bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolutionary tools for phytosanitary risk analysis: phylogenetic signal as a predictor of host range of plant pests and pathogens
Authors: Gilbert Gregory S. , Magarey Roger , Suiter Karl , Webb Campbell O.
Published: May 2012

Assessing risk from a novel pest or pathogen requires knowing which local plant species are susceptible. Empirical data on the local host range of novel pests are usually lacking, but we know that some pests are more likely to attack closely related plant species than species separated by greater evolutionary distance. We use the Global Pest and Disease Database, an internal database maintained by the United States Department of Agriculture Animal and Plant Health Inspection Service – Plant Protection and Quarantine Division (USDA APHIS‐PPQ), to evaluate the strength of the phylogenetic signal in host range for nine major groups of plant pests and pathogens. Eight of nine groups showed significant phylogenetic signal in host range. Additionally, pests and pathogens with more known hosts attacked a phylogenetically broader range of hosts. This suggests that easily obtained data – the number of known hosts and the phylogenetic distance between known hosts and other species of interest – can be used to predict which plant species are likely to be susceptible to a particular pest. This can facilitate rapid assessment of risk from novel pests and pathogens when empirical host range data are not yet available and guide efficient collection of empirical data for risk evaluation.
Updates on endoscopic therapy of esophageal carcinoma
Authors: Isomoto Hajime
Published: May 2012

Endoscopic submucosal dissection (ESD) has the advantage over endoscopic mucosa resection (EMR), permitting removal of gastrointestinal neoplasms en bloc, but is associated with a relatively high risk of complications. Early esophageal cancer (EEC) is indicated when the tumors are confined to the two‐third layer of the lamina propria. Esophageal stricture following semicircular or complete circular esophageal ESD is relatively frequent even if treated by multiple pre‐emptive endoscopic balloon dilatation. Oral prednisolone may offer a novel, safe, and effective option for prevention of post‐ESD stricture associated with ESD for extensive esophageal neoplasms. The procedures include marking, submucosal injection, circumferential mucosal incision and exfoliation of the lesion along the submucosal layer. Complete ESD can achieve a large one‐piece resection, allowing precise histological assessment to prevent recurrence. Clinical outcomes of esophageal ESD have been promising, and the prognosis of EEC patients treated by ESD is likely to be excellent, though further long‐term follow‐up studies are warranted. Notification of a risk of perforation is essential for esophageal ESD. Bleeding during ESD can be managed with coagulation forceps, and postoperative bleeding may be reduced with routine use of the stronger acid suppressant, proton pump inhibitors.
Availability, Brands, Labelling and Salmonella Contamination of Raw Pet Food in the Minneapolis/St. Paul Area
Authors: Mehlenbacher S. , Churchill J. , Olsen K. E. , Bender J. B.
Published: May 2012

The purpose of the study was to characterize the commercially available raw meat pet food diets in the Minneapolis/St. Paul area by (i) determining the number and types of available diets; (ii) assessing pet food stores and brand labels for the provision of precautionary statements regarding the risk of foodborne illness from raw meat; (ii) assessing the labels for Food and Drug Administration (FDA)/American Association of Feed Control Officials (AAFCO) required content and nutrient‐related information; and (iv) culturing purchased diets for the presence of Salmonella. Sixty raw meat diets were purchased, representing 11 different brands from eight different stores. Diets were readily available in the form of raw‐frozen, dehydrated or freeze‐dried varieties from different protein sources, such as lamb, beef, chicken or duck. All stores promoted raw meat diets; however, none provided foodborne illness warnings. Brands varied greatly in their precautionary statements; none of the diets underwent feeding trials; and nutritional adequacy substantiation was through formulation only. The first five ingredients tended to consist of meat, organ meat (by‐products), vegetables, grains and ground bones. Currently, it is required that pet foods have an AAFCO nutritional adequacy statement and provide a guaranteed analysis table. Three brands did not meet these FDA requirements. Thirty‐one (51.7%) of the 60 raw meat diets underwent some degree of processing including dehydration, freeze‐drying or high‐pressure pasteurization. Four of the 60 raw diets (7%) tested positive for Salmonella. Analysis of raw meat pet food labels indicated a lack of foodborne illness warnings. Based on these findings, we recommend that warning statements similar to those required by the United States Department of Agriculture and placed on labels of raw meat intended for human consumption be provided on the labels of raw meat pet food diets.
SERS investigation of possible extraterrestrial life traces: Experimental adsorption of adenine on a Martian meteorite
Authors: CAPORALI Stefano , MOGGI‐CECCHI Vanni , MUNIZ‐MIRANDA Maurizio , PAGLIAI Marco , PRATESI Giovanni , SCHETTINO Vincenzo
Published: May 2012

Abstract– The identification of adenine by surface enhanced Raman scattering (SERS) on different mineral phases of a Martian meteorite Dar al Gani (DaG) 670 has been adopted as a test to verify the capability of this technique to detect trace amounts of organic or biological substances deposited over, or contained in, extraterrestrial materials. Raman spectra of different phases of meteorite (olivine, pyroxene, and ilmenite), representative of Martian basaltic rocks, have been measured by three laser sources with wavelengths at 785, 632.8, and 514.5 nm, coupled to a confocal micro‐Raman apparatus. Adenine deposited on the Martian meteorite cannot be observed in the normal Raman spectra; when, instead, meteorite is treated with silver colloidal nanoparticles, the SERS bands of adenine are strongly enhanced, allowing an easy and simple identification of this nucleobase at subpicogram level.
Alternative, complementary, integrative – conceptual problems in marketing healthcare ideologies and services
Authors: Louhiala Pekka , Puustinen Raimo
Published: May 2012

The terms ‘alternative medicine’, ‘complementary medicine’ and ‘integrative medicine’ are of recent origin. According to Medline and PubMed, ‘alternative medicine’ first appeared in medical journals in 1975, whenNursing Timescommenced a series of articles on topics such as transcendental meditation, spiritual healing and homeopathy. According to the same databases, the first appearance of ‘complementary medicine’ occurred in 1985, whenThe Lancetpublished an article titled ‘Complementary medicine in the United Kingdom’. ‘Integrative medicine’ was introduced in an English language journal in 1995, although it had appeared in German in an article 2 years earlier and in French already in 1951. Since the terms have no historical bearing whatsoever, we claim that they are used, together with many other slogans that thrive in contemporary Western health care, for ideological or commercial reasons to promote ideologies or to facilitate the selling of products and services.
The Spring-Connected Rigid Block Model Based Automatic Synthesis of Planar Linkage Mechanisms: Numerical Issues and Remedies
Authors: Jun Nam Sang , Jang Gang-Won , Young Kim Yoon
Published: May 2012

Because it is difficult to select in advance an appropriate linkage for converting an input motion to a desired output motion, a linkage synthesis method that does not require any baseline linkage would be preferred. To this end, an optimization-based linkage synthesis method that employs a spring-connected rigid block model has recently been suggested and applied for open-path problems. The objective of this study is to expand the method for the synthesis of more complex linkage mechanisms such as closed-loop linkages. Because the direct application of the method originally developed for open-path problems causes several numerical difficulties for closed-loop problems, an alternative optimization-based synthesis formulation is proposed in this investigation. The effectiveness of the suggested formulation is verified through several case studies including the synthesis of mechanisms generating closed paths.
Evaluation of Micro-Pillar Compression Tests for Accurate Determination of Elastic-Plastic Constitutive Relations
Authors: Fei Huiyang , Abraham Amit , Chawla Nikhilesh , Jiang Hanqing
Published: May 2012

The micro-pillar compression test is emerging as a novel way to measure the mechanical properties of materials. In this paper, we systematically conducted finite element analysis to evaluate the capability of using a micro-compression test to probe the mechanical properties of both elastic and plastic materials. We found that this test can provide an alternative way to accurately and robustly measure strain, and to some extent, stress. Therefore, this test can be used to measure some strain related quantities, such as strain to failure, or the stress-strain relations for plastic materials.
Tilting angle of nanocolumnar films fabricated by oblique angle deposition
Authors: Zhu Hao , Cao Wei , Larsen George K. , Toole Ryan , Zhao Yiping
Published: May 2012

The tilting angle, β, of nanocolumns during oblique angle deposition (OAD) as a function of vapor incident angle, θ, has been investigated through both literature survey and systematic experiments. Most experimental data cannot be fit by either the tangent or cosine rule and show strong material dependence. The material-dependent fan angle, φ, can be extracted using the fan-out model proposed by Tanto et al. [J. Appl. Phys. 108, 026107 (2010)]. This fan angle, φ, depends closely on the melting temperature for single element materials, the heat of formation for compound materials, lattice structure, and the complexity of the materials, and is a critical parameter in understanding the fundamental growth mechanism of OAD.
Spin-Orbital Short-Range Order on a Honeycomb-Based Lattice
Authors: Nakatsuji S. , Kuga K. , Kimura K. , Satake R. , Katayama N. , Nishibori E. , Sawa H. , Ishii R. , Hagiwara M. , Bridges F. , Ito T. U. , Higemoto W. , Karaki Y. , Halim M. , Nugroho A. A. , Rodriguez-Rivera J. A. , Green M. A. , Broholm C.
Published: May 2012

Going to Ground

Frustrated systems, in which the geometry of the crystal lattice stands in the way of achieving an energetic minimum on all lattice sites simultaneously, have the potential to remain disordered down to the lowest temperatures. Numerous experimental efforts to find a material with a truly fluctuating ground state have failed because ordering often sets in at a finite temperature owing to symmetry breaking.

Nakatsuji
et al.

(p.
559
; see the Perspective by

Balents

) identify the compound Ba
3
CuSb
2
O
9
as a promising candidate for this state; the Cu-Sb dipoles reside on a hexagonal structure, forming fluctuating spin singlets. Multiple lines of evidence suggest that the material does not order down to the millikelvin temperature range, remaining magnetically isotropic.
Radio-Wave Heating of Iron Oxide Nanoparticles Can Regulate Plasma Glucose in Mice
Authors: Stanley Sarah A. , Gagner Jennifer E. , Damanpour Shadi , Yoshida Mitsukuni , Dordick Jonathan S. , Friedman Jeffrey M.
Published: May 2012

Gene Expression by Remote Control

Techniques that allow remote, noninvasive activation of specific genes in specific tissues could one day be applied to regulate expression of therapeutic proteins in a clinical setting. In a proof-of-concept study,

Stanley
et al.

(p.
604
) showed that heating of iron oxide nanoparticles by radiowaves can remotely activate insulin gene expression in cultured cells and in a mouse model. Heating of membrane-targeted nanoparticles induced opening of a temperature-sensitive membrane channel in the cells and triggered calcium entry. The intracellular calcium signal in turn stimulated expression of an engineered insulin gene, leading to the synthesis and release of insulin. In experiments with mice bearing tumors that expressed the engineered insulin gene, exposure to radiowaves promoted secretion of insulin from the tumors and lowered blood glucose levels in the animals.
Multidimensional Optimality of Microbial Metabolism
Authors: Schuetz Robert , Zamboni Nicola , Zampieri Mattia , Heinemann Matthias , Sauer Uwe
Published: May 2012

Metabolic Networking

Understanding complex biological networks, such as those underlying cellular metabolism, requires evaluation not only of the network connections but also the flux through the various biochemical pathways.

Schuetz
et al.

(p.
601
) explored the evolutionary constraints that appear to be most critical for the metabolic network in the bacteria
Escherichia coli
using a combination of experimental tests of reaction flux under various conditions along with mathematical modeling. As a pathway evolves, there are likely to be competing objectives that must be satisfied. Key objectives for the bacterium were strong performance under a given environmental condition, balanced by a requirement for adaptability—minimizing the adjustments required to respond to changed conditions.
Function, Developmental Genetics, and Fitness Consequences of a Sexually Antagonistic Trait
Authors: Khila Abderrahman , Abouheif Ehab , Rowe Locke
Published: May 2012

Hooking Up in Water Striders

The male water strider
Rheumatobates rileyi
has an extensively modified antenna that is used for forced copulations with females.

Khila
et al.

(p.
585
) describe several microscopic antenna attributes that make the antenna fit perfectly with the female head when the male grasps the female. The features depend upon the expression of the gene
distal-less
(
dll
) during antenna development. Reducing the expression of
dll
compromised male grasping traits, while female antennae were unaffected.
Melanesian Blond Hair Is Caused by an Amino Acid Change in TYRP1
Authors: Kenny Eimear E. , Timpson Nicholas J. , Sikora Martin , Yee Muh-Ching , Moreno-Estrada Andrés , Eng Celeste , Huntsman Scott , Burchard Esteban González , Stoneking Mark , Bustamante Carlos D. , Myles Sean
Published: May 2012

Naturally blond hair in Solomon Islanders maps to a missense mutation in a gene associated with pigmentation.
Impacts of Biodiversity Loss Escalate Through Time as Redundancy Fades
Authors: Reich Peter B. , Tilman David , Isbell Forest , Mueller Kevin , Hobbie Sarah E. , Flynn Dan F. B. , Eisenhauer Nico
Published: May 2012

Give It Time

Experimental ecological studies in recent years have provided a great deal of insight into how species diversify and influence ecosystem properties, but in most cases the experiments have been relatively brief (up to ∼5 years).

Reich
et al.

(p.
589
; see the Perspective by

Cardinale

) performed two 13- and 15-year grassland experiments and found that the effects of plant species richness on community-level processes like biomass production tend to be saturating at early stages but that those impacts grow stronger and more linear as experiments run longer. Stronger influences through time were largely driven by increasing amounts of “complementarity” among species, and these trends were correlated with greater expression of functional diversity in multispecies assemblages. Thus, the effects of diversity grow stronger through time as species gain more and more opportunity to vary in their use of the limiting biological resources in their environment, which emphasizes the functional importance of maintaining diversity in ecosystems.
Spin-Torque Switching with the Giant Spin Hall Effect of Tantalum
Authors: Liu Luqiao , Pai Chi-Feng , Li Y. , Tseng H. W. , Ralph D. C. , Buhrman R. A.
Published: May 2012

Giant Spin Hall

One of the primary challenges in the field of spin-electronics, which exploits the electron's spin rather than its charge, is to create strong currents of electrons with polarized spins. One way to do this is to use a ferromagnet as a polarizer, a principle used in magnetic tunnel junctions; however, these devices suffer from reliability problems. An alternative is the spin Hall effect, where running a charge current through a material generates a spin current in the transverse direction, but the efficiency of this process tends to be small.

Liu
et al.

(p.
555
) now show that the spin Hall effect in Tantalum in its high-resistance β phase generates spin currents strong enough to induce switching of the magnetization of an adjacent ferromagnet; at the same time, Ta does not cause energy dissipation in the ferromagnet. These properties allowed efficient and reliable operation of a prototype three-terminal device.
Substrate-Controlled Succession of Marine Bacterioplankton Populations Induced by a Phytoplankton Bloom
Authors: Teeling Hanno , Fuchs Bernhard M. , Becher Dörte , Klockow Christine , Gardebrecht Antje , Bennke Christin M. , Kassabgy Mariette , Huang Sixing , Mann Alexander J. , Waldmann Jost , Weber Marc , Klindworth Anna , Otto Andreas , Lange Jana , Bernhardt Jörg , Reinsch Christine , Hecker Michael , Peplies Jörg , Bockelmann Frank D. , Callies Ulrich , Gerdts Gunnar , Wichels Antje , Wiltshire Karen H. , Glöckner Frank Oliver , Schweder Thomas , Amann Rudolf
Published: May 2012

Blooming Succession

Algal blooms in the ocean will trigger a succession of microbial predators and scavengers.

Teeling
et al.

(p.
608
) used a combination of microscopy, metagenomics, and metaproteomics to analyze samples from a North Sea diatom bloom over time. Distinct steps of polysaccharide degradation and carbohydrate uptake could be assigned to clades of Flavobacteria and Gammaproteobacteria, which differ profoundly in their transporter profiles and their uptake systems for phosphorus. The phytoplankton/bacterioplankton coupling in coastal marine systems is of crucial importance for global carbon cycling. Bacterioplankton clade succession following phytoplankton blooms may be predictable enough that it can be included in models of global carbon cycling.
Anisotropic Energy Gaps of Iron-Based Superconductivity from Intraband Quasiparticle Interference in LiFeAs
Authors: Allan M. P. , Rost A. W. , Mackenzie A. P. , Xie Yang , Davis J. C. , Kihou K. , Lee C. H. , Iyo A. , Eisaki H. , Chuang T.-M.
Published: May 2012

Uneven Gap

Electron pairs that are responsible for the phenomenon of superconductivity can only be broken by investing a finite amount of energy, called the energy gap. The size of the gap may depend on the position on the Fermi surface; in cuprates, the gap completely disappears at certain points. What happens in the pnictide superconductors is still a subject of debate, not least because there appear to be differences between the different pnictide families.

Allan
et al.

(p.
563
) used scanning tunneling spectroscopy to study the compound LiFeAs. The gap was mapped on three of the five bands on which the Fermi surface resides and was found to be anisotropic in momentum space.
Modeling Ice-Sheet Flow
Authors: Alley Richard B. , Joughin Ian
Published: May 2012

Full-stress flow models for ice sheets promise improved projections of sea-level change.
Impacts of Biodiversity Loss
Authors: Cardinale Bradley
Published: May 2012

How much diversity is needed to maintain the productivity of ecosystems?
Budget Cap Could Gut Next Big Fermilab Project
Authors: Cho Adrian
Published: May 2012

The affordable options for the first stage of the Long-Baseline Neutrino Experiment would severely limit its scientific potential and could leave it only marginally more capable than an existing Fermilab experiment.
Older Dads Have Healthier Kids Than You Think
Authors: Gibbons Ann
Published: May 2012

New data presented at the meeting suggest that children of older fathers and grandfathers may inherit longer telomeres, structures at the tips of chromosomes that may protect against aging and disease.
Quinolone-Resistant Escherichia coli O127a:K63 Serotype with an Extended-Spectrum-Beta-Lactamase Phenotype from a Food Poisoning Outbreak in China
Authors: Hao Rongzhang , Qiu Shaofu , Wang Yong , Yang Guang , Su Wenli , Song Lixue , Zhang Jia , Chen Jiaxu , Jia Leili , Wang Ligui , Song Hongbin
Published: May 2012

We report an atypical enteropathogenic
Escherichia coli
O127a:K63 strain with resistance to quinolones and extended-spectrum cephalosporins isolated from a 2010 food poisoning outbreak involving 112 adults in China. Two resistance genes [
bla
CTX-M-15
,
aac
(
6′
)
-Ib-c
] and five mutations (two in
gyrA
, two in
parC
, one in
parE
) coexisted in this enteropathogenic
E. coli
strain.
Rapid Spoligotyping of Mycobacterium tuberculosis Complex Bacteria by Use of a Microarray System with Automatic Data Processing and Assignment
Authors: Ruettger Anke , Nieter Johanna , Skrypnyk Artem , Engelmann Ines , Ziegler Albrecht , Moser Irmgard , Monecke Stefan , Ehricht Ralf , Sachse Konrad
Published: May 2012

Membrane-based spoligotyping has been converted to DNA microarray format to qualify it for high-throughput testing. We have shown the assay's validity and suitability for direct typing from tissue and detecting new spoligotypes. Advantages of the microarray methodology include rapidity, ease of operation, automatic data processing, and affordability.
Detection of NDM-1, VIM-1, KPC, OXA-48, and OXA-162 Carbapenemases by Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry
Authors: Hrabák Jaroslav , Študentová Vendula , Walková Radka , Žemličková Helena , Jakubů Vladislav , Chudáčková Eva , Gniadkowski Marek , Pfeifer Yvonne , Perry John D. , Wilkinson Kathryn , Bergerová Tamara
Published: May 2012

Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) is a potentially useful tool for the detection of antimicrobial resistance, especially that conferred by β-lactamases. Here we describe a modification of a previously reported MALDI-TOF MS meropenem hydrolysis assay. The modified method was validated on 108 carbapenemase-producing members of the
Enterobacteriaceae
, two NDM-1-producing
Acinetobacter baumannii
isolates, and 35 carbapenem-resistant enterobacteria producing no carbapenemase. The detection of carbapenemases by MALDI-TOF MS seems to be a powerful, quick, and cost-effective method for microbiological laboratories.
Molecular Characterization of Multidrug- and Extensively Drug-Resistant Mycobacterium tuberculosis Strains in Jiangxi, China
Authors: Yuan Xiaoliang , Zhang Tiantuo , Kawakami Kazuyoshi , Zhu Jiaxin , Li Hongtao , Lei Jianping , Tu Shaohua
Published: May 2012

In this study, a total of 77 multidrug-resistant and extensively drug-resistant (MDR and XDR, respectively) isolates of
Mycobacterium tuberculosis
were characterized among samples from patients living in Jiangxi province, China. The following two approaches were used: (i) genotyping all drug-resistant isolates by the 15-locus MIRU-VNTR (mycobacterial interspersed repetitive-unit–variable-number tandem-repeat) method and identifying the Beijing family genotype using the RD105 deletion targeted multiplex PCR and (ii) determining the mutation profiles associated with the resistance to the first-line antituberculous drugs rifampin (RIF) and isoniazid (INH) and the second-line drugs ofloxacin (OFX), kanamycin (KAN), amikacin (AMK), and capreomycin (CAP) with DNA sequencing. Six loci were examined:
rpoB
(for resistance to RIF),
katG
and
mabA-inhA
(INH),
gyrA
and
gyrB
(OFX), and
rrs
(KAN, AMK, and CAP). It is shown that the Beijing genotype was predominant (80.5%) among these strains and that the selected drug-resistant strains were genetically diverse, suggesting that they probably had independently acquired drug resistance. In comparison to the phenotypic data, the sensitivities for the detection of RIF, INH, OFX, and KAN/AMK/CAP resistance by DNA sequencing were 94.8, 80.5, 84.6, and 78.9%, respectively. The most prevalent mutations involved in RIF, INH, OFX, and KAN/AMK/CAP resistance were Ser531Leu in
rpoB
(44.2%), Ser315Thr in
katG
(55.8%) and C-15T in
mabA-inhA
(11.7%), Asp94Gly in
gyrA
(48.7%), and A1401G in
rrs
(73.7%), respectively. Five novel
katG
mutants (Trp191Stop, Thr271Pro, Trp328Phe, Leu546Pro, and Asp695Gly) and six new alleles (Ile569Val, Ile572Met, Phe584Ser, Val615Met, Asp626Glu, and Lys972Thr) in the
rpoB
gene were identified.
Evidence for a Genetic and Physical Interaction between Nonstructural Proteins NS1 and NS4B That Modulates Replication of West Nile Virus
Authors: Youn Soonjeon , Li Tuo , McCune Broc T. , Edeling Melissa A. , Fremont Daved H. , Cristea Ileana M. , Diamond Michael S.
Published: May 2012

Flavivirus NS1 is a nonstructural glycoprotein that is expressed on the cell surface and secreted into the extracellular space. Despite its transit through the secretory pathway, NS1 is an essential gene linked to early viral RNA replication. How this occurs has remained a mystery given the disparate localization of NS1 and the viral RNA replication complex, as the latter is present on the cytosolic face of the endoplasmic reticulum (ER). We recently identified an N-terminal di-amino acid motif in NS1 that modulates protein targeting and affected viral replication. Exchange of two amino acids at positions 10 and 11 from dengue virus (DENV) into West Nile virus (WNV) NS1 (RQ10NK) changed its relative surface expression and secretion and attenuated infectivity. However, the phenotype of WNV containing NS1 RQ10NK was unstable, as within two passages heterogeneous plaque variants were observed. Here, using a mutant WNV encoding the NS1 RQ10NK mutation, we identified a suppressor mutation (F86C) in NS4B, a virally encoded transmembrane protein with loops on both the luminal and cytoplasmic sides of the ER membrane. Introduction of NS4B F86C specifically rescued RNA replication of mutant WNV but did not affect the wild-type virus. Mass spectrometry and coimmunoprecipitation studies established a novel physical interaction between NS1 and NS4B, suggesting a mechanism for how luminal NS1 conveys signals to the cytoplasm to regulate RNA replication.
Therapeutic Blockade of Transforming Growth Factor Beta Fails To Promote Clearance of a Persistent Viral Infection
Authors: Garidou Lucile , Heydari Sara , Gossa Selamawit , McGavern Dorian B.
Published: May 2012

Persistent viral infections often overburden the immune system and are a major cause of disease in humans. During many persistent infections, antiviral T cells are maintained in a state of immune exhaustion characterized by diminished effector and helper functions. In mammalian systems, an extensive immune regulatory network exists to limit unwanted, potentially fatal immunopathology by inducing T cell exhaustion. However, this regulatory network at times overprotects the host and fosters viral persistence by severely dampening adaptive immune responsiveness. Importantly, recent studies have shown that T cell exhaustion is mediated in part by host immunoregulatory pathways (e.g., programmed death 1 [PD-1], interleukin 10 [IL-10]) and that therapeutic blockade of these pathways either before or during persistent infection can promote viral clearance. Transforming growth factor beta (TGF-β) is another immunosuppressive cytokine known to impede both self- and tumor-specific T cells, but its role in regulating antiviral immunity is not entirely understood. In this study, we inhibited TGF-β with three potent antagonists to determine whether neutralization of this regulatory molecule is a viable approach to control a persistent viral infection. Our results revealed that these inhibitors modestly elevate the number of antiviral T cells following infection with a persistent variant of lymphocytic choriomeningitis virus (LCMV) but have no impact on viral clearance. These data suggest that therapeutic neutralization of TGF-β is not an efficacious means to promote clearance of a persistent viral infection.
An In-Frame Deletion in the NS Protein-Coding Sequence of Parvovirus H-1PV Efficiently Stimulates Export and Infectivity of Progeny Virions
Authors: Weiss Nadine , Stroh-Dege Alexandra , Rommelaere Jean , Dinsart Christiane , Salomé Nathalie
Published: May 2012

An in-frame, 114-nucleotide-long deletion that affects the NS-coding sequence was created in the infectious molecular clone of the standard parvovirus H-1PV, thereby generating Del H-1PV. The plasmid was transfected and further propagated in permissive human cell lines in order to analyze the effects of the deletion on virus fitness. Our results show key benefits of this deletion, as Del H-1PV proved to exhibit (i) higher infectivity (lower particle-to-infectivity ratio)in vitroand (ii) enhanced tumor growth suppressionin vivocompared to wild-type H-1PV. This increased infectivity correlated with an accelerated egress of Del H-1PV progeny virions in producer cells and with an overall stimulation of the viral life cycle in subsequently infected cells. Indeed, virus adsorption and internalization were significantly improved with Del H-1PV, which may account for the earlier appearance of viral DNA replicative forms that was observed with Del H-1PV than wild-type H-1PV. We hypothesize that the internal deletion within the NS2 and/or NS1 protein expressed by Del H-1PV results in the stimulation of some step(s) of the viral life cycle, in particular, a maturation step(s), leading to more efficient nuclear export of infectious viral particles and increased fitness of the virus produced.
Neutralization Resistance of Virological Synapse-Mediated HIV-1 Infection Is Regulated by the gp41 Cytoplasmic Tail
Authors: Durham Natasha D. , Yewdall Alice W. , Chen Ping , Lee Rebecca , Zony Chati , Robinson James E. , Chen Benjamin K.
Published: May 2012

Human immunodeficiency virus type 1 (HIV-1) infection can spread efficiently from infected to uninfected T cells through adhesive contacts called virological synapses (VSs). In this process, cell-surface envelope glycoprotein (Env) initiates adhesion and viral transfer into an uninfected recipient cell. Previous studies have found some HIV-1-neutralizing patient sera to be less effective at blocking VS-mediated infection than infection with cell-free virus. Here we employ sensitive flow cytometry-based infection assays to measure the inhibitory potency of HIV-1-neutralizing monoclonal antibodies (MAb) and HIV-1-neutralizing patient sera against cell-free and VS-mediated infection. To various degrees, anti-Env MAbs exhibited significantly higher 50% inhibitory concentration (IC50s) against VS-mediated infection than cell-free infection. Notably, the MAb 17b, which binds a CD4-induced (CD4i) epitope on gp120, displayed a 72-fold reduced efficacy against VS-mediated inocula compared to cell-free inocula. A mutant with truncation mutation in the gp41 cytoplasmic tail (CT) which is unable to modulate Env fusogenicity in response to virus particle maturation but which can still engage in cell-to-cell infection was tested for the ability to resist neutralizing antibodies. The ΔCT mutation increased cell surface staining by neutralizing antibodies, significantly enhanced neutralization of VS-mediated infection, and had reduced or no effect on cell-free infection, depending upon the antibody. Our results suggest that the gp41 CT regulates the exposure of key neutralizing epitopes during cell-to-cell infection and plays an important role in immune evasion. Vaccine strategies should consider immunogens that reflect Env conformations exposed on the infected cell surface to enhance protection against VS-mediated HIV-1 spread.
Substitutions at Amino Acid Positions 143, 148, and 155 of HIV-1 Integrase Define Distinct Genetic Barriers to Raltegravir Resistance
In Vivo
Authors: Fransen Signe , Gupta Soumi , Frantzell Arne , Petropoulos Christos J. , Huang Wei
Published: May 2012

Mutations at amino acids 143, 148, and 155 in HIV-1 integrase (IN) define primary resistance pathways in subjects failing raltegravir (RAL)-containing treatments. Although each pathway appears to be genetically distinct, shifts in the predominant resistant virus population have been reported under continued drug pressure. To better understand this dynamic, we characterized the RAL susceptibility of 200 resistant viruses, and we performed sequential clonal analysis for selected cases. Patient viruses containing Y143R, Q148R, or Q148H mutations consistently exhibited larger reductions in RAL susceptibility than patient viruses containing N155H mutations. Sequential analyses of virus populations from three subjects revealed temporal shifts in subpopulations representing N155H, Y143R, or Q148H escape pathways. Evaluation of molecular clones isolated from different time points demonstrated that Y143R and Q148H variants exhibited larger reductions in RAL susceptibility and higher IN-mediated replication capacity (RC) than N155H variants within the same subject. Furthermore, shifts from the N155H pathway to either the Q148R or H pathway or the Y143R pathway were dependent on the amino acid substitution at position 148 and the secondary mutations in Y143R- or Q148R- or H-containing variants and correlated with reductions in RAL susceptibility and restorations in RC. Our observations in patient viruses were confirmed by analyzing site-directed mutations. In summary, viruses that acquire mutations defining the 143 or 148 escape pathways are less susceptible to RAL and exhibit greater RC than viruses containing 155 pathway mutations. These selective pressures result in the displacement of N155H variants by 143 or 148 variants under continued drug exposure.
HIV-1 Virus-Like Particles Produced by Stably Transfected Drosophila S2 Cells: a Desirable Vaccine Component
Authors: Yang Lifei , Song Yufeng , Li Xiaomin , Huang Xiaoxing , Liu Jingjing , Ding Heng , Zhu Ping , Zhou Paul
Published: May 2012

The development of a successful vaccine against human immunodeficiency virus type 1 (HIV-1) likely requires immunogens that elicit both broadly neutralizing antibodies against envelope spikes and T cell responses that recognize multiple viral proteins. HIV-1 virus-like particles (VLP), because they display authentic envelope spikes on the particle surface, may be developed into such immunogens. However, in one way or the other current systems for HIV-1 VLP production have many limitations. To overcome these, in the present study we developed a novel strategy to produce HIV-1 VLP using stably transfectedDrosophilaS2 cells. We cotransfected S2 cells with plasmids encoding HIV-1 envelope, Gag, and Rev proteins and a selection marker. After stably transfected S2 clones were established, HIV-1 VLP and their immunogenicity in mice were carefully evaluated. Here, we report that HIV-1 envelope proteins are properly cleaved, glycosylated, and incorporated into VLP with Gag. The amount of VLP released into culture supernatants is comparable to those produced by insect cells infected with recombinant baculoviruses. Moreover, cryo-electron microscopy tomography revealed average 17 spikes per purified VLP, and antigenic epitopes on the spikes were recognized by the broadly neutralizing antibodies 2G12, b12, VRC01, and 4E10 but not by PG16. Finally, mice primed with DNA and boosted with VLP in the presence of CpG exhibited anti-envelope antibody responses, including ELISA-binding, neutralizing, antibody-dependent cell-mediated cytotoxicity and antibody-dependent cell-mediated viral inhibition, as well as envelope and Gag-specific CD8 T cell responses. Thus, we conclude that HIV-1 VLP produced by the S2 expression system has many desirable features to be developed into a vaccine component against HIV-1.
BAYESIAN RETRIEVAL USING A SIMILARITY-BASED LEMMATIZER
Authors: MARAGOUDAKIS MANOLIS , LYRAS DIMITRIOS P. , SGARBAS KYRIAKOS
Published: May 2012

The present paper describes a Bayesian network approach to Information Retrieval (IR) from Web documents. The network structure provides an intuitive representation of uncertainty relationships and the embedded conditional probability table is used by inference algorithms in an attempt to identify documents that are relevant to the user's needs, expressed in the form of Boolean queries. Our research has been directed in constructing a probabilistic IR framework that focus on assisting users to perform Ad-hoc retrieval of documents from the various domains such as economics, news, sports, etc. Furthermore, users can integrate feedback regarding the relevance of the retrieved documents in an attempt to improve performance on upcoming requests. Towards these goals, we have expanded the traditional Bayesian network IR system and tested it on several Greek web corpora on different application domains. We have developed two different approaches with regards to the structure: a simple one, where the structure is manually provided, and an automated one, where data mining is used in order to extract the network's structure. Results have depicted competitive performance against successful IR models of different theoretical backgrounds, such as the vector space utilizing tf-idf and the probabilistic model of BM25 in terms of precision-recall curves. In order to further improve the performance of the IR system, we have implemented a novel similarity-based lemmatization framework, reducing thus the ambiguity posed by the plethora of morphological variations of the languages in question. The employed lemmatization framework comprises of 3 core components (i.e. the word segregation, the data cleansing and the lemmatization modules) and is language-independent (i.e. can be applied to other languages with morphological peculiarities and thus improve Ad-hoc retrieval) since it achieves the mapping of an input word to its normalized form by employing two state-of-the-art language independent distance metric models, meaning the Levenshtein Edit distance and the Dice coefficient similarity measure, combined with a language model describing the most frequent inflectional suffixes of the examined language. Experimental results support our claim on the significance of this incorporation to Greek texts web retrieval as results improve by a factor of 4% to 11%.
Seismic investigations of buried tunnel valleys on- and offshore Denmark
Authors: Andersen Theis Raaschou , Huuse Mads , Jørgensen Flemming , Christensen Steen
Published: May 2012

Tunnel valleys on- and offshore Denmark have been investigated based on a database of 1000 km two-dimensional (2D) onshore seismic data, 5600 km 2D offshore seismic data and 1200 km
2
three-dimensional (3D) offshore seismic data. From the 2D data we identified 216 onshore and 674 offshore seismic tunnel valley intersections, and 55 individual valleys were identified from three 3D surveys. The majority of the valleys have depths ranging from 50 to 200 m and widths between 500 and 1500 m. Up to seven generations of tunnel valleys were identified, indicating repeated erosion and deposition within the study area. The valleys were most likely formed by subglacial meltwater erosion during the last three glaciations. Statistical analyses conducted on the data show that there are no significant differences between the onshore and offshore valleys with respect to their depth and shape; they share morphological and structural characteristics. The onshore seismic data have been analysed in conjunction with lithological information from boreholes. The analyses show that tunnel valley bottoms terminate equally commonly in substrates dominated by clay and sand, and that the valley shapes are similar for the two substrates.
Ordovician proglacial sediments in Algeria: insights into the controls on hydrocarbon reservoirs in the In Amenas field, Illizi Basin
Authors: Hirst J. Philip P.
Published: May 2012

Ordovician proglacial deposits form gas reservoirs in the In Amenas field, Illizi Basin, Algeria. Depositional models were developed to understand the context and disposition of the main reservoirs through an evaluation of core and analogous outcrops from the Tassili N'Ajjer.

Tunnel valleys initially accumulated sandstones with tractional structures. Subsequent failures of subaqueous grounding line sediment deposited proglacial debrites comprising poorly sorted argillaceous sandstone with granules. These were interbedded with high-density turbidity sandstones; their fine grain size indicates they were dynamically disconnected from the lithologically varied debrites. A lobate geometry has been defined for one subsurface composite turbidite.

Periodic catastrophic outflows, possibly evacuating subglacial lakes, incised the network of subglacial tunnels and in the process delivered sand to the turbidite outwashes. Bedforms indicate high-energy, transcritical to supercritical outflows that were stable for extended periods. During ice retreat, a period of ice margin stability may have occurred due to grounding over the In Amenas granitic palaeohighs. Outwash fan apices were located along this grounding line with feeder channels developing where the substrate was more easily eroded such as between the palaeohighs. Following further ice retreat, deposition evolved to variably sinuous channels and thence to pelagic fines with dropstones.
The Effects of Tropospheric Ozone on Net Primary Productivity and Implications for Climate Change
Authors: Ainsworth Elizabeth A. , Yendrek Craig R. , Sitch Stephen , Collins William J. , Emberson Lisa D.
Published: May 2012

Tropospheric ozone (O3) is a global air pollutant that causes billions of dollars in lost plant productivity annually. It is an important anthropogenic greenhouse gas, and as a secondary air pollutant, it is present at high concentrations in rural areas far from industrial sources. It also reduces plant productivity by entering leaves through the stomata, generating other reactive oxygen species and causing oxidative stress, which in turn decreases photosynthesis, plant growth, and biomass accumulation. The deposition of O3 into vegetation through stomata is an important sink for tropospheric O3, but this sink is modified by other aspects of environmental change, including rising atmospheric carbon dioxide concentrations, rising temperature, altered precipitation, and nitrogen availability. We review the atmospheric chemistry governing tropospheric O3 mass balance, the effects of O3 on stomatal conductance and net primary productivity, and implications for agriculture, carbon sequestration, and climate change.
Phosphoinositide Signaling
Authors: Boss Wendy F. , Im Yang Ju
Published: May 2012

All things flow and change…even in the stillest matter there is unseen flux and movement.

Attributed to Heraclitus (530–470 BC)

From The Story of Philosophy by Will Durant ( 28 )

Heraclitus, a Greek philosopher, was thinking on a much larger scale than molecular signaling; however, his visionary comments are an important reminder for those studying signaling today. Even in unstimulated cells, signaling pathways are in constant metabolic flux and provide basal signals that travel throughout the organism. In addition, negatively charged phospholipids, such as the polyphosphorylated inositol phospholipids, provide a circuit board of on/off switches for attracting or repelling proteins that define the membranes of the cell. This template of charged phospholipids is sensitive to discrete changes and metabolic fluxes—e.g., in pH and cations—which contribute to the oscillating signals in the cell. The inherent complexities of a constantly fluctuating system make understanding how plants integrate and process signals challenging. In this review we discuss one aspect of lipid signaling: the inositol family of negatively charged phospholipids and their functions as molecular sensors and regulators of metabolic flux in plants.
The Shikimate Pathway and Aromatic Amino Acid Biosynthesis in Plants
Authors: Maeda Hiroshi , Dudareva Natalia
Published: May 2012

l-Tryptophan, l-phenylalanine, and l-tyrosine are aromatic amino acids (AAAs) that are used for the synthesis of proteins and that in plants also serve as precursors of numerous natural products, such as pigments, alkaloids, hormones, and cell wall components. All three AAAs are derived from the shikimate pathway, to which ≥30% of photosynthetically fixed carbon is directed in vascular plants. Because their biosynthetic pathways have been lost in animal lineages, the AAAs are essential components of the diets of humans, and the enzymes required for their synthesis have been targeted for the development of herbicides. This review highlights recent molecular identification of enzymes of the pathway and summarizes the pathway organization and the transcriptional/posttranscriptional regulation of the AAA biosynthetic network. It also identifies the current limited knowledge of the subcellular compartmentalization and the metabolite transport involved in the plant AAA pathways and discusses metabolic engineering efforts aimed at improving production of the AAA-derived plant natural products.
Autophagy: Pathways for Self-Eating in Plant Cells
Authors: Liu Yimo , Bassham Diane C.
Published: May 2012

Plants have developed sophisticated mechanisms to survive when in unfavorable environments. Autophagy is a macromolecule degradation pathway that recycles damaged or unwanted cell materials upon encountering stress conditions or during specific developmental processes. Over the past decade, our molecular and physiological understanding of plant autophagy has greatly increased. Most of the essential machinery required for autophagy seems to be conserved from yeast to plants. Plant autophagy has been shown to function in various stress responses, pathogen defense, and senescence. Some of its potential upstream regulators have also been identified. Here, we describe recent advances in our understanding of autophagy in plants, discuss areas of controversy, and highlight potential future directions in autophagy research.
Growth Control and Cell Wall Signaling in Plants
Authors: Wolf Sebastian , Hématy Kian , Höfte Herman
Published: May 2012

Plant cell walls have the remarkable property of combining extreme tensile strength with extensibility. The maintenance of such an exoskeleton creates nontrivial challenges for the plant cell: How can it control cell wall assembly and remodeling during growth while maintaining mechanical integrity? How can it deal with cell wall damage inflicted by herbivores, pathogens, or abiotic stresses? These processes likely require mechanisms to keep the cell informed about the status of the cell wall. In yeast, a cell wall integrity (CWI) signaling pathway has been described in great detail; in plants, the existence of CWI signaling has been demonstrated, but little is known about the signaling pathways involved. In this review, we first describe cell wall–related processes that may require or can be targets of CWI signaling and then discuss our current understanding of CWI signaling pathways and future prospects in this emerging field of plant biology.
Mechanisms of Stomatal Development
Authors: Pillitteri Lynn Jo , Torii Keiko U.
Published: May 2012

The main route for CO2and water vapor exchange between a plant and the environment is through small pores called stomata. The accessibility of stomata and predictable division series that characterize their development provides an excellent system to address fundamental questions in biology. Stomatal cell-state transition and specification are regulated by a suite of transcription factors controlled by positional signaling via peptide ligands and transmembrane receptors. Downstream effectors include several members of the core cell-cycle genes. Environmentally induced signals are integrated into this essential developmental program to modulate stomatal development or function in response to changes in the abiotic environment. In addition, the recent identification of premitotic polarly localized proteins from both Arabidopsis and maize has laid a foundation for the future understanding of intrinsic cell polarity in plants. This review highlights the mechanisms of stomatal development through characterization of genes controlling cell-fate specification, cell polarity, cell division, and cell-cell communication during stomatal development and discusses the genetic framework linking these molecular processes with the correct spacing, density, and differentiation of stomata.