ideal chemical and biological properties of nanomaterials. For the first time, new nanocomposites with a polydopamine coating on hierarchically ordered macro‐/mesoporous silica functionalized with titanium ions (denoted as HOMMS‐PD‐Ti4+) were prepared through a facile reaction route at room temperature. The applicability of as‐synthesized HOMMS‐PD‐Ti4+ for the selective enrichment of phosphopeptides was tested. The experimental results demonstrate that, by taking advantage of the pure phosphate–Ti4+ interface and high loading amount of Ti4+, HOMMS‐PD‐Ti4+ presents remarkable selectivity for phosphopeptides, even at a low molar ratio of phosphopeptides/non‐phosphopeptides (1:1000) with a very rapid enrichment speed (within 1 min). The superior sensitivity for low‐abundant phosphopeptides and the high selectivity and effectiveness for the enrichment of phosphopeptides from human serum are also proven. These outstanding features demonstrate that HOMMS‐PD‐Ti4+ exhibits great potential in phosphoproteome research in the future.
Switchable Ionic Liquids as Delignification Solvents for Lignocellulosic Materials
Authors: Anugwom Ikenna , Eta Valerie , Virtanen Pasi , Mäki‐Arvela Päivi , Hedenström Mattias , Hummel Michael , Sixta Herbert , Mikkola Jyri‐Pekka 
Published: March 2014

AbstractThe transformation of lignocellulosic materials into potentially valuable resources is compromised by their complicated structure. Consequently, new economical and feasible conversion/fractionation techniques that render value‐added products are intensely investigated. Herein an unorthodox and feasible fractionation method of birch chips (B. pendula) using a switchable ionic liquid (SIL) derived from an alkanol amine (monoethanol amine, MEA) and an organic super base (1,8‐diazabicyclo‐[5.4.0]‐undec‐7‐ene, DBU) with two different trigger acid gases (CO2 and SO2) is studied. After SIL treatment, the dissolved fractions were selectively separated by a step‐wise method using an antisolvent to induce precipitation. The SIL was recycled after concentration and evaporation of anti‐solvent. The composition of undissolved wood after MEA‐SO2‐SIL treatment resulted in 80 wt % cellulose, 10 wt % hemicelluloses, and 3 wt % lignin, whereas MEA‐CO2‐SIL treatment resulted in 66 wt % cellulose, 12 wt % hemicelluloses and 11 wt % lignin. Thus, the MEA‐SO2‐SIL proved more efficient than the MEA‐CO2‐SIL, and a better solvent for lignin removal. All fractions were analyzed by gas chromatography (GC), Fourier transform infrared spectroscopy (FT‐IR), 13C nuclear magnetic resonance spectroscopy (NMR) and Gel permeation chromatography (GPC).