bluuebunny/crossref_metadata_2025 huggingface dataset:
Unidirectional transmission of acoustic waves based on asymmetric excitation of Lamb waves
Authors: Jia Han , Ke Manzhu , Li Chunhui , Qiu Chunyin , Liu Zhengyou
Published: April 2013

In this paper, an easily fabricated acoustic system has been demonstrated to gain unidirectional transmission with good performance. The unidirectional acoustic transmission originates from the asymmetric excitation of zero-order anti-symmetric Lamb modes. The results show that the single-sided patterned ridges on the steel plate enhance the scattering of the incident waves from the structured side and improve the coupling of the Lamb modes in the plate with them, which leads to high transmission ratio and great transmission difference value of acoustic waves along the opposite directions. All the experimental results show good agreement with the numerical simulations. The proposed acoustic system has potential applications in underwater acoustic and medical ultrasonic devices.
Cavity-enhanced optical detection of carbon nanotube Brownian motion
Authors: Stapfner S. , Ost L. , Hunger D. , Reichel J. , Favero I. , Weig E. M.
Published: April 2013

Optical cavities with small mode volume are well-suited to detect the vibration of sub-wavelength sized objects. Here we employ a fiber-based, high-finesse optical microcavity to detect the Brownian motion of a freely suspended carbon nanotube at room temperature under vacuum. The optical detection resolves deflections of the oscillating tube down to 70  pm/Hz1/2. A full vibrational spectrum of the carbon nanotube is obtained and confirmed by characterization of the same device in a scanning electron microscope. Our work extends the principles of high-sensitivity optomechanical detection to molecular scale nanomechanical systems.
Structural basis for angiopoietin-1–mediated signaling initiation
Authors: Yu Xuehong , Seegar Tom C. M. , Dalton Annamarie C. , Tzvetkova-Robev Dorothea , Goldgur Yehuda , Rajashankar Kanagalaghatta R. , Nikolov Dimitar B. , Barton William A.
Published: April 2013

Angiogenesis is a complex cellular process involving multiple regulatory growth factors and growth factor receptors. Among them, the ligands for the endothelial-specific tunica intima endothelial receptor tyrosine kinase 2 (Tie2) receptor kinase, angiopoietin-1 (Ang1) and Ang2, play essential roles in balancing vessel stability and regression during both developmental and tumor-induced angiogenesis. Despite possessing a high degree of sequence identity, Ang1 and Ang2 have distinct functional roles and cell-signaling characteristics. Here, we present the crystal structures of Ang1 both unbound and in complex with the Tie2 ectodomain. Comparison of the Ang1-containing structures with their Ang2-containing counterparts provide insight into the mechanism of receptor activation and reveal molecular surfaces important for interactions with Tie2 coreceptors and associated signaling proteins. Using structure-based mutagenesis, we identify a loop within the angiopoietin P domain, adjacent to the receptor-binding interface, which confers the specific agonist/antagonist properties of the molecule. We demonstrate using cell-based assays that an Ang2 chimera containing the Ang1 loop sequence behaves functionally similarly to Ang1 as a constitutive Tie2 agonist, able to efficiently dissociate the inhibitory Tie1/Tie2 complex and elicit Tie2 clustering and downstream signaling.
The Phytophthora sojae Avr1d Gene Encodes an RxLR-dEER Effector with Presence and Absence Polymorphisms Among Pathogen Strains
Authors: Yin Weixiao , Dong Suomeng , Zhai Luchong , Lin Yachun , Zheng Xiaobo , Wang Yuanchao
Published: April 2013

Soybean root and stem rot is caused by the oomycete pathogen Phytophthora sojae. The interaction between P. sojae and soybean fits the “gene-for-gene” hypothesis. Although more than 10 P. sojae avirulence (Avr) effectors have been genetically identified, nearly half of genetically defined avr genes have been cloned. In a previous bioinformatic and global transcriptional analysis, we identified a P. sojae RxLR effector, Avr1d, which was 125 amino acids in length. Mapping data demonstrated that Avr1d presence or absence in the genome was co-segregated with the Avr1d avirulence phenotype in F2 populations. Transient expression of the Avr1d gene using co-bombardment in soybean isogenic lines revealed that this gene triggered a hypersensitive response (HR) in the presence of Rps1d. Sequencing of Avr1d genes in different P. sojae strains revealed two Avr1d alleles. Although polymorphic, the two Avr1d alleles could trigger Rps1d-mediated HR. P. sojae strains carrying either of the alleles were avirulent on Rps1d soybean lines. Avr1d was upregulated during the germinating cyst and early infection stages. Furthermore, transient expression of Avr1d in Nicotiana benthamiana suppressed BAX-induced cell death and enhanced P. capsici infection. Avr1d also suppressed effector-triggered immunity induction by associating with Avr1b and Rps1b, suggestive of a role in suppressing plant immunity.
Controlled cobalt doping in biogenic magnetite nanoparticles
Authors: Byrne J. M. , Coker V. S. , Moise S. , Wincott P. L. , Vaughan D. J. , Tuna F. , Arenholz E. , van der Laan G. , Pattrick R. A. D. , Lloyd J. R. , Telling N. D.
Published: April 2013

Cobalt-doped magnetite (Co

x

Fe

3 −
x

O
4
) nanoparticles have been produced through the microbial reduction of cobalt–iron oxyhydroxide by the bacterium
Geobacter sulfurreducens
. The materials produced, as measured by superconducting quantum interference device magnetometry, X-ray magnetic circular dichroism, Mössbauer spectroscopy, etc., show dramatic increases in coercivity with increasing cobalt content without a major decrease in overall saturation magnetization. Structural and magnetization analyses reveal a reduction in particle size to less than 4 nm at the highest Co content, combined with an increase in the effective anisotropy of the magnetic nanoparticles. The potential use of these biogenic nanoparticles in aqueous suspensions for magnetic hyperthermia applications is demonstrated. Further analysis of the distribution of cations within the ferrite spinel indicates that the cobalt is predominantly incorporated in octahedral coordination, achieved by the substitution of Fe
2+
site with Co
2+
, with up to 17 per cent Co substituted into tetrahedral sites.
Imaging dipole flow sources using an artificial lateral-line system made of biomimetic hair flow sensors
Authors: Dagamseh Ahmad , Wiegerink Remco , Lammerink Theo , Krijnen Gijs
Published: April 2013

In Nature, fish have the ability to localize prey, school, navigate, etc., using the lateral-line organ. Artificial hair flow sensors arranged in a linear array shape (inspired by the lateral-line system (LSS) in fish) have been applied to measure airflow patterns at the sensor positions. Here, we take advantage of both biomimetic artificial hair-based flow sensors arranged as LSS and beamforming techniques to demonstrate dipole-source localization in air. Modelling and measurement results show the artificial lateral-line ability to image the position of dipole sources accurately with estimation error of less than 0.14 times the array length. This opens up possibilities for flow-based, near-field environment mapping that can be beneficial to, for example, biologists and robot guidance applications.
RNA-Seq of Arabidopsis Pollen Uncovers Novel Transcription and Alternative Splicing
Authors: Loraine Ann E. , McCormick Sheila , Estrada April , Patel Ketan , Qin Peng
Published: April 2013

Pollen grains of Arabidopsis (Arabidopsis thaliana) contain two haploid sperm cells enclosed in a haploid vegetative cell. Upon germination, the vegetative cell extrudes a pollen tube that carries the sperm to an ovule for fertilization. Knowing the identity, relative abundance, and splicing patterns of pollen transcripts will improve our understanding of pollen and allow investigation of tissue-specific splicing in plants. Most Arabidopsis pollen transcriptome studies have used the ATH1 microarray, which does not assay splice variants and lacks specific probe sets for many genes. To investigate the pollen transcriptome, we performed high-throughput sequencing (RNA-Seq) of Arabidopsis pollen and seedlings for comparison. Gene expression was more diverse in seedling, and genes involved in cell wall biogenesis were highly expressed in pollen. RNA-Seq detected at least 4,172 protein-coding genes expressed in pollen, including 289 assayed only by nonspecific probe sets. Additional exons and previously unannotated 5′ and 3′ untranslated regions for pollen-expressed genes were revealed. We detected regions in the genome not previously annotated as expressed; 14 were tested and 12 were confirmed by polymerase chain reaction. Gapped read alignments revealed 1,908 high-confidence new splicing events supported by 10 or more spliced read alignments. Alternative splicing patterns in pollen and seedling were highly correlated. For most alternatively spliced genes, the ratio of variants in pollen and seedling was similar, except for some encoding proteins involved in RNA splicing. This study highlights the robustness of splicing patterns in plants and the importance of ongoing annotation and visualization of RNA-Seq data using interactive tools such as Integrated Genome Browser.
Light-Induced Acclimation of the Arabidopsis chlorina1 Mutant to Singlet Oxygen
Authors: Ramel Fanny , Ksas Brigitte , Akkari Elsy , Mialoundama Alexis S. , Monnet Fabien , Krieger-Liszkay Anja , Ravanat Jean-Luc , Mueller Martin J. , Bouvier Florence , Havaux Michel
Published: April 2013

Singlet oxygen (1O2) is a reactive oxygen species that can function as a stress signal in plant leaves leading to programmed cell death. In microalgae, 1O2-induced transcriptomic changes result in acclimation to 1O2. Here, using a chlorophyll b–less Arabidopsis thaliana mutant (chlorina1 [ch1]), we show that this phenomenon can also occur in vascular plants. The ch1 mutant is highly photosensitive due to a selective increase in the release of 1O2 by photosystem II. Under photooxidative stress conditions, the gene expression profile of ch1 mutant leaves very much resembled the gene responses to 1O2 reported in the Arabidopsis mutant flu. Preexposure of ch1 plants to moderately elevated light intensities eliminated photooxidative damage without suppressing 1O2 formation, indicating acclimation to 1O2. Substantial differences in gene expression were observed between acclimation and high-light stress: A number of transcription factors were selectively induced by acclimation, and contrasting effects were observed for the jasmonate pathway. Jasmonate biosynthesis was strongly induced in ch1 mutant plants under high-light stress and was noticeably repressed under acclimation conditions, suggesting the involvement of this hormone in 1O2-induced cell death. This was confirmed by the decreased tolerance to photooxidative damage of jasmonate-treated ch1 plants and by the increased tolerance of the jasmonate-deficient mutant delayed-dehiscence2.
Surface diffraction on a ψ-circle diffractometer using the χ-axis geometry
Authors: Fister Tim T. , Fuoss Paul H. , Fong Dillon D. , Eastman Jeffrey A. , Folkman Chad M. , Hruszkewycz Stephan O. , Highland Matthew J. , Zhou Hua , Fenter Paul
Published: April 2013

The restricted volume above and below the sample on a six-circle diffractometer can limit the size and complexity of sample environments used in surface diffraction studies. An alternative configuration of the diffractometer, where the sample normal is aligned parallel to the χ axis, allows for ample space above and below the χ circle for instrumentation. The merits of this approach are outlined and angles are derived for the diffraction condition for constant-incident-angle, constant-sample-azimuthal-angle and specular geometries. Using a version of this code written forSPEC(http://www.certif.com/content/spec/), sample specular and nonspecular crystal truncation rods measured from a 5 nm-thick thin film are presented.
The current approach to initial crystallization screening of proteins is under-sampled
Authors: Gorrec Fabrice
Published: April 2013

Protein crystallization conditions that resulted in crystal structures published by scientists at the MRC Laboratory of Molecular Biology (MRC-LMB, Cambridge, UK) have been analysed. It was observed that the more often a crystallization reagent had been used to formulate the initial conditions, the more often it was found in the reported conditions that yielded diffraction quality crystals. The present analysis shows that, despite the broad variety of reagents, they have the same impact overall on the yield of crystal structures. More interestingly, the correlation implies that, although the initial crystallization screen may be considered very large, it is an under-sampled combinatorial approach.
X-ray and synchrotron diffraction studies of 2-(pyridin-2-yl)-1,10-phenanthroline in the role of ligand for two copper polymorphs or hydrogen bonded with 2,2,6,6-tetramethyl-4-oxopiperidinium hexafluorophosphate
Authors: Krause Jeanette A. , Zhao Daoli , Chatterjee Sayandev , Yeung Bonnie M. , Connick William B. , Collins Sibrina N.
Published: April 2013

Different extended packing motifs of dichlorido[2-(pyridin-2-yl)-1,10-phenanthroline]copper(II), [CuCl2(C17H11N3)], are obtained, depending on the crystallization conditions. A triclinic form, (I), is obtained from dimethylformamide–diethyl ether or methanol, whereas crystallization from dimethylformamide–water yields a monoclinic form, (II). In each case, the CuIIcentre is in a five-coordinate distorted square-pyramidal geometry. The extended packing for both forms can be described as a highly offset π-stacking arrangement, with interlayer distances of 3.674 (3) and 3.679 (3) Å for forms (I) and (II), respectively. The reaction of diprotonated Pt(tmpip2NCN)Cl [tmpip2NCN = 2,6-bis(2,2,6,6-tetramethylpiperidylmethyl)benzyl] with AgPF6under acidic conditions, followed by the addition of 2-(pyridin-2-yl)-1,10-phenanthroline, results in a hydrogen-bonded cocrystal, 2,2,6,6-tetramethyl-4-oxopiperidinium hexafluorophosphate–2-(pyridin-2-yl)-1,10-phenanthroline (1/1), C9H18NO+·PF6−·C17H11N3, (III). The extended packing maximizes π–π interactions in a parallel face-to-face arrangement, with an interlayer stacking distance of 3.4960 (14) Å.
The Impact Imperative: Here Come the Women :-)
Authors: Campbell Rosie , Childs Sarah
Published: April 2013

The opposition between Flinders and John is largely a false one, and consequently the argument between them is rather ritualistic. On the major issue – that political science must engage in political and public debate – Flinders and John agree. Whether there was once a golden age of academic engagement or whether we are now at the high point, at one level does not really matter; what matters more is that political scientists should be engaging with, and responsive to, public debate. We set out an ‘impact imperative’ and its sister, the ‘feminist imperative', arguing that feminist scholarship has always sought to engage with the real world of politics. We set out a series of recommendations to institutionalise and normalise impact, engagement and dissemination into work models and working practices, which if well managed should not detract from serious scholarship or require an aggressive campaign strategy for dissemination. Instead our approach is based on cooperation between academics, across disciplinary silos and the methodological divide.
Intelligence, gender, and assessment method affect the accuracy of self‐estimated intelligence
Authors: von Stumm Sophie
Published: April 2013

Self‐estimates of intelligence (SEI), which influence to what extent people engage in and how well they perform at a task, are subject to distortion. Here, the distortion effects of individual differences in intelligence (IQ), gender, and proximal (with reference to test performance) and distal (with reference to IQ score distributions) assessments of SEI were tested in a sample of 200 British adults. The results showed that (1) people with lower IQ misestimated their SEI to a greater extent than people with high IQ; (2) this effect was more pronounced in distal than proximal measures of SEI; (3) SEI means did not differ significantly across gender but the IQ‐related level of SEI distortion did; (4) this effect was greater for distal than proximal measurement; and (5) proximal SEI were on average less distorted than distal SEI scores and also correlated more closely with IQ. Overall, the findings suggest that the distal SEI assessment method resulted in greater gender‐ and IQ‐related distortions of SEI.
Aspects of Internal Self and Object Representations in Disorganized Attachment: Clinical Considerations in the Assessment and Treatment of Chronic and Relapsing Substance Misusers
Authors: Sweet Alistair D.
Published: April 2013

In clinical theory and practice we rarely find an isomorphic fit between early patterns of attachment and discrete clinical disorders or syndromes. Although a linear equivalence is not implied here the author draws out parallels between early disorganized attachment patterns, the internal world of the substance abuser and the ways in which such psychodynamic processes invariably shape and influence the therapeutic encounter. Exploring furtherMain andHesse's (1990) assertion that the essence of disorganized attachment can be summed up asfright without solution, the author develops the idea that active and repeated drug use represents attempts to anaesthetically freeze the self, and in so doing to disable and paralyse internal object imagos that induce feelings of panic, terror and dread. In addition the ingestion of drugs, as other writers on the subject have observed (Rosenfeld, 1965), often provides a type ofinternal inflationof the fragile self, leading to a sense of omnipotent and omniscient superiority on behalf of the substance abusing patient.
Cognitive Therapy's Assimilation of Countertransference: a Psychodynamic Perspective
Authors: Ivey Gavin
Published: April 2013

Increasingly, cognitive therapy (CT) authors are paying attention to understanding and managing countertransference reactions. This paper critically discusses the recent assimilation of countertransference theory and technique evident in the literature. It begins by examining the factors responsible for CT's interest in countertransference, before going on to discuss the cognitive conceptualization of countertransference. Case material is used to illustrate parallels between schema‐focused CT and relational psychoanalytic models. However, despite manifest similarities, it is argued that CT's rejection of the dynamic unconscious means that the respective approaches to how countertransference is understood and worked with are essentially incompatible. The psychoanalytic theory of countertransference is underpinned by a model of mind and associated therapeutic stance, the analytic attitude, which differs fundamentally from the therapeutic stance of CT. The paper concludes with a discussion of a published cognitive case study (Ellis, 2001), which is used to illustrate inherent limitations in the cognitive approach to countertransference.
Human adipose-tissue derived mesenchymal stem cells induce functional de-novo regulatory T cells with methylated FOXP3 gene DNA
Authors: Engela A U , Hoogduijn M J , Boer K , Litjens N H R , Betjes M G H , Weimar W , Baan C C
Published: April 2013

Due to their immunomodulatory properties, mesenchymal stem cells (MSC) are interesting candidates for cellular therapy for autoimmune disorders, graft-versus-host disease and allograft rejection. MSC inhibit the proliferation of effector T cells and induce T cells with a regulatory phenotype. So far it is unknown whether human MSC-induced CD4+CD25+CD127–forkhead box P3 (FoxP3)+ T cells are functional and whether they originate from effector T cells or represent expanded natural regulatory T cells (nTreg). Perirenal adipose-tissue derived MSC (ASC) obtained from kidney donors induced a 2·1-fold increase in the percentage of CD25+CD127–FoxP3+ cells within the CD4+ T cell population from allostimulated CD25–/dim cells. Interleukin (IL)-2 receptor blocking prevented this induction. The ASC-induced T cells (iTreg) inhibited effector cell proliferation as effectively as nTreg. The vast majority of cells within the iTreg fraction had a methylated FOXP3 gene Treg-specific demethylated region (TSDR) indicating that they were not of nTreg origin. In conclusion, ASC induce Treg from effector T cells. These iTreg have immunosuppressive capacities comparable to those of nTreg. Their induction is IL-2 pathway-dependent. The dual effect of MSC of inhibiting immune cell proliferation while generating de-novo immunosuppressive cells emphasizes their potential as cellular immunotherapeutic agent.
Serum levels of high mobility group box 1 correlate with disease severity in recessive dystrophic epidermolysis bullosa
Authors: Petrof Gabriela , Abdul‐Wahab Alya , Proudfoot Laura , Pramanik Rashida , Mellerio Jemima E. , McGrath John A.
Published: April 2013

In the inherited blistering skin disease, recessive dystrophic epidermolysis bullosa (RDEB), there is clinical heterogeneity with variable scarring and susceptibility to malignancy. Currently, however, there are few biochemical markers of tissue inflammation or disease progression. We assessed whether the non‐histone nuclear protein, high mobility group box 1 (HMGB1), which is released from necrotic cells (including keratinocytes in blister roofs), might be elevated in RDEB and whether this correlates with disease severity. We measured serum HMGB1 by ELISA in 26 RDEB individuals (median 21.0 ng/ml, range 3.6–54.9 ng/ml) and 23 healthy controls (median 3.6, range 3.4–5.9 ng/ml) and scored RDEB severity using the Birmingham Epidermolysis Bullosa Severity Score (BEBSS; mean 34/100, range 8–82). There was a positive relationship between the BEBSS and HMGB1 levels (r = 0.54, P = 0.004). This study indicates that serum HMGB1 levels may represent a new biomarker reflecting disease severity in RDEB.
Larval fish assemblages and mesoscale oceanographic structure along the Mesoamerican Barrier Reef System
Authors: Muhling Barbara A. , Smith Ryan H. , Vásquez–Yeomans Lourdes , Lamkin John T. , Johns Elizabeth M. , Carrillo Laura , Sosa‐Cordero Eloy , Malca Estrella
Published: April 2013

The Mesoamerican Barrier Reef System (MBRS) is of high ecological and economic importance to the western Caribbean region, and contains spawning sites for a number of reef fish species. Despite this, little is known of the distribution and transport of pelagic fish larvae in the area, and basic in situ information on larval fish assemblages is lacking. Here we describe the results of two biological oceanography research cruises conducted in winter‐spring of 2006 and 2007, focusing on larval fish assemblages. We use multivariate assemblage analyses to examine vertical and horizontal distribution characteristics of larval fish assemblages, to highlight key distinguishing taxa, and to relate these to the observed oceanographic structure. Our results showed a general separation between the Gulf of Honduras region, which was characterized by weaker currents and high abundances of inshore and estuarine taxa (Eleotridae, Priacanthidae), and the northern MBRS, which was subject to strong northward flow and contained a mixture of mesopelagic and reef‐associated taxa (Myctophidae, Sparidae). Although distinct patterns of vertical distribution were observed among taxa, both shallow and deep living larvae were broadly distributed throughout the study area. Analysis of historical drifter tracks highlighted the strong northward flow and low retention conditions typically present along the northern MBRS, as well as potential connectivity between the western Caribbean Sea, the Gulf of Mexico and the Atlantic Ocean.
Migraine and Stroke: A Continuum of Association in Adults
Authors: Alhazzani Adel , Goddeau Richard P.
Published: April 2013

Migraine and stroke are the most common neurovascular disorders affecting adults. Migraine, particularly with aura, is associated with increased stroke risk both during and between attacks; as such, migraine may be viewed as a potentially modifiable risk factor for stroke. The exact mechanism by which migraine can predispose to stroke remains uncertain.
Waning of “Conditioned Pain Modulation”: A Novel Expression of Subtle Pronociception in Migraine
Authors: Nahman‐Averbuch Hadas , Granovsky Yelena , Coghill Robert C. , Yarnitsky David , Sprecher Elliot , Weissman‐Fogel Irit
Published: April 2013

Objective

To assess the decay of the conditioned pain modulation (CPM) response along repeated applications as a possible expression of subtle pronociception in migraine.

Background

One of the most explored mechanisms underlying the pain modulation system is “diffuse noxious inhibitory controls,” which is measured psychophysically in the lab by the CPM paradigm. There are contradicting reports on CPM response in migraine, questioning whether migraineurs express pronociceptive pain modulation.

Methods

Migraineurs (n = 26) and healthy controls (n = 35), all females, underwent 3 stimulation series, consisting of repeated (1) “test‐stimulus” (Ts) alone that was given first followed by (2) parallel CPM application (CPM‐parallel), and (3) sequential CPM application (CPM‐sequential), in which the Ts is delivered during or following the conditioning‐stimulus, respectively. In all series, the Ts repeated 4 times (0‐3). In the CPM series, repetition “0” consisted of the Ts‐alone that was followed by 3 repetitions of the Ts with a conditioning‐stimulus application.

Results

Although there was no difference between migraineurs and controls for the first CPM response in each series, we found waning of CPM‐parallel efficiency along the series for migraineurs (P = .005 for third vs first CPM), but not for controls. Further, greater CPM waning in the CPM‐sequential series was correlated with less reported extent of pain reduction by episodic medication (r = 0.493, P = .028).

Conclusions

Migraineurs have subtle deficits in endogenous pain modulation which requires a more challenging test protocol than the commonly used single CPM. Waning of CPM response seems to reveal this pronociceptive state. The clinical relevance of the CPM waning effect is highlighted by its association with clinical parameters of migraine.
HYBRID INNOVATION IN MEIJI, JAPAN*
Authors: Nicholas Tom
Published: April 2013

Japan’s hybrid innovation system during the Meiji era provides a useful laboratory for examining the effectiveness of complementary incentives to patents. Patents were introduced in 1885, and by 1911 1.2 million mostly nonpecuniary prizes were awarded at 8,503 competitions. Prizes provided a strong boost to patents, especially in less developed prefectures, and they also induced large spillovers of technical knowledge in prefectures adjacent to those with prizes, relative to distant control prefectures without prizes. Linking competition expenditures with the expected market value of patents induced by the prizes permits a cost–benefit assessment of the prize competitions to be made.
Multiple papules on the trunk and extremities
Authors: Martí Nuria , Monteagudo Carlos , Revert Ángeles , Martin Jose M. , Jordá Esperanza
Published: April 2013

What is your diagnosis?
Molecularly targeted therapies for melanoma
Authors: Liu Lucinda S. , Colegio Oscar R.
Published: April 2013

Systemic and topical targeted therapies are emerging as a rational approach to the management of skin cancers. In this article, we review the molecular pathways critical to the development of melanoma and the novel pharmacologic agents that have been rationally designed to target it. Included is a review of vemurafenib, imatinib, and ipilimumab for metastatic or unresectable melanoma.
New findings on the origin of Cavia intermedia, one of the world's rarest mammals
Authors: Furnari Nina
Published: April 2013

Cavia intermedia, a rare species of cavy found exclusively on Moleques do Sul Island, Brazil, differs from other cavies in genetic and morphological characteristics and has been regarded as phylogenetically closest to Cavia magna. Here, I present morphological evidence for the likely origin of Cavia intermedia from an ancestor shared with Cavia magna: an external female genital organ similar in size and appearance to the male's penis. Masculinization of the female genitalia has been observed in Cavia magna but does not occur in Cavia aperea, which suggests a sister relationship between Cavia magna and Cavia intermedia.
Association of atopic and non‐atopic asthma with emotional symptoms in school children
Authors: Kohlboeck Gabriele , Koletzko Sibylle , Bauer Carl‐Peter , von Berg Andrea , Berdel Dietrich , Krämer Ursula , Schaaf Beate , Lehmann Irina , Herbarth Olf , Heinrich Joachim ,   for the GINI‐plus Study groups,   LISA‐plus Study groups
Published: April 2013

Objective

To date, there is conflicting evidence whether the association between asthma and depression depends on the atopic or non‐atopic asthma phenotype. This study investigates associations between emotional symptoms and atopic and non‐atopic asthma in school‐aged children.

Methods

Cross‐sectional data on asthma and allergic diseases at the 10‐year follow‐up of two birth cohorts were collected by parent‐reported physician diagnoses. Specific IgE levels including most common inhalant allergens (SX1) and food allergens (FX5) were measured by RAST‐CAP FEIA. Atopic asthma was defined as asthma ever and positive specific IgE test, non‐atopic asthma as asthma ever and no IgE sensitization. Emotional symptoms were assessed by parent‐reported strength and difficulty questionnaire. Logistic regression modeling were applied to determine likelihood of emotional symptoms in children with atopic and non‐atopic asthma controlling for socio‐demographic factors, body mass index, atopic eczema, allergic rhinitis, and pubertal development.

Results

Non‐atopic asthma was associated with about 3‐fold higher likelihood of emotional symptoms compared to children with no asthma (ORadj = 2.90, CI95% = 1.46–5.73). Atopic asthma was not associated with emotional symptoms (ORadj = 1.35, CI95% = 0.81–2.26).

Conclusions

Atopic and non‐atopic asthma in children might have different etiologies, whereas for non‐atopic asthma, emotional symptoms are relevant, this is not the case in atopic asthma. The relationship between the non‐atopic asthma phenotype and emotional symptoms might be dependent on gender.
The Distribution of Economic Insecurity: Italy and the U.S. over the Great Recession
Authors: D'Ambrosio Conchita , Rohde Nicholas
Published: April 2013

We estimate the distribution of economic insecurity in Italy and the U.S. using data from 1994 to 2010. Economic insecurity for each individual is assumed to depend on both current wealth and the changes in wealth that have been experienced in the past. The first element plays the role of the buffer stock that can be relied on in the case of an adverse future event. The second element reflects the individual's confidence in his ability to overcome any losses in the future. With respect to this second element, experiences in the recent past are given greater weight than experiences that occurred in the more distant past. The results confirm that the great recession has had a dramatic effect on the distribution of economic insecurity in both countries with the effect being much stronger in the U.S.
Quantification of growth–defense trade‐offs in a common currency: nitrogen required for phenolamide biosynthesis is not derived from ribulose‐1,5‐bisphosphate carboxylase/oxygenase turnover
Authors: Ullmann‐Zeunert Lynn , Stanton Mariana A. , Wielsch Nathalie , Bartram Stefan , Hummert Christian , Svatoš Aleš , Baldwin Ian T. , Groten Karin
Published: April 2013

Induced defenses are thought to be economical: growth and fitness‐limiting resources are only invested into defenses when needed. To date, this putative growth–defense trade‐off has not been quantified in a common currency at the level of individual compounds. Here, a quantification method for 15N–labeled proteins enabled a direct comparison of nitrogen (N) allocation to proteins, specifically, ribulose‐1,5‐bisposphate carboxylase/oxygenase (RuBisCO), as proxy for growth, with that to small N‐containing defense metabolites (nicotine and phenolamides), as proxies for defense after herbivory. After repeated simulated herbivory, total N decreased in the shoots of wild‐type (WT) Nicotiana attenuata plants, but not in two transgenic lines impaired in jasmonate defense signaling (irLOX3) and phenolamide biosynthesis (irMYB8). N was reallocated among different compounds within elicited rosette leaves: in the WT, a strong decrease in total soluble protein (TSP) and RuBisCO was accompanied by an increase in defense metabolites, irLOX3 showed a similar, albeit attenuated, pattern, whereas irMYB8 rosette leaves were the least responsive to elicitation, with overall higher levels of RuBisCO. Induced defenses were higher in the older compared with the younger rosette leaves, supporting the hypothesis that tissue developmental stage influences defense investments. We propose that MYB8, probably by regulating the production of phenolamides, indirectly mediates protein pool sizes after herbivory. Although the decrease in absolute N invested in TSP and RuBisCO elicited by simulated herbivory was much larger than the N‐requirements of nicotine and phenolamide biosynthesis, 15N flux studies revealed that N for phenolamide synthesis originates from recently assimilated N, rather than from RuBisCO turnover.
Degenerate polymerase chain reaction strategy with DNA microarray for detection of multiple and various subtypes of virus during blood screening
Authors: Takizawa Kazuya , Nakashima Tatsuo , Mizukami Takuo , Kuramitsu Madoka , Endoh Daiji , Kawauchi Shigeto , Sasaki Kohsuke , Momose Haruka , Kiba Yoshiharu , Mizutani Tetsuya , Furuta Rika A. , Yamaguchi Kazunari , Hamaguchi Isao
Published: April 2013

Background

The risk of transferring blood‐borne infections during transfusion is continually increasing because of newly emerging and reemerging viruses. Development of a rapid screening method for emerging viruses that might be transmitted by transfusion is required to eliminate such pathogens during blood donor screening. Owing to increased use of human materials in organ transplants and cell therapy, the risk of donor‐transmitted viral infections is also increasing. Although nucleic acid amplification technology (NAT) is dedicated to blood screening, a small, convenient detection system is needed at the laboratory and hospital level.

Study Design and Methods

We developed a new pathogen detection system that can detect multiple viruses simultaneously, using originally designed degenerate polymerase chain reaction primers to amplify a wide range of viral genotypes. Amplified samples were identified using a DNA microarray of pathogen‐specific probes.

Results

We detected very low copy numbers of multiple subtypes of viruses, such as human hepatitis C virus (HCV), human hepatitis B virus (HBV), human parvovirus B19 (PVB19), and West Nile virus (WNV), using a single plate. We also detected all genotypes of human immunodeficiency virus (HIV) but sensitivity was less than for the other viruses.

Conclusion

We developed a microarray assay using novel primers for detection of a wide range of multiple pathogens and subtypes. Our NAT system was accurate and reliable for detection of HIV, HBV, HCV, PVB19, and WNV, with respect to specificity, sensitivity, and genotype inclusivity. Our system could be customized and extended for emerging pathogens and is suitable as a future NAT system.
The Dendrimer SEALs: Infiltrate, Search and Destroy
Authors: Artzi Natalie
Published: April 2013

Rational biomaterial design enables selective targeting and chemotherapeutic agent release to liver cells.
PAIN MANAGEMENT, END-OF-LIFE CARE AND DEMENTIA: ADDRESSING THE GAPS BETWEEN THEORY AND PRACTISE
Authors: Peisah C , Weaver J
Published: April 2013

Background

Pain is frequently an undetected cause of agitation and distress in dementia; and thus often a cause of behavioural and psychological symptom of dementia (BPSD). Despite a plethora of tools specifically designed to assess pain in people with dementia, and empirical investigation of pain management protocols, successful pain assessment and management, and end of life care of people with cognitive impairment, particularly in residential care and inpatient facilities, still eludes us.

Methods

We reviewed the current literature and surveyed staff of residential care and inpatient facilities within the Northern Sydney Local Health District regarding pain assessment and management, and end of life care in people with cognitive impairment.

Results

We describe some of the barriers to the assessment of pain and end of life symptoms in people with cognitive impairment and identified practical solutions for facilitating assessment and management of these symptoms. We recommend a range of education strategies for addressing this issue.

Discussion

There is a discordance between theoretical knowledge in the area of pain assessment and management and end of life care, and actual practice, which needs addressing.

Conclusion

More extensive education and training about pain, end of life care and dementia is needed.
UK-born Pakistani-origin infants are relatively more adipose than white British infants: findings from 8704 mother-offspring pairs in the Born-in-Bradford prospective birth cohort
Authors: West Jane , Lawlor Debbie A , Fairley Lesley , Bhopal Raj , Cameron Noel , McKinney Patricia A , Sattar Naveed , Wright John
Published: April 2013

Background

Previous studies have shown markedly lower birth weight among infants of South Asian origin compared with those of White European origin. Whether such differences mask greater adiposity in South Asian infants and whether they persist across generations in contemporary UK populations is unclear. Our aim was to compare birth weight, skinfold thickness and cord leptin between Pakistani and White British infants and to investigate the explanatory factors, including parental and grandparental birthplace.

Methods

We examined the differences in birth weight and skinfold thickness between 4649 Pakistani and 4055 White British infants born at term in the same UK maternity unit and compared cord leptin in a subgroup of 775 Pakistani and 612 White British infants.

Results

Pakistani infants were lighter (adjusted mean difference −234 g 95% CI −258 to −210) and were smaller in both subscapular and triceps skinfold measurements. The differences for subscapular and triceps skinfold thickness (mean z-score difference −0.27 95% CI −0.34 to −0.20 and −0.23 95% CI −0.30 to −0.16, respectively) were smaller than the difference in birth weight (mean z-score difference −0.52 95% CI −0.58 to −0.47) and attenuated to the null with adjustment for birth weight (0.03 95% CI −0.03 to 0.09 and −0.01 95% CI −0.08 to 0.05, respectively). Cord leptin concentration (indicator of fat mass) was similar in Pakistani and White British infants without adjustment for birth weight, but with adjustment became 30% higher (95% CI 17% to 44%) among Pakistani infants compared with White British infants. The magnitudes of difference did not differ by generation.

Conclusions

Despite being markedly lighter, Pakistani infants had similar skinfold thicknesses and greater total fat mass, as indicated by cord leptin, for a given birth weight than White British infants. Any efforts to reduce ethnic inequalities in birth weight need to consider differences in adiposity and the possibility that increasing birth weight in South Asian infants might inadvertently worsen health by increasing relative adiposity.
Effects of previous nitrogen fertilization on soil-solution chemistry after final felling and soil scarification at two nitrogen-limited forest sites
Authors: Ring Eva , Högbom Lars , Jansson Gunnar
Published: April 2013

Nitrogen (N) fertilization and soil scarification are common measures used in commercial forestry in the boreal zone. This study was performed to investigate how previous N fertilization in two N-limited Scots pine (Pinus sylvestris L.) stands affected the soil-solution chemistry after final felling and also to determine the effect of subsequent soil scarification. Nitrogen had been applied to study plots at different intervals, resulting in total applications of 0, 450, 900, or 1800 kg N·ha−1. Soil-solution samples were collected before and after whole-tree harvesting of the P. sylvestris stand, from undisturbed soil and also after harvesting from soil below furrows, tilts, and areas between furrows created by disc trenching. After harvesting, the K+ concentration was lower at higher N fertilization intensities. No overall effect on the N concentrations was detected. Electrical conductivity and the concentrations of Na+, K+, Mg2+, Ca2+, Cl−, NO3−–N, total N, and total C were all affected by soil scarification. The highest concentrations of these variables were found below tilts and the lowest concentrations below furrows. The experiment was repeated, at a lower monitoring intensity, at a site where the previous total N application amounted to 0 and 450 kg N·ha−1. Here the NO3−–N concentration responded to disc trenching in a similar way to that observed in the main experiment. The study shows that previous N fertilization of N-limited forest does not necessarily affect the soil-solution chemistry significantly after whole-tree harvesting.
Antecedent glycemic control reduces severe hypoglycemia-induced neuronal damage in diabetic rats
Authors: Reno Candace M. , Tanoli Tariq , Bree Adam , Daphna-Iken Dorit , Cui Chen , Maloney Susan E. , Wozniak David F. , Fisher Simon J.
Published: April 2013

Brain damage due to severe hypoglycemia occurs in insulin-treated people with diabetes. This study tests the hypothesis that chronic insulin therapy that normalizes elevated blood glucose in diabetic rats would be neuroprotective against brain damage induced by an acute episode of severe hypoglycemia. Male Sprague-Dawley rats were split into three groups: 1) control, non-diabetic; 2) STZ-diabetic; and 3) insulin-treated STZ-diabetic. After 3 wk of chronic treatment, unrestrained awake rats underwent acute hyperinsulinemic severe hypoglycemic (10–15 mg/dl) clamps for 1 h. Rats were subsequently analyzed for brain damage and cognitive function. Severe hypoglycemia induced 15-fold more neuronal damage in STZ-diabetic rats compared with nondiabetic rats. Chronic insulin treatment of diabetic rats, which nearly normalized glucose levels, markedly reduced neuronal damage induced by severe hypoglycemia. Fortunately, no cognitive defects associated with the hypoglycemia-induced brain damage were observed in any group. In conclusion, antecedent blood glucose control represents a major modifiable therapeutic intervention that can afford diabetic subjects neuroprotection against severe hypoglycemia-induced brain damage.
Glucagon-like peptide-1 receptor-mediated endosomal cAMP generation promotes glucose-stimulated insulin secretion in pancreatic β-cells
Authors: Kuna Ramya S. , Girada Shravan Babu , Asalla Suman , Vallentyne Joyprashant , Maddika Subbareddy , Patterson James T. , Smiley David L. , DiMarchi Richard D. , Mitra Prasenjit
Published: April 2013

Glucagon-like peptide-1 receptor (GLP-1R) plays a major role in promoting glucose-stimulated insulin secretion in pancreatic β-cells. In the present study, we synthesized a novel functional analog of GLP-1 conjugated to tetramethyl rhodamine to monitor the internalization of the receptor. Our data show that after being internalized the receptor is sorted to lysosomes. In endosomes, receptor-ligand complex is found to be colocalized with adenylate cyclase. Pharmacological inhibition of endocytosis attenuates GLP-1R-mediated cAMP generation and consequent downstream protein kinase A substrate phosphorylation and glucose-stimulated insulin secretion. Our study underlines a paradigm shift in GLP-1R signaling and trafficking. The receptor ligand complex triggers cAMP generation both in plasma membrane and in endosomes, which has implications for receptor-mediated regulation of insulin secretion.
Stress peptide PACAP engages multiple signaling pathways within the carotid body to initiate excitatory responses in respiratory and sympathetic chemosensory afferents
Authors: Roy Arijit , Derakhshan Fatemeh , Wilson Richard J. A.
Published: April 2013

Consistent with a critical role in respiratory and autonomic stress responses, the carotid bodies are strongly excited by pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide implicated in stress responses throughout the sympathetic nervous system. PACAP excites isolated carotid body glomus cells via activation of PAC1 receptors, with one study suggesting PAC1-induced excitation is due entirely to protein kinase A (PKA)-mediated inhibition of TASK channels. However, in other systems, PAC1 is known to be coupled to multiple intracellular signaling pathways, including PKA, phospholipase C (PLC), phospholipase D (PLD), and protein kinase C (PKC), that trigger multiple downstream effectors including increased Ca2+ mobilization, inhibition of various K+ channels, and activation of nonselective cation channels. This study tests if non-PKA/TASK channel signaling helps mediate the stimulatory effects of PACAP on the carotid body. Using an ex vivo arterially perfused rat carotid body preparation, we show that PACAP-38 stimulates carotid sinus nerve activity in a biphasic manner (peak response, falling to plateau). PKA blocker H-89 only reduced the plateau response (∼41%), whereas the TASK-1-like K+ channel blocker/transient receptor potential vanilloid 1 channel agonist anandamide only inhibited the peak response (∼48%), suggesting involvement of additional pathways. The PLD blocker CAY10594 significantly inhibited both peak and plateau responses. The PLC blocker U73122 decimated both peak and plateau responses. Brefeldin A, a blocker of Epac (cAMP-activated guanine exchange factor, reported to link Gs-coupled receptors with PLC/PLD), also reduced both phases of the response, as did blocking signaling downstream of PLC/PLD with the PKC inhibitors chelerythrine chloride and GF109203X. Suggesting the involvement of non-TASK ion channels in the effects of PACAP, the A-type K+ channel blocker 4-aminopyridine, and the putative transient receptor potential channel (TRPC)/T-type calcium channel blocker SKF96365 each significantly inhibited the peak and steady-state responses. These data suggest the stimulatory effect of PACAP-38 on carotid body sensory activity is mediated through multiple signaling pathways: the PLC-PKC pathways predominates, with TRPC and/or T-type channel activation and Kv channel inactivation; only partial involvement is attributable to PKA and PLD activation.