bluuebunny/crossref_metadata_2025 huggingface dataset:
Phylogeny and taxonomic revision of the spider mite genera Aponychus, Paraponychus and Stylophoronychus using morphology (Acari : Tetranychidae)
Authors: Hernandes Fabio A. , Feres Reinaldo J. F.
Published: October 2013

Despite their great importance as pests of cultivated plants worldwide, members of the family Tetranychidae have never been subjected to a thorough cladistic analysis to reveal the history and relationships among related genera. Herein, we provide the first phylogenetic analysis and taxonomic review of species of the genera Aponychus, Paraponychus and Stylophoronychus using morphological characters. The results indicate a monophyletic clade uniting the aforementioned genera, although none of the three genera were recovered as monophyletic. We reinstate the tribe Aponychini as the taxon containing those three genera. Aponychus bambusae and A. aequilibris are herein considered junior synonyms of Stylophoronychus vannus and A. corpuzae, respectively.
Odd-skipped related-1 controls neural crest chondrogenesis during tongue development
Authors: Liu Han , Lan Yu , Xu Jingyue , Chang Ching-Fang , Brugmann Samantha A. , Jiang Rulang
Published: October 2013

Significance

Development of the tongue is a major vertebrate adaptation to terrestrial life. Interestingly, although the tongues of birds and mammals initially develop similarly, the bird tongue is underpinned by an extensive internal skeleton, whereas the oral part of the mammalian tongue is boneless, which is critical not only for feeding but also for phonetic articulation and oral health. This paper shows that the mouse embryonic tongue, but not that in chick, expresses high levels of the odd-skipped related-1 (Osr1) transcription factor, which represses expression of SRY-box containing gene-9 (Sox9), the master regulator of cartilage formation. Mice lacking Osr1 function develop a cartilage in the anterior tongue reminiscent of that in chick. These data provide unique insights into the mechanisms of tongue development and evolution.
High-performance, low-voltage electroosmotic pumps with molecularly thin silicon nanomembranes
Authors: Snyder Jessica L. , Getpreecharsawas Jirachai , Fang David Z. , Gaborski Thomas R. , Striemer Christopher C. , Fauchet Philippe M. , Borkholder David A. , McGrath James L.
Published: October 2013

Significance

Electroosmotic pumps (EOPs) are a class of pumps in which fluid is driven through a capillary or porous media within an electric field. Current research on EOPs concerns the development of new materials in which high electroosmotic flow rates can be achieved for low voltages. Such pumps could be used for portable microfluidic devices. Porous nanocrystalline silicon (pnc-Si) is a material that is formed into a 15-nm-thick nanomembrane. pnc-Si membranes are shown here to have high electroosmotic flow rates at low applied voltages due to the high electric fields achieved over the ultrathin membrane. A prototype EOP was designed using pnc-Si membranes and shown to pressurize fluid through capillary tubing at voltages as low as 250 mV.
Microclimate moderates plant responses to macroclimate warming
Authors: De Frenne Pieter , Rodríguez-Sánchez Francisco , Coomes David Anthony , Baeten Lander , Verstraeten Gorik , Vellend Mark , Bernhardt-Römermann Markus , Brown Carissa D. , Brunet Jörg , Cornelis Johnny , Decocq Guillaume M. , Dierschke Hartmut , Eriksson Ove , Gilliam Frank S. , Hédl Radim , Heinken Thilo , Hermy Martin , Hommel Patrick , Jenkins Michael A. , Kelly Daniel L. , Kirby Keith J. , Mitchell Fraser J. G. , Naaf Tobias , Newman Miles , Peterken George , Petřík Petr , Schultz Jan , Sonnier Grégory , Van Calster Hans , Waller Donald M. , Walther Gian-Reto , White Peter S. , Woods Kerry D. , Wulf Monika , Graae Bente Jessen , Verheyen Kris
Published: October 2013

Significance

Around the globe, climate warming is increasing the dominance of warm-adapted species—a process described as “thermophilization.” However, thermophilization often lags behind warming of the climate itself, with some recent studies showing no response at all. Using a unique database of more than 1,400 resurveyed vegetation plots in forests across Europe and North America, we document significant thermophilization of understory vegetation. However, the response to macroclimate warming was attenuated in forests whose canopies have become denser. This microclimatic effect likely reflects cooler forest-floor temperatures via increased shading during the growing season in denser forests. Because standing stocks of trees have increased in many temperate forests in recent decades, microclimate may commonly buffer understory plant responses to macroclimate warming.
Viroporin activity of the JC polyomavirus is regulated by interactions with the adaptor protein complex 3
Authors: Suzuki Tadaki , Orba Yasuko , Makino Yoshinori , Okada Yuki , Sunden Yuji , Hasegawa Hideki , Hall William W. , Sawa Hirofumi
Published: October 2013

Significance

Viroporins are small, hydrophobic viral proteins that form pores on host cell membranes, and their expression can increase the production of progeny virus particles. Recently, we have shown that human JC polyomavirus agnoprotein acts as a viroporin. We have investigated the role of host cellular proteins in the viroporin activity of the agnoprotein. We demonstrated that an interaction of the agnoprotein with the δ subunit of AP-3 prevents AP-3–mediated vesicular trafficking and blocks the targeted transport of the agnoprotein for lysosomal degradation. These findings demonstrate a previously undescribed paradigm in virus–host interactions regulating virus replication and suggest that viroporins of other viruses may also be regulated by specific interactions with host cellular proteins.
Gating of the proton-gated ion channel from
Gloeobacter violaceus
at pH 4 as revealed by X-ray crystallography
Authors: Gonzalez-Gutierrez Giovanni , Cuello Luis G. , Nair Satish K. , Grosman Claudio
Published: October 2013

Significance

Determination of the structure of ion channels in their physiologically relevant states remains a major challenge. Structural models of the unliganded closed-channel and the fully liganded open-channel conformations of different members of the nicotinic-receptor superfamily have been generated using cryoelectron microscopy or X-ray crystallography. In this paper, we describe the structure of what appears to be the closed-channel conformation in its liganded state. We used X-ray crystallography to solve the structure of two mutants of a proton-gated bacterial ortholog that exhibit a reduced equilibrium constant for the closed-to-open transition; to favor the ligand-bound state, the crystals were grown at pH ∼4.0. Compared with the liganded open-channel conformation, the closed-channel conformation presents a narrower pore, but an indistinguishable extracellular domain.
Combining two strategies to improve perfusion and drug delivery in solid tumors
Authors: Stylianopoulos Triantafyllos , Jain Rakesh K.
Published: October 2013

Significance

Vascular normalization and stress-alleviation treatments are promising strategies to improve tumor perfusion and delivery of drugs. Vascular normalization is more effective for tumors with hyperpermeable but uncompressed vessels, whereas stress alleviation is more beneficial for compressed but low-permeable vessels. In the case of tumors with hyperpermeable and compressed vessels, the two strategies need to be combined for improved treatment.
MIP-1α/CCL3-mediated maintenance of leukemia-initiating cells in the initiation process of chronic myeloid leukemia
Authors: Baba Tomohisa , Naka Kazuhito , Morishita Soji , Komatsu Norio , Hirao Atsushi , Mukaida Naofumi
Published: October 2013

In the initiation process of chronic myeloid leukemia (CML), a small number of transformed leukemia-initiating cells (LICs) coexist with a large number of normal hematopoietic cells, gradually increasing thereafter and eventually predominating in the hematopoietic space. However, the interaction between LICs and normal hematopoietic cells at the early phase has not been clearly delineated because of the lack of a suitable experimental model. In this study, we succeeded in causing a marked leukocytosis resembling CML from restricted foci of LICs in the normal hematopoietic system by direct transplantation of BCR-ABL gene–transduced LICs into the bone marrow (BM) cavity of nonirradiated mice. Herein, we observed that BCR-ABL+lineage−c-kit− immature leukemia cells produced high levels of an inflammatory chemokine, MIP-1α/CCL3, which promoted the development of CML. Conversely, ablation of the CCL3 gene in LICs dramatically inhibited the development of CML and concomitantly reduced recurrence after the cessation of a short-term tyrosine kinase inhibitor treatment. Finally, normal hematopoietic stem/progenitor cells can directly impede the maintenance of LICs in BM in the absence of CCL3 signal.
Identifying Targets for Antimicrobial Stewardship in Children's Hospitals
Authors: Gerber Jeffrey S. , Kronman Matthew P. , Ross Rachael K. , Hersh Adam L. , Newland Jason G. , Metjian Talene A. , Zaoutis Theoklis E.
Published: October 2013

Objective.

Antimicrobial stewardship programs (ASPs) are recommended to optimize antimicrobial use for hospitalized patients. Although mechanisms for the implementation of ASPs have been described, data-driven approaches to prioritize specific conditions and antimicrobials for intervention have not been established. We aimed to develop a strategy for identifying high-impact targets for antimicrobial stewardship efforts.

Design.

Retrospective cross-sectional study.

Setting and Patients.

Children admitted to 32 freestanding children's hospitals in the United States in 2010.

Methods.

We identified the conditions with the largest proportional contribution to the total days of antibiotic therapy prescribed to all hospitalized children. For the 4 highest-using conditions, we examined variability between hospitals in antibiotic selection patterns for use of either first- or second-line therapies depending on the condition. Antibiotic use was determined using standardized probability of exposure to selected agents and standardized days of therapy per 1,000 patient-days, adjusting for patient demographics and severity of illness.

Results.

In 2010, 524,364 children received 2,082,929 days of antibiotic therapy. Surgical patients received 43% of all antibiotics. The 4 highest-using conditions—pneumonia, appendicitis, cystic fibrosis, and skin and soft-tissue infection—represent 1% of all conditions yet accounted for more than 10% of all antibiotic use. Wide variability in antibiotic use occurred for 3 of these 4 conditions.

Conclusions.

Antibiotic use in children's hospitals varied broadly across institutions when examining diagnoses individually and adjusting for severity of illness. Identifying conditions with both frequent and variable antimicrobial use informs the prioritization of high-impact targets for future antimicrobial stewardship interventions.
Telling metabolic stories to explore metabolomics data: a case study on the yeast response to cadmium exposure
Authors: Milreu Paulo Vieira , Klein Cecilia Coimbra , Cottret Ludovic , Acuña Vicente , Birmelé Etienne , Borassi Michele , Junot Christophe , Marchetti-Spaccamela Alberto , Marino Andrea , Stougie Leen , Jourdan Fabien , Crescenzi Pierluigi , Lacroix Vincent , Sagot Marie-France
Published: October 2013

Motivation: The increasing availability of metabolomics data enables to better understand the metabolic processes involved in the immediate response of an organism to environmental changes and stress. The data usually come in the form of a list of metabolites whose concentrations significantly changed under some conditions, and are thus not easy to interpret without being able to precisely visualize how such metabolites are interconnected.

Results: We present a method that enables to organize the data from any metabolomics experiment into metabolic stories. Each story corresponds to a possible scenario explaining the flow of matter between the metabolites of interest. These scenarios may then be ranked in different ways depending on which interpretation one wishes to emphasize for the causal link between two affected metabolites: enzyme activation, enzyme inhibition or domino effect on the concentration changes of substrates and products. Equally probable stories under any selected ranking scheme can be further grouped into a single anthology that summarizes, in a unique subnetwork, all equivalently plausible alternative stories. An anthology is simply a union of such stories. We detail an application of the method to the response of yeast to cadmium exposure. We use this system as a proof of concept for our method, and we show that we are able to find a story that reproduces very well the current knowledge about the yeast response to cadmium. We further show that this response is mostly based on enzyme activation. We also provide a framework for exploring the alternative pathways or side effects this local response is expected to have in the rest of the network. We discuss several interpretations for the changes we see, and we suggest hypotheses that could in principle be experimentally tested. Noticeably, our method requires simple input data and could be used in a wide variety of applications.

Availability and implementation: The code for the method presented in this article is available at http://gobbolino.gforge.inria.fr.

Contact: pvmilreu@gmail.com; vincent.lacroix@univ-lyon1.fr; marie-france.sagot@inria.fr

Supplementary information:  Supplementary data are available at Bioinformatics online.
Fast pairwise IBD association testing in genome-wide association studies
Authors: Han Buhm , Kang Eun Yong , Raychaudhuri Soumya , de Bakker Paul I. W. , Eskin Eleazar
Published: October 2013

Motivation: Recently, investigators have proposed state-of-the-art Identity-by-descent (IBD) mapping methods to detect IBD segments between purportedly unrelated individuals. The IBD information can then be used for association testing in genetic association studies. One approach for this IBD association testing strategy is to test for excessive IBD between pairs of cases (‘pairwise method’). However, this approach is inefficient because it requires a large number of permutations. Moreover, a limited number of permutations define a lower bound for P-values, which makes fine-mapping of associated regions difficult because, in practice, a much larger genomic region is implicated than the region that is actually associated.

Results: In this article, we introduce a new pairwise method ‘Fast-Pairwise’. Fast-Pairwise uses importance sampling to improve efficiency and enable approximation of extremely small P-values. Fast-Pairwise method takes only days to complete a genome-wide scan. In the application to the WTCCC type 1 diabetes data, Fast-Pairwise successfully fine-maps a known human leukocyte antigen gene that is known to cause the disease.

Availability: Fast-Pairwise is publicly available at: http://genetics.cs.ucla.edu/graphibd.

Contact:  eeskin@cs.ucla.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Influence of Bioprocessed Wheat Bran on the Physical and Chemical Properties of Dough and on Wheat Bread Texture
Authors: Hartikainen Katri , Poutanen Kaisa , Katina Kati
Published: October 2013

The aim of this work was to assess the influence of wheat bran addition on the rheological properties of dough and on subsequent wheat bread volume and texture. Two types of bioprocessed bran (fermentation with yeast or with yeast plus enzymes) were studied in breadmaking at a substitution level of 20% (sufficient to deliver 6 g of dietary fiber per 100 g of product, the minimum for the European Food Safety Authority high‐fiber nutrition claim). Fermentation activated endogenous enzymes of bran, which together with exogenous enzymes modified the state of fiber in bran, resulting in solubilization of arabinoxylans and slight degradation of the insoluble fiber. Fermentation and enzyme treatment of bran compensated for the increased hardness (+100%) and the volume‐decreasing (–21%) effect observed with untreated bran. Analysis with partial least squares regression suggested the efficacy of bioprocessing to be based on solubilization of arabinoxylans, smaller particle size of bran, lower pasting viscosity of starch, improved resistance to extension, and accelerated CO2 production.
Intra-sexual selection in cooperative mammals and birds: why are females not bigger and better armed?
Authors: Young Andrew J. , Bennett Nigel C.
Published: October 2013

In cooperatively breeding mammals and birds, intra-sexual reproductive competition among females may often render variance in reproductive success higher among females than males, leading to the prediction that intra-sexual selection in such species may have yielded the differential exaggeration of competitive traits among females. However, evidence to date suggests that female-biased reproductive variance in such species is rarely accompanied by female-biased sexual dimorphisms. We illustrate the problem with data from wild Damaraland mole-rat,
Fukomys damarensis
, societies: the variance in lifetime reproductive success among females appears to be higher than that among males, yet males grow faster, are much heavier as adults and sport larger skulls and incisors (the weapons used for fighting) for their body lengths than females, suggesting that intra-sexual selection has nevertheless acted more strongly on the competitive traits of males. We then consider potentially general mechanisms that could explain these disparities by tempering the relative intensity of selection for competitive trait exaggeration among females in cooperative breeders. Key among these may be interactions with kin selection that could nevertheless render the variance in inclusive fitness lower among females than males, and fundamental aspects of the reproductive biology of females that may leave reproductive conflict among females more readily resolved without overt physical contests.
The evolutionary psychology of women's aggression
Authors: Campbell Anne
Published: October 2013

Evolutionary researchers have identified age, operational sex ratio and high variance in male resources as factors that intensify female competition. These are discussed in relation to escalated intrasexual competition for men and their resources between young women in deprived neighbourhoods. For these women, fighting is not seen as antithetical to cultural conceptions of femininity, and female weakness is disparaged. Nonetheless, even where competitive pressures are high, young women's aggression is less injurious and frequent than young men's. From an evolutionary perspective, I argue that the intensity of female aggression is constrained by the greater centrality of mothers, rather than fathers, to offspring survival. This selection pressure is realized psychologically through a lower threshold for fear among women. Neuropsychological evidence is not yet conclusive but suggests that women show heightened amygdala reactivity to threatening stimuli, may be better able to exert prefrontal cortical control over emotional behaviour and may consciously register fear more strongly via anterior cingulate activity. The impact of testosterone and oxytocin on the neural circuitry of emotion is also considered.
Altererythrobacter xiamenensis sp. nov., an algicidal bacterium isolated from red tide seawater
Authors: Lei Xueqian , Li Yi , Chen Zhangran , Zheng Wei , Lai Qiliang , Zhang Huajun , Guan Chengwei , Cai Guanjing , Yang Xujun , Tian Yun , Zheng Tianling
Published: October 2013

A Gram-stain-negative, yellow-pigmented, aerobic bacterial strain, designated LY02T, was isolated from red tide seawater in Xiamen, Fujian Province, China. Growth was observed at temperatures from 4 to 44 °C, at salinities from 0 to 9 % and at pH from 6 to 10. Phylogenetic analysis based on 16S rRNA gene sequencing revealed that the isolate was a member of the genus

Altererythrobacter

, which belongs to the family

Erythrobacteraceae

. Strain LY02T was related most closely to

Altererythrobacter marensis

MSW-14T (97.2 % 16S rRNA gene sequence similarity), followed by

Altererythrobacter ishigakiensis

JPCCMB0017T (97.1 %),

Altererythrobacter epoxidivorans

JCS350T (97.1 %) and

Altererythrobacter luteolus

SW-109T (97.0 %). The dominant fatty acids were C18 : 1ω7c, C17 : 1ω6c and summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c). DNA–DNA hybridization showed that strain LY02T possessed low DNA–DNA relatedness to

A. marensis

MSW-14T,

A. ishigakiensis

JPCCMB0017T,

A. epoxidivorans

JCS350T and

A. luteolus

SW-109T (mean±sd of 33.2±1.3, 32.1±1.0, 26.7±0.7 and 25.2±1.1 %, respectively). The G+C content of the chromosomal DNA was 61.2 mol%. The predominant respiratory quinone was ubiquinone-10 (Q-10). According to its morphology, physiology, fatty acid composition and 16S rRNA gene sequence data, the novel strain most appropriately belongs to the genus

Altererythrobacter

, but can readily be distinguished from recognized species. The name Altererythrobacter xiamenensis sp. nov. is proposed (type strain LY02T = CGMCC 1.12494T = KCTC 32398T = NBRC 109638T).
Analysis of the microbial ecology between Helicobacter pylori and the gastric microbiota of Mongolian gerbils
Authors: Zaman Cynthia , Osaki Takako , Hanawa Tomoko , Yonezawa Hideo , Kurata Satoshi , Kamiya Shigeru
Published: October 2013

Animal models are essential forin vivoanalysis ofHelicobacter-related diseases. Mongolian gerbils are used frequently to studyHelicobacter pylori-induced gastritis and its consequences. The presence of some gastric microbiota with a suppressive effect onH. pylorisuggests inhibitory gastric bacteria againstH. pyloriinfection. The aim of the present study was to analyse the microbial ecology betweenH. pyloriand the gastric microbiota of Mongolian gerbils. Gastric mucosa samples ofH. pylori-negative and -positive gerbils were orally inoculated to five (Group 1) and six (Group 2) gerbils, respectively, and the gerbils were challenged withH. pyloriinfection. The colonization rate (40 %) ofH. pyloriin Group 1 gerbils was lower than the rate (67 %) in Group 2 gerbils. Culture filtrate of the gastric mucosa samples of Group 1 gerbils inhibited thein vitrogrowth ofH. pylori. Three lactobacilli species,Lactobacillus reuteri,Lactobacillus johnsoniiandLactobacillus murinus, were isolated by anaerobic culture from the gerbils in Groups 1 and 2, and identified by genomic sequencing. It was demonstrated that the three different strains of lactobacilli exhibited an inhibitory effect on thein vitrogrowth ofH. pylori. The results suggested that lactobacilli are the dominant gastric microbiota of Mongolian gerbils and the three lactobacilli isolated from the gastric mucosa samples with an inhibitory effect onH. pylorimight have an anti-infective effect againstH. pylori.
Improved exome prioritization of disease genes through cross-species phenotype comparison
Authors: Robinson Peter N. , Köhler Sebastian , Oellrich Anika ,   Sanger Mouse Genetics Project, Wang Kai , Mungall Christopher J. , Lewis Suzanna E. , Washington Nicole , Bauer Sebastian , Seelow Dominik , Krawitz Peter , Gilissen Christian , Haendel Melissa , Smedley Damian
Published: October 2013

Numerous new disease-gene associations have been identified by whole-exome sequencing studies in the last few years. However, many cases remain unsolved due to the sheer number of candidate variants remaining after common filtering strategies such as removing low quality and common variants and those deemed unlikely to be pathogenic. The observation that each of our genomes contains about 100 genuine loss-of-function variants makes identification of the causative mutation problematic when using these strategies alone. We propose using the wealth of genotype to phenotype data that already exists from model organism studies to assess the potential impact of these exome variants. Here, we introduce PHenotypic Interpretation of Variants in Exomes (PHIVE), an algorithm that integrates the calculation of phenotype similarity between human diseases and genetically modified mouse models with evaluation of the variants according to allele frequency, pathogenicity, and mode of inheritance approaches in our Exomiser tool. Large-scale validation of PHIVE analysis using 100,000 exomes containing known mutations demonstrated a substantial improvement (up to 54.1-fold) over purely variant-based (frequency and pathogenicity) methods with the correct gene recalled as the top hit in up to 83% of samples, corresponding to an area under the ROC curve of >95%. We conclude that incorporation of phenotype data can play a vital role in translational bioinformatics and propose that exome sequencing projects should systematically capture clinical phenotypes to take advantage of the strategy presented here.
High diffraction efficiency in crystals curved by surface damage
Authors: Ferrari Claudio , Buffagni Elisa , Bonnini Elisa , Korytar Dusan
Published: October 2013

Diffraction profiles of curved Si and GaAs crystals obtained by a controlled damage process on one side of planar crystals have been investigated at X-ray energiesE= 17, 59 and 120 keV. AtE= 17 and 59 keV in the condition of slight curvature, that is when the diffracting plane bending over the extinction length is lower than the Darwin width, the Laue diffraction profiles with lattice planes parallel or inclined with respect to the curvature radiusRshow an enhancement of integrated intensity proportional to 1/R, much larger than in the corresponding perfect bent crystals. AtE= 120 keV, in the condition of strong curvature, the crystals behave as bent perfect crystals with integrated intensity corresponding to that of a mosaic crystal. These crystals are proposed as optical elements for focusing hard X-ray beams.
Effect of Mg doping on the growth aspects, crystalline perfection, and optical and thermal properties of congruent LiNbO3single crystals
Authors: Riscob B. , Bhaumik Indranil , Ganesamoorthy S. , Bhatt R. , Vijayan N. , Karnal A. K. , Wahab M. A. , Bhagavannarayana G.
Published: October 2013

Mg-doped congruent lithium niobate single crystals were grown by the Czochralski technique. High-quality single crystals were grown using a novel seeding technique in a resistive heating furnace. Analysis of crystalline perfection carried out by a multi-crystal X-ray diffractometer revealed that the grown crystals do not contain any structural grain boundaries but do contain point defects. The transmission characteristics showed an enhancement of band gap with an increase in Mg concentration. Conoscopy patterns revealed that the grown crystals are homogeneous and the incorporation of Mg into the lattice does not affect the optical sign (negative uniaxial) of the crystal. The refractive index measurements carried out using a prism coupler showed an increase in the optical birefringence (Δn), while the refractive index was found to decrease with the increase in doping concentration. Further, thermal conductivity was found to decrease with Mg incorporation in the lattice owing to phonon scattering from the Mg ions and, as a consequence, at high concentrations (>4 mol%) crack formation occurred. However, optimization of growth conditions reveals that a slower pulling rate leads to crack-free lithium niobate crystals even at 6 mol% Mg doping.
6,6′-Diethoxy-2,2′-[4-methyl-1,2-phenylenebis(nitrilomethanylylidene)]diphenol acetonitrile monosolvate
Authors: Li Lei , Zeng Suyuan
Published: October 2013

The title solvated Schiff base compound, C25H26N2O4·CH3CN, possesses an O2N2donor set affording a potentially tetradentate metal complex ligand. The central ring makes dihedral angles of 6.7 (3) and 48.4 (2)° with the pendant rings. Intramolecular N—H...O hydrogen-bonding interactions are observed.
2-Isopropyl-4-methoxy-5-methylphenyl acetate
Authors: Oubabi Radouane , Auhmani Aziz , Ait Itto My Youssef , Driss Mohamed , Soumhi El Hassane
Published: October 2013

In the title compound, C13H18O3, the benzene ring is almost perpendicular to the acetoxy plane, making a dihedral angle of 89.33 (11)°. In the crystal, molecules are linked by weak C—H...O hydrogen bonds, forming a zigzag chain along thec-axis direction.
Optimized Development of Sebaceous Fingermarks on Nonporous Substrates with Conformal Columnar Thin Films
Authors: Muhlberger Sarah A. , Pulsifer Drew P. , Lakhtakia Akhlesh , Martín‐Palma Raúl J. , Shaler Robert C.
Published: October 2013

A form of physical vapor deposition, called the conformal‐evaporated‐film‐by‐rotation (CEFR) method, was optimized for the conformal deposition of columnar thin films (CTFs) on sebaceous fingermarks. Relying on the surface topology of the fingermark, the CTF development technique is different from traditional development techniques. After the optimization of the development conditions, the CTF development technique was found to be superior to traditional development methods on several nonporous substrates: the smooth side of Scotch® Multitask, Gorilla®, and Scotch® Duct tapes; clear and black soft plastics; stained and sealed walnut and cherry woods; partial bloody fingermarks on stainless steel; and discharged cartridge casings. It was equally as good as other development techniques on other substrates, but worse on a few. The optimization study is expected to assist in designing a mobile CEFR apparatus capable of on‐scene development of fingermarks.
Deciphering the relationship between vulnerability to ethanol‐induced behavioral sensitization and ethanol consumption in outbred mice
Authors: Legastelois Rémi , Botia Béatrice , Coune Fabien , Jeanblanc Jérôme , Naassila Mickaël
Published: October 2013

Ethanol (EtOH)‐induced behavioral sensitization (EIBS) is proposed to play a role in early and recurring steps of alcohol dependence, but its impact on alcohol abuse is not clear. EIBS development is dependent upon animal species, strain and also individual factors. We proposed here to decipher the co‐expression of EIBS and EtOH intake in individual animals among outbred Swiss mice, which exhibit heterogeneity that parallels what may occur in humans. To do so, mice were exposed to a two‐bottle choice with free access to water or 10% EtOH for 6 days just before and immediately after chronic intraperitoneal 2.5 g/kg ethanol injections once a day for 10 consecutive days. Based on their sensitization scores, mice were split into resistant and sensitized animals. First, we showed that individual susceptibility to EIBS is inversely correlated with voluntary EtOH consumption. Exposure to repeated EtOH during EIBS development increased subsequent EtOH intake among the entire population. Very interestingly, subsequent analyses suggested that the less the mice are sensitized the more they increase their EtOH intake; however, resistant mice were sensitive to EtOH adulteration with quinine, whereas sensitized ones maintained their EtOH intake levels, therefore exhibiting a compulsive‐like drinking pattern. In addition, we showed that resistant mice do not exhibit a weaker sensitivity to the aversive properties of EtOH that may contribute to their higher level of EtOH intake compared to sensitized mice. This study confirms and extends previous data showing a deep relationship between propensity for EtOH consumption and susceptibility to EIBS in Swiss mice.
Long‐lasting, experience‐dependent alcohol preference in Drosophila
Authors: Peru y Colón de Portugal Raniero L. , Ojelade Shamsideen A. , Penninti Pranav S. , Dove Rachel J. , Nye Matthew J. , Acevedo Summer F. , Lopez Antonio , Rodan Aylin R. , Rothenfluh Adrian
Published: October 2013

To understand the molecular and neural mechanisms underlying alcohol addiction, many models ranging from vertebrates to invertebrates have been developed. In Drosophila melanogaster, behavioral paradigms from assaying acute responses to alcohol and to behaviors more closely modeling addiction have emerged in recent years. However, both the CAFÉ assay, similar to a two‐bottle choice consumption assay, as well as conditioned odor preference, where ethanol is used as the reinforcer, are labor intensive and have low throughput. To address this limitation, we have established a novel ethanol consumption preference assay, called FRAPPÉ, which allows for fast, high throughput measurement of consumption in individual flies, using a fluorescence plate reader. We show that naïve flies do not prefer to consume ethanol, but various pre‐exposures, such as ethanol vapor or voluntary ethanol consumption, induce ethanol preference. This ethanol‐primed preference is long lasting and is not driven by calories contained in ethanol during the consumption choice. Our novel experience‐dependent model of ethanol preference in Drosophila—a highly genetically tractable organism—therefore recapitulates salient features of human alcohol abuse and will facilitate the molecular understanding of the development of alcohol preference.
Single institutional series of neuroendocrine tumors managed in the Australian Capital Territory
Authors: Malik Laeeq , Chua Yu Jo , Butt Nadeem S , Yip Desmond
Published: October 2013

Aims

Retrospective review of neuroendocrine tumors (NETs) treated within the Australian Capital Territory to describe the local epidemiology and assess prognostic clinicopathological factors.

Methods

Patients with histologically proven non‐pulmonary low to intermediate grade NETs were identified from our hospital clinical database. Data were analyzed according to epidemiological, clinical and histopathological characteristics.

Results

Of the 107 included patients, the most common primary tumor site was jejunum/ileum (32%), followed by rectum (22%) and pancreas (11.2%). In total, 32% had distant metastases at presentation, most commonly in the liver. Most patients were symptomatic at diagnosis, while 22.4% of cases were found incidentally. Second malignancies, in particular of gastrointestinal origin, were diagnosed in 33.6%. Surgical debulking was the most common treatment (59.8%) while 18% had multimodality therapy. With a median follow‐up of 25 months from diagnosis, about 78% of patients are still alive. Median time to first relapse was 15 months and the 5‐year survival rate was 80% for NETs of jejunum/ileum. Univariate survival analysis revealed tumor location, high Ki67 index, raised plasma chromogranin A, and urine 5‐hydroxyindoleacetic acid upon diagnosis to be associated with shorter 5‐year survival.

Conclusion

The epidemiologic characteristics and long‐term outcome in our series are comparable to other reported studies. This analysis presents some important prognostic factors which could be used for risk stratification in patients with NETs.
Intra‐arterial chemotherapy for retinoblastoma. Challenges of a prospective study
Authors: Parareda Andreu , Català Jaume , Carcaboso Angel M. , Sola Teresa , Cruz Ofelia , Díaz Jesús , Salvador Héctor , de Torres Carmen , Álvarez‐Sampons Alexandra , Suñol Mariona , Vinent Joan , Guimaraens Leopoldo , Prat Joan , Mora Jaume
Published: October 2013

Purpose

To report the efficacy and complications of intra‐ophthalmic artery melphalan (IAM) for treatment of patients with advanced intra‐ocular retinoblastoma.

Methods

Patients with newly diagnosed, unilateral, group D retinoblastoma were included in a phase II protocol. Children with relapsed‐refractory disease after systemic chemoreduction were later treated under the same guidelines. Melphalan (3–5 mg/procedure) was injected through a 1.2 F microcatheter placed into the ophthalmic artery every 21 days.

Results

Eleven patients (12 eyes, eight as primary treatment) received 33 IAM procedures. The phase II protocol closed prematurely because of low accrual. The IAM technique was overall safe and could be performed successfully in 31 of 33 (94%) attempts. After the second administration of IAM, very good partial response was achieved in all treated eyes. With a median follow‐up time of 29.5 months (range 6–57), ocular salvage was achieved in 7 of 12 (58%) eyes. No systemic adverse events were observed. Two patients developed diffuse arteriolar sclerosis, hyperpigmentation of the retinal pigment epithelium and partial retinal atrophy after the second IAM. Both eyes were preserved with no tumour activity, good motility and perception of light, 56 and 30 months after the last IAM treatment. Multinucleated macrophages with intracytoplasmic foreign material were found in the choroid and the retina in 2 of 5 enucleated eyes.

Conclusion

Our study reports the activity and reproducibility of IAM in advanced retinoblastoma but also underlines the challenges of performing prospective studies on this treatment modality. Toxicity was limited to only ocular vascular events.
10 Shifting Territorialities under the Inka Empire: The Case of the Rapayán Valley in the Central Andean Highlands
Authors: Mantha Alexis
Published: October 2013

I examine the changing patterns of territoriality generated by the Inkas upon their conquest of a middle‐range society of the Rapayán Valley in the Upper Marañón drainage of the northern central Andes of Peru. The territorial‐hegemonic model as well as Robert Sack's conception of territoriality—considered a strategy of social control through space—are used to discuss architectural and settlement pattern changes characterizing the transition between the Late Intermediate Period (C.E. 1000–1450) and the Late Horizon (Inka; C.E. 1450–1532). I argue that before the Inka conquest, territoriality was achieved through ceremonies honoring the Rapayán Valley's founding ancestors held at the location of highly visible above‐ground mortuary monuments distributed across the Rapayán landscape. Upon their conquest of the Rapayán Valley, the Inkas attempted to redefine local territorial practices and categories through various means and used simultaneously direct and indirect strategies of governance. [territoriality, Inka, Andes, Rapayán, Upper Marañón]
Detrimental effects of acute hyperglycaemia on the rat heart
Authors: Mapanga R. F. , Joseph D. , Symington B. , Garson K.‐L. , Kimar C. , Kelly‐Laubscher R. , Essop M.Faadiel
Published: October 2013

Aim

Hyperglycaemia is an important risk factor for acute myocardial infarction. It can lead to increased induction of non‐oxidative glucose pathways (NOGPs) – polyol and hexosamine biosynthetic pathways, advanced glycation end products and protein kinase C – that may contribute to cardiovascular diseases onset. However, the precise underlying mechanisms remain poorly understood. Here we hypothesized that acute hyperglycaemia increases myocardial oxidative stress and NOGP activation resulting in cardiac dysfunction during ischaemia–reperfusion and that inhibition of, and/or shunting flux away from NOGPs [by benfotiamine (BFT) treatment], leads to cardioprotection.

Methods

We employed several experimental systems: (i) Isolated rat hearts were perfused ex vivo with Krebs‐Henseleit buffer containing 33 mm glucose vs. controls (11 mm glucose) ± global ischaemia and reperfusion ± BFT (first 20 min of reperfusion); (ii) Infarct size determination as per the ischaemic protocol, but with regional ischaemia and reperfusion ± BFT treatment; in separate experiments, NOGP inhibitors were also employed for (i) and (ii); and (iii) In vivo coronary ligations performed on streptozotocin‐treated rats ± BFT treatment (early reperfusion).

Results

Acute hyperglycaemia generated myocardial oxidative stress, NOGP activation and apoptosis, but caused no impairment of cardiac function during pre‐ischaemia, thereby priming hearts for later damage. Following ischaemia–reperfusion (under hyperglycaemic conditions), such effects were exacerbated together with cardiac contractile dysfunction. Moreover, inhibition of respective NOGPs and shunting away by BFT treatment (in part) improved cardiac function during ischaemia–reperfusion.

Conclusion

Coordinate NOGP activation in response to acute hyperglycaemia results in contractile dysfunction during ischaemia–reperfusion, allowing for the development of novel cardioprotective agents.
Electronic health records for biological sample collection: feasibility study of statin‐induced myopathy using the Clinical Practice Research Datalink
Authors: O'Meara Helen , Carr Daniel F. , Evely Jane , Hobbs Mark , McCann Gerard , van Staa Tjeerd , Pirmohamed Munir
Published: October 2013

Aims

Electronic healthcare records (EHRs) are increasingly used to store clinical information. A secondary benefit of EHRs is their use, in an anonymized form, for observational research. The Clinical Practice Research Datalink (CPRD) contains EHRs from primary care in the UK and, despite 1083 peer‐reviewed research publications, has never been used to obtain pharmacogenetic samples. Using a statin‐induced myopathy paradigm, we evaluated using the CPRD to obtain patient samples for a pharmacogenetic study targeting 250 cases and 500 controls from UK general practitioner (GP) practices.

Methods

The CPRD identified potential patients fitting specific case‐definition criteria (active rhabdomyolysis or creatine phosphokinase > four times the upper limit of normal), and corresponding GP practices were asked to invite patient participation. Consenting patients were requested to provide either saliva or blood samples and to complete an ethnicity questionnaire. Control subjects were recruited from the same GP practice (saliva) or a small number of practices (blood). Samples were forwarded for DNA extraction.

Results

Thirty‐six months of recruitment yielded DNA samples from 149 statin‐induced myopathy cases and 587 tolerant controls. Data show that contacting patients through their GP is a reliable method for obtaining samples without compromising anonymity. Saliva collection directly from patients was considerably less effective than blood sampling. After 10 months of recruitment, saliva sampling was suspended in favour of blood sampling.

Conclusions

We demonstrate the potential of EHRs for identifying accurately phenotyped cases and controls for pharmacogenetic studies. Recruitment was successful only because of the willingness of GP practices to participate and the existence of strong doctor–patient relationships. The present study provides a model that can be implemented in future genetic analyses using EHRs.
A Comparison of Marginal and Conditional Models for Capture–Recapture Data with Application to Human Rights Violations Data
Authors: Mitchell Shira , Ozonoff Al , Zaslavsky Alan M. , Hedt-Gauthier Bethany , Lum Kristian , Coull Brent A.
Published: October 2013

Human rights data presents challenges for capture–recapture methodology. Lists of violent acts provided by many different groups create large, sparse tables of data for which saturated models are difficult to fit and for which simple models may be misspecified. We analyze data on killings and disappearances in Casanare, Colombia during years 1998 to 2007. Our estimates differ whether we choose to model marginal reporting probabilities and odds ratios, versus modeling the full reporting pattern in a conditional (log-linear) model. With 2629 observed killings, a marginal model we consider estimates over 9000 killings, while conditional models we consider estimate 6000–7000 killings. The latter agree with previous estimates, also from a conditional model. We see a twofold difference between the high sample coverage estimate of over 10,000 killings and low sample coverage lower bound estimate of 5200 killings. We use a simulation study to compare marginal and conditional models with at most two-way interactions and sample coverage estimators. The simulation results together with model selection criteria lead us to believe the previous estimates of total killings in Casanare may have been biased downward, suggesting that the violence was worse than previously thought. Model specification is an important consideration when interpreting population estimates from capture recapture analysis and the Casanare data is a protypical example of how that manifests.
In beauty we trust: Children prefer information from more attractive informants
Authors: Bascandziev Igor , Harris Paul L.
Published: October 2013

Preschool children were presented with slides on a computer screen showing a novel object, together with two informants, one with an attractive and one with a less attractive face. Children were asked which informant they would like to ask about the name of the novel object. After hearing the informants provide conflicting names, they were asked who they thought was correct. Children were more likely to endorse names provided by the person with the more attractive face, a bias that cannot be justified on epistemic grounds. The implications of this finding are discussed.
Human microtubule‐associated protein tau mediates targeted killing of CD30+ lymphoma cells in vitro and inhibits tumour growth in vivo
Authors: Hristodorov Dmitrij , Nordlohne Johannes , Mladenov Radoslav , Huhn Michael , Fischer Rainer , Thepen Theo , Barth Stefan
Published: October 2013

Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL) are rare lymphoproliferative cancer types. Although most HL patients can be cured by chemo‐ and radio‐therapy, 4–50% of patients relapse and have a poor prognosis. The need for improved therapeutic options for patients with relapsed or refractory disease has been addressed by CD30‐specific antibody‐based immunotherapeutics. However, available CD30‐specific monoclonal antibodies (mAbs), antibody drug conjugates (ADCs) or chimeric immunotoxins suffer from the requirement of a functional host immunity, undesirable immune reactions or heterogeneity and instability, respectively. Here, we present a new fusion protein comprised of the CD30‐specific antibody single‐chain fragment Ki4(scFv) and the human pro‐apoptotic effector protein, microtubule‐associated protein tau (MAPT). Ki4(scFv)‐MAP selectively induced apoptosis in rapidly proliferating L540cy, L428, and Karpas 299 cells in a dose‐dependent manner. Tubulin polymerization assays confirmed that Ki4(scFv)‐MAP stabilizes microtubules, suggesting a mechanism for its pro‐apoptotic action. Dose‐finding experiments proved that Ki4(scFv)‐MAP is well tolerated in mice compared to the previously reported Ki4(scFv)‐ETA'. Ki4(scFv)‐MAP significantly inhibited growth of subcutaneous L540cy xenograft tumours in mice. Our data present a novel approach for the treatment of CD30+ lymphomas, combining the binding specificity of a target‐specific antibody fragment with the selective cytotoxicity of MAPT towards proliferating lymphoma cells.