bluuebunny/crossref_metadata_2025 huggingface dataset:
New approaches to the autosomal recessive polycystic kidney disease patient with dual kidney–liver complications
Authors: Telega Grzegorz , Cronin David , Avner Ellis D.
Published: April 2013

Improved neonatal medical care and renal replacement technology have improved the long‐term survival of patients with ARPKD. Ten‐yr survival of those surviving the first year of life is reported to be 82% and is continuing to improve further. However, despite increases in overall survival and improved treatment of systemic hypertension and other complications of their renal disease, nearly 50% of survivors will develop ESRD within the first decade of life. In addition to renal pathology, patients with ARPKD develop ductal plate malformations with cystic dilation of intra‐ and extrahepatic bile ducts resulting in CHF and Caroli syndrome. Many patients with CHF will develop portal hypertension with resulting esophageal varices, splenomegaly, hypersplenism, protein losing enteropathy, and gastrointestinal bleeding. Management of portal hypertension may require EBL of esophageal varices or porto‐systemic shunting. Complications of hepatic involvement can include ascending cholangitis, cholestasis with malabsorption of fat‐soluble vitamins, and rarely benign or malignant liver tumors. Patients with ARPKD who eventually reach ESRD, and ultimately require kidney transplantation, present a unique set of complications related to their underlying hepato‐biliary disease. In this review, we focus on new approaches to these challenging patients, including the indications for liver transplantation in ARPKD patients with severe chronic kidney disease awaiting kidney transplant. While survival in patients with ARPKD and isolated kidney transplant is comparable to that of age‐matched pediatric patients who have received kidney transplants due to other primary renal diseases, 64–80% of the mortality occurring in ARPKD kidney transplant patients is attributed to cholangitis/sepsis, which is related to their hepato‐biliary disease. Recent data demonstrate that surgical mortality among pediatric liver transplant recipients is decreased to <10% at one yr. The immunosuppressive regimen used for kidney transplant recipients is adequate for most liver transplant recipients. We therefore suggest that in a select group of ARPKD patients with recurrent cholangitis or complications of portal hypertension, combined liver–kidney transplant is a viable option. Although further study is necessary to confirm our approach, we believe that combined liver–kidney transplantation can potentially decrease overall mortality and morbidity in carefully selected ARPKD patients with ESRD and clinically significant CHF.
The role of nitric oxide and hemoglobin in plant development and morphogenesis
Authors: Hebelstrup Kim H. , Shah Jay K. , Igamberdiev Abir U.
Published: April 2013

Plant morphogenesis is regulated endogenously through phytohormones and other chemical signals, which may act either locally or distant from their place of synthesis. Nitric oxide (NO) is formed by a number of controlled processes in plant cells. It is a central signaling molecule with several effects on control of plant growth and development, such as shoot and root architecture. All plants are able to express non‐symbiotic hemoglobins at low concentration. Their function is generally not related to oxygen transport or storage; instead they effectively oxidize NO to NO3− and thereby control the local cellular NO concentration. In this review, we analyze available data on the role of NO and plant hemoglobins in morphogenetic processes in plants. The comparison of the data suggests that hemoglobin gene expression in plants modulates development and morphogenesis of organs, such as roots and shoots, through the localized control of NO, and that hemoglobin gene expression should always be considered a modulating factor in processes controlled directly or indirectly by NO in plants.
Identification and biosynthesis of acylphloroglucinols in Hypericum gentianoides
Authors: Crispin Matthew C. , Hur Manhoi , Park Taeseong , Kim Young Hwan , Wurtele Eve Syrkin
Published: April 2013

Species of the genus Hypericum contain a rich array of unusual polyketides, however, only a small proportion of the over 450 Hypericum species, other than the popular medicinal supplement St. John's Wort (Hypericum perforatum), have even been chemically characterized. Hypericum gentianoides, a small annual used medicinally by Cherokee Americans, contains bioactive acylphloroglucinols. Here, we identify acylphloroglucinol constituents of H. gentianoides and determine a potential pathway to their synthesis. Liquid chromatography/electrospray ionization‐mass spectrometry (LC/ESI‐MS) and HPLC‐UV indicate that the level of accumulation and profile of acylphloroglucinols in H. gentianoides vary little seasonally when grown in a greenhouse, but do vary with development and are highly dependent on the accession, highlighting the importance of the selection of plant material for study. We identify the chemical structures of the nine prevalent polyketides, based on LC/ESI‐MS and hybrid quadrupole orthogonal time‐of‐flight (Q‐TOF) mass spectrometry; these metabolites include one monomeric phlorisobutyrophenone (PIB) derivative and eight dimeric acylphloroglucinols. Q‐TOF spectrometry was used to identify eight additional PIB derivatives that were not detected by LC/ESI‐MS. These data lead us to propose that diacylphloroglucinols are synthesized via modification of PIB to yield diverse phloroglucinol and filicinic acids moieties, followed by dimerization of a phloroglucinol and a filicinic acid monomer to yield the observed complement of diacylphloroglucinols. The metabolomics data from H. gentianoides are accessible in plant metabolomics resource (PMR) (http://www.metnetdb.org/pmr), a public metabolomics database with analysis software for plants and microbial organisms.
Strategies in health‐promoting dialogues – primary healthcare nurses' perspectives – a qualitative study
Authors: Hörnsten Åsa , Lindahl Karin , Persson Kristina , Edvardsson Kristina
Published: April 2013

Aim and objectives

The aim of this study was to describe dialogic strategies about health and lifestyle used by primary healthcare nurses (PHNs) in the Västerbotten Intervention Programme (VIP) in Sweden.

Background

The VIP offers all citizens aged 40, 50 and 60 in Västerbotten County an individual health check‐up followed by a health‐promoting dialogue with a specialist PHN. Inconsistencies in previous reports of the effects of lifestyle counselling and health promotion suggest that it is important to study dialogues about health and lifestyle to understand health‐promoting strategies and to highlight aspects important to improving their effects.

Method

In 2010, we conducted in‐depth interviews with ten experienced PHNs working with the VIP at eight healthcare centres in Västerbotten County, Sweden. Qualitative content analysis was used to illuminate the nurses' strategies in health‐promoting dialogues. The Regional Ethics Board (Dno 06‐126M) approved the study.

Results

The PHNs used various strategies in dialogues about health and lifestyle that fell under the five themes ‘Guiding patients vs. pressuring them; Adjusting to patients vs. directing the conversation; Inspiring confidence vs. instilling fear; Motivating and supporting patients vs. demanding responsibility; and lastly, Introducing emotionally charged subjects or avoiding them'.

Conclusions

The results of this study may add knowledge about the difficulties and opportunities in health counselling. In the discussion, we suggest professional reflection as a means to increase knowledge and awareness about the self and context in the process of health counselling.
Glucosamine Induces Activated T Cell Apoptosis Through Reduced T Cell Receptor
Authors: Chen N.‐H. , Cheong K. A. , Kim C.‐H. , Noh M. , Lee A.‐Y.
Published: April 2013

Glucosamine (GlcN), like N‐acetylglucosamine (GlcNAc), is salvaged into the hexosamine pathway and is converted to UDP‐GlcNAc. Golgi N‐glycan branching enzymes produce N‐glycans, using UDP‐GlcNAc as a substrate, which attach to the T cell receptor (TCR) and cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4). These findings suggest that GlcN exerts the immunoregulation through TCR signalling, which could be involved not only in cytokine production but also activated T cell apoptosis. In fact, a preliminary study showed that GlcN reduced the number of CD3+ T cells of NC/Nga mice with AD‐like skin lesions. Therefore, whether apoptosis of T cells would be one of the potential molecular mechanisms of GlcN‐induced immunosuppression was investigated. Cultured human primary along with Jurkat T cells and purified T cells from NC/Nga mice with or without Df‐induced AD‐like skin lesion were used for the study. Glucosamine treatment increased the number of T cells expressing β1,6GlcNAc‐branched N‐glycans, with reduced ZAP‐70 phosphorylation and enhanced CTLA‐4 expression. Glucosamine treatment reduced the number of activated T cells from both the human primary and Jurkat cells and the dermatitis‐induced mice. The expression of FasL and activated caspases, particularly caspase‐3, was increased, whereas the phosphorylation of PI3K, Akt and NF‐κB was decreased by GlcN treatment. Therefore, in addition to down‐regulating TCR signalling and promoting CTLA‐4 expression, GlcN may also suppress T cell function by enhancing apoptosis of activated T cells, through both extrinsic and intrinsic apoptotic signalling pathways, which were regulated by the inhibition of PI3K/Akt and NF‐κB phosphorylation.
It Is Not Old‐Fashioned, It Is Vintage, Vintage Fashion and The Complexities of 21st Century Consumption Practices
Authors: Veenstra Aleit , Kuipers Giselinde
Published: April 2013

This article reviews consumption practices concerning vintage, a fashion style based on used or retro‐style garments. Existing studies connect vintage with authenticity, nostalgia and identity. We explore how the vintage style deploys and comments on consumer culture, bypassing producers by wearing old garments to communicate ‘authentic’ identities. We argue that existing theories on consumption, fashion and subculture cannot fully explain vintage practices. Bypassing the dichotomies and one‐dimensional explanations of these theories, we show that vintage, with its ambivalent relation to both subcultural distinction practices and mainstream consumer culture, serves as a prism through which to examine and understand the complexities and subtleties of 21st century consumption practices.
Graffiti as a Form of Contentious Political Participation
Authors: Waldner Lisa K. , Dobratz Betty A.
Published: April 2013

Graffiti is a popular topic in the sociological, criminological, and linguistic literature with several book length treatments of various types of graffiti including tagging, gang graffiti, murals, and “bombings”. Yet, political sociologists have paid little attention to the role of graffiti as a form of contentious politics despite the often political nature of graffiti messages. As a result, most of the political research on graffiti is by non‐sociologists. We believe this is an oversight and that both political sociologists and social movement scholars need to seriously consider this form of micro‐level political participation. In this review we (1) demonstrate why some forms of graffiti should be considered a serious form of political participation; (2) compare and contrast graffiti to other forms of resistance including squatting and culture jamming; (3) review research findings on graffiti; and (4) discuss some of the conceptual and methodological challenges for doing graffiti research.
Race and Sex Discrimination in the Employment Process
Authors: Skaggs Sheryl , Bridges Jennifer
Published: April 2013

In this article, we outline the evidence demonstrating the pervasiveness of sex and race/ethnic workplace discrimination, paying particular attention to the areas of hiring, compensation, and evaluations and promotions. Key sociological explanations for why and how these forms of employment discrimination occur are also examined. Although discrimination is often considered as discrete acts that occur within employment arrangements, the existing research suggests the presence of an underlying set of processes and choices that accumulate over time. These processes have clear implications for how discrimination is understood and the ways in which such events compound over career trajectories. Based on our examination of this literature, we suggest areas for improved theorizing, measurement, and analysis.
Reflectance confocal microscopy for the characterization of mycosis fungoides and correlation with histology: a pilot study
Authors: Li Wei , Dai Hui , Li Zhao , Xu Ai‐E
Published: April 2013

Background

Mycosis fungoides (MF) is cutaneous lymphoma of the T‐cell lineage. MF is a diagnostic challenge. In vivo reflectance confocal microscopy (RCM) reproducible imaging technique already reported to be useful in the diagnosis of skin diseases. The aims of our study were to define RCM features of MF and to evaluate its feasibility in biopsy site selection.

Methods

Each lesion was selected for RCM evaluation from 10 patients with an established diagnosis of MF. Subsequently, a biopsy of the same areas evaluated with RCM was rendered for histopathological examination.

Results

A series of RCM features of MF was identified and shown to correlate well with histopathological evaluation. We could find hyperkeratosis in five patients (10 : 50%); disarray of honeycomb of stratum spinosum in three patients (10 : 30%). In 10 patients (10 : 100%) of the MF, we could find that dermal papillary rings were weak reflected light; round to oval cells diffusely widespread throughout the epidermis and in the papillary dermis, infiltration of inflammatory cells in superficial dermis. Two (10 : 20%) of them can find vesicle area opaca in plaque stage MF, filled with monomorphous weakly refractile oval to round cells.

Conclusion

The utility of RCM as a diagnostic tool for MF awaits further evaluation, although it appears to be promising for biopsy site selection.
A novel HLA‐DRB1 allele, DRB1*01:54, identified by sequence‐based typing
Authors: Barbuti S. , Curcio M. , Marchetti L. , Vittorio O. , Mariotti M. L , Scatena F.
Published: April 2013

The new HLA DRB1*01:54 differs from DRB1*01:02:01 by one nucleotide at exon 2.
Chemical constituents of the essential oils of wild oat and crabgrass and their effects on the growth and allelochemical production of wheat
Authors: Zhou Bin , Kong Chui‐Hua , Wang Peng , Li Yong‐Hua
Published: April 2013

The interference of allelopathic weeds with crop plants might be mediated by volatile allelochemicals. In this study, the essential oil constituents of two weeds, wild oat (Avena fatua) and crabgrass (Digitaria sanguinalis), were investigated in relation to their effects on the growth and allelochemical production of wheat (Triticum aestivum). Subsequently, by means of gas chromatography and gas chromatography‐mass spectrometry, 52 compounds were identified from the crabgrass essential oil, particularly a signaling compound called methyl jasmonate, while 28 constituents were detected in the wild oat essential oil. Both essential oils were rich in terpenoids and inhibited the growth of wheat in air, filter paper and soil media but their inhibition varied with the growth medium and the weed species. In both the air and the filter paper media, there were not significant differences in the dry weight of wheat between the wild oat and the crabgrass essential oils. However, there was a greater reduction in the dry weight of the wheat root and plant with the wild oat essential oil than with the crabgrass essential oil in the soil medium. Furthermore, the production of the allelochemical, 2,4‐dihydroxy‐7‐methoxy‐1,4‐benzoxazin‐3‐one, in wheat was induced by the essential oils. The results suggest that allelopathic interference with wheat by wild oat and crabgrass affects not only the biomass allocation, but also the allelochemical production, of wheat.
Atomic layer deposition of titanium dioxide using titanium tetrachloride and titanium tetraisopropoxide as precursors
Authors: Chaukulkar Rohan P. , Agarwal Sumit
Published: April 2013

Most atomic layer deposition (ALD) processes for metal oxides involve the use of a metal precursor and an oxygen source, such as H2O, O3, or an O2 plasma. These ALD processes lead to the formation of an undesirable interfacial oxide during deposition on semiconductor surfaces. As an alternative, some metal oxides other than TiO2 have been deposited using metal alkoxides as the oxygen source. In this article, we report on the ALD of TiO2 using TiCl4 and titanium tetraisopropoxide (TTIP) as precursors. Our surface infrared spectroscopy data shows that over the temperature range of 150–250 °C and the duration of a typical ALD cycle (∼1–10 s), in both half-reaction cycles, the surface reaction mechanism is dominated by alkyl-transfer from the TTIP ligands to Ti-Cl species. At 250 °C, which is the onset for TTIP thermal decomposition, the contribution of the direct decomposition reaction to film growth is negligible. The growth per cycle, ∼0.7 Å at 200 °C, is higher than H2O-based ALD of TiO2 from either TiCl4 or TTIP, but similar to O2-plasma-based processes. X-ray photoelectron spectroscopy data show TiO2 films with only the +4 oxidation state of Ti, and the Cl content is estimated to be 2.5–3.5%. UV–Vis spectroscopy shows a band gap of ∼3.0 eV, which is comparable to the values reported in the literature for amorphous TiO2 thin films.
Selective etching of TiN over TaN and vice versa in chlorine-containing plasmas
Authors: Shin Hyungjoo , Zhu Weiye , Liu Lei , Sridhar Shyam , Donnelly Vincent M. , Economou Demetre J. , Lenox Chet , Lii Tom
Published: April 2013

Selectivity of etching between physical vapor-deposited TiN and TaN was studied in chlorine-containing plasmas, under isotropic etching conditions. Etching rates for blanket films were measured in-situ using optical emission of the N2 (C3Πu →B3Πg) bandhead at 337 nm to determine the etching time, and transmission electron microscopy to determine the starting film thickness. The etching selectivity in Cl2/He or HCl/He plasmas was poor (<2:1). There was a window of very high selectivity of etching TiN over TaN by adding small amounts (<1%) of O2 in the Cl2/He plasma. Reverse selectivity (10:1 of TaN etching over TiN) was observed when adding small amounts of O2 to the HCl/He plasma. Results are explained on the basis of the volatility of plausible reaction products.
New method for determining flat-band voltage in high mobility semiconductors
Authors: Winter Roy , Ahn Jaesoo , McIntyre Paul C. , Eizenberg Moshe
Published: April 2013

The method that is commonly used for determining the flat-band voltage (VFB) and the flat-band capacitance (CFB) of metal oxide semiconductor (MOS) capacitors depends on many parameters and can only be used in the case of low interface trap density (Dit) when the capacitance–voltage measurements are carried out at high frequencies. This paper demonstrates a new and simple method for determining VFB and CFB. The method is based on the point of inflection in the capacitance–voltage curve. This method does not require the knowledge of material or experimental parameters and can be used on high Dit and high border trap density MOS structures at all frequencies.
Low temperature oxidation of plutonium
Authors: Nelson Art J. , Roussel Paul
Published: April 2013

The initial oxidation of gallium stabilized δ-plutonium metal at 193 K has been followed using x-ray photoelectron spectroscopy. On exposure to Langmuir quantities of oxygen, plutonium rapidly forms a trivalent oxide followed by a tetravalent plutonium oxide. The growth modes of both oxides have been determined. Warming the sample in vacuum, the tetravalent oxide reduces to the trivalent oxide. The kinetics of this reduction reaction have followed and the activation energy has been determined to be 38.8 kJ mol−1.
Reorganization of Southern Ocean Plankton Ecosystem at the Onset of Antarctic Glaciation
Authors: Houben Alexander J. P. , Bijl Peter K. , Pross Jörg , Bohaty Steven M. , Passchier Sandra , Stickley Catherine E. , Röhl Ursula , Sugisaki Saiko , Tauxe Lisa , van de Flierdt Tina , Olney Matthew , Sangiorgi Francesca , Sluijs Appy , Escutia Carlota , Brinkhuis Henk ,   and the Expedition 318 Scientists
Published: April 2013

Southern Change

Antarctica has been mostly covered by ice since the inception of large-scale continental glaciation during the Oligocene, which profoundly altered the isotopic and mineralogical records of the sediments surrounding the continent.

Houben
et al.

(p.
341
) found records of the corresponding living systems in the fossil marine dinoflagellate cysts, which revealed that a microplankton ecosystem, similar to the one that exists today, appeared simultaneously with the first major Antarctic glaciation approximately 34 million years ago.
Resilience and Recovery of Overexploited Marine Populations
Authors: Neubauer Philipp , Jensen Olaf P. , Hutchings Jeffrey A. , Baum Julia K.
Published: April 2013

History Matters

Fishery-induced mortality is not the sole driver of fish population dynamics, and shifts in population abundance are also subject to ecological impacts. In a meta-analysis,

Neubauer
et al.

(p.
347
) showed how some fish-stock recoveries have been slower than theoretically predicted. They discovered that a species' exploitation history is also an important predictor of recovery. The data indicate that even extreme limitations in harvest pressure may not allow for the timely recovery of collapsed stocks.
Physical and Virtual Laboratories in Science and Engineering Education
Authors: de Jong Ton , Linn Marcia C. , Zacharia Zacharias C.
Published: April 2013

The world needs young people who are skillful in and enthusiastic about science and who view science as their future career field. Ensuring that we will have such young people requires initiatives that engage students in interesting and motivating science experiences. Today, students can investigate scientific phenomena using the tools, data collection techniques, models, and theories of science in physical laboratories that support interactions with the material world or in virtual laboratories that take advantage of simulations. Here, we review a selection of the literature to contrast the value of physical and virtual investigations and to offer recommendations for combining the two to strengthen science learning.
Professional Development for Science Teachers
Authors: Wilson Suzanne M.
Published: April 2013

The Next Generation Science Standards will require large-scale professional development (PD) for all science teachers. Existing research on effective teacher PD suggests factors that are associated with substantial changes in teacher knowledge and practice, as well as students’ science achievement. But the complexity of the U.S. educational system continues to thwart the search for a straightforward answer to the question of how to support teachers. Interventions that take a systemic approach to reform hold promise for improving PD effectiveness.
Outside the Pipeline: Reimagining Science Education for Nonscientists
Authors: Feinstein Noah Weeth , Allen Sue , Jenkins Edgar
Published: April 2013

Educational policy increasingly emphasizes knowledge and skills for the preprofessional “science pipeline” rather than helping students use science in daily life. We synthesize research on public engagement with science to develop a research-based plan for cultivating competent outsiders: nonscientists who can access and make sense of science relevant to their lives. Schools should help students access and interpret the science they need in response to specific practical problems, judge the credibility of scientific claims based on both evidence and institutional cues, and cultivate deep amateur involvement in science.
The Helicase-Like Domains of Type III Restriction Enzymes Trigger Long-Range Diffusion Along DNA
Authors: Schwarz Friedrich W. , Tóth Júlia , van Aelst Kara , Cui Guanshen , Clausing Sylvia , Szczelkun Mark D. , Seidel Ralf
Published: April 2013

Sliding Restriction

Helicase enzymes access the genetic information stored in double-helical DNA and RNA by opening the individual strands. Pseudo-helicases, including bacterial Type III restriction enzymes, use adenosine triphosphate (ATP) hydrolysis to communicate between two distant restriction sites on the same DNA and excise it only if the DNA is sensed as “foreign.”

Schwarz
et al.

(p.
353
) show that the bacterial Type III restriction enzyme, EcoP15I, undergoes an ATP-dependent conformational switch that promotes sliding along the DNA to allow the enzyme to localize to its target.
Global Charcoal Mobilization from Soils via Dissolution and Riverine Transport to the Oceans
Authors: Jaffé Rudolf , Ding Yan , Niggemann Jutta , Vähätalo Anssi V. , Stubbins Aron , Spencer Robert G. M. , Campbell John , Dittmar Thorsten
Published: April 2013

Dissolving Charcoal

Biomass burning produces 40 to 250 million tons of charcoal per year worldwide. Much of this is preserved in soils and sediments for thousands of years. However, the estimated production rate of charcoal is significantly larger than that of decomposition, and

Jaffe
et al.

(p.
345
; see the Perspective by

Masiello and Louchouarn

) calculate that a large fraction of the charcoal produced by fires is lost from the land through dissolution and transport to the oceans.
Response to Comments on “
Drosophila
Dosage Compensation Involves Enhanced Pol II Recruitment to Male X-Linked Promoters”
Authors: Vaquerizas Juan M. , Cavalli Florence M. G. , Conrad Thomas , Akhtar Asifa , Luscombe Nicholas M.
Published: April 2013

Ferrari
et al
. and Straub and Becker wrongly claim that an error in the computational analysis calls into question the conclusions of Conrad
et al
. All the available evidence, including the reanalyzed genomic data, show that the conclusions and the key message of the study remain unchanged: RNA polymerase II recruitment to male X-linked promoters is an important regulatory step during dosage compensation.
Polarization-Controlled Tunable Directional Coupling of Surface Plasmon Polaritons
Authors: Lin Jiao , Mueller J. P. Balthasar , Wang Qian , Yuan Guanghui , Antoniou Nicholas , Yuan Xiao-Cong , Capasso Federico
Published: April 2013

Controlling Light Propagation

Surface plasmons are light-induced collective electronic excitations in a metal that offer the possibility of manufacturing optoelectronic devices at nanometer scale. Before such shrinking can be achieved, the propagation direction and lifetime of the plasmonic excitations have to be controlled (see the Perspective by

Miroshnichenko and Kivshar

).

Rodríguez-Fortuño
et al.

(p.
328
) show how this is done using polarized light. Alternatively, using an array of metallic nanoantennae (in this case, slits) patterned into a thin gold film,

Lin
et al.

(p.
331
) present a further improvement on current plasmonic coupling schemes that has the potential to encode information contained in both the intensity and polarization of light.
Bat and Rat Neurons Differ in Theta-Frequency Resonance Despite Similar Coding of Space
Authors: Heys James G. , MacLeod Katrina M. , Moss Cynthia F. , Hasselmo Michael E.
Published: April 2013

Bats, Grids, and Oscillations

Nearly all animals move around in a three-dimensional (3D) world; however, very little is known about the neural circuitry underlying the representation of 3D space (see the Perspective by

Barry and Doeller

). Using whole-cell patch recordings in slices of entorhinal cortex,

Heys
et al.

(p.
363
) found that bat entorhinal stellate cells must generate grid patterns without theta-frequency oscillatory mechanisms. In another study,
Yartsev and Ulanovsky
(p.
367
) used telemetry to record activity from the hippocampus of bats while they were flying around. They found that active pyramidal cells—or place cells—in hippocampal area CA1 fired in positions, depending on where the animals were in the room.
Opportunities and Challenges in Next Generation Standards
Authors: Stage E. K. , Asturias H. , Cheuk T. , Daro P. A. , Hampton S. B.
Published: April 2013

Goals for literacy, math, and science education may increase citizens' capacity to argue from evidence.
Generating Improvement Through Research and Development in Education Systems
Authors: Donovan M. Suzanne
Published: April 2013

To effectively address problems in education, research must be shaped around a problem of practice. Reorienting research and development in this way must overcome three obstacles. First, the incentive system for university researchers must be changed to reward research on problems of practice. Second, the contexts must be created that will allow the complexity of problems of practice to be understood and addressed by interdisciplinary teams of researchers, practitioners, and education designers. And third, meaningful experimentation must become acceptable in school systems in order to develop a better understanding of how to effectively stimulate and support the desired changes.
Great Apes and Zoonoses
Authors: Sharp Paul M. , Rayner Julian C. , Hahn Beatrice H.
Published: April 2013

Comparing the origins of AIDS and malaria may provide insight for gauging the prospect of future pathogen transmissions from apes to humans.
Heterochronic Genes Turn Back the Clock in Old Neurons
Authors: Nix Paola , Bastiani Michael
Published: April 2013

A signaling pathway is implicated in the age-dependent decline of neuron regeneration.

[Also see Report by

Zou
et al.

]
Serpentine Figures in Edinburgh
Edinburgh International Science Festival
Various venues, Edinburgh, Scotland. Through 7 April 2013. www.sciencefestival.co.uk/
Authors: Dixon Deborah , Straughan Elizabeth
Published: April 2013

Our reviewers sample some of the art-science events at this year's Edinburgh International Science Festival.
Request Would Let Science Rebound From Sequester
Authors: Mervis Jeffrey
Published: April 2013

President Barack Obama last week submitted a $3.8 trillion budget request to Congress for 2014 that, if enacted, would boost the research budgets of nearly every federal agency.
Detection of Methicillin-Resistant Staphylococcus aureus by a Duplex Droplet Digital PCR Assay
Authors: Kelley KaShonda , Cosman Angela , Belgrader Phillip , Chapman Brenda , Sullivan Donna C.
Published: April 2013

Health care-associated infections with methicillin-resistant
Staphylococcus aureus
(MRSA) contribute to significant hospitalization costs. We report here a droplet digital PCR (ddPCR) assay, which is a next-generation emulsion-based endpoint PCR assay for high-precision MRSA analysis. Reference cultures of MRSA, methicillin-susceptible
S. aureus
(MSSA), and confounders were included as controls. Copan swabs were used to sample cultures and collect specimens for analysis from patients at a large teaching hospital. Swab extraction and cell lysis were accomplished using magnetic-driven agitation of silica beads. Quantitative PCR (qPCR) (Roche Light Cycler 480) and ddPCR (Bio-Rad QX100 droplet digital PCR system) assays were used to detect genes for the staphylococcal protein SA0140 (SA) and the methicillin resistance (
mecA
) gene employing standard TaqMan chemistries. Both qPCR and ddPCR assays correctly identified culture controls for MRSA (76), MSSA (12), and confounder organisms (36) with 100% sensitivity and specificity. Analysis of the clinical samples (211 negative and 186 positive) collected during a study of MRSA nasal carriage allowed direct comparison of the qPCR and ddPCR assays to the Cepheid MRSA GeneXpert assay. A total of 397 clinical samples were examined in this study. Cepheid MRSA GeneXpert values were used to define negative and positive samples. Both the qPCR and ddPCR assays were in good agreement with the reference assay. The sensitivities for the qPCR and ddPCR assays were 96.8% (95% confidence interval [CI], 93.1 to 98.5%) and 96.8% (95% CI, 93.1 to 98.5%), respectively. Both the qPCR and ddPCR assays had specificities of 91.9% (95% CI, 87.5 to 94.9%) for qPCR and 91.0% (95% CI, 86.4 to 94.2%) for ddPCR technology.
Evaluation of Vancomycin Susceptibility Testing for Methicillin-Resistant Staphylococcus aureus: Comparison of Etest and Three Automated Testing Methods
Authors: Rybak Michael J. , Vidaillac Celine , Sader Helio S. , Rhomberg Paul R. , Salimnia Hossein , Briski Lawrence E. , Wanger Audrey , Jones Ronald N.
Published: April 2013

We evaluated the ability of four commercial MIC testing systems (MicroScan, Vitek 2, Phoenix, and Etest) to detect vancomycin MIC values of ≤1 to ≥2 in 200 methicillin-resistant
Staphylococcus aureus
(MRSA) strains compared to the Clinical and Laboratory Standards Institute broth microdilution (BMD) reference methods. Compared to the BMD method, absolute agreement (0 ± dilution) was highest for the Phoenix system (66.2%) and the MicroScan turbidity method (61.8%), followed by the Vitek 2 system (54.3%). The Etest produced MIC values 1 to 2 dilutions higher than those produced by the BMD method (36.7% agreement). Of interest, the MicroScan system (prompt method) was more likely to overcall an MIC value of 1 mg/liter (74.1%), whereas the Phoenix (76%) and Vitek 2 (20%) systems had a tendency to undercall an MIC of 2 mg/liter. The ability to correctly identify vancomycin MIC values of 1 and 2 has clinical implications and requires further evaluation.
Evaluation of the Verigene Gram-Positive Blood Culture Nucleic Acid Test for Rapid Detection of Bacteria and Resistance Determinants
Authors: Wojewoda Christina M. , Sercia Linda , Navas Maria , Tuohy Marion , Wilson Deborah , Hall Geraldine S. , Procop Gary W. , Richter Sandra S.
Published: April 2013

Rapid identification of pathogens from blood cultures can decrease lengths of stay and improve patient outcomes. We evaluated the accuracy of the Verigene Gram-positive blood culture (BC-GP) nucleic acid test for investigational use only (Nanosphere, Inc., Northbrook, IL) for the identification of Gram-positive bacteria from blood cultures. The detection of resistance genes (
mecA
in
Staphylococcus aureus
and
Staphylococcus epidermidis
and
vanA
or
vanB
in
Enterococcus faecium
and
Enterococcus faecalis
) by the BC-GP assay also was assessed. A total of 186 positive blood cultures (in BacT/Alert FA bottles) with Gram-positive cocci observed with Gram staining were analyzed using the BC-GP assay. The BC-GP results were compared with the identification and susceptibility profiles obtained with routine methods in the clinical laboratory. Discordant results were arbitrated with additional biochemical, cefoxitin disk, and repeat BC-GP testing. The initial BC-GP organism identification was concordant with routine method results for 94.6% of the blood cultures. Only 40% of the
Streptococcus pneumoniae
identifications were correct. The detection of the
mecA
gene for 69 blood cultures with only
S. aureus
or
S. epidermidis
was concordant with susceptibility testing results. For 3 of 6 cultures with multiple
Staphylococcus
spp.,
mecA
detection was reported but was correlated with oxacillin resistance in a species other than
S. aureus
or
S. epidermidis
. The detection of
vanA
agreed with susceptibility testing results for 45 of 46 cultures with
E. faecalis
or
E. faecium
. Comparison of the mean times to results for each organism group showed that BC-GP results were available 31 to 42 h earlier than phenotypic identifications and 41 to 50 h earlier than susceptibility results.
Simple Multiplex PCR Assay for Identification of Beijing Family Mycobacterium tuberculosis Isolates with a Lineage-Specific Mutation in
Rv0679c
Authors: Nakajima Chie , Tamaru Aki , Rahim Zeaur , Poudel Ajay , Maharjan Bhagwan , Khin Saw Aye  , Ling Hong , Hattori Toshio , Iwamoto Tomotada , Fukushima Yukari , Suzuki Haruka , Suzuki Yasuhiko , Matsuba Takashi
Published: April 2013

The Beijing genotype of
Mycobacterium tuberculosis
is known to be a worldwide epidemic clade. It is suggested to be a possibly resistant clone against BCG vaccination and is also suggested to be highly pathogenic and prone to becoming drug resistant. Thus, monitoring the prevalence of this lineage seems to be important for the proper control of tuberculosis. The Rv0679c protein of
M. tuberculosis
has been predicted to be one of the outer membrane proteins and is suggested to contribute to host cell invasion. Here, we conducted a sequence analysis of the
Rv0679c
gene using clinical isolates and found that a single nucleotide polymorphism, C to G at position 426, can be observed only in the isolates that are identified as members of the Beijing genotype family. Here, we developed a simple multiplex PCR assay to detect this point mutation and applied it to 619 clinical isolates. The method successfully distinguished Beijing lineage clones from non-Beijing strains with 100% accuracy. This simple, quick, and cost-effective multiplex PCR assay can be used for a survey or for monitoring the prevalence of Beijing genotype
M. tuberculosis
strains.
Divergent Kinetics of Proliferating T Cell Subsets in Simian Immunodeficiency Virus (SIV) Infection: SIV Eliminates the “First Responder” CD4
+
T Cells in Primary Infection
Authors: Wang Xiaolei , Xu Huanbin , Pahar Bapi , Lackner Andrew A. , Veazey Ronald S.
Published: April 2013

Although increased lymphocyte turnover in chronic human immunodeficiency virus and simian immunodeficiency virus (SIV) infection has been reported in blood, there is little information on cell turnover in tissues, particularly in primary SIV infection. Here we examined the levels of proliferating T cell subsets in mucosal and peripheral lymphoid tissues of adult macaques throughout SIV infection. To specifically label cells in S-phase division, all animals were inoculated with bromodeoxyuridine 24 h prior to sampling. In healthy macaques, the highest levels of proliferating CD4
+
and CD8
+
T cells were in blood and, to a lesser extent, in spleen. Substantial percentages of proliferating cells were also found in intestinal tissues, including the jejunum, ileum, and colon, but very few proliferating cells were detected in lymph nodes (axillary and mesenteric). Moreover, essentially all proliferating T cells in uninfected animals coexpressed CD95 and many coexpressed CCR5 in the tissues examined. Confocal microscopy also demonstrated that proliferating cells were substantial viral target cells for SIV infection and viral replication. After acute SIV infection, percentages of proliferating CD4
+
and CD8
+
T cells were significantly higher in tissues of chronically infected macaques and macaques with AIDS than in those of the controls. Surprisingly, however, we found that proliferating CD4
+
T cells were selectively decreased in very early infection (8 to 10 days postinoculation [dpi]). In contrast, levels of proliferating CD8
+
T cells rapidly increased after SIV infection, peaked by 13 to 21 dpi, and thereafter remained significantly higher than those in the controls. Taken together, these findings suggest that SIV selectively infects and destroys dividing, nonspecific CD4
+
T cells in acute infection, resulting in homeostatic changes and perhaps continuing loss of replication capacity to respond to nonspecific and, later, SIV-specific antigens.
Inhibition of Hepatitis C Virus (HCV) Replication by Specific RNA Aptamers against HCV NS5B RNA Replicase
Authors: Lee Chang Ho , Lee Young Ju , Kim Ji Hyun , Lim Jong Hoon , Kim Jung-Hye , Han Wonkyo , Lee Soo-Han , Noh Gyu-Jeong , Lee Seong-Wook
Published: April 2013

This study identified specific and avid RNA aptamers consisting of 2′-hydroxyl- or 2′-fluoropyrimidines against hepatitis C virus (HCV) NS5B replicase, an enzyme that is essential for HCV replication. These aptamers acted as potent decoys to competitively impede replicase-catalyzed RNA synthesis activity. Cytoplasmic expression of the 2′-hydroxyl aptamer efficiently inhibited HCV replicon replication in human liver cells through specific interaction with, and sequestration of, the target protein without either off-target effects or escape mutant generation. A selected 2′-fluoro aptamer could be truncated to a chemically manufacturable length of 29 nucleotides (nt), with increase in the affinity to HCV NS5B. Noticeably, transfection of the truncated aptamer efficiently suppressed HCV replication in cells without escape mutant appearance. The aptamer was further modified through conjugation of a cholesterol or galactose-polyethylene glycol ligand for
in vivo
availability and liver-specific delivery. The conjugated aptamer efficiently entered cells and inhibited genotype 1b subgenomic and genotype 2a full-length HCV JFH-1 RNA replication without toxicity and innate immunity induction. Importantly, a therapeutically feasible amount of the conjugated aptamer was delivered
in vivo
to liver tissue in mice. Therefore, cytoplasmic expression of 2′-hydroxyl aptamer or direct administration of chemically synthesized and ligand-conjugated 2′-fluoro aptamer against HCV NS5B could be a potent anti-HCV approach.
Suppressed Th17 Levels Correlate with Elevated PIAS3, SHP2, and SOCS3 Expression in CD4 T Cells during Acute Simian Immunodeficiency Virus Infection
Authors: Bixler Sandra L. , Sandler Netanya G. , Douek Daniel C. , Mattapallil Joseph J.
Published: April 2013

T helper 17 (Th17) cells play an important role in mucosal immune homeostasis and maintaining the integrity of the mucosal epithelial barrier. Loss of Th17 cells has been extensively documented during human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections. The lack of effective repopulation of Th17 cells has been associated with chronic immune activation mediated by the translocation of microbial products. Using
ex vivo
analysis of purified peripheral blood CD4 T cells from SIV-infected rhesus macaques, we show that the suppression of interleukin-17 (IL-17) expression correlated with upregulated expression of negative regulatory genes PIAS3, SHP2, and SOCS3 in CD4 T cells. Suppressed Th17 expression was accompanied by elevated levels of soluble CD14 (sCD14) and lipopolysaccharide binding protein (LBP) in the plasma during early stages of infection. Plasma viral loads rather than sCD14 or LBP levels correlated with acute immune activation. Additionally, we observed a significant increase in the expression of CD14 on peripheral blood monocytes that correlated with IL-23 expression and markers of microbial translocation. Taken together, our results provide new insights into the early events associated with acute SIV pathogenesis and suggest additional mechanisms playing a role in suppression of Th17 cells.
The Mature Virion of Ectromelia Virus, a Pathogenic Poxvirus, Is Capable of Intrahepatic Spread and Can Serve as a Target for Delayed Therapy
Authors: Ma Xueying , Xu Ren-Huan , Roscoe Felicia , Whitbeck J. Charles , Eisenberg Roselyn J. , Cohen Gary H. , Sigal Luis J.
Published: April 2013

Orthopoxviruses (OPVs), which include the agent of smallpox (variola virus), the zoonotic monkeypox virus, the vaccine and zoonotic species vaccinia virus, and the mouse pathogen ectromelia virus (ECTV), form two types of infectious viral particles: the mature virus (MV), which is cytosolic, and the enveloped virus (EV), which is extracellular. It is believed that MVs are required for viral entry into the host, while EVs are responsible for spread within the host. Following footpad infection of susceptible mice, ECTV spreads lymphohematogenously, entering the liver at 3 to 4 days postinfection (dpi). Afterwards, ECTV spreads intrahepatically, killing the host. We found that antibodies to an MV protein were highly effective at curing mice from ECTV infection when administered after the virus reached the liver. Moreover, a mutant ECTV that does not make EV was able to spread intrahepatically and kill immunodeficient mice. Together, these findings indicate that MVs are sufficient for the spread of ECTV within the liver and could have implications regarding the pathogenesis of other OPVs, the treatment of emerging OPV infections, as well as strategies for preparedness in case of accidental or intentional release of pathogenic OPVs.
Impact of H216 on the DNA Binding and Catalytic Activities of the HIV Restriction Factor APOBEC3G
Authors: Harjes Stefan , Solomon William C. , Li Ming , Chen Kuan-Ming , Harjes Elena , Harris Reuben S. , Matsuo Hiroshi
Published: April 2013

APOBEC3G has an important role in human defense against retroviral pathogens, including HIV-1. Its single-stranded DNA cytosine deaminase activity, located in its C-terminal domain (A3Gctd), can mutate viral cDNA and restrict infectivity. We used time-resolved nuclear magnetic resonance (NMR) spectroscopy to determine kinetic parameters of A3Gctd's deamination reactions within a 5′-CCC hot spot sequence. A3Gctd exhibited a 45-fold preference for 5′-CCC substrate over 5′-CCU substrate, which explains why A3G displays almost no processivity within a 5′-CCC motif. In addition, A3Gctd's shortest substrate sequence was found to be a pentanucleotide containing 5′-CCC flanked on both sides by a single nucleotide. A3Gctd as well as full-length A3G showed peak deamination velocities at pH 5.5. We found that H216 is responsible for this pH dependence, suggesting that protonation of H216 could play a key role in substrate binding. Protonation of H216 appeared important for HIV-1 restriction activity as well, since substitutions of H216 resulted in lower restriction
in vivo
.
High, Broad, Polyfunctional, and Durable T Cell Immune Responses Induced in Mice by a Novel Hepatitis C Virus (HCV) Vaccine Candidate (MVA-HCV) Based on Modified Vaccinia Virus Ankara Expressing the Nearly Full-Length HCV Genome
Authors: Gómez Carmen E. , Perdiguero Beatriz , Cepeda María Victoria , Mingorance Lidia , García-Arriaza Juan , Vandermeeren Andrea , Sorzano Carlos Óscar S. , Esteban Mariano
Published: April 2013

A major goal in the control of hepatitis C infection is the development of a vaccine. Here, we have developed a novel HCV vaccine candidate based on the highly attenuated poxvirus vector MVA (referred to as MVA-HCV) expressing the nearly full-length (7.9-kbp) HCV sequence, with the aim to target almost all of the T and B cell determinants described for HCV. In infected cells, MVA-HCV produces a polyprotein that is subsequently processed into the structural and nonstructural HCV proteins, triggering the cytoplasmic accumulation of dense membrane aggregates. In both C57BL/6 and transgenic HLA-A2-vaccinated mice, MVA-HCV induced high, broad, polyfunctional, and long-lasting HCV-specific T cell immune responses. The vaccine-induced T cell response was mainly mediated by CD8 T cells; however, although lower in magnitude, the CD4
+
T cells were highly polyfunctional. In homologous protocol (MVA-HCV/MVA-HCV) the main CD8
+
T cell target was p7+NS2, whereas in heterologous combination (DNA-HCV/MVA-HCV) the main target was NS3. Antigenic responses were also detected against other HCV proteins (Core, E1-E2, and NS4), but the magnitude of the responses was dependent on the protocol used. The majority of the HCV-induced CD8
+
T cells were triple or quadruple cytokine producers. The MVA-HCV vaccine induced memory CD8
+
T cell responses with an effector memory phenotype. Overall, our data showed that MVA-HCV induced broad, highly polyfunctional, and durable T cell responses of a magnitude and quality that might be associated with protective immunity and open the path for future considerations of MVA-HCV as a prophylactic and/or therapeutic vaccine candidate against HCV.