bluuebunny/crossref_metadata_2025 huggingface dataset:
Apolipoprotein E mimetic peptide, CN‐105, improves outcomes in ischemic stroke
Authors: Tu Tian Ming , Kolls Brad J. , Soderblom Erik J. , Cantillana Viviana , Ferrell Paul Durham , Moseley M. Arthur , Wang Haichen , Dawson Hana N. , Laskowitz Daniel T.
Published: March 2017

Objective

At present, the absence of a pharmacological neuroprotectant represents an important unmet clinical need in the treatment of ischemic and traumatic brain injury. Recent evidence suggests that administration of apolipoprotein E mimetic therapies represent a viable therapeutic strategy in this setting. We investigate the neuroprotective and anti‐inflammatory properties of the apolipoprotein E mimetic pentapeptide, CN‐105, in a microglial cell line and murine model of ischemic stroke.

Methods

Ten to 13‐week‐old male C57/BL6 mice underwent transient middle cerebral artery occlusion and were randomly selected to receive CN‐105 (0.1 mg/kg) in 100 μL volume or vehicle via tail vein injection at various time points. Survival, motor‐sensory functional outcomes using rotarod test and 4‐limb wire hanging test, infarct volume assessment using 2,3,5‐Triphenyltetrazolium chloride staining method, and microglial activation in the contralateral hippocampus using F4/80 immunostaining were assessed at various time points. In vitro assessment of tumor necrosis factor‐alpha secretion in a microglial cell line was performed, and phosphoproteomic analysis conducted to explore early mechanistic pathways of CN‐105 in ischemic stroke.

Results

Mice receiving CN‐105 demonstrated improved survival, improved functional outcomes, reduced infarct volume, and reduced microglial activation. CN‐105 also suppressed inflammatory cytokines secretion in microglial cells in vitro. Phosphoproteomic signals suggest that CN‐105 reduces proinflammatory pathways and lower oxidative stress.

Interpretation

CN‐105 improves functional and histological outcomes in a murine model of ischemic stroke via modulation of neuroinflammatory pathways. Recent clinical trial of this compound has demonstrated favorable pharmacokinetic and safety profile, suggesting that CN‐105 represents an attractive candidate for clinical translation.
In Vivo Examination of an Injectable Hydrogel System Crosslinked by Peptide–Oligosaccharide Interaction in Immunocompetent Nude Mice
Authors: Tondera Christoph , Wieduwild Robert , Röder Elisabeth , Werner Carsten , Zhang Yixin , Pietzsch Jens
Published: March 2017

Hydrogels can serve as matrices to mimic natural tissue function and be used for wide‐ranging applications such as tissue regeneration and drug delivery. Injectable hydrogels are particularly favorable because their uses are minimally invasive. However, creating moldable substance for injection often results in compromised function and stability. This study reports an injectable hydrogel system crosslinked by peptide–oligosaccharide noncovalent interaction. The dynamic network shows fast self‐healing, a property essential for injectability. Injected hydrogels in immunocompetent mice and release of encapsulated compound are monitored up to 9 months by magnetic resonance imaging (MRI) and optical imaging. This surprisingly stable hydrogel does not cause adverse inflammatory response, as analyzed by measuring cytokine levels, immunohistochemistry, and MRI. Hydrogel degradation is associated with invasion of macrophages and vascular formation. The facile synthesis, high biocompatibility, and stability of this injectable hydrogel can lead to various experimental and clinical applications in regenerative medicine and drug delivery.
Langkettige Alkylcyanide, beispiellose flüchtige Verbindungen aus Pseudomonas‐ und Micromonospora‐Bakterien
Authors: Montes Vidal Diogo , von Rymon‐Lipinski Anna‐Lena , Ravella Srinivasa , Groenhagen Ulrike , Herrmann Jennifer , Zaburannyi Nestor , Zarbin Paulo H. G. , Varadarajan Adithi R. , Ahrens Christian H. , Weisskopf Laure , Müller Rolf , Schulz Stefan
Published: March 2017

Langkettige aliphatische Nitrile, eine neue Naturstoffklasse, wurden durch Analyse flüchtiger Verbindungen aus Bakterienkulturen gefunden. Diese Nitrile werden von Gram‐positiven Micromonospora echinospora und Gram‐negativen Pseudomonas veronii produziert, jedoch mit unterschiedlichen Strukturmerkmalen. Eine flexible Abfolge von Kettenverlängerungen und Dehydratisierung in der Fettsäurebiosynthese führt zu unverzweigten gesättigten Nitrilen und entsprechenden ungesättigten Nitrilen mit ω−7‐Doppelbindung, wie (Z)‐11‐Octadecennitril, oder zu methylverzweigten ungesättigten Nitrilen mit einer Doppelbindung in C‐3‐Position, z. B. (Z)‐13‐Methyltetradec‐3‐ennitril. Die Biosynthese dieser Verbindungen beginnt mit Fettsäuren, die zuerst in ihre Amide und schließlich unter Wasserabspaltung zu Nitrilen umgewandelt werden. Die Strukturen und die Biosynthese der 19 natürlich vorkommenden Verbindungen wurden durch Massenspektrometrie, Synthese und Fütterungsexperimente mit deuterierten Vorstufen aufgeklärt. Einige der Nitrile zeigten antimikrobielle Aktivität, z. B. gegen MRSA‐Stämme.
Rh/Cu‐Catalyzed Cascade [4+2] Vinylic C−H O‐Annulation and Ring Contraction of α‐Aryl Enones with Alkynes in Air
Authors: Zhao Yinsong , Li Shiqing , Zheng Xuesong , Tang Junbin , She Zhijie , Gao Ge , You Jingsong
Published: March 2017

An unprecedented Rh‐catalyzed ketone‐directed vinylic C−H activation/[4+2] O‐annulation of α‐aryl enones with internal alkynes followed by a Cu‐catalyzed ring contraction in air to provide multiaryl‐substituted furan derivatives has been developed. The preliminary mechanism study identifies the active pyrylium salt as the key intermediate.
A Dimeric Bis(melamine)‐Substituted Bispidine for Efficient Transmembrane H+/Cl− Cotransport
Authors: Shinde Sopan Valiba , Talukdar Pinaki
Published: March 2017

A 3,7‐diazabicyclo[3.3.1]nonane linking to two melamines is a unique transmembrane H+/Cl− carrier. In the solid state, the V‐shaped compound forms a HCl‐bound zig‐zag network through cooperative protonation and hydrogen bond interactions. In the lipid membrane, the receptor forms a dimeric self‐assembly involving multiple H+ and Cl− leading to the efficient transport of the acid. The pH‐dependent Cl− efflux observed for the compound was rationalized based on a gradual protonation model that confers an active transmembrane carrier at physiological pH.
Measuring Spin⋅⋅⋅Spin Interactions between Heterospins in a Hybrid [2]Rotaxane
Authors: Boulon Marie‐Emmanuelle , Fernandez Antonio , Moreno Pineda Eufemio , Chilton Nicholas F. , Timco Grigore , Fielding Alistair J. , Winpenny Richard E. P.
Published: March 2017

Use of molecular electron spins as qubits for quantum computing will depend on the ability to produce molecules with weak but measurable interactions between the qubits. Here we demonstrate use of pulsed EPR spectroscopy to measure the interaction between two inequivalent spins in a hybrid rotaxane molecule.
Transition‐Metal‐Catalyzed Utilization of Methanol as a C1 Source in Organic Synthesis
Authors: Natte Kishore , Neumann Helfried , Beller Matthias , Jagadeesh Rajenahally V.
Published: March 2017

Methanol is used as a common solvent, cost‐effective reagent, and sustainable feedstock for value‐added chemicals, pharmaceuticals, and materials. Among the various applications, the utilization of methanol as a C1 source for the formation of carbon–carbon, carbon–nitrogen, and carbon–oxygen bonds continues to be important in organic synthesis and drug discovery. In particular, the synthesis of C‐, N‐, and O‐methylated products is of central interest because these motifs are found in a large number of natural products as well as fine and bulk chemicals. In this Minireview, we summarize the utilization of methanol as a C1 source in methylation, methoxylation, formylation, methoxycarbonylation, and oxidative methyl ester formation reactions.
Silica‐Encapsulated Pt‐Sn Intermetallic Nanoparticles: A Robust Catalytic Platform for Parahydrogen‐Induced Polarization of Gases and Liquids
Authors: Zhao Evan W. , Maligal‐Ganesh Raghu , Xiao Chaoxian , Goh Tian‐Wei , Qi Zhiyuan , Pei Yuchen , Hagelin‐Weaver Helena E. , Huang Wenyu , Bowers Clifford R.
Published: March 2017

Recently, a facile method for the synthesis of size‐monodisperse Pt, Pt3Sn, and PtSn intermetallic nanoparticles (iNPs) that are confined within a thermally robust mesoporous silica (mSiO2) shell was introduced. These nanomaterials offer improved selectivity, activity, and stability for large‐scale catalytic applications. Here we present the first study of parahydrogen‐induced polarization NMR on these Pt‐Sn catalysts. A 3000‐fold increase in the pairwise selectivity, relative to the monometallic Pt, was observed using the PtSn@mSiO2 catalyst. The results are explained by the elimination of the three‐fold Pt sites on the Pt(111) surface. Furthermore, Pt‐Sn iNPs are shown to be a robust catalytic platform for parahydrogen‐induced polarization for in vivo magnetic resonance imaging.
Internet Safety and the Silver Surfer: The Relationship Between Gist Reasoning and Adults' Risky Online Behavior
Authors: White Claire M. , Gummerum Michaela , Wood Stacey , Hanoch Yaniv
Published: March 2017

Currently, fewer older adults are online compared with younger generations. However, with many new initiatives aiming to significantly increase the number of older internet users, they will increasingly be exposed to potential victimisation from internet fraud, a fundamental issue affecting all adult internet users. Despite this, little research has examined online risk‐taking across the adult lifespan or adults' reasoning about risky online behaviors. Using fuzzy trace theory, we investigated adults' online risk‐taking behavior and intentions, and whether these behaviors were related to different ways of reasoning about risk, namely, gist reasoning (using qualitative, intuitive knowledge) and verbatim reasoning (using quantitative, specific knowledge). Participants (326 adults, 18–79 years old, Mage = 49.54 years) reported their past risk‐taking behavior, future online risk intentions, gist and verbatim reasoning about online risk, sensation seeking, and time spent online. Age was negatively correlated with past risk‐taking, time online, future risk intentions, and sensation seeking. However, time spent online was positively related to future risk intentions, suggesting that spending more time using the internet could lead individuals to take more risks. Increased verbatim reasoning predicted increased intentions to take online risks, while gist reasoning predicted reduced intentions to take risks online. Our findings extend online risk research applying fuzzy trace theory to adolescents and young adults and suggest that online safety training incorporating gist‐based reasoning strategies could benefit all adults and, in particular, older generations. Copyright © 2017 John Wiley & Sons, Ltd.
Is What You Feel What They See? Prominent and Subtle Identity Signaling in Intergroup Interactions
Authors: Matherly Ted , Pocheptsova Ghosh Anastasiya
Published: March 2017

Individuals often signal group affiliations to others, and the display of such identity signals is frequently rather subtle. While prior work has focused on understanding an individual's choices of subtle versus prominent signals, in this work, we look at the downstream consequences of such choices. Specifically, we explore how the prominence of identity signals may affect one's behavior in intergroup interactions. Drawing from literature on processing fluency, we propose that the use of difficult to process (subtle) identity signals in intergroup interactions leads signalers to experience identity threat, lowering confidence in their identity and leading them to engage in behaviors to recover from this experience. Across three different identity domains (college affiliation, political affiliation, and brand loyalty), we show that when individuals use difficult to process identity signals, they derogate out‐group members in communication and behave less cooperatively in intergroup interactions. We find that these effects depend upon the observability of the signals by out‐group members and only occur for individuals who are highly identified with the in‐group. We also find that the effects are attenuated when behavior towards members of the out‐group is made public. Copyright © 2017 John Wiley & Sons, Ltd.
A highly sensitive detection of chloramphenicol based on chemiluminescence immunoassays with the cheap functionalized Fe3O4@SiO2 magnetic nanoparticles
Authors: Linyu Wang , Manwen Yao , Chengzhi Fang , Xi Yao
Published: March 2017

A strategy has been applied to chloramphenicol (CAP) detection with chemiluminescence immunoassays (CLIA) based on cheap functionalized Fe3O4@SiO2 magnetic nanoparticles (Fe–MNPs). The strategy that bovine serum albumin (BSA) was immobilized on cheap functionalized Fe–MNPs and that the CAP molecules were then immobilized on BSA, avoided the long process of dialysis for preparation of the BSA‐CAP conjugates. The samples were detected for both methods that utilized two different kinds of functionalized Fe–MNPs (amine‐functionalized Fe3O4@SiO2 and carboxylic acid‐functionalized Fe3O4@SiO2). The sensitivities and limits of detection (LODs) of the two methods were obtained and compared based on inhibition curves. The 50% inhibition concentrations (IC50) values of the two methods were about 0.024 ng ml−1 and 0.046 ng ml−1 respectively and LODs were approximately 0.0002 ng ml−1 and 0.001 ng ml−1 respectively. These methods were much more sensitive than that of any traditional enzyme‐linked immunosorbent assay (ELISA) previously reported. Therefore, such chemiluminescence methods could be easily adapted for small molecule detection in a variety of foods using Fe–MNPs.
Identification of novel NF‐κB transcriptional targets in TNFα‐treated HeLa and HepG2 cells
Authors: Zhou Fei , Xu Xinhui , Wang Danyang , Wu Jian , Wang Jinke
Published: March 2017

Identification of target genes of NF‐κB is critical for deeply understanding its biological functions. Here, we identified five novel NF‐κB target genes. Firstly, we found that 20 NF‐κB potential target genes (PTGs) identified by ChIP‐Seq and Genechip assay were enriched into the KEGG term of Pathways in cancer, 16 of them were enriched into the KEGG pathways of small cell lung cancer, chronic myeloid leukemia, basal cell carcinoma, pancreatic cancer, and colorectal cancer. Among these PTGs, there are many documented NF‐κB target genes. Therefore, NF‐κB may play important role in cancer progression by transcriptionally regulating these genes. Apart from the known target genes, we also found some novel PTGs including CYCS, MITF, FZD1, FZD8, and PIAS1. We subsequently demonstrated whether NF‐κB transcriptionally control the five PTGs. The ChIP‐Seq assay revealed that NF‐κB/p65 bound to these genes in TNFα‐treated HeLa. The bioinformatic analysis indicated that the NF‐κB binding regions (i.e., ChIP‐Seq peaks) contained κB sites and NF‐κB/RelA DNA‐binding motif. The ChIP‐qPCR assay also confirmed that NF‐κB bound to these regions in both TNFα‐treated HeLa and HepG2 cells. The reporter construct showed that NF‐κB could regulate luciferase expression via its binding region. Finally, qPCR and Western blot assay demonstrated that NF‐κB indeed regulated the expression of these genes in the TNFα‐treated HeLa and HepG2 cells. In a word, CYCS, MITF, FZD1, FZD8, and PIAS1 were identified as bona fide NF‐κB target genes. These findings provide more insights into the role of NF‐κB in cancers.
The association between type of out‐of‐home mental health treatment and juvenile justice recidivism for youth with trauma exposure
Authors: Robst John , Armstrong Mary , Dollard Norin
Published: March 2017

Background

High rates of mental health disorders and exposure to trauma among the juvenile justice population highlight the importance of understanding whether and how mental health services can help prevent further justice system involvement as well as provide treatment.

Aims

We had two principal questions: Is out‐of‐home mental health treatment after arrest associated with reduced recidivism among young people who have been exposed to trauma? Are particular types of out‐of‐home treatment associated with better outcomes? We hypothesised that type of residential setting would affect outcomes among those with histories of serious trauma.

Methods

Primary data sources included Florida Juvenile Justice, Child Welfare and Medicaid data from July 2002 through June 2008. We identified all Florida Juvenile Justice cases with a record of ‘severe emotional disturbance’. Two groups were identified – one for whom an arrest was followed within 90 days by out‐of‐home placement for mental health treatment and the other for whom there was some other out‐of‐home placement. Generalised estimating equations (GEE) were used to calculate associations with likelihood of re‐arrest during a 12 month at risk period.

Results

Young people who had experienced severe trauma and were sent to out‐of‐home treatment settings after conviction for a criminal offence had lower recidivism rates when receiving treatment in foster care than other out‐of‐home placements, while those with less severe or no trauma histories had lower recidivism rates with any out‐of‐home placement.

Conclusions and implications for practice

We believe that this is the first study to have considered how trauma histories may mediate outcomes for young people in out‐of‐home placements after arrest or conviction for a criminal offence. Findings suggest that case managers and clinicians should consider the trauma histories when making decisions about the appropriate treatment setting in these circumstances. Copyright © 2017 John Wiley & Sons, Ltd.
A Mixed N‐Heterocyclic Carbene/2,2′‐Bipyridine‐Supported Robust Ruthenium(II) Oxidation Precatalyst for Benzylic C−H Oxidation
Authors: Gupta Suraj K. , Choudhury Joyanta
Published: March 2017

Catalytic oxidation of hydrocarbons to the oxygenated derivatives has been an important research area for a long time and the search for well‐defined, tunable, efficient, selective, and robust oxidation (pre)catalysts is still on. To further develop the applicability of N‐heterocyclic carbene (NHC) ligands, herein we report a mixed NHC/bipyridine‐supported ruthenium(II) oxidation precatalyst, [(Npy^CNHC)RuII(Npy^Npy)(CH3CN)2](PF6)(CF3SO3), 1 (Npy^CNHC=a bidentate ′2‐pyridyl‐NHC′ neutral ligand, Npy^Npy=2,2′‐bipyridine) consisting of two cis‐disposed loosely bound solvent ligands, which was successfully utilized for catalytic benzylic C−H oxidation of a variety of aromatic hydrocarbons to the corresponding ketones in 65–90 % yields with the mild sacrificial oxidant NaIO4. The ligand backbone was found to be robust under oxidizing conditions. The presence of these ligands around the ruthenium center was crucial for the system, as the known RuCl3/NaIO4 and [Ru(para‐cymene)Cl2]2/NaIO4 combinations were proved to be completely ineffective precatalysts under similar conditions. The scope and mechanistic aspects of this precatalyst were also evaluated.
Hydrodeoxygenation of Fatty Acids, Triglycerides, and Ketones to Liquid Alkanes by a Pt–MoOx/TiO2 Catalyst
Authors: Kon Kenichi , Toyao Takashi , Onodera Wataru , Siddiki S. M. A. H. , Shimizu Ken‐ichi
Published: March 2017

Various supported metal catalysts are screened for hydrogenation of lauric acid and 2‐octanone as model reactions for the transformation of biomass‐derived oxygenates to liquid alkanes (biofuels) in a batch reactor under solvent‐free conditions. Among the catalysts tested, Pt and MoOx co‐loaded on TiO2 (Pt–MoOx/TiO2) shows the highest yields of n‐alkanes for both of the reactions. Pt–MoOx/TiO2 selectively catalyzes the hydrodeoxygenation of various fatty acids and triglycerides to n‐alkanes without C−C bond cleavage under 50 bar H2 and shows higher turnover numbers than the catalysts in the literature. Pt–MoOx/TiO2 is effective also for the hydrodeoxygenation of various ketones to the corresponding alkanes. In situ IR study of the reaction of adsorbed acetone under H2 suggests that the high activity of Pt–MoOx/TiO2 is attributed to the cooperation between Pt and Lewis acid sites of the MoOx/TiO2 support.
Molecular Assemblies of Metal Complexes via Base‐Pairing of Nucleic Acids in the Crystalline State
Authors: Nakaya Manabu , Ohtani Ryo , Sugimoto Kunihisa , Nakamura Masaaki , Lindoy Leonard F. , Hayami Shinya
Published: March 2017

The nature of the molecular assemblies formed in the crystalline state by cobalt(II) terpyridine (terpy) complexes incorporating appended adenine (A) or thymine (T) bases was found to be controlled by which bases are present. Single‐crystals of the cobalt(II) complexes [Co(A‐C6‐terpy)2](BF4)2 (1) and [Co(T‐C6‐terpy)2](BF4)2 (2) have needle and block habits, respectively. Subsequent mixing of 1 and 2 in MeOH resulted in isolation of [Co(A‐C6‐terpy)1.5(T‐C6‐terpy)0.5](BF4)2 (3) as plate‐like crystals. A 3D network structure is present in 1 that incorporates 1D chains, whereas 2 adopts a 2D stacked structure constructed from ladder‐type assemblies. For 3, “dimer‐rings” consisting of [Co(A‐C6‐terpy)2]2+ and [Co(A‐C6‐terpy)(T‐C6‐terpy)]2+ units are generated by means of base‐pairing between A and T. Notably, 3 displays the first crystal structure of a heteroleptic cobalt(II) complex of [Co(A‐C6‐terpy)(T‐C6‐terpy)](BF4)2. These assembly differences involving the terpyridine cobalt(II) complex units in 1–3 affect the cooperativities influencing their spin crossover (SCO) behavior. The influence of the terminal nucleobases on the resulting assembly has been probed by investigating the co‐crystallization of [Co(terpy)2](BF4)2 (4) with [Co(C6‐terpy)2](BF4)2 (5) and 1 with 5.
Information order effects in clinical psychological diagnoses
Authors: Cwik Jan Christopher , Margraf Jürgen
Published: March 2017

Despite the wide application and long history of diagnostic systems, several sources of diagnostic errors remain in the criterion‐based diagnosing of mental disorders. The aim of this study was to investigate whether the presentational order of diagnosis‐relevant information and pretreatment reports predict diagnostic errors. One hundred twenty psychotherapists participated in the present online study. The study employed a 2 (symptom presentation: core symptoms at vignette's beginning vs. core symptoms at the end of the case vignette) × 2 (pretreatment report: receiving a pretreatment report with an incongruent diagnosis to the case vignette vs. receiving no pretreatment report) between‐subjects experimental design, with random assignment. Participants were asked to make diagnoses after reading three case vignettes describing patients with different disorder constellations. Additionally, participants rated their confidence in the diagnoses and their estimation of the severity of each diagnosed condition. Results indicated that order of symptom descriptions predicted the correctness of diagnostic decisions, with a recency effect causing more fully correct diagnostic decisions in cases where diagnostic information was presented last. Receiving incongruent pretreatment reports was predictive for diagnostic errors. In conclusion, the results of this study indicate that diagnoses of mental disorders can depend on the way symptoms are presented or reported.

Key Practitioner Message:

Therapists' diagnostic decisions are not influenced by pretreatment reports.

Diagnostic decisions are affected by information order effects.

Diagnostic accuracy of psychotherapists is debatable.

High rate of misdiagnoses in case vignette with comorbid disorders.
Integrating CdSe Quantum Dots with a [FeFe]‐Hydrogenase Mimic into a Photocathode for Hydrogen Evolution at a Low Bias Voltage
Authors: Wen Min , Wu Hao‐Lin , Jian Jing‐Xin , Wang Xu‐Zhe , Li Xu‐Bing , Chen Bin , Tung Chen‐Ho , Wu Li‐Zhu
Published: March 2017

A simple [FeFe]‐hydrogenase mimic, Fe2S2(CO)6, was integrated with CdSe quantum dots to form a sensitized electrode on a p‐NiO layer, which can start to catalyze proton reduction at a bias voltage as positive as ≈0.3 V (vs. NHE) in neutral water. The result provides a promising way to overcome the much more negative onset bias of [FeFe]‐hydrogenase mimics for H2 evolution under mild conditions.
Flight performance in the altricial zebra finch: Developmental effects and reproductive consequences
Authors: Crino Ondi L. , Klaassen van Oorschot Brett , Crandell Kristen E. , Breuner Creagh W. , Tobalske Bret W.
Published: March 2017

The environmental conditions animals experience during development can have sustained effects on morphology, physiology, and behavior. Exposure to elevated levels of stress hormones (glucocorticoids, GCs) during development is one such condition that can have long‐term effects on animal phenotype. Many of the phenotypic effects of GC exposure during development (developmental stress) appear negative. However, there is increasing evidence that developmental stress can induce adaptive phenotypic changes. This hypothesis can be tested by examining the effect of developmental stress on fitness‐related traits. In birds, flight performance is an ideal metric to assess the fitness consequences of developmental stress. As fledglings, mastering takeoff is crucial to avoid bodily damage and escape predation. As adults, takeoff can contribute to mating and foraging success as well as escape and, thus, can affect both reproductive success and survival. We examined the effects of developmental stress on flight performance across life‐history stages in zebra finches (Taeniopygia guttata). Specifically, we examined the effects of oral administration of corticosterone (CORT, the dominant avian glucocorticoid) during development on ground‐reaction forces and velocity during takeoff. Additionally, we tested for associations between flight performance and reproductive success in adult male zebra finches. Developmental stress had no effect on flight performance at all ages. In contrast, brood size (an unmanipulated variable) had sustained, negative effects on takeoff performance across life‐history stages with birds from small broods performing better than birds from large broods. Flight performance at 100 days posthatching predicted future reproductive success in males; the best fliers had significantly higher reproductive success. Our results demonstrate that some environmental factors experienced during development (e.g. clutch size) have stronger, more sustained effects than others (e.g. GC exposure). Additionally, our data provide the first link between flight performance and a direct measure of reproductive success.
Consumptive and nonconsumptive effect ratios depend on interaction between plant quality and hunting behavior of omnivorous predators
Authors: Stephan Jörg G. , Stenberg Johan A. , Björkman Christer
Published: March 2017

Predators not only consume prey but exert nonconsumptive effects in form of scaring, consequently disturbing feeding or reproduction. However, how alternative food sources and hunting mode interactively affect consumptive and nonconsumptive effects with implications for prey fitness have not been addressed, impending functional understanding of such tritrophic interactions. With a herbivorous beetle, two omnivorous predatory bugs (plant sap as alternative food, contrasting hunting modes), and four willow genotypes (contrasting suitability for beetle/omnivore), we investigated direct and indirect effects of plant quality on the beetles key reproductive traits (oviposition rate, clutch size). Using combinations of either or both omnivores on different plant genotypes, we calculated the contribution of consumptive (eggs predated) and nonconsumptive (fewer eggs laid) effect on beetle fitness, including a prey density‐independent measure (c:nc ratio). We found that larger clutches increase egg survival in presence of the omnivore not immediately consuming all eggs. However, rather than lowering mean, the beetles generally responded with a frequency shift toward smaller clutches. However, female beetles decreased mean and changed clutch size frequency with decreasing plant quality, therefore reducing intraspecific exploitative competition among larvae. More importantly, variation in host plant quality (to omnivore) led to nonconsumptive effects between one‐third and twice as strong as the consumptive effects. Increased egg consumption on plants less suitable to the omnivore may therefore be accompanied by less searching and disturbing the beetle, representing a “cost” to the indirect plant defense in the form of a lower nonconsumptive effect. Many predators are omnivores and altering c:nc ratios (with egg retention as the most direct link to prey fitness) via plant quality and hunting behavior should be fundamental to advance ecological theory and applications. Furthermore, exploring modulation of fitness traits by bottom‐up and top‐down effects will help to explain how and why species aggregate.
Guided Self‐help for Eating Disorders: A Systematic Review and Metaregression
Authors: Traviss‐Turner Gemma D. , West Robert M. , Hill Andrew J.
Published: March 2017

Background

Evidence‐based self‐help is a recommended first stage of treatment for mild–moderate eating disorders. The provision of guidance enhances outcome. The literature evaluating exclusively ‘guided’ self‐help (GSH) has not been systematically reviewed.

Methods

The aim was to establish the effectiveness of GSH for reducing global eating disorder psychopathology and abstinence from binge eating, compared with controls. Results were pooled using random effects meta‐analysis and heterogeneity explored using metaregression.

Results

Thirty randomised controlled trials met the inclusion criteria. Results showed an overall effect of GSH on global eating disorder psychopathology (−0.46) and binge abstinence (−0.20). There was strong evidence for an association between diagnosis of binge eating disorder and binge abstinence.

Discussion

Current interventions need to be adapted to address features other than binge eating. Further research is required to help us understand the effectiveness of GSH in children and young people, invariably high dropout rates and how technology can enhance interventions. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.
A climatology of easterly waves in the tropical Western Hemisphere
Authors: Belanger J. I. , Jelinek M. T. , Curry J. A.
Published: March 2017

To understand the relationship among easterly waves, tropical cyclones (TCs), and the large‐scale environment, a robust climatology of easterly waves for the tropical Western Hemisphere has been developed. The foundation for the climatology is a new easterly wave tracking algorithm that identifies westwards propagating disturbances over the tropical East Pacific, Atlantic, and Africa. To assess the issue of track dependencies and easterly wave representation, climatologies are prepared separately from the NCEP‐NCAR, CFS‐R, ERA‐40, and ERA‐Interim reanalyses. The source code for the easterly wave‐tracking algorithm along with the easterly wave climatology for each atmospheric reanalysis is publicly available from NOAA's National Centers for Environmental Information.
Observations of the reduction in surface artifact frequency as a result of multimodal plowing
Authors: O'Neal Michael A. , Lowery Darrin
Published: March 2017

The frequency and distribution of plowzone artifacts are compared with the timing and duration of two plow modes at two study locales on the Delmarva Peninsula, United States. Our results indicate that historic moldboard plowing created a maximum plowzone of ca. 0.30 m, in which artifacts were retained over time. Later, soil‐conservative chisel plowing mixed the top ca. 0.15 m of soil, creating a shallow, minimum plowzone. With time and repeated plowing, our data suggest that the number of artifacts at the surface diminished via a combination of vertical mixing and/or degradation, physical and chemical weathering, and avocational collecting. When moldboard plowing is reapplied to fields after decades of chisel plowing, the historic maximum plowzone is inverted and the surface is re‐saturated with artifacts. This inverted maximum plowzone retains an inherent pattern of artifact transport from moldboard plowing, which supports other studies that have measured such displacements over time. Our results suggest that the frequency of artifacts observed at the surface of agricultural fields, or lack thereof, is a likely outcome of natural and mechanical processes, and removal within the minimum plowzone. This inevitable depletion of artifacts may have negative repercussions for many research designs that systematically sample the plowzone.
Resistance mutations of hepatitis B virus in entecavir‐refractory patients
Authors: Yamada Norie , Sugiyama Ryuichi , Nitta Sayuri , Murayama Asako , Kobayashi Minoru , Okuse Chiaki , Suzuki Michihiro , Yasuda Kiyomi , Yotsuyanagi Hiroshi , Moriya Kyoji , Koike Kazuhiko , Wakita Takaji , Kato Takanobu
Published: March 2017

The emergence of resistance mutations in the reverse transcriptase gene of hepatitis B virus (HBV) is associated with treatment failure. Entecavir (ETV) is one of the most potent anti‐HBV reagents; it has a very low resistance rate and is used as the first‐line treatment for chronic hepatitis B. In this study, we isolated HBVs in 4 ETV‐refractory patients (2 with viral breakthrough, 1 with partial virological response, and 1 with flare‐up) and assessed ETV resistance using replication‐competent 1.38‐fold HBV genome‐length molecular clones. The full genome sequences of infected HBVs in ETV‐refractory patients were determined. The HBV molecular clones were generated with the patient‐derived sequences. After transfection of these molecular clones into HepG2 cells, viral replications and ETV susceptibilities were evaluated by measuring the amount of intracellular core‐particle‐associated HBV DNA using Southern blotting and real‐time polymerase chain reaction. Among these cases, ETV‐resistant variants were detected in 2 patients with viral breakthrough and responsible amino acid mutations in reverse transcriptase were successfully identified in these variants. No ETV‐resistant mutation was detected in the other cases. The identified ETV‐resistant mutations did not confer resistance to tenofovir disoproxil fumarate. Conclusion: The HBV replication model with patient‐derived sequences is useful for assessing replication efficiency, susceptibility to anti‐HBV reagents, and responsible resistance mutations and can aid in choosing the appropriate treatment strategy for treatment‐failure cases of chronic hepatitis B. (Hepatology Communications 2017;1:110‐121)
Assessment of corrosion in retrieved spine implants
Authors: Panagiotopoulou V. C. , Hothi H. S. , Anwar H. A. , Molloy S. , Noordeen H. , Rezajooi K. , Sutcliffe J. , Skinner J. A. , Hart A. J.
Published: March 2017

Recently the use of dissimilar metals in spine instrumentation has increased, especially in the case of adult deformities, where rods made from Cobalt Chrome alloys (CoCr) are used with Titanium (Ti) screws. The use of dissimilar metals increases the risk of galvanic corrosion and patients have required revision spine surgery due to severe metallosis that may have been caused by corrosion. We aimed to assess the presence of corrosion in spine implant retrievals from constructs with two types of material combinations: similar (Ti/Ti) and dissimilar (CoCr/Ti). First, we devised a grading score for corrosion of the rod‐fixture junctions. Then, we applied this score to a collection of retrieved spine implants. Our proposed corrosion grading score was proven reliable (kappa > 0.7). We found no significant difference in the scores between 4 CoCr and 11 Ti rods (p = 0.0642). There was no indication that time of implantation had an effect on the corrosion score (p = 0.9361). We recommend surgeons avoid using implants designs with dissimilar metals to reduce the risk of corrosion whilst a larger scale study of retrieved spine implants is conducted. Future studies can now use our scoring system for spine implant corrosion. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 632–638, 2018.
Preparation and characterization of alloys of the Ti–15Mo–Nb system for biomedical applications
Authors: Martins Júnior J. R. S. , Matos A. A. , Oliveira R. C. , Buzalaf M. A. R. , Costa I. , Rocha L. A. , Grandini C. R.
Published: March 2017

In the development of new metallic biomaterials, the Ti–15Mo alloy has great prominence because of its excellent corrosion resistance and good combination of mechanical properties. In this study, the element niobium was added to the Ti–15Mo alloy, forming the Ti–15Mo–Nb system for the purpose of improving their properties and promoting its application as a biomaterial. These alloys are very promising to use as biomedical implants, because they integrate a new class of titanium alloys without the presence of aluminum and vanadium, which may cause cytotoxic effects. The alloys were produced by arc‐melting and characterized by density, X‐ray diffraction, scanning electron microscopy, microhardness, elastic modulus, corrosion, and cytotoxicity assays. The developed alloys have β phase predominance (with bcc crystalline structure). The addition of niobium decreases the microhardness and elastic modulus, with values around 80 GPa, which is well below that of the metallic alloys used commercially for this type of application. Very low passive current densities were found for all alloys studied showing that the passive film on these alloys is highly protective. In vitro cytotoxicity tests revealed that the introduction of niobium did not cause cytotoxic effects in the studied alloys. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 639–648, 2018.
N‐ethyl‐N‐nitrosourea–Induced Adaptor Protein 2 Sigma Subunit 1 (Ap2s1) Mutations Establish Ap2s1 Loss‐of‐Function Mice
Authors: Gorvin Caroline M , Rogers Angela , Stewart Michelle , Paudyal Anju , Hough Tertius A , Teboul Lydia , Wells Sara , Brown Steve DM , Cox Roger D , Thakker Rajesh V
Published: March 2017

The adaptor protein‐2 sigma subunit (AP2σ), encoded by AP2S1, forms a heterotetrameric complex, with AP2α, AP2β, and AP2μ subunits, that is pivotal for clathrin‐mediated endocytosis, and AP2σ loss‐of‐function mutations impair internalization of the calcium‐sensing receptor (CaSR), a G‐protein–coupled receptor, and cause familial hypocalciuric hypercalcemia type‐3 (FHH3). Mice with AP2σ mutations that would facilitate investigations of the in vivo role of AP2σ, are not available, and we therefore embarked on establishing such mice. We screened >10,000 mice treated with the mutagen N‐ethyl‐N‐nitrosourea (ENU) for Ap2s1 mutations and identified 5 Ap2s1 variants, comprising 2 missense (Tyr20Asn and Ile123Asn) and 3 intronic base substitutions, one of which altered the invariant donor splice site dinucleotide gt to gc. Three‐dimensional modeling and cellular expression of the missense Ap2s1 variants did not reveal them to alter AP2σ structure or CaSR‐mediated signaling, but investigation of the donor splice site variant revealed it to result in an in‐frame deletion of 17 evolutionarily conserved amino acids (del17) that formed part of the AP2σ α1‐helix, α1‐β3 loop, and β3 strand. Heterozygous mutant mice (Ap2s1+/del17) were therefore established, and these had AP2σ haplosufficiency but were viable with normal appearance and growth. Ap2s1+/del17 mice, when compared with Ap2s1+/+ mice, also had normal plasma concentrations of calcium, phosphate, magnesium, creatinine, urea, sodium, potassium, and alkaline phosphatase activity; normal urinary fractional excretion of calcium, phosphate, sodium, and potassium; and normal plasma parathyroid hormone (PTH) and 1,25‐dihydroxyvitamin D (1,25(OH)2) concentrations. However, homozygous Ap2s1del17/del17 mice were non‐viable and died between embryonic days 3.5 and 9.5 (E3.5–9.5), thereby indicating that AP2σ likely has important roles at the embryonic patterning stages and organogenesis of the heart, thyroid, liver, gut, lungs, pancreas, and neural systems. Thus, our studies have established a mutant mouse model that is haplosufficient for AP2σ. © 2017 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.
The Notch Ligand Jagged1 Regulates the Osteoblastic Lineage by Maintaining the Osteoprogenitor Pool
Authors: Lawal Rialnat A , Zhou Xichao , Batey Kaylind , Hoffman Corey M , Georger Mary A , Radtke Freddy , Hilton Matthew J , Xing Lianping , Frisch Benjamin J , Calvi Laura M
Published: March 2017

Notch signaling is critical for osteoblastic differentiation; however, the specific contribution of individual Notch ligands is unknown. Parathyroid hormone (PTH) regulates the Notch ligand Jagged1 in osteoblastic cells. To determine if osteolineage Jagged1 contributes to bone homeostasis, selective deletion of Jagged1 in osteolineage cells was achieved through the presence of Prx1 promoter‐driven Cre recombinase expression, targeting mesenchymal stem cells (MSCs) and their progeny (PJag1 mice). PJag1 mice were viable and fertile and did not exhibit any skeletal abnormalities at 2 weeks of age. At 2 months of age, however, PJag1 mice had increased trabecular bone mass compared to wild‐type (WT) littermates. Dynamic histomorphometric analysis showed increased osteoblastic activity and increased mineral apposition rate. Immunohistochemical analysis showed increased numbers of osteocalcin‐positive mature osteoblasts in PJag1 mice. Also increased phenotypically defined Lin–/CD45–/CD31–/Sca1–/CD51+ osteoblastic cells were measured by flow cytometric analysis. Surprisingly, phenotypically defined Lin–/CD45–/CD31–/Sca1+/CD51+ MSCs were unchanged in PJag1 mice as measured by flow cytometric analysis. However, functional osteoprogenitor (OP) cell frequency, measured by Von Kossa+ colony formation, was decreased, suggesting that osteolineage Jagged1 contributes to maintenance of the OP pool. The trabecular bone increases were not due to osteoclastic defects, because PJag1 mice had increased bone resorption. Because PTH increases osteoblastic Jagged1, we sought to understand if osteolineage Jagged1 modulates PTH‐mediated bone anabolism. Intermittent PTH treatment resulted in a significantly greater increase in BV/TV in PJag1 hind limbs compared to WT. These findings demonstrate a critical role of osteolineage Jagged1 in bone homeostasis, where Jagged1 maintains the transition of OP to maturing osteoblasts. This novel role of Jagged1 not only identifies a regulatory loop maintaining appropriate populations of osteolineage cells, but also provides a novel approach to increase trabecular bone mass, particularly in combination with PTH, through modulation of Jagged1. © 2017 American Society for Bone and Mineral Research.
Impact of Calcium and Two Doses of Vitamin D on Bone Metabolism in the Elderly: A Randomized Controlled Trial
Authors: Rahme Maya , Sharara Sima Lynn , Baddoura Rafic , Habib Robert H , Halaby Georges , Arabi Asma , Singh Ravinder J , Kassem Moustapha , Mahfoud Ziyad , Hoteit Maha , Daher Rose T , Bassil Darina , El Ferkh Karim , El-Hajj Fuleihan Ghada
Published: March 2017

The optimal dose of vitamin D to optimize bone metabolism in the elderly is unclear. We tested the hypothesis that vitamin D, at a dose higher than recommended by the Institute of Medicine (IOM), has a beneficial effect on bone remodeling and mass. In this double-blind trial we randomized 257 overweight elderly subjects to receive 1000 mg of elemental calcium citrate/day, and the daily equivalent of 3750 IU/day or 600 IU/day of vitamin D3 for 1 year. The subjects’ mean age was 71 ± 4 years, body mass index 30 ± 4 kg/m2, 55% were women, and 222 completed the 12-month follow-up. Mean serum 25 hydroxyvitamin D (25OHD) was 20 ng/mL, and rose to 26 ng/mL in the low-dose arm, and 36 ng/mL in the high-dose arm, at 1 year (p < 0.05). Plasma parathyroid hormone, osteocalcin, and C-terminal telopeptide (Cross Laps) levels decreased significantly by 20% to 22% in both arms, but there were no differences between the two groups for any variable, at 6 or 12 months, with the exception of serum calcitriol, which was higher in the high-dose group at 12 months. Bone mineral density (BMD) increased significantly at the total hip and lumbar spine, but not the femoral neck, in both study arms, whereas subtotal body BMD increased in the high-dose group only, at 1 year. However, there were no significant differences in percent change BMD between the two study arms at any skeletal site. Subjects with serum 25OHD <20 ng/mL and PTH level >76 pg/mL showed a trend for higher BMD increments at all skeletal sites, in the high-dose group, that reached significance at the hip. Adverse events were comparable in the two study arms. This controlled trial shows little additional benefit in vitamin D supplementation at a dose exceeding the IOM recommendation of 600 IU/day on BMD and bone markers, in overweight elderly individuals. © 2017 American Society for Bone and Mineral Research.
Low Serum DHEAS Predicts Increased Fracture Risk in Older Men: The MrOS Sweden Study
Authors: Ohlsson Claes , Nethander Maria , Kindmark Andreas , Ljunggren Östen , Lorentzon Mattias , Rosengren Björn E , Karlsson Magnus K , Mellström Dan , Vandenput Liesbeth
Published: March 2017

The adrenal-derived hormones dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are the most abundant circulating hormones and their levels decline substantially with age. DHEAS is considered an inactive precursor, which is converted into androgens and estrogens via local metabolism in peripheral target tissues. The predictive value of serum DHEAS for fracture risk is unknown. The aim of this study was, therefore, to assess the associations between baseline DHEAS levels and incident fractures in a large cohort of older men. Serum DHEAS levels were analyzed with mass spectrometry in the population-based Osteoporotic Fractures in Men study in Sweden (n = 2568, aged 69 to 81 years). Incident X-ray validated fractures (all, n = 594; non-vertebral major osteoporotic, n = 255; hip, n = 175; clinical vertebral, n = 206) were ascertained during a median follow-up of 10.6 years. DHEAS levels were inversely associated with the risk of any fracture (hazard ratio [HR] per SD decrease = 1.14, 95% confidence interval [CI] 1.05–1.24), non-vertebral major osteoporotic fractures (HR = 1.31, 95% CI 1.16–1.48), and hip fractures (HR = 1.18, 95% CI 1.02–1.37) but not clinical vertebral fractures (HR = 1.09, 95% CI 0.95–1.26) in Cox regression models adjusted for age, body mass index (BMI) and prevalent fractures. Further adjustment for traditional risk factors for fracture, bone mineral density (BMD), and/or physical performance variables as well as serum sex steroid levels only slightly attenuated the associations between serum DHEAS and fracture risk. Similarly, the point estimates were only marginally reduced after adjustment for FRAX estimates with BMD. The inverse association between serum DHEAS and all fractures or major osteoporotic fractures was nonlinear, with a substantial increase in fracture risk (all fractures 22%, major osteoporotic fractures 33%) for those participants with serum DHEAS levels below the median (0.60 μg/mL). In conclusion, low serum DHEAS levels are a risk marker of mainly non-vertebral fractures in older men, of whom those with DHEAS levels below 0.60 μg/mL are at highest risk. © The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.