bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring protein structure and dynamics through a project‐oriented biochemistry laboratory module
Authors: Lipchock James M. , Ginther Patrick S. , Douglas Bonnie B. , Bird Kelly E. , Patrick Loria J.
Published: March 2017

Here, we present a 10‐week project‐oriented laboratory module designed to provide a course‐based undergraduate research experience in biochemistry that emphasizes the importance of biomolecular structure and dynamics in enzyme function. This module explores the impact of mutagenesis on an important active site loop for a biomedically‐relevant human enzyme, protein tyrosine phosphatase 1B (PTP1B). Over the course of the semester students guide their own mutant of PTP1B from conception to characterization in a cost‐effective manner and gain exposure to fundamental techniques in biochemistry, including site‐directed DNA mutagenesis, bacterial recombinant protein expression, affinity column purification, protein quantitation, SDS‐PAGE, and enzyme kinetics. This project‐based approach allows an instructor to simulate a research setting and prepare students for productive research beyond the classroom. Potential modifications to expand or contract this module are also provided. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(5):403–410, 2017.
Definition and Assessment of Disability in Mental Disorders under the Perspective of the International Classification of Functioning Disability and Health (ICF)
Authors: Linden Michael
Published: March 2017

This article provides an overview of definitions and assessment instruments of disability, an important topic in the diagnosis and treatment of chronic illnesses, and in expert appraisals in social and forensic medicine. Health problems are manifested not only in symptoms, but also regularly in impairment or disability in everyday life, which is especially true for mental disorders. According to the International Classification of Functioning, Disability and Health (ICF) of the World Health Organization, disability can be understood as chronic suffering from symptoms of illness, or limitations of executing capacities, or inability to participate in selected areas of life. Operationally, disability can be defined as “capacity limitations which hinder the ability to execute needed activities and thereby participation in a given environment”. This capacity–context–interaction model shows that there is no general disability but only context‐related disability, which has manifold consequences for diagnosis and care. Copyright © 2017 John Wiley & Sons, Ltd.
“This is an EU crisis requiring an EU solution”: Nation and transnational talk in negotiating warrants for further inclusion of refugees
Authors: Sambaraju Rahul , McVittie Chris , Nolan Philip
Published: March 2017

Discursive social psychological research shows the centrality of treating arrival nations as unitary entities that are incompatible for nonnation others (immigrants, asylum seekers, and refugees) in legitimately warranting their exclusion. We extend these findings for the current Special Issue and for broader literature in examining inclusion issues in the European Union (EU) in the ongoing context of the “refugee crisis.” We offer a discursive analysis of transcribed talk in the Dáil Éireaan (Irish Parliament) for the year 2015 when issues of migration and refugees were prominent. Analysis shows that Deputies treat the adequacy of ongoing inclusion efforts as a concern. This was worked up through foregrounding possibilities for Ireland to take up inclusive efforts and managed through avowals of commitment to inclusion juxtaposed to treating the issue and responses to it as EU concerns. Findings show that unique aspects and sovereignty of nations can be downplayed in negotiating warrants for inclusion. Alongside this, in specific contexts and settings transnational collectives, such as the EU, can be treated as stand‐ins for nations and used to negotiate inclusion of nonnation others. These are discussed in relation to implications for inclusion advocacy.
The 5′‐AG5CC‐3′ Fragment from the Human CPEB3 Ribozyme Forms an Ultrastable Parallel RNA G‐Quadruplex
Authors: Kulikov Katharina , Nozinovic Senada , Kath‐Schorr Stephanie
Published: March 2017

An unusually thermostable G‐quadruplex is formed by a sequence fragment of a naturally occurring ribozyme, the human CPEB3 ribozyme. Strong evidence is provided for the formation of a uniquely stable intermolecular G‐quadruplex structure consisting of five tetrad layers, by using CD spectroscopy, UV melting curves, 2D NMR spectroscopy, and gel shift analysis. The cationic porphyrin TMPyP4 destabilizes the complex.
Aggressive lymphoma presenting as dysphagia: A rare cause of dysphagia
Authors: Castresana Daniel , Bansal Pranshu , Vasef Mohammed A. , Kapoor Vidit , Leone Christopher , Quintana Dulcinea
Published: March 2017

Key Clinical Message

Diffuse large B‐cell lymphoma (DLBCL) can involve the esophagus from local spread, distant metastasis and very rarely can also be the primary site. Once DLBCL is diagnosed, caution should be exercised in further evaluation for local treatments of sites like adnexal masses as was seen in this case; sometimes it is DLBCL at atypical sites.
Core–Shell Zeolite Y@γ‐Al2O3 Nanorod Composites: Optimized Fluid Catalytic Cracking Catalyst Assembly for Processing Heavy Oil
Authors: Jiao Wenqian , Wu Xuezhong , Li Gang , Xue Teng , Wang Yimeng , Tang Yi
Published: March 2017

Compositions, structures, and distributions of the active phases in fluid catalytic cracking (FCC) catalysts have an essentially important impact on their porosities, acidities, and thus cracking capabilities for processing heavy oil fractions. Here, we report a facile approach for fabrication of core–shell zeolite Y@γ‐Al2O3 nanorod composites by controlling the attachment of boehmite nanorods on the external surface of zeolite crystals, and thus regulating the dispersion and combination of the active alumina matrix on zeolite components in the FCC catalyst. The synthesized discrete boehmite nanorods possess a large quantity of positive charges and can directly electrostatically interact with the negative surface of zeolite crystals, leading to the formation of core–shell zeolite Y@γ‐Al2O3 nanorod composites (nY@Al2O3). The optimized 4Y@Al2O3 composite (Y/γ‐Al2O3 weight ratio of 4) with zeolite crystals fully embedded by alumina nanorods shows enhanced textural properties, acidity accessibilities, and improved cracking ability of 1,3,5‐triisopropyl benzene. Taking it as the main active component, the produced FCC catalyst shows better contaminant resistant ability and especially higher gasoline yield in the cracking of heavy oil, which could potentially bring practical economic profits for the oil‐refining industry.
Direct Solid Lewis Acid Catalyzed Wood Liquefaction into Lactic Acid: Kinetic Evidences that Wood Pretreatment Might Not be a Prerequisite
Authors: Swesi Youssef , Nguyen Chuc , Ha Vu Thi Thu , Rataboul Franck , Eternot Marion , Fongarland Pascal , Essayem Nadine
Published: March 2017

The objective of the present work was to determine if wood sawdust can be used instead of isolated cellulose in the general solid‐acid‐catalyzed production of chemicals. The kinetics of model cellulose and pine‐wood sawdust liquefaction into lactic acid were determined in the presence of a solid Lewis acid, ZrW. The catalytic hydrolysis of pine wood was performed at 190 °C in a large‐scale batch reactor (2.5 L). Similar kinetic curves of lactic formation were obtained for cellulose and wood as substrates. Moreover, the initial lactic acid production rate of pine‐wood sawdust was higher than that of model cellulose, proving that, in spite of the presence of lignin/hemicellulose, the catalyst drives the transformation towards lactic acid formation. However, our results give also evidence of solid‐catalyst deactivation for both cellulose and wood substrates. This result indicates that if wood pretreatment can be bypassed, the bottleneck will be the solid‐catalyst regeneration and recycling.
Supramolecular Covalence in Bifurcated Chalcogen Bonding
Authors: Bora Pankaj Lochan , Novák Martin , Novotný Jan , Foroutan‐Nejad Cina , Marek Radek
Published: March 2017

Supramolecular interactions are generally classified as noncovalent. However, recent studies have demonstrated that many of these interactions are stabilized by a significant covalent component. Herein, for systems of the general structure [MX6]2−:YX2(M=Se or Pt; Y=S, Se, or Te; X=F, Cl, Br, I), featuring bifurcated chalcogen bonding, it is shown that, although electrostatic parameters are useful for estimating the long‐range electrostatic component of the interaction, they fail to predict the correct order of binding energies in a series of compounds. Instead, the Lewis basicity of the individual substituents X on the chalcogen atom governs the trends in the binding energies through fine‐tuning the covalent character of the chalcogen bond. The effects of substituents on the binding energy and supramolecular electron sharing are consistently identified by an arsenal of theoretical methods, ranging from approaches based on the quantum chemical topology to analytical tools based on the localized molecular orbitals. The chalcogen bonding investigated herein is driven by orbital interactions with significant electron sharing; this can be designated as supramolecular covalence.
Improved Infrared Spectra Prediction by DFT from a New Experimental Database
Authors: Katari Madanakrishna , Nicol Edith , Steinmetz Vincent , van der Rest Guillaume , Carmichael Duncan , Frison Gilles
Published: March 2017

This work aims to improve the computation of infrared spectra of gas‐phase cations using DFT methods. Experimental infrared multiple photon dissociation (IRMPD) spectra for ten Zn and Ru organometallic complexes have been used to provide reference data for 64 vibrational modes in the 900–2000 cm−1 range. The accuracy of the IR vibrational frequencies predicted for these bands has been assessed over five DFT functionals and three basis sets. The functionals include the popular B3LYP and M06‐2X hybrids and the range‐separated hybrids (RSH) CAM‐B3LYP, LC‐BLYP, and ωB97X‐D. B3LYP gives the best mean absolute error (MAE) and root‐mean‐square error (RMSE) values of 7.1 and 9.6 cm−1, whilst the best RSH functional, ωB97X‐D, gives 12.8 and 16.6 cm−1, respectively. Using linear correlations instead of scaling factors improves the prediction accuracy significantly for all functionals. Experimental and computed spectra for a single complex can show significant differences even when the molecular structure is calculated correctly, and a means of defining confidence limits for any given computed structure is also provided.
Chemical synthesis of long RNAs with terminal 5′‐phosphate groups
Authors: Pradère Ugo , Halloy François , Hall Jonathan
Published: March 2017

Long structured RNAs are useful biochemical and biological tools. They are usually prepared enzymatically, but this precludes their site‐specific modification with functional groups for chemical biology studies. One solution is to perform solid‐phase synthesis of multiple RNAs loaded with 5′‐terminal phosphate groups, so that RNAs can be concatenated using template ligation reactions. However, there are currently no readily available reagents suitable for the incorporation of the phosphate group into long RNAs by solid‐phase synthesis. Here we describe an easy‐to‐prepare phosphoramidite reagent suitable for the chemical introduction of 5′‐terminal phosphate groups into long RNAs. The phosphate is protected by a dinitrobenzhydryl group that serves as an essential lipophilic group for the separation of oligonucleotide by‐products. The phosphate is unmasked quantitatively by brief UV irradiation. We demonstrate the value of this reagent in the preparation of a library of long structured RNAs that are site‐specifically modified with functional groups.
Coordination of N2and Other Small Molecules to the Phosphorus Centre of RPW(CO)5: A Theoretical Study on the Janus Facets of the Stabilization/Activation Problem
Authors: Espinosa Ferao Arturo , Streubel Rainer
Published: March 2017

Bonding of neutral terminal phosphinidene tungsten(0) complexes stabilized by ligands bound to phosphorus (ligand‐to‐P) have been studied using a large testbed of predominantly N‐ligands. Most complexes (1 a–r,v–zand2 l) exhibit a pyramidal P centre with a formal single ligand‐to‐P bond order. Three ligand‐to‐P complexes (1 s–u) exhibit planar sp2‐hybridization of P and P,N bonds featuring double bond character. All derivatives with C‐ligands (1 v,x–z) exhibit a ligand‐to‐P bond strength intermediate between the P−N single and double bonded species. Remarkably, dinuclear complexes containing CN−(1 p,w), N3−(1 r) and N2(1–3 t) as bridging ligands between two phosphorus centres show intertwined terminal W(CO)5fragments. In particular, the case of N2bridging ligand (1–3 t) represents a noteworthy example of activation, displaying a weakened N,N bond and two sets of very strong P,N double bonds, the latter resembling the activation‐picture of dinitrogen by transition metal complexes. Bond dissociation energies (BDEs) of ligand‐to‐P bonds do not show any correlation with a range of bond strength descriptors, but display some meaningful, roughly linear variation with the ligand softness. Based on Haaland's definition of dative bonding, a reasonable linear correlation of BDE with dativity (d1) and the dative covalence energy (DCE1) was found. A moderate correlation was also obtained with the vertical ionization potential of the ligand (I(L)) as well as with the ligands HOMO energy.
An Optically Active Polymer for Broad‐Spectrum Enantiomeric Recognition of Chiral Acids
Authors: Yan Jijun , Kang Chuanqing , Bian Zheng , Ma Xiaoye , Jin Rizhe , Du Zhijun , Gao Lianxun
Published: March 2017

Recognition of enantiomers of chiral acids by anion–π or lone pair–π interactions has not yet been investigated but is a significant and attractive challenge. This study reports an optically active polymer‐based supramolecular system with capabilities of discriminating enantiomers of various chiral acids. The polymer featuring alternate π‐acidic naphthalenediimides (NDIs) and methyl l‐phenylalaninates in the backbone exhibits an unprecedented slow self‐assembly process that is susceptible to perturbation by various chiral acids. Thus, the combination of anion–π or lone pair–π interactions and sensitivity of the polymeric self‐assembly process to external chiral species endows the system with recognition capabilities. This is the first time that anion–π or lone pair–π interactions have been applied in the recognition of enantiomers of various chiral acids with a single system. The results shed light on new strategies for material design by integrating π‐acidic aromatic systems and chiral building blocks to afford relevant advanced functions.
Protection of Platinum‐Based Micromotors from Thiol Toxicity by Using Manganese Oxide
Authors: Minh Tam Do , Safdar Muhammad , Jänis Janne
Published: March 2017

Platinum‐based micromotors have shown many exciting applications when functionalized using gold–thiol chemistry. However, thiols are known to bind to the Pt surface, which can lead to serious deactivation of the catalyst. In this paper, it is demonstrated that MnO2can be used to protect Pt‐based micromotors prior to the thiol treatment, thus fully avoiding the catalyst poisoning. This approach will greatly facilitate the use of the functionalized Pt micromotors for which the thiol toxicity has been a limiting factor.
Metallapentalenofurans and Lactone‐Fused Metallapentalynes
Authors: Lu Zhengyu , Zhu Congqing , Cai Yuanting , Zhu Jun , Hua Yuhui , Chen Zhixin , Chen Jiangxi , Xia Haiping
Published: March 2017

Metalla‐aromatics are attractive species because they exhibit the properties of both organometallics and aromatics. Reported metal‐bridged polycyclic aromatic complexes, as well as Möbius aromatic species, are still rare. Herein, we present the construction of two new metal‐bridged polycyclic aromatic frameworks, α‐metallapentalenofurans and lactone‐fused metallapentalynes, by the reactions of osmapentalyne with terminal aryl alkynes in the presence of H2O or HBF4/H2O, respectively. DFT calculations show that the α‐metallapentalenofurans possess rare planar Craig‐type Möbius aromaticity derived from the 11‐center‐12‐electron dπ–pπ π‐conjugation. This study offers a new route for the construction of polycyclic metalla‐aromatics as well as planar Möbius aromatic species.
Designer Metallic Acceptor‐Containing Halogen Bonds: General Strategies
Authors: Zhang Xinxing , Bowen Kit
Published: March 2017

Being electrostatic interactions in nature, hydrogen bonding (HB) and halogen bonding (XB) are considered to be two parallel worlds. In principle, all the applications that HB have could also be applied to XB. However, there has been no report on an anionic, metallic XB acceptor, but metal anions have been observed to be good HB acceptors. This missing mosaic piece of XB theory is because common metal anions are reactive for XB donors. In view of this, two strategies are proposed for designing metallic acceptor‐containing XB using ab initio calculations. The first one is to utilize a metal cluster anion with a high electron detachment energy, such as the superatom, Al13− as the XB acceptor. The second strategy is to design a ligand‐passivated/protected metal core that can maintain the negative charge; several exotic clusters, such as PtH5−, PtZnH5−, and PtMgH5−, are used as examples. Based on these two strategies, it is anticipated that more metallic acceptor‐containing XBs will be discovered.
PLA2G7 associates with hormone receptor negativity in clinical breast cancer samples and regulates epithelial‐mesenchymal transition in cultured breast cancer cells
Authors: Lehtinen Laura , Vainio Paula , Wikman Harriet , Huhtala Heini , Mueller Volkmar , Kallioniemi Anne , Pantel Klaus , Kronqvist Pauliina , Kallioniemi Olli , Carpèn Olli , Iljin Kristiina
Published: March 2017

Breast cancer is the leading cause of cancer‐related deaths in women due to distinct cancer subtypes associated with early recurrence and aggressive metastatic progression. High lipoprotein‐associated phospholipase A2 (PLA2G7) expression has previously been associated with aggressive disease and metastasis in prostate cancer. Here, we explore the expression pattern and functional role of PLA2G7 in breast cancer. First, a bioinformatic analysis of genome‐wide gene expression data from 970 breast samples was carried out to evaluate the expression pattern of PLA2G7 mRNA in breast cancer. Second, the expression profile of PLA2G7 was studied in 1042 breast cancer samples including 89 matched lymph node metastasis samples using immunohistochemistry. Third, the effect of PLA2G7 silencing on genome‐wide gene expression profile was studied and validated in cultured breast cancer cells expressing PLA2G7 at high level. Last, the expression pattern of PLA2G7 mRNA was investigated in 24 nonmalignant tissue samples and 65 primary and 7 metastatic tumour samples derived from various organs using qRT‐PCR. The results from clinical breast cancer samples indicated that PLA2G7 is overexpressed in a subset of breast cancer samples compared to its expression in benign breast tissue samples and that high PLA2G7 expression associated with hormone receptor negativity as well as with poor prognosis in a subset of breast cancer samples. In vitro functional studies highlighted the putative role of PLA2G7 in the regulation of epithelial‐mesenchymal transition (EMT)‐related signalling pathways, vimentin and E‐cadherin protein expression as well as cell migration in cultured breast cancer cells. Furthermore, supporting the findings in breast and prostate cancer, high PLA2G7 mRNA expression was associated with metastatic cancer in four additional organs of origin. In conclusion, our results indicate that PLA2G7 is highly expressed in a subset of metastatic and aggressive breast cancers and in metastatic samples of various tissues of origin and promotes EMT and migration in cultured breast cancer cells.
Predictors and long‐term outcome of super‐responders to cardiac resynchronization therapy
Authors: Ghani Abdul , Delnoy Peter Paul H.M. , Adiyaman Ahmet , Ottervanger Jan Paul , Ramdat Misier Anand R. , Smit Jaap Jan J. , Elvan Arif
Published: March 2017

Background

The level of improvement in left ventricular ejection fraction (LVEF) in super‐responders to cardiac resynchronization therapy (CRT) is exceptional. However, the long‐term prognosis remains unknown in a large population.

Hypothesis

Whether super‐responders haven good long‐term outcomes.

Methods

We registered 347 patients with primary CRT‐D indication. Super‐response was defined by LVEF >50% at follow‐up echocardiogram. Best‐subset regression analysis identified predictors of super‐response. Endpoints were major adverse cardiac events (MACE; eg, all‐cause mortality or heart failure hospitalization, cardiac death, and appropriate ICD therapy).

Results

Fifty‐six (16%) patients with LVEF >50% were classified as super‐responders. Female sex (OR: 3.06, 95% CI: 1.54‐6.05), nonischemic etiology (OR: 2.70, 95% CI: 1.29‐5.68), higher LVEF at baseline (OR: 1.07, 95% CI: 1.02‐1.13), and wider QRS duration (OR: 1.17, 95% CI: 1.04‐1.32) were predictors of super‐response. Cumulative incidence of MACE at a median of 5.3 years was 18% in super‐responders, 22% in responders, and 51% in nonresponders (P < 0.001). None of super responders died from cardiac death, compared to 9% of responders and 25% of non‐responders (P < 0.001). None of super‐responders experienced appropriate ICD therapy, compared with 10% of responders and 21% of non‐responders (P < 0.001). In super‐responders, the adjusted hazard ratio was 0.37 (95% CI: 0.19‐0.73) for MACE and 0.44 (95% CI: 0.20‐0.95) for total mortality, compared with non‐responders.

Conclusions

Female sex, non‐ischemic etiology, higher baseline LVEF, and wider QRS duration were independently associated with super‐response. Super‐response was associated with persistent excellent prognosis regarding survival and appropriate ICD therapy during long‐term follow‐up.
TRAF3/CYLD mutations identify a distinct subset of human papillomavirus‐associated head and neck squamous cell carcinoma
Authors: Hajek Michael , Sewell Andrew , Kaech Susan , Burtness Barbara , Yarbrough Wendell G. , Issaeva Natalia
Published: March 2017

BACKGROUND

The incidence of human papillomavirus (HPV)‐associated (HPV‐positive) head and neck squamous cell carcinoma (HNSCC) of the oropharynx has dramatically increased over the last decade and continues to rise. Newly diagnosed HPV‐positive HNSCCs in the United States currently outnumber any other HPV‐associated cancers, including cervical cancer. Despite introduction of the HPV vaccine, the epidemic of HPV‐positive HNSCC is expected to continue for approximately 60 years. Compared with patients who have tobacco‐associated HNSCC, those who have HPV‐positive HNSCC have better overall survival and response to treatment. Current treatment, including chemotherapy and radiation therapy, is associated with lifelong morbidity, and there are limited treatments and no curative options for patients who develop recurrent metastatic disease. Therapeutic de‐escalation (decreased radiation dose) is being tested through clinical trials; however, those studies select patients based solely on tumor and patient smoking characteristics. Mechanisms of HPV‐driven carcinogenesis in HNSCC are not well understood, which limits new therapeutic strategies and hinders the appropriate selection of patients for de‐escalation therapy.

METHODS

The authors analyzed HNSCC data from The Cancer Genome Atlas to identify molecular characteristics that correlate with outcomes and integration status of the HPV genome.

RESULTS

The current investigations identified a subset of HPV‐positive HNSCCs with mutations in the genes TRAF3 (tumor necrosis factor receptor‐associated factor 3) and CYLD (cylindromatosis lysine 63 deubiquitinase). Defects in TRAF3 and CYLD correlated with the activation of transcriptional factor nuclear factor κB, episomal HPV status of tumors, and improved patient survival.

CONCLUSIONS

Defects in TRAF3/CYLD were accompanied with the activation of nuclear factor κB signaling and maintenance of episomal HPV in tumors, suggesting that these mutations may support an alternative mechanism of HPV tumorigenesis in head and neck tumors. Cancer 2017;123:1778–1790. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
[18F]‐FDG PET/CT in the staging and management of indolent lymphoma: A prospective multicenter PET registry study
Authors: Metser Ur , Dudebout Jill , Baetz Tara , Hodgson David C. , Langer Deanna L. , MacCrostie Pamela , Mak Victor , Tau Noam
Published: March 2017

BACKGROUND

To measure the clinical impact of pretreatment fludeoxyglucose positron emission tomography/computed tomography (PET/CT) on the staging and management of apparent limited stage indolent lymphoma being considered for curative radiation therapy.

METHODS

We conducted a prospective multicenter registry study that included 197 patients accrued between May 1, 2012, and December 31, 2015. Pre‐PET/CT stage, determined by clinical and CT data, was documented. If pre‐PET/CT stage was indeterminate, a stage was assigned to the patient by the referring oncologist according to best clinical judgment and treatment intent. After PET/CT, revised stage and planned management were recorded and compared with data on actual treatment received available through provincial databases (n = 155).

RESULTS

PET/CT resulted in the upstaging of 47 (23.9%) patients with presumed limited stage disease (stage I‐II) to advanced stage disease (stage III‐IV) (P < .0001). Ten (5.1%) patients were downstaged by PET/CT, 4 of whom migrated from advanced to limited stage disease. Twenty‐eight (14.2%) patients with a specific pre‐PET/CT stage had equivocal PET/CT findings that required further evaluation to confirm disease extent. After PET/CT, 95 (61.3%) patients were planned to receive active treatment. Of the 59 patients planned for radiotherapy alone post‐PET/CT, 34 (57.6%) received this treatment (P = .002), and nearly 80% of them (n = 27) had confirmed limited stage disease.

CONCLUSION

PET/CT has a significant impact on staging and management in patients with apparent limited stage indolent lymphoma who are being considered for curative radiotherapy. PET/CT should be routinely incorporated into the workup of these patients. Cancer 2017;123:2860–66. © 2017 American Cancer Society.
Differential neuronal and glial expression of nuclear factor I proteins in the cerebral cortex of adult mice
Authors: Chen Kok‐Siong , Harris Lachlan , Lim Jonathan W. C. , Harvey Tracey J. , Piper Michael , Gronostajski Richard M. , Richards Linda J. , Bunt Jens
Published: March 2017

The nuclear factor I (NFI) family of transcription factors plays an important role in the development of the cerebral cortex in humans and mice. Disruption of nuclear factor IA (NFIA), nuclear factor IB (NFIB), or nuclear factor IX (NFIX) results in abnormal development of the corpus callosum, lateral ventricles, and hippocampus. However, the expression or function of these genes has not been examined in detail in the adult brain, and the cell type‐specific expression of NFIA, NFIB, and NFIX is currently unknown. Here, we demonstrate that the expression of each NFI protein shows a distinct laminar pattern in the adult mouse neocortex and that their cell type‐specific expression differs depending on the family member. NFIA expression was more frequently observed in astrocytes and oligodendroglia, whereas NFIB expression was predominantly localized to astrocytes and neurons. NFIX expression was most commonly observed in neurons. The NFI proteins were equally distributed within microglia, and the ependymal cells lining the ventricles of the brain expressed all three proteins. In the hippocampus, the NFI proteins were expressed during all stages of neural stem cell differentiation in the dentate gyrus, with higher expression intensity in neuroblast cells as compared to quiescent stem cells and mature granule neurons. These findings suggest that the NFI proteins may play distinct roles in cell lineage specification or maintenance, and establish the basis for further investigation of their function in the adult brain and their emerging role in disease.
Directional excitatory input to direction‐selective ganglion cells in the rabbit retina
Authors: Percival Kumiko A. , Venkataramani Sowmya , Smith Robert G. , Taylor W. Rowland
Published: March 2017

Directional responses in retinal ganglion cells are generated in large part by direction‐selective release of γ‐aminobutyric acid from starburst amacrine cells onto direction‐selective ganglion cells (DSGCs). The excitatory inputs to DSGCs are also widely reported to be direction‐selective, however, recent evidence suggests that glutamate release from bipolar cells is not directional, and directional excitation seen in patch‐clamp analyses may be an artifact resulting from incomplete voltage control. Here, we test this voltage‐clamp‐artifact hypothesis in recordings from 62 ON‐OFF DSGCs in the rabbit retina. The strength of the directional excitatory signal varies considerably across the sample of cells, but is not correlated with the strength of directional inhibition, as required for a voltage‐clamp artifact. These results implicate additional mechanisms in generating directional excitatory inputs to DSGCs.
Light Harvesting and Photocurrent Generation in a Conjugated Polymer Nanoparticle–Reduced Graphene Oxide Composite
Authors: Ghosh Arnab , Jana Bikash , Maiti Sourav , Bera Rajesh , Ghosh Hirendra N. , Patra Amitava
Published: March 2017

Polymer–graphene nanocomposites are promising candidates for light harvesting applications such as photocatalysis and photovoltaics, where significant charge separation occurs due to photoinduced electron transfer. Much attention has been paid to using reduced graphene oxide (r‐GO) as template for anchoring various nanomaterials due to its efficient electron accepting and transport properties. Here, poly[2‐methoxy‐5‐(2‐ethylhexyloxy)‐1,4‐phenylenevinylene] (MEH‐PPV) nanoparticles are prepared from MEH‐PPV polymer and the change in photophysical properties upon formation of polymer nanoparticles (PNPs) from the molecular state are investigated by using steady‐state and time‐resolved spectroscopy. Nanocomposites are constructed by adding hexadecylamine‐functionalized positively charged MEH‐PPV PNPs to a solution of negatively charged r‐GO. Steady‐state and time‐resolved spectroscopy are also used to study the electronic interactions between PNPs and r‐GO. Ultrafast femtosecond up‐conversion and transient absorption spectroscopy unequivocally confirms the electron transfer process from the excited state of MEH‐PPV PNPs to r‐GO at the interface of the nanocomposite. Analysis reveals that the charge separation time is found to be pulse‐width‐limited (<100 fs). Due to charge separation in these nanocomposites, an increase (2.6 fold) of photocurrent under visible light illumination is obtained. The fundamental understanding of the charge transfer dynamics affords new opportunities to design efficient light‐harvesting systems based on inorganic–organic hybrids.
Phenoxazine Derivative Operates as an Efficient Surface‐Grafted Molecular Relay to Enhance the Performance and Stability of CdS‐ and CdSe‐Sensitized TiO2 Solar Cells
Authors: Shen Chao , Wang Xingzhu , Tang Shasha , Courté Marc , Fichou Denis
Published: March 2017

We report on a new phenoxazine derivative, 10‐butyl‐phenoxazine‐3‐carboxylic acid (BPCA), that we designed to operate as a molecular relay in semiconductor‐sensitized solar cells (SSCs). After BPCA surface modification and in the presence of a cobalt‐bipyridyl complex acting as a redox mediator, both TiO2/CdS/BPCA and TiO2/CdSe/BPCA SSCs exhibit enhanced photovoltaic performance and stability. In particular, the power conversion efficiencies of CdS and CdSe‐based solar cells are improved by 90 % and 57 %, respectively. Furthermore, after 300 s the JSC of TiO2/CdS/BPCA SSCs is stabilized at 30 % of its initial value, while in the same time CdS‐based devices retain only 1 % of their initial JSC. The origin of the improvement arises from the excellent electron‐donating property of BPCA and its role as a powerful molecular relay in non‐polysulfide based SSCs.
Reactions of Dilithium Dibenzopentalenides with Cr(CO)3(CH3CN)3: Unexpected Formation of a Cubic Tetramer of an Anionic Hydrodibenzopentalenyl Complex
Authors: Kuwabara Takuya , Kurokawa Nobuaki , Saito Masaichi
Published: March 2017

To explore the coordination chemistry of dibenzopentalene dianion, reactions of two dilithium dibenzopentalenides having different silyl substituents with Cr(CO)3(CH3CN)3 were investigated. The products were unexpected anionic complexes, [Li(Et2O)]+[Cr(η5‐9‐hydrodibenzopentalenyl)(CO)3]−. The proton at the 9‐position is derived from Cr(CO)3(CH3CN)3, as evidenced by the use of Cr(CO)3(CD3CN)3. The X‐ray diffraction analysis revealed that the chromium is coordinated by an anionic five‐membered ring of the pentalene skeleton, and the lithium atom is coordinated by oxygen atoms of the carbonyl groups. The complexes form a dimer or a cage‐like tetramer via carbonyl–lithium interactions, depending on the bulk of the silyl groups. The cubic tetramer appears to retain its cage structure in nonpolar solvents such as benzene.
Silica‐Based Nanoparticles as Bifunctional and Bimodal Imaging Contrast Agents
Authors: Lechevallier Séverine , Mauricot Robert , Gros‐Dagnac Hélène , Chevreux Sylviane , Lemercier Gilles , Phonesouk Erick , Golzio Muriel , Verelst Marc
Published: March 2017

New bifunctional and bimodal nanoparticles (NPs) have been elaborated and characterised. They are based on silica NPs that incorporate a silylated ruthenium tris‐bipyridine complex. The resulting suspension of amine‐modified NPs with diameters of 20 nm was post‐functionalised with a stable gadolinium ion complex. Interest in these NPs lies mainly in the confinement of optical and magnetic imaging agents (Ru and Gd complexes, respectively) within the NP volume. Their potential use as a bimodal probe (luminescence/magnetic resonance imaging) and theranostic agent (photodynamic therapy/imaging) is described. The biological potential of these NPs has been studied on HCT‐116 cells and microscopy and cytotoxicity results are given.
Adverse Drug Reactions in Children: The Double‐Edged Sword of Therapeutics
Authors: Elzagallaai AA , Greff MJE , Rieder MJ
Published: March 2017

Adverse drug reactions (ADRs) represent a major health problem worldwide, with high morbidity and mortality rates. ADRs are classified into Type A (augmented) and Type B (bizarre) ADRs, with the former group being more common and the latter less common but often severe and clinically more problematic due to their unpredictable nature and occurrence at any dose. Pediatric populations are especially vulnerable to ADRs due to the lack of data for this age group from the drug development process and because of the wide use of off‐label and unlicensed use of drugs. Children are more prone to specific types of ADRs because of the level of maturity of body systems involved in absorption, metabolism, transportation, and elimination of drugs. This state‐of‐the‐art review provides an overview of definitions, classifications, epidemiology, and pathophysiology of ADRs and discusses the available evidence for related risk factors and causes of ADRs in the pediatric population.
Interferometry‐based direct comparison of transport phenomena associated with the growth processes of organic and inorganic crystals
Authors: Haridas Divya , Srivastava Atul
Published: March 2017

Non‐intrusive dynamic measurements of concentration fields around solution‐grown protein and inorganic crystals using a Mach‐Zehnder interferometer have been reported. Sodium chlorate (inorganic) and hen‐egg‐white lysozyme (protein) crystals have been employed as model materials. Mass transport phenomenon during the growth process is visualized in the form of interferometric images. Development of concentration boundary layers in the vicinity of the two types of crystals has been investigated. Results are presented in the form of interferometric images, contours of two‐ dimensional concentrations and gradient fields. Primary findings of the experimental study clearly reveal the differences in the transport phenomena associated with the growth processes of inorganic and protein crystals. Fringe patterns recorded during the growth of inorganic crystal showed substantial deformation in the vicinity of the crystal top surface whereas the fringe deformation was seen to be very mild in the case of protein crystals. Qualitative interpretation of the images revealed strong concentration gradients in the vicinity of the growing NaClO3 crystal as compared to those observed for the lysozyme crystals. Based on the interferometric observations, the strength of transport phenomena associated with the two categories of crystals has been quantified and reported in terms of non‐dimensional parameters such as the Rayleigh number.
Recovery of shape and size in a developing organ pair
Authors: Green Amelia A. , Mosaliganti Kishore R. , Swinburne Ian A. , Obholzer Nikolaus D. , Megason Sean G.
Published: March 2017

Background: Paired organs in animals are largely bilaterally symmetric despite inherent noise in most biological processes. How is precise organ shape and size achieved during development despite this noise? Examining paired organ development is a challenge because it requires repeated quantification of two structures in parallel within living embryos. Here we combine bilateral quantification of morphology through time with asymmetric perturbations to study regulation of organ shape, size, and symmetry in developing organ pairs. Results: We present quantitative live imaging tools to measure the shape and size of the developing inner ears on both the left and right side simultaneously over time. By quantifying variation between the left and right inner ear (intrinsic noise) and between different individuals (extrinsic noise), we find that initial variability decreases over time in normal development to achieve symmetry. Early asymmetry is increased by environmental stress, but symmetry is still recovered over subsequent developmental time. Using multiple unilateral perturbations including Fgf signaling and ultraviolet light, we find that growth can be adjusted to compensate for a range of initial size and shape differences. Conclusions: We propose that symmetry in developmental systems does not emerge through precise deterministic bilateral development, but rather through feedback mechanisms that adjust morphogenesis rates to account for variation. Developmental Dynamics 246:451–465, 2016. © 2017 Wiley Periodicals, Inc.
Evaluating multiple spatial scales to understand the distribution of anuran beta diversity in the Brazilian Atlantic Forest
Authors: Melchior Lara G. , Rossa‐Feres Denise de C. , da Silva Fernando R.
Published: March 2017

We partitioned the total beta diversity in the species composition of anuran tadpoles to evaluate if species replacement and nestedness components are congruent at different spatial resolutions in the Brazilian Atlantic Forest. We alternated the sampling grain and extent of the study area (among ponds at a site, among ponds within regions, among sites within regions, and among sites within regions pooled together) to assess the importance of anuran beta diversity components. We then performed variation partitioning to evaluate the congruence of environmental descriptors and geographical distance in explaining the spatial distribution of the species replacement and nestedness components. We found that species replacement was the main component of beta diversity, independent of the sampling grain and extent. Furthermore, when considering the same sampling grain and increasing the extent, the values of species replacement increased. On the other hand, when considering the same extent and increasing the sampling grain, the values of species replacement decreased. At the smallest sampling grain and extent, the environmental descriptors and geographic distance were not congruent and alternated in the percentage of variation explaining the spatial distribution of species replacement and nestedness. At the largest spatial scales (SSs), the biogeographical regions showed higher values of the percentage explaining the variation in the beta diversity components. We found high values of species replacement independently of the spatial resolution, but the processes driving community assembly seem to be dependent on the SS. At small scales, both stochastic and deterministic factors might be important processes structuring anuran tadpole assemblages. On the other hand, at a large spatial grain and extent, the processes restricting species distributions might be more effective for drawing inferences regarding the variation in anuran beta diversity in different regions of the Brazilian Atlantic Forest.
Past freeze–thaw events on Pinus seeds increase seedling herbivory
Authors: Connolly Brian M. , Guiden Peter W. , Orrock John L.
Published: March 2017

Seed and seedling survival are key components of plant population persistence. Although freeze–thaw events are experienced by many dispersed seeds in temperate ecosystems, it is unclear whether freeze–thaw stresses experienced by seeds can alter seedling susceptibility to herbivores during the growing season. We evaluated how freezing stress (temperature at −6°C for 6 h) experienced by seeds of two conifer species (Pinus resinosa and Pinus strobus) affects seedling herbivory by a generalist herbivore (Spodoptera exigua). For both Pinus species, herbivores consumed twofold more seedling biomass from freeze–thaw‐treated plants than seedlings from the constant temperature treatment. Herbivores grew ~66% faster when feeding on freeze–thaw P. resinosa seedlings relative to controls, but herbivore growth rate did not differ between treatments for P. strobus. Our results show that the thermal environment experienced by a seed can have subsequent effects on plant–herbivore interactions, suggesting that (1) early ontogenetic stress could be a cryptic, yet unappreciated, determinant of future herbivory and (2) increasingly frequent cold events, such as those projected under winter climate change, may amplify seedling herbivory and reduce recruitment in managed and natural conifer forests.
Differential impacts of wildfire on the population dynamics of an old‐forest species
Authors: Rockweit Jeremy T. , Franklin Alan B. , Carlson Peter C.
Published: March 2017

Ecological disturbances shape and maintain natural communities, but climate change and human land use can alter disturbance regimes and affect population persistence and vital rates in unpredictable ways. Species inhabiting landscapes shaped by wildfire have evolved mechanisms allowing them to persist under this dynamic disturbance type, which creates habitats of varying quality for these species. We utilized data from a 26‐yr demographic study of northern spotted owls to analyze the influence of wildfire on apparent survival and recruitment rates. Wildfires occurred across different years and affected different spotted owl territories, which allowed us to implement a retrospective Before‐After‐Control‐Impact (BACI) analysis and model the potential effect of wildfire extent and severity. Our results indicated that mixed‐severity fires that burned at predominantly low‐severity had little effect on survival and recruitment while fires characterized by more medium to high burn severities negatively affected spotted owl survival, with varying effects on recruitment. Reduced survival and increased recruitment rates on some territories affected by medium to high severity fires suggested that post‐fire habitat quality was reduced resulting in territories that were marginally capable of supporting owls. We hypothesize these territories may have represented “sinks” that were supported by nearby “source” territories in a spatially heterogeneous landscape created by the mixed‐severity fire regime of the region.
Predictors of short‐term clinical response to cardiac resynchronization therapy
Authors: Linde Cecilia , Abraham William T. , Gold Michael R. , Daubert J. Claude , Tang Anthony S.L. , Young James B. , Sherfesee Lou , Hudnall J. Harrison , Fagan Dedra H. , Cleland John G.
Published: March 2017

Aims

Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in patients with symptomatic heart failure and QRS prolongation but there is uncertainty about which patient characteristics predict short‐term clinical response.

Methods and results

In an individual patient meta‐analysis of three double‐blind, randomized trials, clinical composite score (CCS) at 6 months was compared in patients assigned to CRT programmed on or off. Treatment–covariate interactions were assessed to measure likelihood of improved CCS at 6 months. MIRACLE, MIRACLE ICD, and REVERSE trials contributed data for this analysis (n = 1591). Multivariable modelling identified QRS duration and left ventricular ejection fraction (LVEF) as predictors of CRT clinical response (P < 0.05). The odds ratio for a better CCS at 6 months increased by 3.7% for every 1% decrease in LVEF for patients assigned to CRT‐on compared to CRT‐off, and was greatest when QRS duration was between 160 and 180 ms.

Conclusions

In symptomatic chronic heart failure patients (NYHA class II–IV), longer QRS duration and lower LVEF independently predict early clinical response to CRT.
On the Porous Silicate HPM‐5
Authors: Jo Donghui , Mayoral Alvaro , Hong Suk Bong , Camblor Miguel A.
Published: March 2017

HPM‐5, a porous aluminosilicate with an intricate and so far unsolved structure, has been synthesized by using 1,2,3‐trimethylimidazolium in hydroxide medium in the absence of fluoride anions. It consistently displays an ill‐defined XRD pattern with broad and overlapped reflections and contains a large concentration of defects, as evidenced by IR and 29Si MAS NMR spectroscopy. 1H MAS NMR spectroscopy confirmed the existence of highly deshielded protons (δ = –11.6 ppm) assigned to hydrogen atoms in relatively strong Si–O–H···O–Si hydrogen bonds (O···O distance ≈ 2.64 Å) The calcined material shows limited microporosity (0.07–0.09 cm3 g–1). The results of a high‐resolution transmission electron microscopy study suggest HPM‐5 may be far more complicated than “standard” layered zeolites and may consist of low‐density layers profusely decorated by holes. The resulting lace‐like layers may be too unstable to withstand reactions characteristic of more conventional layered materials (both delamination and expansion by silylation); although the derivatives show an increase in the specific surface area, the layers are apparently disassembled and, at most, only ribbons remain.
Molecular Tweezers Inhibit PARP‐1 by a New Mechanism
Authors: Wilch Constanze , Talbiersky Peter , Berchner‐Pfannschmidt Utta , Schaller Torsten , Kirsch Michael , Klärner Frank‐Gerrit , Schrader Thomas
Published: March 2017

The inhibition of PARP‐1 (poly[ADP‐ribose]polymerase 1), a key enzyme for DNA quality control, has been achieved with synthetic molecular tweezers through a noncompetitive mechanism with an IC50 value of 3 µm. Displacement as well as electrophoretic mobility shift assays and molecular dynamics experiments point to a simultaneous inclusion of lysine side‐chains in the cavity of the tweezers and the coordination of one phosphate arm to the central Zn2+ ion of the zinc finger; thereby, lesioned DNA is displaced.