bluuebunny/crossref_metadata_2025 huggingface dataset:
Nucleolar Dominance
Authors: Pikaard Craig S
Published: January 2014

Nucleolar dominance is an epigenetic phenomenon that describes the formation of nucleoli, the sites of ribosome synthesis, at specific loci of chromosomes inherited from only one progenitor of a genetic hybrid. These loci, known as nucleolus organiser regions (NORs), consist of
ribosomal RNA (rRNA)
genes that are repeated in hundreds of copies. The molecular basis for nucleolar dominance is the silencing of rRNA genes at some NORs, but not others, a manifestation of a dosage control system that regulates the number of active rRNA genes depending on the cellular demand for ribosomes and protein synthesis. rRNA gene silencing involves cytosine methylation, histone post‐translational modifications and noncoding RNAs, but the precise mechanisms by which specific sets of rRNA genes are chosen for silencing are unclear.

Key Concepts:

In genetic hybrids, genes inherited from the different parents, or progenitors, can be differentially expressed.

Nucleolar dominance in genetic hybrids involves the selective silencing of ribosomal RNA gene loci that span millions of base pairs on eukaryotic chromosomes.

Ribosomal RNA gene silencing involves epigenetic modifications of chromosomal chromatin, including cytosine methylation and repressive histone post‐translational modifications.

Nucleolar dominance is not a regulatory phenomenon unique to hybrids but a manifestation of a dosage control system that operates in all eukaryotes to control the number of active rRNA genes.

Nucleolar dominance may result from inactivation of entire nucleolus organiser regions (NORs) rather than silencing decisions made one rRNA gene at a time.
Sensory Rhodopsins
Authors: Tsukamoto Takashi , Sudo Yuki
Published: January 2014

Motile organisms sense and respond to extracellular stimuli to survive in the various environments in which they live, by changing their movement to migrate towards more favourable habitats or to avoid more harmful habitats. Light is one of the most important signals that provide critical information to biological systems and therefore many organisms utilise light not only as an energy source but also as a signal. Sensory rhodopsin is a photochemically reactive membrane‐embedded protein consisting of seven transmembrane alpha‐helices, which binds the chromophore retinal (vitamin A aldehyde). Sensory rhodopsin is broadly distributed through all three biological kingdoms, eukarya, bacteria and archaea, indicating the biological significance of their light signal conversion.

Key Concepts:

Many organisms can sense and respond to light stimuli.

Photoactive retinal proteins play important roles in light signal transduction in various organisms.

The
trans
–
cis
photoisomerisation of the retinal chromophore triggers the cyclic photoreaction, leading to structural changes of the protein moiety.

Photoactivated sensory rhodopsins regulate the activity of the cognate transducer molecules, which control the motility and morphology of the organisms.

Sensory rhodopsins have become a focus of interest in part because of their importance to the general understanding of light signal conversion and because of potential application for the novel technology named ‘optogenetics’, in which retinal proteins are utilised to control biological activity with high temporal and spatial resolutions.
Young, John Zachary
Authors: De Sio Fabio
Published: January 2014

John Zachary Young (1907–1997) was a British zoologist and anatomist, pioneer of the experimental study of the cellular bases of learning and memory and of British brain science. He discovered the giant axon of the squid, which was to become the most successful experimental model for the study of the nerve impulse mechanism and of the physicochemical properties of neuron membranes. His work on learning and memory in

Octopus vulgaris

represents one of the earliest attempts of employing simple experimental systems in the study of complex mental functions.
Molecular Genetics of the Neuronal Ceroid Lipofuscinoses
Authors: Mole Sara E
Published: January 2014

The neuronal ceroid lipofuscinoses (NCLs) are a group of clinically and genetically heterogenenous neurodegenerative disorders characterised by the accumulation of autofluorescent storage material in many cell types. Most display autosomal recessive inheritance. More than 400 mutations have been described in 13 genes:
PPT1
,
TPP1
,
CLN3
,
CLN5
,
CLN6
,
MFSD8
,
CLN8
,
CTSD, GRN, ATP13A2, KCTD7, CTSF
and
DNAJC5
, and none show obvious mutation hotspots. The functions of most of these genes remain elusive. The majority of the genetic defects identified are private, but there are geographically widespread or localised common founder mutations. The NCLs exemplify both phenotypic convergence and divergence, and there can be very wide disease severity caused by mutations in the same gene. Some recently identified mutations are in genes that are associated with other diseases. The recent expansion of knowledge in the genetic understanding of the NCLs is leading to improved diagnostic approaches, and the recent adoption of a new nomenclature.

Key Concepts:

More than 400 mutations are known across 13 genes causing disease in families diagnosed with NCL.

Most NCLs are autosomal recessive.

NCLs are a heterogenous group of disorders with common features of progressive degeneration of the brain, and often the retina, and intracellular storage of material similar to ceroid and lipofuscin.

NCLs are monogenic disorders.

One type of NCL is autosomal dominant.

There remain families diagnosed with NCL in which the genetic cause is not yet determined.
Hennig, Emil Hans Willi (The Father of Cladism)
Authors: Minelli Alessandro
Published: January 2014

Emil Hans Willi Hennig was a German systematist and entomologist. As a specialist in Diptera, he published a fundamental treatise on dipteran larvae and taxonomic monographs on several families. Hennig, however, is best known for his theoretical and methodological contributions to biological systematics. Indeed, he is considered the founder of phylogenetic systematics, or cladistics. Hennig articulated a method by which the evolutionary relationships of organisms (phylogeny) can be reconstructed and this reconstruction is subsequently turned into a hierarchical classification. This method contrasted with the mainstream approach to biological systematics adopted till the 1960s, but eventually succeeded to replace it, although in a modified version in respect to Hennig's original outline. Hennig's phylogenetic systematics has heavily impacted other biological disciplines, especially biogeography.
Behavioural Genetics in the Postgenomics Era
Authors: Charney Evan
Published: January 2014

There is growing evidence that the complexity of higher organisms does not correlate with the ‘complexity’ of the genome (the human genome contains fewer protein coding genes than corn, and many genes are preserved across species). Rather, complexity is associated with the complexity of the pathways and processes whereby the cell utilises the
deoxyribonucleic acid
molecule, and much else, in the process of phenotype formation. These processes include the activity of the epigenome, noncoding
ribonucleic acids
, alternative splicing and post‐translational modifications. Not accidentally, all of these processes appear to be of particular importance for the human brain, the most complex organ in nature. Because these processes can be highly environmentally reactive, they are a key to understanding behavioural plasticity and highlight the importance of the developmental process in explaining behavioural outcomes.

Key Concepts:

Humans possess fewer protein‐coding genes than maize (i.e. corn) and about the same number as a nematode.

There is now strong evidence that the complexity of higher organisms correlates with the relative amount of noncoding RNA rather than the number of protein‐coding genes.

Epigenetic processes are key to every aspect of human development from cellular differentiation to learning and memory.

Epigenetic mechanisms provide an explanation on the molecular level as to how the pre‐ and postnatal environments can impact offspring's behaviour.

Alternative splicing is one mechanism that enables the human body to create over 100 000 proteins with a genome that contains only 20 000 protein coding genes.

Each gene in the human genome is not ‘encoded’ for the production of a single protein.

Isoforms can have very different and even antithetical physiological effects.

Alternative splicing patterns are modulated in response to external stimuli, such as depolarisation of neurons, activation of signal transduction cascades and stress.

Post‐translational modification supplements alternative splicing as a means of creating protein diversity with a limited number of protein coding genes.

DNA is not the sole biological agent of inheritance.
Using Event Centrality to Predict Depressive Symptoms after a Romantic Conflict: A Prospective Design
Authors: Boals Adriel
Published: January 2014

Using cross‐sectional analyses, event centrality has been shown to be related to a number of poor psychological outcomes, including depressive symptoms and posttraumatic stress disorder symptoms. In the current study, we examined the ability of event centrality of a recent conflict in or breakup of a romantic relationship to prospectively predict depressive symptoms. Replicating previous findings, ratings of event centrality to a recent romantic conflict or breakup were significantly associated with depressive symptoms and posttraumatic stress disorder symptoms at Time 1. These relationships remained significant after controlling for closure and perceived insight. In addition, Time 1 event centrality prospectively predicted Time 2 depressive symptoms, particularly for participants who were split from their romantic partners at Time 2. This prediction remained significant after controlling for Time 1 depressive symptoms. The results of the study suggest that levels of event centrality for romantic conflicts prospectively predict subsequent mental health outcomes. Copyright © 2014 John Wiley & Sons, Ltd.
Examining the Life Script of African‐Americans: A Test of the Cultural Life Script
Authors: Coleman Justin T.
Published: January 2014

Life scripts are expectations of the timings of important events in the normative life and are considered to represent an idealized lifecourse. However, whether they always represent an idealized lifecourse has not yet been tested in groups that may experience an increased prevalence of negative emotional events, such as historically unfairly treated minorities. In the present study, 255 African‐American adults completed a test of the life script. To ascertain the existence of a unique, African‐American life script, half nominated events likely to happen in the prospective life of a typical infant and half nominated those events for a prototypical infant of their race. Whereas some novel events specifically relevant to African‐Americans were mentioned in the current study, and a larger proportion of infrequently mentioned events were present compared with previous studies, overall, the findings support the expectations of the life script, as described by Rubin and Berntsen. Copyright © 2014 John Wiley & Sons, Ltd.
Active smoking status in chronic rhinosinusitis is associated with higher serum markers of inflammation and lower serum eosinophilia
Authors: Berania Ilyes , Endam Leandra Mfuna , Filali‐Mouhim Abdelali , Boisvert Pierre , Boulet Louis‐Philippe , Bossé Yohan , Desrosiers Martin
Published: January 2014

Background

Smoking negatively affects postoperative evolution in patients with chronic rhinosinusitis (CRS); however, the mechanism remains incompletely described. In the lung, smoking increases expression of proinflammatory genes and is associated with an elevation of inflammatory serum markers. Our objective is to determine the impact of smoking on these biomarkers in CRS.

Methods

Two existing populations of patients previously phenotyped for genetic association studies (206 patients with refractory CRS and 408 patients with CRS and nasal polyposis) were stratified according to self‐reported smoking status and available serum biomarkers (complete blood count [CBC], total immunoglobulin E [IgE]). Asthma and bacterial cultures were evaluated.

Results

Active smoking was low in both groups (genetics of chronic rhinosinusitis 1 [GCRS1]: 11.2%; genetics of chronic rhinosinusitis 2 [GCRS2]: 9.4%). Total white blood cell (WBC) count was significantly higher in active smokers than in those who had never smoked and ex‐smokers. Serum eosinophilia and prevalence of self‐reported asthma was lower in active smokers than never‐smokers. In the GCRS2 population, endoscopically‐collected cultures trended toward a lower recovery rate of Staphylococcus aureus in smokers (p = 0.07). Never‐smokers and ex‐smokers had similar levels of WBCs and eosinophils.

Conclusion

Our study reveals that active tobacco smoking is associated with increases in markers of systemic inflammation in patients with CRS. The proinflammatory effect of smoking seems not only to act locally on sinus mucosa as previously described, but may also influence levels of inflammatory biomarkers systemically, suggesting that smoking‐induced changes have profound implications for health. Nevertheless, these changes may be potentially reversible; thus smoking cessation in CRS patients is strongly advised, and may have an impact on response of CRS to therapy.
Preparation of a liquid benzoxazine based on cardanol and the thermal stability of its graphene oxide composites
Authors: Xu Guo‐mei , Shi Tiejun , Liu Jianhua , Wang Qidong
Published: January 2014

A novel liquid benzoxazine was synthesized by Mannich reaction of cardanol, paraformaldehyde, and allylamine. The benzoxazine structure was characterized by 1H‐NMR and FTIR. The liquid benzoxazine could dissolve easily in many solvents. The curing behavior of the benzoxazine was characterized by differential scanning calorimetry (DSC) and its curing temperature was about 233°C. A benzoxazine‐functional silane coupling agent (BFSca) was synthesized with paraformaldehyde, phenolphthalein, and aminopropyltriethoxysilane. Graphene oxide (GO) was also made via improved Hummer's method. Then benzoxazine/GO composites were prepared using BFSca by solution blending and the curing behaviors of the composites were also characterized by IR, DSC, and thermogravimetric analysis. The minimum curing temperature and the highest 5% weight loss temperature for the composites was, respectively, 185 and 399.8°C. The SEM images of benzoxazine/GO composites demonstrated that BFSca had improved the dispersion of GO in the benzoxazine and also enhanced the thermal decomposition temperature of the composites. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40353.
Do blog citations correlate with a higher number of future citations? Research blogs as a potential source for alternative metrics
Authors: Shema Hadas , Bar‐Ilan Judit , Thelwall Mike
Published: January 2014

Journal‐based citations are an important source of data for impact indices. However, the impact of journal articles extends beyond formal scholarly discourse. Measuring online scholarly impact calls for new indices, complementary to the older ones. This article examines a possible alternative metric source, blog posts aggregated at ResearchBlogging.org, which discuss peer‐reviewed articles and provide full bibliographic references. Articles reviewed in these blogs therefore receive “blog citations.” We hypothesized that articles receiving blog citations close to their publication time receive more journal citations later than the articles in the same journal published in the same year that did not receive such blog citations. Statistically significant evidence for articles published in 2009 and 2010 support this hypothesis for seven of 12 journals (58%) in 2009 and 13 of 19 journals (68%) in 2010. We suggest, based on these results, that blog citations can be used as an alternative metric source.
Acceleration Strategies in the New Developmental Education Landscape
Authors: Venezia Andrea , Hughes Katherine L.
Published: January 2014

The college completion agenda, in concert with recent research, has brought scrutiny to the shortcomings of community college remedial programs. Remedial, or developmental, education has come to be seen as a hindrance to student progress and attainment rather than as a support. In this chapter, the authors describe new approaches to help students prepare for and move into college‐level courses more quickly, while cautioning that we do not know yet whether many of them are effective.
Exploring bacterial phenotypic diversity using factorial design and FTIR multivariate fingerprinting
Authors: Wehrli Patrick M. , Lindberg Erika , Svensson Olof , Sparén Anders , Josefson Mats , Dunstan R. Hugh , Wold Agnes E. , Gottfries Johan
Published: January 2014

Transmission Fourier transform infrared (FTIR) spectra were obtained from cultures of Staphylococcus aureus that were grown under sets of various environmental conditions enclosing ranges of potential conditions in wound sites. The primary aim of this study was to determine whether bacterial phenotypic diversity could be characterized by FTIR spectroscopy analyses of cultures of S. aureus grown under variable sets of environmental conditions. Designing experiments with full factorial design has shown to be a powerful way to explore an expectedly large array of phenotypic diversity of S. aureus. Various combinations of environmental conditions caused the bacteria to adapt their phenotype, which was assessed via FTIR spectral fingerprinting. Transmission FTIR spectroscopy was found to be superior to other vibrational spectroscopy techniques for this purpose because of its high sensitivity, reproducibility, and rapidity of analysis. The sample preparation presented was fundamental for reproducible results. Different spectral preprocessing methods were compared in combination with scaling methods to obtain distinguishable phenotypes in principal component analysis (PCA) models. Spectral preprocessing with combined filters, including standard normal variate transformation, Savitzky–Golay smoothing, and use of the first derivative in a PCA model with unit variance scaling, gave the most optimal clustering for the data in this study. Spectra obtained from each treatment group were found to have a unique FTIR profile with good reproducibility, and thus PCA resulted in full separation between all groups on three principal components. In conclusion, transmission FTIR spectroscopy in conjunction with design of experiment, and multivariate analysis are powerful tools to investigate phenotypic diversity of S. aureus. Copyright © 2014 John Wiley & Sons, Ltd.
Palladium‐Catalyzed Coupling Reaction of Perfluoroarenes with Diarylzinc Compounds
Authors: Ohashi Masato , Doi Ryohei , Ogoshi Sensuke
Published: January 2014

This report describes the first Pd0‐catalyzed cross‐coupling of hexafluorobenzene (C6F6) with diarylzinc compounds to give a variety of pentafluorophenyl arenes. This reaction could be applied to other perfluoroarenes, such as octafluorotoluene, pentafluoropyridine, and perfluoronaphthalene, to give the corresponding polyfluorinated coupling products. The optimal ligand in this catalytic reaction was PCy3, and lithium iodide was indispensable as an additive for the coupling reaction. One of the roles of lithium iodide in this catalytic reaction was to promote the oxidative addition of one CF bond of C6F6 to palladium. Stoichiometric reactions revealed that an expected oxidative‐addition product, trans‐[Pd(C6F5)I(PCy3)2], generated from the reaction of [Pd(PCy3)2] with C6F6 in the presence of lithium iodide, was not involved in the catalytic cycle. Instead, a transient three‐coordinate, monophosphine‐ligated species, [Pd(C6F5)I(PCy3)], emerged as a potential intermediate in the catalytic cycle. Therefore, we isolated a novel PdII complex, [Pd(C6F5)I(PCy3)(py)], in which pyridine (py) acted as a labile ligand to generate the transient species. In fact, in the presence of lithium iodide, this PdII complex was found to react smoothly with diphenylzinc to give the desired pentafluorophenyl benzene, whereas the same reaction conducted in the absence of lithium iodide resulted in a decreased yield of pentafluorophenyl benzene, which indicated that the other role of lithium iodide was to enhance the reactivity of the organozinc species during the transmetalation step.
Controllable Blinking‐to‐Nonblinking Behavior of Aqueous CdTeS Alloyed Quantum Dots
Authors: Dong Chaoqing , Liu Heng , Zhang Aidi , Ren Jicun
Published: January 2014

Semiconductor quantum dots (QDs) are very important optical nanomaterials with a wide range of potential applications. However, the blinking of single QDs is an intrinsic drawback for some biological and photoelectric applications based on single‐dot emission. In this work, we systematically investigated the effects of certain synthetic conditions on the blinking behavior of aqueous CdTeS alloyed QDs, and observed that blinking behaviors of QDs were able to be controlled by the structure and concentration of the thiol compounds that were used as surface ligands. In optimal conditions, completely nonblinking QDs were prepared using certain thiol ligands as stabilizers in aqueous phase. The suppressed blinking mechanism was mainly attributed to elimination of QDs surface traps by coordination of thiol ligands with vacant Cd atoms, formation of appropriate CdS coating on QDs, and controlling the growth dynamics of QDs. Nonblinking QDs show high quantum yield, small size, and good solubility, and will be applied to some fields that were previously limited by blinking of traditional QDs.
Hückel and Möbius Expanded para‐Benziporphyrins: Synthesis and Aromaticity Switching
Authors: Szyszko Bartosz , Sprutta Natasza , Chwalisz Paulina , Stępień Marcin , Latos‐Grażyński Lechosław
Published: January 2014

The four expanded p‐benziporphyrins A,C‐di‐p‐benzi[24]pentaphyrin(1.1.1.1.1), N‐fused A‐p‐benzi[24]pentaphyrin, A,D‐di‐p‐benzi[28]hexaphyrin(1.1.1.1.1.1), and A,C‐di‐p‐benzi[28]hexaphyrin(1.1.1.1.1.1) were obtained in three‐component Lindsey‐type macrocyclizations. These compounds were explored as macrocyclic ligands and as potential aromaticity switches. A BODIPY‐like difluoroboron complex was obtained from the A,C‐di‐p‐benzi[24]pentaphyrin, whereas A,C‐di‐p‐benzi[28]hexaphyrin yielded a Möbius‐aromatic PdII complex containing fused pyrrole and phenylene subunits. Conformational behavior, tautomerism, and acid‐base chemistry of the new macrocycles were characterized by means of NMR spectroscopy and DFT calculations. Free base N‐fused A‐p‐benzi[24]pentaphyrin showed temperature‐dependent Hückel–Möbius aromaticity switching, whereas the A,C‐di‐p‐benzi[28]hexaphyrin formed a Möbius‐aromatic dication.
Total Synthesis and Structure Revision of Didemnaketal B
Authors: Fuwa Haruhiko , Muto Takashi , Sekine Kumiko , Sasaki Makoto
Published: January 2014

Didemnaketal B, a structurally complex spiroacetal that exhibits potent HIV‐1 protease inhibitory activity, was originally discovered by Faulkner and his colleagues from the ascidian Didemnum sp. collected at Palau. Its absolute configuration was proposed on the basis of degradation/derivatization experiments of the authentic sample. However, our total synthesis of the proposed structure of didemnaketal B questioned the stereochemical assignment made by Faulkner et al. Here we describe in detail our first total synthesis of the proposed structure 2 of didemnaketal B, which features 1) a convergent synthesis of the C7–C21 spiroacetal domain by means of a strategy exploiting Suzuki–Miyaura coupling, 2) an Evans syn‐aldol reaction and a vinylogous Mukaiyama aldol reaction for the assembly of the C1–C7 acyclic domain, and 3) a Nozaki–Hiyama–Kishi reaction for the construction of the C21–C28 side chain domain. The NMR spectroscopic discrepancies observed between synthetic 2 and the authentic sample as well as careful inspection of the Faulkner’s stereochemical assignment led us to postulate that the absolute configuration of the C10–C20 domain of 2 has been erroneously assigned. Accordingly, the total synthesis of the revised structure 65 was achieved to show that the NMR spectroscopic properties of synthetic 65 were in good agreement with those of the authentic sample. Furthermore, application of the phenylglycine methyl ester (PGME) method to the C7–C21 spiroacetal domain enabled us to establish the absolute configuration of didemnaketal B.
Origin of the dopaminergic innervation of adult neurogenic areas
Authors: Höglinger Günter U. , Arias‐Carrión Oscar , Ipach Bastian , Oertel Wolfgang H.
Published: January 2014

Adult neurogenesis, a specific form of brain plasticity in mammals occurring in the subventricular zone (SVZ) and the subgranular zone (SGZ), is subject to complex regulations. Dopamine has been identified as a regulatory factor in rodents, nonhuman primates, and humans. We therefore studied in detail the origin of the dopaminergic innervation to the SVZ and SGZ in rodents. Postmortem anterograde and retrograde tracing combined with immunofluorescence procedures indicate a topographic organization of midbrain dopaminergic projections toward the SVZ. The substantia nigra pars compacta (SNc) projects specifically into the rostral migratory stream, the anterior SVZ, and the dorsal part of the medial and posterior SVZ. In contrast, the ventral tegmental area (VTA) innervates specifically the ventral part of the medial and posterior SVZ. Both VTA and SNc dopaminergic neurons innervate homogenously the lower and upper blade of the dentate gyrus, including the SGZ. Based on these findings, we suggest that the neurogenic areas are in a position to be differentially affected by region‐specific changes in dopamine signaling, the functional implication of which must be further elucidated. J. Comp. Neurol. 522:2336–2348, 2014. © 2014 Wiley Periodicals, Inc.
Axotomy‐induced target disconnection promotes an additional death mechanism involved in motoneuron degeneration in amyotrophic lateral sclerosis transgenic mice
Authors: Haulcomb Melissa M. , Mesnard Nichole A. , Batka Richard J. , Alexander Thomas D. , Sanders Virginia M. , Jones Kathryn J.
Published: January 2014

The target disconnection theory of amyotrophic lateral sclerosis (ALS) pathogenesis suggests that disease onset is initiated by a peripheral pathological event resulting in neuromuscular junction loss and motoneuron (MN) degeneration. Presymptomatic mSOD1G93A mouse facial MN (FMN) are more susceptible to axotomy‐induced cell death than wild‐type (WT) FMN, which suggests additional CNS pathology. We have previously determined that the mSOD1 molecular response to facial nerve axotomy is phenotypically regenerative and indistinguishable from WT, whereas the surrounding microenvironment shows significant dysregulation in the mSOD1 facial nucleus. To elucidate the mechanisms underlying the enhanced mSOD1 FMN loss after axotomy, we superimposed the facial nerve axotomy model on presymptomatic mSOD1 mice and investigated gene expression for death receptor pathways after target disconnection by axotomy vs. disease progression. We determined that the TNFR1 death receptor pathway is involved in axotomy‐induced FMN death in WT and is partially responsible for the mSOD1 FMN death. In contrast, an inherent mSOD1 CNS pathology resulted in a suppressed glial reaction and an upregulation in the Fas death pathway after target disconnection. We propose that the dysregulated mSOD1 glia fail to provide support the injured MN, leading to Fas‐induced FMN death. Finally, we demonstrate that, during disease progression, the mSOD1 facial nucleus displays target disconnection‐induced gene expression changes that mirror those induced by axotomy. This validates the use of axotomy as an investigative tool in understanding the role of peripheral target disconnection in the pathogenesis of ALS. J. Comp. Neurol. 522:2349–2376, 2014. © 2014 Wiley Periodicals, Inc.
Evaluation of the effect of fluconazole and ketoconazole on the pharmacokinetics of tofacitinib in healthy adult subjects
Authors: Gupta Pankaj , Chow Vincent , Wang Ronnie , Kaplan Irina , Chan Gary , Alvey Christine , Ni Grace , Ndongo Marie‐Noella , LaBadie Robert R. , Krishnaswami Sriram
Published: January 2014

Tofacitinib is a novel, oral JAK inhibitor that is being investigated as a targeted immunomodulator. Tofacitinib is predominantly metabolized by cytochrome P450 (CYP) 3A4 and to a lesser extent by CYP2C19. Two Phase 1, randomized, open‐label, single sequence studies in 24 healthy subjects (12 per study) characterized the effects of fluconazole (moderate CYP3A4/potent CYP2C19 inhibitor) and ketoconazole (potent CYP3A4 inhibitor) on tofacitinib pharmacokinetics. In the fluconazole study, subjects received a single tofacitinib 30 mg dose. After 72 hours, subjects received fluconazole 400 mg, followed by 200 mg once daily (QD; days 2–7) plus tofacitinib 30 mg on day 5. In the ketoconazole study, a single tofacitinib 10 mg dose was administered. After 24 hours, subjects received ketoconazole (400 mg QD; days 1–3) plus tofacitinib 10 mg on day 3. Treatment comparisons were made using mixed‐effect models. Tofacitinib area under the curve and maximal plasma concentration increased by 79% and 27%, respectively, with fluconazole co‐administration and by 103% and 16%, respectively, with ketoconazole co‐administration. Tofacitinib half‐life increased by approximately 1 hour during co‐administration with fluconazole or ketoconazole. Co‐administration of moderate to potent CYP3A4 inhibitors is likely to increase the systemic exposure of tofacitinib and thus may warrant dosage adjustments or restrictions.
Comparison study of plasma coenzyme Q10 levels in healthy subjects supplemented with ubiquinol versus ubiquinone
Authors: Langsjoen Peter H. , Langsjoen Alena M.
Published: January 2014

The bioavailability of the reduced form of coenzyme Q10 (ubiquinol) was compared to oxidized coenzyme Q10 (ubiquinone) with identical soft gel capsule excipients by measuring steady state plasma coenzyme Q10 (CoQ10) levels in 12 healthy volunteers. After baseline levels of ubiquinol, ubiquinone, total CoQ10, α‐tocopherol, and total cholesterol were obtained, follow‐up lab work was performed after 4 weeks of 200 mg/day of ubiquinone, after 4 weeks washout, and after 4 weeks of 200 mg/day of ubiquinol. Plasma total CoQ10 increased from 0.9 to 2.5 µg/mL (P < 0.001) after 4 weeks of ubiquinone and increased from 0.9 to 4.3 µg/mL (P < 0.001) after 4 weeks of ubiquinol. Total CoQ10/cholesterol ratio increased from 0.2 to 0.7 µmol/mmol after 4 weeks of ubiquinone and increased from 0.2 to 1.2 µmol/mmol after 4 weeks of ubiquinol. Both the increase in plasma CoQ10 and the increase in CoQ10/cholesterol ratio were significantly better after ubiquinol (P < 0.005 and P < 0.001, respectively) than after ubiquinone indicating superior bioavailability. Plasma ubiquinol/total CoQ10 ratio increased from baseline during ubiquinol supplementation (P < 0.005) and remained unchanged after ubiquinone supplementation. No side effects were noted in this study.
Magnesium chloride, dioxane and water‐ternary phase diagram and powder XRD data
Authors: Jin Miaomiao , Sun Yuzhu , Li Ping , Yu Jianguo , Ulrich Joachim
Published: January 2014

The separation and purification of magnesium chloride from brines, and concentration of other valuable elements from those brines are important for industrial use. Basic data are needed to design industrial processes. Therefore, the phase equilibrium of the ternary system magnesium chloride–dioxane‐water (MgCl2‐C4H8O2‐H2O) at five different temperatures (278.15K, 288.15K, 298.15K, 308.15K and 318.15K) is studied systematically by an isothermal solution saturation method. The achieved data are presented and compared to literature, if existing. The XRPD pattern of MgCl2·6H2O·C4H8O2 and MgCl2·2C4H8O2 are also obtained and presented.
Exploring Communities of Facilitators: Orientations toward Restorative Justice
Authors: Paul Gregory D. , Borton Ian M.
Published: January 2014

Although current research on restorative justice largely has overlooked facilitators' roles in victim‐offender conferences, research on third parties suggests that they are more than neutral process guides. The study examined in this article involved an exploration of restorative justice facilitators' backgrounds, perceived responsibilities, and ideal outcomes to arrive at a theory of facilitated justice rooted in facilitator orientation and conference context. Based on individual interviews with facilitators from two restorative justice organizations, the results of this study suggest the presence of four orientations rooted in participant orientation and outcome orientation. These orientations lead to the development of a theory of facilitated justice.
What Moves Us: Dance and Neuroscience Implications for Conflict Approaches
Authors: Beausoleil Emily , LeBaron Michelle
Published: January 2014

Despite its worldwide use in grassroots conflict approaches, dance, and the body more generally, remain largely unaddressed within conflict theory and conventional practice. We argue that the body is an essential focus of conflict theory and a ready resource for conflict practice by exploring the implications of compelling discoveries within the field of neuroscience. Examining the embodied dimensions of cognition, emotion, and memory, the physical roots of empathy, and the relationship of right‐ and left‐brain processes to conflict, we outline neuroscientific underpinnings of dance‐based approaches to conflict and the range of creative tools that arises from its use.
The protein phosphatase 2A B56γ regulatory subunit is required for heart development
Authors: Varadkar Prajakta , Despres Daryl , Kraman Matthew , Lozier Julie , Phadke Aditi , Nagaraju Kanneboyina , Mccright Brent
Published: January 2014

Background: Protein Phosphatase 2A (PP2A) function is controlled by regulatory subunits that modulate the activity of the catalytic subunit and direct the PP2A complex to specific intracellular locations. To study PP2A's role in signal transduction pathways that control growth and differentiation in vivo, a transgenic mouse lacking the B56γ regulatory subunit of PP2A was made. Results: Lack of PP2A activity specific to the PP2A‐B56γ holoenzyme, resulted in the formation of an incomplete ventricular septum and a decrease in the number of ventricular cardiomyocytes. During cardiac development, B56γ is expressed in the nucleus of α‐actinin‐positive cardiomyocytes that contain Z‐bands. The pattern of B56γ expression correlated with the cardiomyocyte apoptosis we observed in B56γ‐deficient mice during mid to late gestation. In addition to the cardiac phenotypes, mice lacking B56γ have a decrease in locomotive coordination and gripping strength, indicating that B56γ has a role in controlling PP2A activity required for efficient neuromuscular function. Conclusions: PP2A‐B56γ activity is required for efficient cardiomyocyte maturation and survival. The PP2A B56γ regulatory subunit controls PP2A substrate specificity in vivo in a manner that cannot be fully compensated for by other B56 subunits. Developmental Dynamics 243:778–790, 2014. © 2014 Wiley Periodicals, Inc.
Fracture risk and areal bone mineral density in adolescent females with anorexia nervosa
Authors: Faje Alexander T. , Fazeli Pouneh K. , Miller Karen K. , Katzman Debra K. , Ebrahimi Seda , Lee Hang , Mendes Nara , Snelgrove Deirdre , Meenaghan Erinne , Misra Madhusmita , Klibanski Anne
Published: January 2014

Objective

To (i) compare fracture prevalence in adolescent females with anorexia nervosa (AN) versus normal‐weight controls and (ii) examine whether reductions in areal bone mineral density (aBMD) predict fracture risk in females with AN.

Method

Four‐hundred eighteen females (310 with active AN and 108 normal‐weight controls) 12‐ to 22‐years‐old were studied cross‐sectionally. Lifetime fracture history was recorded by a physician during participant interviews. Body composition and aBMD measurements of the whole body, whole body less head, lumbar spine, and hip were assessed by dual‐energy X‐ray absorptiometry, and bone mineral apparent density (BMAD) was calculated for the lumbar spine.

Results

Participants with AN and normal‐weight controls did not differ for chronological age, sexual maturity, or height. The lifetime prevalence of prior fracture was 59.8% higher in those with AN as compared to controls (31.0% vs. 19.4%, p = 0.02), and the fracture incidence rate peaked in our cohort after the diagnosis of AN. Lower aBMD and lumbar BMAD were not associated with a higher prevalence of fracture in the AN or control group on univariate or multivariate analyses. Compared to controls, fracture prevalence was significantly higher in the subgroup of girls with AN who had normal aBMD or only modest reductions of aBMD (Z‐scores > −1 or −1.5).

Discussion

This is the first study to show that the risk of fracture during childhood and adolescence is significantly higher in patients with AN than in normal‐weight controls. Fracture prevalence is increased in this cohort of participants with AN even without significant reductions in aBMD. © 2014 Wiley Periodicals, Inc. (Int J Eat Disord 2014; 47:458–466)
Structure Evolution and Up‐Conversion Studies of ZnX2O4:Er3+/Yb3+(X = Al3+, Ga3+, In3+) Nanoparticles
Authors: Wiglusz R. J. , Watras A. , Malecka M. , Deren P. J. , Pazik R.
Published: January 2014

A series of ZnX2O4:Er3+/Yb3+(X = Al3+, Ga3+, In3+) nanoparticles were obtained by using a modified Pechini technique. The crystal structure, morphology, and chemical composition of the engineered compounds were characterized in detail by means of X‐ray diffraction, Micro‐Raman spectroscopy, transmission electron microscopy (TEM) and selected area electron diffraction, and energy‐dispersive X‐ray spectroscopy. Particle sizes were estimated by using theoretical calculations (Scherrer and Rietveld methods) as well as experimental techniques [TEM and dynamic light scattering (DLS)] and were, furthermore, cross‐compared. The calculated average grain size, for dry powders, is in the range 20–45 nm. The hydrodynamic size was measured by using the DLS technique on nonmodified, surfactant‐free particles of the whole ZnX2O4series. The up‐conversion properties of the particles were discussed in detail. The low value of the green‐to‐red ratio points to a significant contribution of non‐radiative pathways, such as multiphonon relaxation or cross relaxation processes, to the depopulation of the green band, which feeds and favors the red emission of Er3+in the up‐conversion process.
Synthesis and Evaluation of an Enantiomerically Enriched Bifunctional Chelator for 64Cu‐Based Positron Emission Tomography (PET) Imaging
Authors: Chong Hyun‐Soon , Sun Xiang , Zhong Yongliang , Bober Kamil , Lewis Michael R. , Liu Dijie , Ruthengael Varyanna C. , Sin Inseok , Kang Chi Soo
Published: January 2014

We report the synthesis and evaluation of an enantiomerically enriched bifunctional chelator, (S)‐C‐NE3TA. The bifunctional chelator was efficiently prepared by regioselective and stereoselective ring opening of an aziridinium ion. The new chiral chelator instantly and almost completely bound to 64Cu at room temperature. The corresponding 64Cu‐radiolabeled complex remained intact in human serum for 48 h without any measurable transchelation and was tolerant to a rigorous EDTA challenge for 24 h. The 64Cu‐radiolabeled (S)‐C‐NE3TA complex was stable in mice and produced an excellent biodistribution profile. The results of the in vitro and in vivo evaluations indicate that the new optically active chelator is a promising candidate for PET imaging applications.
Dirhodium(II)‐Catalyzed Cross‐Coupling Reactions of Aryl Aldehydes with Arylboronic Acids in Water
Authors: Kuang Yi , Wang Yuanhua
Published: January 2014

In this report, dirhodium(II) catalysts with axial phosphanes ligands were employed to catalyze cross‐coupling reactions of aromatic aldehydes with arylboronic acids to generate ketones in neat water. The overall reaction is proposed to occur through a cascade process involving the dirhodium‐catalyzed addition of boronic acids to aldehydes followed by the dehydrogenative oxidation of alcohols.
Developing the Scope of O→C Aryl Migrations: Exploring Amide Substrates as Potential Precursors for Asymmetric Reactions
Authors: Ameen Dana , Snape Timothy J.
Published: January 2014

A new and mild method for the production of diasteromerically enriched α‐aryl carbonyl compounds has been achieved. Although only modest diastereoselectivies are observed, they demonstrate the potential of the method for further optimisation. It also appears that reactions that proceed through a five‐membered spirocyclic transition state rearrange, whereas those proceeding through a six‐membered transition state do not, but stop at the diaryl ether stage.
Hidden Flexibility of Strychnine
Authors: Schmidt Manuel , Reinscheid Frauke , Sun Han , Abromeit Hans , Scriba Gerhard K. E. , Sönnichsen Frank D. , John Michael , Reinscheid Uwe M.
Published: January 2014

The prototypic molecule for conformational rigidity, that is, strychnine, exhibits fast conformational exchange on the NMR timescale at room temperature. A comprehensive description of this up‐to‐now‐hidden stereodynamic behavior is presented, which combines experimental and computational data.
From Van Gogh to Lady Gaga: Artist eccentricity increases perceived artistic skill and art appreciation
Authors: Van Tilburg Wijnand Adriaan Pieter , Igou Eric Raymond
Published: January 2014

We examined the impact of eccentricity on the evaluation of artistic skills and the quality of artworks. Based on the notion that artists are typically perceived as eccentric, creative and skilled, we tested the hypothesis that eccentricity increases perceptions of artistic quality. In Study 1, Van Gogh's Sunflowers painting was evaluated more positively when he was said to have cut off his left ear lobe than when this information was not presented. In Study 2, participants liked art more when the artist was eccentric. In Study 3, the evaluation of fictitious art increased because of the artist's eccentric appearance. Study 4 established that the eccentricity effect was specific to unconventional as opposed to conventional art. In Study 5, Lady Gaga's music was more appreciated when she was displayed as highly eccentric; however, the eccentricity effect emerged only when the display seemed authentic. These novel findings indicate that art evaluations are partly rooted in perceptions of artists' eccentricity and evidence the importance of perceived authenticity and skills for these attributions. Copyright © 2014 John Wiley & Sons, Ltd.
Rapid target gene validation in complex cancer mouse models using re‐derived embryonic stem cells
Authors: Huijbers Ivo J , Bin Ali Rahmen , Pritchard Colin , Cozijnsen Miranda , Kwon Min‐Chul , Proost Natalie , Song Ji‐Ying , de Vries Hilda , Badhai Jitendra , Sutherland Kate , Krimpenfort Paul , Michalak Ewa M , Jonkers Jos , Berns Anton
Published: January 2014

Human cancers modeled in Genetically Engineered Mouse Models (GEMMs) can provide important mechanistic insights into the molecular basis of tumor development and enable testing of new intervention strategies. The inherent complexity of these models, with often multiple modified tumor suppressor genes and oncogenes, has hampered their use as preclinical models for validating cancer genes and drug targets. In our newly developed approach for the fast generation of tumor cohorts we have overcome this obstacle, as exemplified for three GEMMs; two lung cancer models and one mesothelioma model. Three elements are central for this system; (i) The efficient derivation of authentic Embryonic Stem Cells (ESCs) from established GEMMs, (ii) the routine introduction of transgenes of choice in these GEMM‐ESCs by Flp recombinase‐mediated integration and (iii) the direct use of the chimeric animals in tumor cohorts. By applying stringent quality controls, the GEMM‐ESC approach proofs to be a reliable and effective method to speed up cancer gene assessment and target validation. As proof‐of‐principle, we demonstrate that MycL1 is a key driver gene in Small Cell Lung Cancer.
Preparation of biodiesel from waste frying oil using a green and renewable solid catalyst derived from egg shell
Authors: Niju Subramaniapillai , Sheriffa Begum Kader Mohamed Meera , Anantharaman Narayanan
Published: January 2014

Biodiesel was produced from waste frying oil using calcium oxide derived from the calcination of egg shell as a heterogeneous base catalyst. The catalyst was characterized by X‐ray diffraction, Fourier transform infrared (FTIR) spectroscopy, Brunauer–Emmett–Teller analysis, scanning electron microscopy, and energy‐dispersive atomic X‐ray spectrometry. The effects of reaction variables such as methanol/oil molar ratio, amount of catalyst, reaction temperature, and reaction time on biodiesel yield were investigated. The activity of the egg shell‐derived CaO was compared with the commercial CaO. A high biodiesel yield of 95.05% and conversion of 96.11% were obtained at 3 wt % catalyst (based on oil weight), methanol/oil molar ratio of 9:1, reaction temperature of 65°C, and reaction time of 3 h. The structure of biodiesel was characterized by FTIR, and the biodiesel conversion was determined by 1H nuclear magnetic resonance spectroscopy. © 2014 American Institute of Chemical Engineers Environ Prog, 34: 248–254, 2015
STEM‐Net: an evolutionary network architecture for smart and sustainable cities
Authors: Aloi Gianluca , Bedogni Luca , Felice Marco Di , Loscrì Valeria , Molinaro Antonella , Natalizio Enrico , Pace Pasquale , Ruggeri Giuseppe , Trotta Angelo , Zema Nicola Roberto
Published: January 2014

The concept of smart city has emerged worldwide as a feasible answer to the challenges raised by the increasing urbanisation. From the technological point of view, guaranteeing ubiquitous connectivity, reliable communications and seamless integration of multiple network access technologies are mandatory in a smart city. This is in contrast with the current infrastructure deployment in several urban areas, which is characterised by lack of ubiquitous connectivity and coverage and by fragmentation of networks that are usually deployed by different operators and without any centralised control by the city authorities. In this paper, we look at the heterogeneity of devices and network technologies under a different perspective by not perceiving it as a limitation but as a potential to increase the connectivity in a smart city. We propose a new generation of network nodes, called stem nodes, based on the innovative idea of ‘stemness’, which pushes forward the well‐known self‐configuration and self‐management concepts towards the idea of node mutation and evolution. We also deployed prototypes that demonstrate the stem‐node architecture and basic operations in different hardware platforms of common communication devices (an Alix‐based router, a laptop and a smartphone). Copyright © 2014 John Wiley & Sons, Ltd.