bluuebunny/crossref_metadata_2025 huggingface dataset:
Northward ho! Obama, Diefenbaker and the North American Arctic
Authors: Dodds Klaus J.
Published: October 2015

President Barrack Obama became, in September 2015, the first US president to travel north of the Arctic Circle. Having started his Alaskan itinerary in Anchorage, attending and speaking at a conference involving Secretary of State John Kerry and invited guests, the president travelled north to the small town of Kotzebue, a community of some 3000 people with the majority of inhabitants identifying as native American. Delivered to an audience in the local high school numbering around 1000, the 41st US president placed his visit within a longer presidential tradition of northern visitation:

I did have my team look into what other Presidents have done when they visited Alaska. I’m not the first President to come to Alaska.Warren Harding spent more than two weeks here – which I would love to do. But I can't leave Congress alone that long. (Laughter.) Something might happen. When FDR visited – Franklin Delano Roosevelt – his opponents started a rumor that he left his dog, Fala, on the Aleutian Islands – and spent 20 million taxpayer dollars to send a destroyer to pick him up. Now, I’m astonished that anybody would make something up about a President. (Laughter.) But FDR did not take it lying down. He said, “I don't resent attacks, and my family doesn't resent attacks – but Fala does resent attacks. He's not been the same dog since.” (Laughter.) President Carter did some fishing when he visited. And I wouldn't mind coming back to Alaska to do some fly-fishing someday. You cannot see Alaska in three days. It's too big. It's too vast. It's too diverse. (Applause.) So I’m going to have to come back. I may not be President anymore, but hopefully I’d still get a pretty good reception. (Applause.) And just in case, I’ll bring Michelle, who I know will get a good reception. (Applause.) . . .. But there's one thing no American President has done before – and that's travel above the Arctic Circle. (Applause.) So I couldn't be prouder to be the first, and to spend some time with all of you (Obama 2015a).
The ‘Old Arctics’: notices of Franklin Search expedition veterans in the British press, 1876–1934
Authors: McCorristine Shane , Herrmann Victoria
Published: October 2015

The lives of the commanders and officers associated with the British naval searches for the lost John Franklin northwest passage expedition in the 1850s are well-known through their own writings or those of later biographers. The post-Arctic careers of ordinary crew members, on the other hand, are barely known at all. Following digital searches of nineteenth and early-twentieth century British newspapers, we have compiled a list of some notices, obituaries, and reminiscences that shed light on the later years of the ‘Old Arctics’.
An Enhanced Real-Time Regional Ionospheric Model Using IGS Real-Time Service (IGS-RTS) Products
Authors: Abdelazeem Mohamed , Çelik Rahmi N. , El-Rabbany Ahmed
Published: October 2015

Recently, the International Global Navigation Satellite System (GNSS) Service (IGS) has launched the Real-Time Service (IGS-RTS). The RTS products enable real-time precise positioning applications. For single-frequency Real-Time Precise Point Positioning (RT-PPP), ionospheric delay mitigation is a major challenge. To overcome this challenge, we developed a Real-Time Regional Ionospheric Model (RT-RIM) over Europe using the RTS satellite orbits and clock products. The model has spatial and temporal resolution of 1° × 1° and 15 minutes, respectively. Global Positioning System (GPS) observations from 60 IGS and EUREF reference stations are processed using the Bernese 5·2 PPP module in order to extract the Real-Time Vertical Electron Content (RT-VTEC). The PPP convergence time and positioning accuracy using the RTS products is estimated and compared with dual frequency PPP and single-frequency PPP obtained through the combined rapid IGS Global Ionospheric Maps (IGS-GIM) over three consecutive days under high solar activity and one of them under active geomagnetic activity. The results show that the proposed model improves PPP accuracy and convergence time under the mid-latitude region about 40%, 55% and 40% for the horizontal, height and three-dimensional (3D) components respectively in comparison with the IGS-GIM.
Tradable rights in conservation: useful policy tool or industry in themselves?
Authors: REESON ANDREW
Published: October 2015

In recent decades, markets have become widely used for environmental resources. Prime examples include water rights where trade enables water to be allocated to the most profitable crops, and allows farmers more flexibility to cope with climatic variability (Bjornlund 2003). Similarly, tradable rights for air pollution minimize the cost of meeting air quality targets (Stavins 1998). The same principles can potentially be widely applied to biodiversity conservation. In this issue, we are fortunate to have a short but diverse series of papers on tradable rights in conservation.
Party Formation through Petitions: The Whigs and the Bank War of 1832–1834
Authors: Carpenter Daniel , Schneer Benjamin
Published: October 2015

When President Andrew Jackson removed the public deposits from the Bank of the United States, he set off an economic and political crisis from which, scholars agree, the Whig Party emerged. We argue that petitioning in response to removal of the deposits shaped the emergence of the Whig Party, crystallizing a new line of Jacksonian opposition and dispensing with older lines of National Republican rhetoric and organization. Where petitioning against removal of the deposits was higher, the Whigs were more likely to emerge with organization and votes in the coming years. We test this implication empirically by using a new database of petitions sent to Congress during the banking crisis. We find that petitioning activity in 1834 is predictive of increased support for Whig Party candidates in subsequent presidential elections as well as stronger state Whig Party organization.
The influential child: How children affect their environment and influence their own risk and resilience
Authors: Davidov Maayan , Knafo-Noam Ariel , Serbin Lisa A. , Moss Ellen
Published: October 2015

Views regarding children's influence on their environment and their own development have undergone considerable changes over the years. Following Bell's (1968) seminal paper, the notion of children's influence and the view of socialization as a bidirectional process have gradually gained wide acceptance. However, empirical research implementing this theoretical advancement has lagged behind. This Special Section compiles a collection of new empirical works addressing multiple forms of influential child processes, with special attention to their consequences for children's and others’ positive functioning, risk and resilience. By addressing a wide variety of child influences, this Special Section seeks to advance integration of influential child processes into myriad future studies on development and psychopathology and to promote the translation of such work into preventive interventions.
(Positive) power to the child: The role of children's willing stance toward parents in developmental cascades from toddler age to early preadolescence
Authors: Kochanska Grazyna , Kim Sanghag , Boldt Lea J.
Published: October 2015

In a change from the once-dominant view of children as passive in the parent-led process of socialization, children are now seen as active agents who can considerably influence that process. However, these newer perspectives typically focus on the child's antagonistic influence, due either to a difficult temperament or aversive, resistant, negative behaviors that elicit adversarial responses from the parent and lead to future coercive cascades in the relationship. Children's capacity to act as receptive, willing, even enthusiastic, active socialization agents is largely overlooked. Informed by attachment theory and other relational perspectives, we depict children as able to adopt an active willing stance and to exert robust positive influence in the mutually cooperative socialization enterprise. A longitudinal study of 100 community families (mothers, fathers, and children) demonstrates that willing stance (a) is a latent construct, observable in diverse parent–child contexts, parallel at 38, 52, and 67 months and longitudinally stable; (b) originates within an early secure parent–child relationship at 25 months; and (c) promotes a positive future cascade toward adaptive outcomes at age 10. The outcomes include the parent's observed and child-reported positive, responsive behavior, as well as child-reported internal obligation to obey the parent and parent-reported low level of child behavior problems. The construct of willing stance has implications for basic research in typical socialization and in developmental psychopathology as well as for prevention and intervention.
Child effects and child care: Implications for risk and adjustment
Authors: Snell Emily K. , Hindman Annemarie H. , Belsky Jay
Published: October 2015

Evocative effects of child characteristics on the quality and quantity of child care were assessed in two studies using longitudinal data from the NICHD Study of Early Child Care. We focus on the influence of child characteristics on two important aspects of the child care experience: language stimulation provided by caregivers and quantity of care. In Study 1, associations between the developmental status of children aged 15 to 54 months and the language stimulation provided by their caregivers were examined using path models, and longitudinal child effects were detected across the earliest time points of the study. In Study 2, the associations among child behavior, temperament, development, and time in care were examined. Little evidence was found for such child effects on time in care. The results are discussed in terms of the effects of child care on child development and implications for developmental processes, particularly for children at greatest risk for developmental delay or psychopathology.
The association of temperament and maternal empathy with individual differences in infants’ neural responses to emotional body expressions
Authors: Rajhans Purva , Missana Manuela , Krol Kathleen M. , Grossmann Tobias
Published: October 2015

We examined the role of infant temperament and maternal dispositional empathy in the neural processing of happy and fearful emotional body expressions in 8-month-old infants by measuring event-related brain potentials. Our results revealed that infants’ tendency to approach novel objects and people was positively correlated with the neural sensitivity (attention allocation) to fearful expressions, while infant fearfulness was negatively correlated to the neural sensitivity to fearful expressions. Maternal empathic concern was associated with infants’ neural discrimination between happy and fearful expression, with infants of more empathetically concerned mothers showing greater neural sensitivity (attention allocation) to fearful compared to happy expressions. It is critical that our results also revealed that individual differences in the sensitivity to emotional information are explained by an interaction between infant temperament and maternal empathic concern. Specifically, maternal empathy appears to impact infants’ neural responses to emotional body expressions, depending on infant fearfulness. These findings support the notion that the way in which infants respond to emotional signals in the environment is fundamentally linked to their temperament and maternal empathic traits. This adds an early developmental neuroscience dimension to existing accounts of social–emotional functioning, suggesting a complex and integrative picture of why and how infants’ emotional sensitivity varies.
Neuroimaging of phonetic perception in bilinguals
Authors: GOLESTANI NARLY
Published: October 2015

This review addresses the cortical basis of phonetic processing in bilinguals and of phonetic learning, with a focus on functional magnetic resonance imaging studies of phonetic perception. Although results vary across studies depending on stimulus characteristics, task demands, and participants’ previous experience with the non-native/second-language sounds, taken together, the literature reveals involvement of overlapping brain regions during phonetic processing in the first and second language of bilinguals, with special involvement of regions of the dorsal audio-motor interface including frontal and posterior cortices during the processing of new, or ‘difficult’ speech sounds. These findings converge with the brain imaging literature on language processing in bilinguals more generally, during semantic and syntactic processing of words and of connected speech. More brain imaging work can serve to better elucidate the precise mechanisms underlying phonetic encoding and its interaction with articulatory processes, in particular where multiple phonetic repertoires have been or are being acquired.
Physiological responses of grapevines to biodynamic management
Authors: Botelho Renato Vasconcelos , Roberti Roberta , Tessarin Paola , Garcia-Mina José María , Rombolà Adamo Domenico
Published: October 2015

A 3-year (2011–2013) field trial was carried out in a mature vineyard (Vitis viniferaL., cv. Sangiovese), planted in 2003, to assess physiological responses of grapevines to biodynamic management. Starting in 2007, the vineyard was managed with organic production protocols in accordance with EC Regulations (834/2007). In 2008, the vineyard (2 ha) was divided in two large plots, with each plot having similar soil physico-chemical properties. One of the plots was managed with organic protocols per EC Regulations and the other with biodynamic practices, consisting of spray application of preparations 500, 500 K, fladen and 501. During the 2011–2013 season, the biodynamic preparations were used at least twice per year, with the exception of 501 that was applied only once in 2013. Concentration of hormones and mineral elements in biodynamic preparations were determined. Biodynamically managed vines showed lower stomatal conductance in all years and lower leaf water potential in 2012. Leaf photosynthetic activity was not influenced by cultivation method. Biodynamic management led to an increase in leaf enzymatic activities of endochitinase (EC 3.2.1.14), exochitinase (β-N-acetylhexosaminidase, EC 3.2.1.52 and chitin 1,4-β-chitobiosidase) and β-1,3-glucanase (EC 3.2.1.39), which are typically correlated with plant biotic and abiotic stresses and associated with induced plant resistance. Year effects were observed with 1,3-β-glucanase, whose activity in 2012 was 4.1-fold higher than in 2013. Disease incidence and grape yields were not different between organic and biodynamic treatments. This study provided a strong indication of a stimulation of natural defense compounds in grapes grown under biodynamic cultivation, but subsequent effects on plant protection and productivity require further evaluation.
Disparity between projected geographic ranges of rare species: a case study of Echinomorpha nishihirai (Scleractinia)
Authors: Hoogenboom M.O. , Frank G.E. , Blowes S.A. , Chase T.J. , Zawada K.J.A. , Dornelas M.
Published: October 2015

Rare and cryptic species can be easily missed during ecological surveys of coral communities. This study reveals a disparity in the reported geographic range of a rare species,Echinomorpha nishihirai,between three different sources; none of which are wholly consistent with the available published occurrence records. Discrepancies in the species ranges reported in two comprehensive online databases are greater for rare, compared with common, coral species, suggesting a need for a more cautious treatment of rare species in biogeographic studies.
Fruits of Trauma?
Authors: Moore Melinda M. , Cerel Julie , Jobes David A.
Published: October 2015

Abstract. Background: While there is evidence that suicide-bereaved individuals may be at higher risk for trauma-related outcomes, such as posttraumatic stress disorder or prolonged grief, positive psychology suggests that suicide bereavement may also promote personal growth within the confines of distress characterized as posttraumatic growth (PTG). Aims: The aim of this study was to investigate PTG and what variables, such as reflective rumination, resilience, personality variables, and mood states, contribute to PTG among suicide-bereaved parents. Method: Online survey methods were employed using a convenience sample of 154 parents bereaved by the suicide death of their child within 2 years. Results: Multiple regression analyses revealed that resilience inversely predicted PTG scores, but reflective rumination did not predict PTG. PTG scores were in the low–moderate range and were lower than those of parents bereaved by other causes of death. Items endorsed most strongly corresponded to the PTG factors Relating to Others, Spiritual Change, and Appreciation of Life. Conclusion: In this study, PTG manifests among suicide-bereaved parents, but may be complicated by the proximity to the death and by concurrent brooding and reflective rumination unique to answering the question of “why” in this population.
Association Between Adolescent Suicide and Sociodemographic Factors in Chile
Authors: Cuadrado Cristóbal , Zitko Pedro , Covarrubias Trinidad , Hernandez Dunia , Sade Cristina , Klein Carolina , Gomez Alejandro
Published: October 2015

Abstract. Background: Adolescent suicide rates (ASR) are a matter of concern worldwide. Causes of this trend are not understood and could correspond to socioeconomic factors such as inequality. Aim: To investigate sociodemographic variables related to ASR, particularly the potential association with indicators of socioeconomic inequality. Method: Cross-sectional ecological study analyzing data from 29 health districts with univariate and multivariable multilevel Poisson models. Results: ASR were higher in male adolescents and at increasing age. No association was found between ASR and inequality (Gini coefficient and 20/20 ratio). Analysis revealed that living in a single-parent family is associated with ASR. Conclusions: The usual demographic patterns of adolescent suicide apply in Chile. An emerging variable of interest is single-parent family. No cross-sectional association between social inequality and ASR was found based on conflicting evidence. These results should be explored in future prospective population studies to further understand associated social factors.
Re-Examination of Classic Risk Factors for Suicidal Behavior in the Psychiatric Population
Authors: Dennis Brittany B. , Roshanov Pavel S. , Bawor Monica , ElSheikh Wala , Garton Sue , DeJesus Jane , Rangarajan Sumathy , Vair Judith , Sholer Heather , Hutchinson Nichole , Lordan Elisabeth , Thabane Lehana , Samaan Zainab
Published: October 2015

Abstract. Background: For decades we have understood the risk factors for suicide in the general population but have fallen short in understanding what distinguishes the risk for suicide among patients with serious psychiatric conditions. Aims: This prompted us to investigate risk factors for suicidal behavior among psychiatric inpatients. Method: We reviewed all psychiatric hospital admissions (2008–2011) to a centralized psychiatric hospital in Ontario, Canada. Using multivariable logistic regression we evaluated the association between potential risk factors and lifetime history of suicidal behavior, and constructed a model and clinical risk score to predict a history of this behavior. Results: The final risk prediction model for suicidal behavior among psychiatric patients (n = 2,597) included age (in three categories: 60–69 [OR = 0.74, 95% CI = 0.73–0.76], 70–79 [OR = 0.45, 95% CI = 0.44–0.46], 80+ [OR = 0.31, 95% CI = 0.30–.31]), substance use disorder (OR = 1.30, 95% CI = 1.27–1.32), mood disorder (OR = 1.49, 95% CI = 1.47–1.52), personality disorder (OR = 2.30, 95% CI = 2.25–2.36), psychiatric disorders due to general medical condition (OR = 0.52, 95% CI = 0.50–0.55), and schizophrenia (OR = 0.42, 95% CI = 0.41–0.43). The risk score constructed from the risk prediction model ranges from −9 (lowest risk, 0% predicted probability of suicidal behavior) to +5 (highest risk, 97% predicted probability). Conclusion: Risk estimation may help guide intensive screening and treatment efforts of psychiatric patients with high risk of suicidal behavior.
Celebrating the 2015 Class of Fellows
Authors:   AGU
Published: October 2015

The new class of AGU Fellows has been selected and will be recognized at the upcoming Fall Meeting in San Francisco, Calif.
Astrobiology Hearing Ranges Beyond Life as We Know It
Authors: Showstack Randy
Published: October 2015

Space research has made strides identifying where extraterrestrial life might reside but not what kind of life, if any, it could be, scientists told Congress last week.
Pore‐formation by adenylate cyclase toxoid activates dendritic cells to prime CD8+ and CD4+ T cells
Authors: Svedova Martina , Masin Jiri , Fiser Radovan , Cerny Ondrej , Tomala Jakub , Freudenberg Marina , Tuckova Ludmila , Kovar Marek , Dadaglio Gilles , Adkins Irena , Sebo Peter
Published: October 2015

The adenylate cyclase toxin‐hemolysin (CyaA) of Bordetella pertussis is a bi‐functional leukotoxin. It penetrates myeloid phagocytes expressing the complement receptor 3 and delivers into their cytosol its N‐terminal adenylate cyclase enzyme domain (~400 residues). In parallel, ~1300 residue‐long RTX hemolysin moiety of CyaA forms cation‐selective pores and permeabilizes target cell membrane for efflux of cytosolic potassium ions. The non‐enzymatic CyaA‐AC− toxoid, has repeatedly been successfully exploited as an antigen delivery tool for stimulation of adaptive T‐cell immune responses. We show that the pore‐forming activity confers on the CyaA‐AC− toxoid a capacity to trigger Toll‐like receptor and inflammasome signaling‐independent maturation of CD11b‐expressing dendritic cells (DC). The DC maturation‐inducing potency of mutant toxoid variants in vitro reflected their specifically enhanced or reduced pore‐forming activity and K+ efflux. The toxoid‐induced in vitro phenotypic maturation of DC involved the activity of mitogen activated protein kinases p38 and JNK and comprised increased expression of maturation markers, interleukin 6, chemokines KC and LIX and granulocyte‐colony‐stimulating factor secretion, prostaglandin E2 production and enhancement of chemotactic migration of DC. Moreover, i.v. injected toxoids induced maturation of splenic DC in function of their cell‐permeabilizing capacity. Similarly, the capacity of DC to stimulate CD8+ and CD4+ T‐cell responses in vitro and in vivo was dependent on the pore‐forming activity of CyaA‐AC−. This reveals a novel self‐adjuvanting capacity of the CyaA‐AC− toxoid that is currently under clinical evaluation as a tool for delivery of immunotherapeutic anti‐cancer CD8+ T‐cell vaccines into DC.
Measuring fast stochastic displacements of bio-membranes with dynamic optical displacement spectroscopy
Authors: Monzel C. , Schmidt D. , Kleusch C. , Kirchenbüchler D. , Seifert U. , Smith A-S , Sengupta K. , Merkel R.
Published: October 2015

Stochastic displacements or fluctuations of biological membranes are increasingly recognized as an important aspect of many physiological processes, but hitherto their precise quantification in living cells was limited due to a lack of tools to accurately record them. Here we introduce a novel technique—dynamic optical displacement spectroscopy (DODS), to measure stochastic displacements of membranes with unprecedented combined spatiotemporal resolution of 20 nm and 10 μs. The technique was validated by measuring bending fluctuations of model membranes. DODS was then used to explore the fluctuations in human red blood cells, which showed an ATP-induced enhancement of non-Gaussian behaviour. Plasma membrane fluctuations of human macrophages were quantified to this accuracy for the first time. Stimulation with a cytokine enhanced non-Gaussian contributions to these fluctuations. Simplicity of implementation, and high accuracy make DODS a promising tool for comprehensive understanding of stochastic membrane processes.
Pronounced polarization-induced energy level shifts at boundaries of organic semiconductor nanostructures
Authors: Cochrane K. A. , Schiffrin A. , Roussy T. S. , Capsoni M. , Burke S. A.
Published: October 2015

Organic semiconductor devices rely on the movement of charge at and near interfaces, making an understanding of energy level alignment at these boundaries an essential element of optimizing materials for electronic and optoelectronic applications. Here we employ low temperature scanning tunneling microscopy and spectroscopy to investigate a model system: two-dimensional nanostructures of the prototypical organic semiconductor, PTCDA (3,4,9,10-perylenetetracarboxylic dianhydride) adsorbed on NaCl (2 ML)/Ag(111). Pixel-by-pixel scanning tunneling spectroscopy allows mapping of occupied and unoccupied electronic states across these nanoislands with sub-molecular spatial resolution, revealing strong electronic differences between molecules at the edges and those in the centre, with energy level shifts of up to 400 meV. We attribute this to the change in electrostatic environment at the boundaries of clusters, namely via polarization of neighbouring molecules. The observation of these strong shifts illustrates a crucial issue: interfacial energy level alignment can differ substantially from the bulk electronic structure in organic materials.
Hydrodynamic schooling of flapping swimmers
Authors: Becker Alexander D. , Masoud Hassan , Newbolt Joel W. , Shelley Michael , Ristroph Leif
Published: October 2015

Fish schools and bird flocks are fascinating examples of collective behaviours in which many individuals generate and interact with complex flows. Motivated by animal groups on the move, here we explore how the locomotion of many bodies emerges from their flow-mediated interactions. Through experiments and simulations of arrays of flapping wings that propel within a collective wake, we discover distinct modes characterized by the group swimming speed and the spatial phase shift between trajectories of neighbouring wings. For identical flapping motions, slow and fast modes coexist and correspond to constructive and destructive wing–wake interactions. Simulations show that swimming in a group can enhance speed and save power, and we capture the key phenomena in a mathematical model based on memory or the storage and recollection of information in the flow field. These results also show that fluid dynamic interactions alone are sufficient to generate coherent collective locomotion, and thus might suggest new ways to characterize the role of flows in animal groups.
A higher order visual neuron tuned to the spatial amplitude spectra of natural scenes
Authors: Dyakova Olga , Lee Yu-Jen , Longden Kit D. , Kiselev Valerij G. , Nordström Karin
Published: October 2015

Animal sensory systems are optimally adapted to those features typically encountered in natural surrounds, thus allowing neurons with limited bandwidth to encode challengingly large input ranges. Natural scenes are not random, and peripheral visual systems in vertebrates and insects have evolved to respond efficiently to their typical spatial statistics. The mammalian visual cortex is also tuned to natural spatial statistics, but less is known about coding in higher order neurons in insects. To redress this we here record intracellularly from a higher order visual neuron in the hoverfly. We show that the cSIFE neuron, which is inhibited by stationary images, is maximally inhibited when the slope constant of the amplitude spectrum is close to the mean in natural scenes. The behavioural optomotor response is also strongest to images with naturalistic image statistics. Our results thus reveal a close coupling between the inherent statistics of natural scenes and higher order visual processing in insects.
Quantifying the stabilizing effects of protein–ligand interactions in the gas phase
Authors: Allison Timothy M. , Reading Eamonn , Liko Idlir , Baldwin Andrew J. , Laganowsky Arthur , Robinson Carol V.
Published: October 2015

The effects of protein–ligand interactions on protein stability are typically monitored by a number of established solution-phase assays. Few translate readily to membrane proteins. We have developed an ion-mobility mass spectrometry approach, which discerns ligand binding to both soluble and membrane proteins directly via both changes in mass and ion mobility, and assesses the effects of these interactions on protein stability through measuring resistance to unfolding. Protein unfolding is induced through collisional activation, which causes changes in protein structure and consequently gas-phase mobility. This enables detailed characterization of the ligand-binding effects on the protein with unprecedented sensitivity. Here we describe the method and software required to extract from ion mobility data the parameters that enable a quantitative analysis of individual binding events. This methodology holds great promise for investigating biologically significant interactions between membrane proteins and both drugs and lipids that are recalcitrant to characterization by other means.
Acidic phospholipids govern the enhanced activation of IgG-B cell receptor
Authors: Chen Xiangjun , Pan Weiling , Sui Yinqiang , Li Hua , Shi Xiaoshan , Guo Xingdong , Qi Hai , Xu Chenqi , Liu Wanli
Published: October 2015

B cells that express the isotype-switched IgG-B cell receptor (IgG-BCR) are one of the driving forces for antibody memory. To allow for a rapid memory IgG antibody response, IgG-BCR evolved into a highly effective signalling machine. Here, we report that the positively charged cytoplasmic domain of mIgG (mIgG-tail) specifically interacts with negatively charged acidic phospholipids. The key immunoglobulin tail tyrosine (ITT) in mIgG-tail is thus sequestered in the membrane hydrophobic core in quiescent B cells. Pre-disruption of such interaction leads to excessive recruitment of BCRs and inflated BCR signalling upon antigen stimulation, resulting in hyperproliferation of primary B cells. Physiologically, membrane-sequestered mIgG-tail can be released by antigen engagement or Ca2+ mobilization in the initiation of B cell activation. Our studies suggest a novel regulatory mechanism for how dynamic association of mIgG-tail with acidic phospholipids governs the enhanced activation of IgG-BCR.
Charge-transfer crystallites as molecular electrical dopants
Authors: Méndez Henry , Heimel Georg , Winkler Stefanie , Frisch Johannes , Opitz Andreas , Sauer Katrein , Wegner Berthold , Oehzelt Martin , Röthel Christian , Duhm Steffen , Többens Daniel , Koch Norbert , Salzmann Ingo
Published: October 2015

Ground-state integer charge transfer is commonly regarded as the basic mechanism of molecular electrical doping in both, conjugated polymers and oligomers. Here, we demonstrate that fundamentally different processes can occur in the two types of organic semiconductors instead. Using complementary experimental techniques supported by theory, we contrast a polythiophene, where molecular p-doping leads to integer charge transfer reportedly localized to one quaterthiophene backbone segment, to the quaterthiophene oligomer itself. Despite a comparable relative increase in conductivity, we observe only partial charge transfer for the latter. In contrast to the parent polymer, pronounced intermolecular frontier-orbital hybridization of oligomer and dopant in 1:1 mixed-stack co-crystallites leads to the emergence of empty electronic states within the energy gap of the surrounding quaterthiophene matrix. It is their Fermi–Dirac occupation that yields mobile charge carriers and, therefore, the co-crystallites—rather than individual acceptor molecules—should be regarded as the dopants in such systems.
Nanometer-size hard magnetic ferrite exhibiting high optical-transparency and nonlinear optical-magnetoelectric effect
Authors: Ohkoshi Shin-ichi , Namai Asuka , Imoto Kenta , Yoshikiyo Marie , Tarora Waka , Nakagawa Kosuke , Komine Masaya , Miyamoto Yasuto , Nasu Tomomichi , Oka Syunsuke , Tokoro Hiroko
Published: October 2015

Development of nanometer-sized magnetic particles exhibiting a large coercive field (Hc) is in high demand for densification of magnetic recording. Herein, we report a single-nanosize (i.e., less than ten nanometers across) hard magnetic ferrite. This magnetic ferrite is composed of ε-Fe2O3, with a sufficiently high Hc value for magnetic recording systems and a remarkably high magnetic anisotropy constant of 7.7 × 106 erg cm−3. For example, 8.2-nm nanoparticles have an Hc value of 5.2 kOe at room temperature. A colloidal solution of these nanoparticles possesses a light orange color due to a wide band gap of 2.9 eV (430 nm), indicating a possibility of transparent magnetic pigments. Additionally, we have observed magnetization-induced second harmonic generation (MSHG). The nonlinear optical-magnetoelectric effect of the present polar magnetic nanocrystal was quite strong. These findings have been demonstrated in a simple iron oxide, which is highly significant from the viewpoints of economic cost and mass production.
Characterization of aggregate/aggresome structures formed by polyhedrin of Bombyx mori nucleopolyhedrovirus
Authors: Guo Zhong-Jian , Tao Liu-Xing , Dong Xian-Yun , Yu Meng-Han , Tian Ting , Tang Xu-Dong
Published: October 2015

Virus infections often lead to formation of aggregates and aggresomes in host cells. In this study, production of aggregates and aggresomes by the highly expressed protein polyhedrin of Bombyx mori nucleopolyhedrovirus (BmNPV) at 24 h postinfection (p.i.) was detected with a fluorescent molecular dye and verified by colocalization of polyhedrin with aggresomal markers, GFP-250 and γ−tubulin. Polyhedrin aggregates showed hallmark characteristics of aggresomes: formation was microtubule-dependent; they colocalized with heat shock cognates/proteins of the 70-kDa family (HSC/HSP70s), ubiquitinated proteins and recruited the mitochondria. Aggregated polyhedrin protein gradually gained its active conformation accompanying progress of BmNPV infection. At 48 h p.i. recovered polyhedrin bound directly to Bombyx mori microtubule-associated protein 1-light chain 3 (BmLC3), an autophagosome marker and was colocalized with BmLC3 to the isolation membrane of autophagosome, implying the involvement of polyhedrin in cellular autophagy. Inhibition of autophagy by 3-methyladenine (3-MA) dramatically resulted in decrease of polyhedrin expression and polyhedra particle production. These observations suggested that highly expressed polyhedrin forms aggregate to get involved in cellular autophagy then play an important role in polyhedra production.
Giant Dielectric Permittivity in Ferroelectric Thin Films: Domain Wall Ping Pong
Authors: Quan Jiang An , Jian Meng Xiang , Wei Zhang David , Hyuk Park Min , Yoo Sijung , Jin Kim Yu , Scott James F. , Seong Hwang Cheol
Published: October 2015

The dielectric permittivity in ferroelectric thin films is generally orders of magnitude smaller than in their bulk. Here, we discover a way of increasing dielectric constants in ferroelectric thin films by ca. 500% by synchronizing the pulsed switching fields with the intrinsic switching time (nucleation of domain plus forward growth from cathode to anode). In a 170-nm lead zirconate titanate thin film with an average grain size of 850 nm this produces a dielectric constant of 8200 with the maximum nucleus density of 3.8 μm−2, which is one to three orders of magnitude higher than in other dielectric thin films. This permits smaller capacitors in memory devices and is a step forward in making ferroelectric domain-engineered nano-electronics.
Worldwide Prevalence of Human Papillomavirus and Relative Risk of Prostate Cancer: A Meta-analysis
Authors: Yang Lin , Xie Shuanghua , Feng Xiaoshuang , Chen Yuheng , Zheng Tongzhang , Dai Min , Zhou Cindy Ke , Hu Zhibin , Li Ni , Hang Dong
Published: October 2015

Despite the increasing number of studies conducted recently to evaluate the association between HPV infections and the risk of prostate cancer, the results remain inconclusive. Furthermore, the prevalence and distribution of overall and individual HPV types worldwide in prostate cancer has not been reported until now. Therefore, we estimated the prevalence of HPV in prostate cancer by pooling data of 46 studies with 4919 prostate cancer cases, taking into account the heterogeneity of major related parameters, including study region, specimen type, HPV DNA source, detection method, publication calendar period and Gleason score. Moreover, we tested the association of HPV infections with prostate cancer risks by a meta-analysis of 26 tissue-based case-control studies. We found that the prevalence of HPV infection was 18.93% (95% CI = 17.84–20.05%) in prostate cancer cases and most of which were high-risk HPV types (17.73%, 95% CI = 16.52–18.99%). The prevalence varied by region, PCR primers used, publication calendar period and Gleason score. Our study also showed a significantly increased risk of prostate cancer with the positivity of overall HPV detected in prostate tissues (OR = 1.79, 95% CI = 1.29–2.49) and revealed the geographic variation of association strength (P < 0.001). In conclusion, HPV infections may contribute to the risk of prostate cancer.
IL-1β promotes Th17 differentiation by inducing alternative splicing of FOXP3
Authors: Mailer Reiner K. W. , Joly Anne-Laure , Liu Sang , Elias Szabolcs , Tegner Jesper , Andersson John
Published: October 2015

CD4+FOXP3+ regulatory T (Treg) cells are essential for maintaining immunological self-tolerance. Treg cell development and function depend on the transcription factor FOXP3, which is present in several distinct isoforms due to alternative splicing. Despite the importance of FOXP3 in the proper maintenance of Treg cells, the regulation and functional consequences of FOXP3 isoform expression remains poorly understood. Here, we show that in human Treg cells IL-1β promotes excision of FOXP3 exon 7. FOXP3 is not only expressed by Treg cells but is also transiently expressed when naïve T cells differentiate into Th17 cells. Forced splicing of FOXP3 into FOXP3Δ2Δ7 strongly favored Th17 differentiation in vitro. We also found that patients with Crohn’s disease express increased levels of FOXP3 transcripts lacking exon 7, which correlate with disease severity and IL-17 production. Our results demonstrate that alternative splicing of FOXP3 modulates T cell differentiation. These results highlight the importance of characterizing FOXP3 expression on an isoform basis and suggest that immune responses may be manipulated by modulating the expression of FOXP3 isoforms, which has broad implications for the treatment of autoimmune diseases.
Size effects in the magnetic anisotropy of embedded cobalt nanoparticles: from shape to surface
Authors: Oyarzún Simón , Tamion Alexandre , Tournus Florent , Dupuis Véronique , Hillenkamp Matthias
Published: October 2015

Strong size-dependent variations of the magnetic anisotropy of embedded cobalt clusters are evidenced quantitatively by combining magnetic experiments and advanced data treatment. The obtained values are discussed in the frame of two theoretical models that demonstrate the decisive role of the shape in larger nanoparticles and the predominant role of the surface anisotropy in clusters below 3 nm diameter.
Accurate and Efficient Resolution of Overlapping Isotopic Envelopes in Protein Tandem Mass Spectra
Authors: Xiao Kaijie , Yu Fan , Fang Houqin , Xue Bingbing , Liu Yan , Tian Zhixin
Published: October 2015

It has long been an analytical challenge to accurately and efficiently resolve extremely dense overlapping isotopic envelopes (OIEs) in protein tandem mass spectra to confidently identify proteins. Here, we report a computationally efficient method, called OIE_CARE, to resolve OIEs by calculating the relative deviation between the ideal and observed experimental abundance. In the OIE_CARE method, the ideal experimental abundance of a particular overlapping isotopic peak (OIP) is first calculated for all the OIEs sharing this OIP. The relative deviation (RD) of the overall observed experimental abundance of this OIP relative to the summed ideal value is then calculated. The final individual abundance of the OIP for each OIE is the individual ideal experimental abundance multiplied by 1 + RD. Initial studies were performed using higher-energy collisional dissociation tandem mass spectra on myoglobin (with direct infusion) and the intact E. coli proteome (with liquid chromatographic separation). Comprehensive data at the protein and proteome levels, high confidence and good reproducibility were achieved. The resolving method reported here can, in principle, be extended to resolve any envelope-type overlapping data for which the corresponding theoretical reference values are available.
Molecular Magnetic Resonance Imaging of Tumor Response to Therapy
Authors: Shuhendler Adam J. , Ye Deju , Brewer Kimberly D. , Bazalova-Carter Magdalena , Lee Kyung-Hyun , Kempen Paul , Dane Wittrup K. , Graves Edward E. , Rutt Brian , Rao Jianghong
Published: October 2015

Personalized cancer medicine requires measurement of therapeutic efficacy as early as possible, which is optimally achieved by three-dimensional imaging given the heterogeneity of cancer. Magnetic resonance imaging (MRI) can obtain images of both anatomy and cellular responses, if acquired with a molecular imaging contrast agent. The poor sensitivity of MRI has limited the development of activatable molecular MR contrast agents. To overcome this limitation of molecular MRI, a novel implementation of our caspase-3-sensitive nanoaggregation MRI (C-SNAM) contrast agent is reported. C-SNAM is triggered to self-assemble into nanoparticles in apoptotic tumor cells and effectively amplifies molecular level changes through nanoaggregation, enhancing tissue retention and spin-lattice relaxivity. At one-tenth the current clinical dose of contrast agent and following a single imaging session, C-SNAM MRI accurately measured the response of tumors to either metronomic chemotherapy or radiation therapy, where the degree of signal enhancement is prognostic of long-term therapeutic efficacy. Importantly, C-SNAM is inert to immune activation, permitting radiation therapy monitoring.
A Nanoparticle-based Sensor Platform for Cell Tracking and Status/Function Assessment
Authors: Yeo David , Wiraja Christian , Chuah Yon Jin , Gao Yu , Xu Chenjie
Published: October 2015

Nanoparticles are increasingly popular choices for labeling and tracking cells in biomedical applications such as cell therapy. However, all current types of nanoparticles fail to provide real-time, noninvasive monitoring of cell status and functions while often generating false positive signals. Herein, a nanosensor platform to track the real-time expression of specific biomarkers that correlate with cell status and functions is reported. Nanosensors are synthesized by encapsulating various sensor molecules within biodegradable polymeric nanoparticles. Upon intracellular entry, nanosensors reside within the cell cytoplasm, serving as a depot to continuously release sensor molecules for up to 30 days. In the absence of the target biomarkers, the released sensor molecules remain ‘Off’. When the biomarker(s) is expressed, a detectable signal is generated (On). As a proof-of-concept, three nanosensor formulations were synthesized to monitor cell viability, secretion of nitric oxide and β-actin mRNA expression.
Hyperisampsins H–M, Cytotoxic Polycyclic Polyprenylated Acylphloroglucinols from Hypericum sampsonii
Authors: Zhu Hucheng , Chen Chunmei , Tong Qingyi , Chen Xintao , Yang Jing , Liu Junjun , Sun Bin , Wang Jianping , Yao Guangmin , Luo Zengwei , Xue Yongbo , Zhang Yonghui
Published: October 2015

Six new polycyclic polyprenylated acylphloroglucinols (PPAPs), named hyperisampsins H–M (1–6), were isolated from the aerial parts of Hypericum sampsonii, together with five known analogs (7–11). The structures of 1–6 were established by extensive spectroscopic analyses, including HRESIMS and NMR. In addition, the absolute configurations of these new compounds were determined by electronic circular dichroism (ECD) calculations. Compounds 1 and 2 represent the first examples of PPAPs possessing a unique γ-lactone ring at C-23, while 3–6 differed from normal PPAPs with an unprecedented 1,2-dioxane ring. Compounds 1–7 were evaluated for their cytotoxic activities against a panel of human cancer cell lines in vitro, of which 3, 4 and 6 exhibited significant cytotoxic activities with IC50 values ranging from 0.56 to 3.00 μM. Moreover, compound 3 induces leukemia cell apoptotic death, evidenced by activation of caspase-3, degradation of PARP, up-regulation of Bax and down-regulation of Bcl-2 and Bcl-xl.
CNOT3 suppression promotes necroptosis by stabilizing mRNAs for cell death-inducing proteins
Authors: Suzuki Toru , Kikuguchi Chisato , Sharma Sahil , Sasaki Toshio , Tokumasu Miho , Adachi Shungo , Natsume Tohru , Kanegae Yumi , Yamamoto Tadashi
Published: October 2015

The CCR4-NOT complex is conserved in eukaryotes and is involved in mRNA metabolism, though its molecular physiological roles remain to be established. We show here that CNOT3-depleted mouse embryonic fibroblasts (MEFs) undergo cell death. Levels of other complex subunits are decreased in CNOT3-depleted MEFs. The death phenotype is rescued by introduction of wild-type (WT), but not mutated CNOT3 and is not suppressed by the pan-caspase inhibitor, zVAD-fluoromethylketone. Gene expression profiling reveals that mRNAs encoding cell death-related proteins, including receptor-interacting protein kinase 1 (RIPK1) and RIPK3, are stabilized in CNOT3-depleted MEFs. Some of these mRNAs bind to CNOT3 and in the absence of CNOT3 their poly(A) tails are elongated. Inhibition of RIPK1-RIPK3 signaling by a short-hairpin RNA or a necroptosis inhibitor, necrostatin-1, confers viability upon CNOT3-depleted MEFs. Therefore, we conclude that CNOT3 targets specific mRNAs to prevent cells from being disposed to necroptotic death.
Mammalian Host-Versus-Phage immune response determines phage fate in vivo
Authors: Hodyra-Stefaniak Katarzyna , Miernikiewicz Paulina , Drapała Jarosław , Drab Marek , Jończyk-Matysiak Ewa , Lecion Dorota , Kaźmierczak Zuzanna , Beta Weronika , Majewska Joanna , Harhala Marek , Bubak Barbara , Kłopot Anna , Górski Andrzej , Dąbrowska Krystyna
Published: October 2015

Emerging bacterial antibiotic resistance draws attention to bacteriophages as a therapeutic alternative to treat bacterial infection. Examples of phage that combat bacteria abound. However, despite careful testing of antibacterial activity in vitro, failures nevertheless commonly occur. We investigated immunological response of phage antibacterial potency in vivo. Anti-phage activity of phagocytes, antibodies and serum complement were identified by direct testing and by high-resolution fluorescent microscopy. We accommodated the experimental data into a mathematical model. We propose a universal schema of innate and adaptive immunity impact on phage pharmacokinetics, based on the results of our numerical simulations. We found that the mammalian-host response to infecting bacteria causes the concomitant removal of phage from the system. We propose the notion that this effect as an indirect pathway of phage inhibition by bacteria with significant relevance for the clinical outcome of phage therapy.