bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis and Biological Evaluation of Andrographolide Derivatives as Potent Anti‐HIV Agents
Authors: Tang Chunlei , Liu Yajuan , Wang Bin , Gu Guolong , Yang Liumeng , Zheng Yongtang , Qian Hai , Huang Wenlong 
Published: May 2012

AbstractIn an attempt to develop potent anti‐HIV drugs, 20 andrographolide derivatives were designed, synthesized, and evaluated for their in vitro anti‐HIV activity. The screening results revealed that five compounds showed potent anti‐HIV activities with therapeutic indices (TI) above 10. The most promising compound 6f shows a significant TI close to 34.07, with the potency to be a new lead.
Comparative reaction engineering studies for succinic acid production from sucrose by metabolically engineered Escherichia coli in fed‐batch‐operated stirred tank bioreactors
Authors: Hoefel Torben , Faust Georg , Reinecke Liv , Rudinger Nicolas , Weuster‐Botz Dirk 
Published: May 2012

AbstractThis study presents a comparative reaction engineering analysis of metabolically engineered sucrose‐utilizing Escherichia coli derived from E. coli K12 MG1655 for the anaerobic production of succinic acid. Production capacities of 16 different recombinant strains were evaluated in 48 parallel fed‐batch‐operated milliliter‐scale stirred tank bioreactors (10 mL) with continuous CO2 sparging. The effects of recombinant sucrose‐utilization systems (csc‐operon or scr‐operon), enhancements of anaplerotic reactions (pck, ppc, maeA, maeB or heterologous pyc) and gene deletions (ldhA, adhE, ack‐pta and ptsG) were studied with respect to the overall process performances of the respective recombinant strains. Both sucrose‐utilization systems enabled the production of succinic acid from sucrose in E. coli K12 MG1655. Maximum succinate production was observed by overexpressing the pyruvate carboxylase from Corynebacterium glutamicum resulting in a succinate concentration of 26.8 g L–1 after 48 h and a cell‐specific productivity of 0.14 g g–1 h–1. Further experiments in a fed‐batch‐operated laboratory‐scale stirred tank bioreactor (2 L) showed that micro‐aerobic conditions preceding the anaerobic phase enhance succinic acid production of E. coli K12 MG1655‐derived strains. The work demonstrates the importance of parallel approaches within the scope of applied metabolic engineering studies.
Silica biotemplating by self‐assembling peptides via serine residues activated by the peptide amino terminal group
Authors: Kasotakis Emmanouil , Mitraki Anna 
Published: May 2012

AbstractSelf‐assembling biological materials increasingly serve as templates for the binding of inorganic materials and fabrication of composite nanowires, tubes, etc. with important applications in nanobiotechnology. We have previously reported the use of a self‐assembling octapeptide building block as scaffold for the systematic introduction of metal‐binding residues, namely cysteines, at the first two amino acids within the sequence (Kasotakis et al., Biopolymers 2009, 92, 164‐172). We have also reported unexpected behavior of serine within the octapeptide NH2NSGAITIGCONH2 (Asparagine‐Serine‐Glycine‐Alanine‐Isoleucine‐Threonine‐Isoleucine‐Glycine) in nucleating gold and platinum nanoparticles. Herein, we report that this serine residue is instrumental in nucleating silica nanoparticles on the surface of the self‐assembled fibrils from TEOS (tetraethyl orthosilicate) precursors. We carried out a systematic investigation of the adjacent functionalities and we propose that this serine residue is rendered abnormally nucleophilic through proton abstraction by the N‐terminal amino group of the peptide. Peptides with a threonine or a cysteine residue at position 2 are also able to nucleate silica nanoparticles. We propose that rationally designed self‐assembling peptides bearing hydroxyl groups adjacent to free amine functionalities could be used for targeted templating of biogenic and even nonbiogenic oxides. © 2012 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 98: 501–509, 2012.
Engineering biomaterials to integrate and heal: The biocompatibility paradigm shifts
Authors: Bryers James D. , Giachelli Cecilia M. , Ratner Buddy D. 
Published: May 2012

AbstractThis article focuses on one of the major failure routes of implanted medical devices, the foreign body reaction (FBR)—that is, the phagocytic attack and encapsulation by the body of the so‐called “biocompatible” biomaterials comprising the devices. We then review strategies currently under development that might lead to biomaterial constructs that will harmoniously heal and integrate into the body. We discuss in detail emerging strategies to inhibit the FBR by engineering biomaterials that elicit more biologically pertinent responses. Biotechnol. Bioeng. 2012; 109:1898–1911. © 2012 Wiley Periodicals, Inc.
Network‐Assisted Investigation of Antipsychotic Drugs and Their Targets
Authors: Sun Jingchun , Xu Hua , Zhao Zhongming 
Published: May 2012

AbstractAntipsychotic drugs are tranquilizing psychiatric medications primarily used in the treatment of schizophrenia and similar severe mental disorders. So far, most of these drugs have been discovered without knowing much on the molecular mechanisms of their actions. The available large amount of pharmacogenetics, pharmacometabolomics, and pharmacoproteomics data for many drugs makes it possible to systematically explore the molecular mechanisms underlying drug actions. In this study, we applied a unique network‐based approach to investigate antipsychotic drugs and their targets. We first retrieved 43 antipsychotic drugs, 42 unique target genes, and 46 adverse drug interactions from the DrugBank database and then generated a druggene network and a drugdrug interaction network. Through druggene network analysis, we found that seven atypical antipsychotic drugs tended to form two clusters that could be defined by drugs with different target receptor profiles. In the drugdrug interaction network, we found that three drugs (zuclopenthixol, ziprasidone, and thiothixene) tended to have more adverse drug interactions than others, while clozapine had fewer adverse drug interactions. This investigation indicated that these antipsychotics might have different molecular mechanisms underlying the drug actions. This pilot network‐assisted investigation of antipsychotics demonstrates that network‐based analysis is useful for uncovering the molecular actions of antipsychotics.
Enantio‐ and Chemoselective Differentiation of Protected α‐Amino Acids and β‐Homoamino Acids with a Single Copper(II) Host
Authors: Joyce Leo A. , Canary James W. , Anslyn Eric V. 
Published: May 2012

AbstractThe association between an achiral copper(II)‐containing host 1 and chiral carboxylates has been expanded beyond previous studies to new chiral carboxylate guests, both α‐amino acids and β‐homoamino acids. The observed exciton‐coupled circular dichroism (ECCD) signals for the enantiomers of each carboxylate were equal and opposite, and these signals differed in size and shape between the individual amino acids. Linear discriminant analysis (LDA) was applied as a statistical analysis technique to differentiate the amino acids, both enantioselectively and chemoselectively, giving the absolute configuration and identity of the amino acid. The identity of each of the α‐amino acids and β‐homoamino acids were determined independently by LDA, and then the two were considered together. Each of these analyses showed good differentiation of the amino acid guests with the use of only one host molecule.
Predicting Drug Metabolism by Cytochrome P450 2C9: Comparison with the 2D6 and 3A4 Isoforms
Authors: Rydberg Patrik , Olsen Lars 
Published: May 2012

AbstractBy the use of knowledge gained through modeling of drug metabolism mediated by the cytochrome P450 2D6 and 3A4 isoforms, we constructed a 2D‐based model for site‐of‐metabolism prediction for the cytochrome P450 2C9 isoform. The similarities and differences between the models for the 2C9 and 2D6 isoforms are discussed through structural knowledge from the X‐ray crystal structures and trends in experimental data. The final model was validated on an independent test set, resulting in an area under the curve value of 0.92, and a site of metabolism was found among the top two ranked atoms for 77 % of the compounds.
Review and perspective: neuromechanical considerations for predicting muscle activation patterns for movement
Authors: Ting Lena H. , Chvatal Stacie A. , Safavynia Seyed A. , Lucas McKay J. 
Published: May 2012

SUMMARYMuscle coordination may be difficult or impossible to predict accurately based on biomechanical considerations alone because of redundancy in the musculoskeletal system. Because many solutions exist for any given movement, the role of the nervous system in further constraining muscle coordination patterns for movement must be considered in both healthy and impaired motor control. On the basis of computational neuromechanical analyses of experimental data combined with modeling techniques, we have demonstrated several such neural constraints on the temporal and spatial patterns of muscle activity during both locomotion and postural responses to balance perturbations. We hypothesize that subject‐specific and trial‐by‐trial differences in muscle activation can be parameterized and understood by a hierarchical and low‐dimensional framework that reflects the neural control of task‐level goals. In postural control, we demonstrate that temporal patterns of muscle activity may be governed by feedback control of task‐level variables that represent the overall goal‐directed motion of the body. These temporal patterns then recruit spatially‐fixed patterns of muscle activity called muscle synergies that produce the desired task‐level biomechanical functions that require multijoint coordination. Moreover, these principles apply more generally to movement, and in particular to locomotor tasks in both healthy and impaired individuals. Overall, understanding the goals and organization of the neural control of movement may provide useful reduced dimension parameter sets to address the degrees‐of‐freedom problem in musculoskeletal movement control. More importantly, however, neuromechanical analyses may lend insight and provide a framework for understanding subject‐specific and trial‐by‐trial differences in movement across both healthy and motor‐impaired populations. Copyright © 2012 John Wiley & Sons, Ltd.
Well‐being, Positivity and Mental Health: An Introduction to the Special Issue
Authors: MacLeod Andrew K. 
Published: May 2012

Enhancing well‐being, as opposed to reducing distress, has traditionally not been a focus for clinical practice. There are differences in views about the nature of well‐being, but enhancing well‐being in clinical settings is a straightforward goal whatever concept of well‐being is adopted. Reasons for adopting a well‐being enhancing, as well as a distress‐reducing, focus include the fact that many psychological problems do not fit the simple acute treatment model of disorder, that positive experience inhibits negative experience, and that people can benefit from therapists seeing them as more than the sum of their problems. In recent years, well‐being has been of increasing interest to researchers and clinicians, and enhancing well‐being is emerging as a potentially valuable element of effective clinical practice. Copyright © 2012 John Wiley & Sons, Ltd.Key Practitioner Message

Enhancing well-being has been relatively neglected as a therapeutic goal.
There are good reasons for seeing well‐being enhancement as a valuable goal for clinical practice, alongside the more traditional goal of distress‐reduction.
Useful work is emerging in this area from clinicians and clinical researchers.
Ethanol‐induced locomotor activity in adolescent rats and the relationship with ethanol‐induced conditioned place preference and conditioned taste aversion
Authors: Acevedo María Belén , Nizhnikov Michael E. , Spear Norman E. , Molina Juan C. , Pautassi Ricardo M. 
Published: May 2012

AbstractAdolescent rats exhibit ethanol‐induced locomotor activity (LMA), which is considered an index of ethanol's motivational properties likely to predict ethanol self‐administration, but few studies have reported or correlated ethanol‐induced LMA with conditioned place preference (CPP) by ethanol at this age. The present study assessed age‐related differences in ethanol's motor stimulating effects and analyzed the association between ethanol‐induced LMA and conventional measures of ethanol‐induced reinforcement. Experiment 1 compared ethanol‐induced LMA in adolescent and adult rats. Subsequent experiments analyzed ethanol‐induced CPP and conditioned taste aversion (CTA) in adolescent rats evaluated for ethanol‐induced LMA. Adolescent rats exhibit a robust LMA after high‐dose ethanol. Ethanol‐induced LMA was fairly similar across adolescents and adults. As expected, adolescents were sensitive to ethanol's aversive reinforcement, but they also exhibited CPP. These measures of ethanol reinforcement, however, were not related to ethanol‐induced LMA. Spontaneous LMA in an open field was, however, negatively associated with ethanol‐induced CTA. © 2012 Wiley Periodicals, Inc. Dev Psychobiol 55: 429–442, 2013
Synaptotagmin‐1 promotes the formation of axonal filopodia and branches along the developing axons of forebrain neurons
Authors: Greif Karen F. , Asabere Nana , Lutz Gordon J. , Gallo Gianluca 
Published: May 2012

AbstractSynaptotagmin‐1 (syt1) is a Ca2+‐binding protein that functions in regulation of synaptic vesicle exocytosis at the synapse. Syt1 is expressed in many types of neurons well before synaptogenesis begins both in vivo and in vitro. To determine if expression of syt1 has a functional role in neuronal development before synapse formation, we examined the effects of syt1 overexpression and knockdown on the growth and branching of the axons of cultured primary embryonic day 8 chicken forebrain neurons. In vivo these neurons express syt1, and most have not yet extended axons. We present evidence that syt1 plays a role in regulating axon branching, while not regulating overall axon length. To study the effects of overexpression of syt1, we used adenovirus‐mediated infection to introduce a syt1‐YFP construct, or control GFP construct, into neurons. Syt1 levels were reduced using RNA interference. Overexpression of syt1 increased the formation of axonal filopodia and branches. Conversely, knockdown of syt1 decreased the number of axonal filopodia and branches. Time‐lapse analysis of filopodial dynamics in syt1‐overexpressing cells demonstrated that elevation of syt1 levels increased both the frequency of filopodial initiation and their lifespan. Taken together these data indicate that syt1 regulates the formation of axonal filopodia and branches before engaging in its conventional functions at the synapse. © 2011 Wiley Periodicals, Inc. Develop Neurobiol, 2013
Highly Efficient Dehydrogenation of 5‐Benzyl‐3‐phenyl‐2‐thioxoimidazolidin‐4‐one: Microwave versus Flash Vacuum Pyrolysis Conditions
Authors: Pepino Ana J. , Peláez Walter J. , Moyano Elizabeth L. , Argüello Gustavo A. 
Published: May 2012

Abstract5‐Benzyl‐3‐phenyl‐2‐thioxoimidazolidin‐4‐one underwent thermal dehydrogenation to afford 5‐benzylidene‐2‐thioxoimidaxolidin‐4‐one under microwave and flash vacuum pyrolysis conditions. A high predominance of the Z‐isomer over the E‐isomer of the imidazolidinone product was achieved. By using DFT and NBO calculations, the mechanism of the dehydrogenation and the selectivity were also explored.
Solid‐Phase Synthesis of 5′‐O‐[N‐(Acyl)sulfamoyl]adenosine Derivatives
Authors: Redwan Itedale Namro , Ingemyr Hanna Jacobson , Ljungdahl Thomas , Lawson Christopher P. , Grøtli Morten 
Published: May 2012

AbstractThe solid‐phase synthesis of 5′‐O‐[N‐(acyl)sulfamoyl]adenosine derivatives is described. The use of a Rink amide polystyrene solid support together with an appropriately protected ribo‐purine starting material allowed for the development of a highly reliable and practical route for the solid‐phase synthesis of 5′‐O‐[N‐(acyl)sulfamoyl]adenosines. The developed procedure enables the efficient parallel synthesis of the target compounds in high yields. These compounds are non‐hydrolysable isosteres of acyl‐adenylates, which play an important role in a range of different metabolic pathways such as ribosomal and non‐ribosomal peptide synthesis, fatty acid oxidation or enzyme regulation; some adenylate‐forming enzymes are potential drug targets.
Planar‐Chiral Bis‐silanols and Diols as H‐Bonding Asymmetric Organocatalysts
Authors: Beemelmanns Christine , Husmann Ralph , Whelligan Daniel K. , Özçubukçu Salih , Bolm Carsten 
Published: May 2012

AbstractThe successful development of planar‐chiral bis‐silanols 3a–d and their application as asymmetric organocatalysts in hetero‐Diels–Alder (HDA) reactions is described. All precursors were easily prepared by addition of commerically available silyl electrophiles to a dilithiated [2.2]paracyclophane derivative followed by silane oxidations. The analogous bis‐carbinols 7a–c have been prepared by addition of suitable Grignard reagents to bis‐methoxycarbonyl derivative 6. Both racemic as well as enantiopure planar‐chiral bis‐silanols and bis‐carbinols were obtained in good yields. The catalytic activities of the bis‐silanols were analyzed by monitoring HDA reactions between Rawal's diene and aldehydes by in situ IR spectroscopy and comparing the resulting data with those obtained in catalyses with the corresponding bis‐carbinol derivatives. The results show for the first time that planar‐chiral bis‐silanols with hydrogen‐bonding capabilities can be applied as asymmetric organocatalysts leading to enantiomerically enriched products.
Depression subtypes and 5‐year risk of dementia and Alzheimer disease in patients aged 70 years
Authors: Vilalta‐Franch Joan , López‐Pousa Secundino , Llinàs‐Reglà Jordi , Calvó‐Perxas Laia , Merino‐Aguado Javier , Garre‐Olmo Josep 
Published: May 2012

ObjectiveThe objective of this study was to estimate several subtypes of depressive disorders as risk factors for dementia and Alzheimer disease (AD) specifically.MethodsThis is a population‐based cohort study using a sample of 451 non‐demented older people. Adjusted Cox proportional hazard models were calculated to determine the association of depression with dementia or AD development after 5 years. Baseline evaluation included the Cambridge Mental Disorders of the Elderly Examination (CAMDEX). Depressive disorders (major episode [MD] and minor depressive disorders [MDDIS]) were assessed following DSM‐IV criteria and further classified according to the age at onset (early versus late onset). In turn, all late‐onset depressions were grouped as with or without depression‐executive dysfunction syndrome (DEDS). Dementia (and dementia subtypes) diagnoses were made using the CAMDEX. When the patients were deceased, the Retrospective Collateral Dementia Interview was used.ResultsLate‐onset depressions (both MD and MDDIS) were associated with increased dementia (hazard ratio [HR] = 2.635; 95% CI = 1.153–6.023; and HR = 2.517; 95% CI = 1.200–5.280, respectively), and AD (HR = 6.262; 95% CI = 2.017–19.446; and HR = 4.208; 95% CI = 1.828–9.685, respectively) after adjustment by age, gender, marital status, education, cognitive impairment, executive function and stroke history. A second model revealed that only late‐onset depressions with DEDS increased the risk for both dementia (late‐onset MD with DEDS: HR = 6.262; 95% CI = 2.017–19.446; late‐onset MDDIS with DEDS: HR = 4.208; 95% CI = 1.828–9.685) and AD (late‐onset MD with DEDS: HR = 7.807; 95% CI = 1.567–38.894; late‐onset MDDIS with DEDS: HR = 6.099; 95% CI = 2.123–17.524).ConclusionsLate‐onset depressive episodes with DEDS are risk factors for dementia and AD development, regardless of the severity of the depression. Copyright © 2012 John Wiley & Sons, Ltd.
The diagnosis of depression and use of antidepressants in nursing home residents with and without dementia
Authors: van Asch Iris F. M. , Nuyen Jasper , Veerbeek Marjolein A. , Frijters Dinnus H. M. , Achterberg Wilco P. , Pot Anne Margriet 
Published: May 2012

ObjectiveTo compare the prevalence of diagnosed depressive disorders, depressive symptoms and use of antidepressant medication between nursing home residents with and without dementia.MethodsThis cross‐sectional study used Minimal Data Set of the Resident Assessment Instrument 2.1 data collected in seven nursing homes located in an urbanized region in the Netherlands. Trained nurse assistants recorded all medical diagnoses made by a medical specialist, including dementia and depressive disorder, and medication use. Depressive symptoms were measured with the Depression Rating Scale. Multivariate logistic regression analysis was used to compare data between residents with and without dementia.ResultsIncluded in the study were 1885 nursing home residents (aged 65 years or older), of which 837 had dementia. There was no significant difference in the prevalence of diagnosed depressive disorder between residents with (9.6%) and without dementia (9.8%). Residents with dementia (46.4%) had more depressive symptoms than residents without dementia (22.6%). Among those with depressive symptoms, residents with dementia had the same likelihood of being diagnosed with a depressive disorder as residents without dementia. Among residents with a diagnosed depressive disorder, antidepressant use did not differ significantly between residents with dementia (58.8%) and without dementia (57.3%). The same holds true for residents with depressive symptoms, where antidepressant use was 25.3% in residents with dementia and 24.6% in residents without dementia.ConclusionsRegarding the prevalence rates of diagnosed depressive disorder and antidepressant use found in this study, our findings demonstrate that there is room for improvement not only for the detection of depression but also with regard to its treatment. Copyright © 2012 John Wiley & Sons, Ltd.
Synthesis and Anti‐HIV Activity of Triazolo‐Fused 3′,5′‐Cyclic Nucleoside Analogues Derived from an Intramolecular Huisgen 1,3‐Dipolar Cycloaddition
Authors: Sun Jingbo , Liu Xinyu , Li Hongming , Duan Ronghui , Wu Jinchang 
Published: May 2012

AbstractTriazolo‐fused 3′,5′‐cyclic nucleoside analogues were synthesized by an intramolecular 1,3‐dipolar cycloaddition of nucleoside‐derived azido‐alkynes in a regio‐ and stereospecific manner. The thymine nucleoside base in these target compounds was transformed successfully into the corresponding 5‐methylcytosine component. The synthesized compounds were examined in a MAGI assay for exploring the anti‐HIV activity and in a H9 T lymphocytes assay for measuring the cell toxicity.
Chemical Composition of the Volatile Oil from the Roots of Selinum tenuifoliumWall.
Authors: Chauhan Rajendra S. , Nautiyal Mohan C. , Tava Aldo , Mella Mariella 
Published: May 2012

AbstractThe essential oil from the underground parts of Selinum tenuifolium Wall. (Apiaceae) was extracted by hydrodistillation using a Clevenger‐type apparatus, and analyzed by GC/FID and GC/MS. Nine constituents, representing 97.7% of the total oil, were identified, five of which belong to the class of polyacetylenes. The structures of the compounds 1–5 were elucidated by using IR, MS, and 1H‐ and 13C‐NMR data after purification by column chromatography. The major constituent detected was nona‐3,5‐diyne (1; 85.6% of the total volatiles), followed by nona‐3,5‐diyn‐2‐one (2), nona‐4,6‐diyn‐3‐one (3), nona‐3,5‐diyn‐2‐ol (4), and nona‐4,6‐diyn‐3‐ol (5), accounting for 3.0, 2.5, 2.2, and 3.1% of the total volatiles, respectively. The latter four polyacetylenes, 2–5, were never reported in plants so far, and, therefore should be regarded as novel compounds.