bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of Evidence to Characterize National Measles and Rubella Exposure and Immunization Histories
Authors: Thompson Kimberly M. , Odahowski Cassie L. , Goodson James L. , Reef Susan E. , Perry Robert T.
Published: August 2015

Population immunity depends on the dynamic levels of immunization coverage that countries achieve over time and any transmission of viruses that occur within the population that induce immunity. In the context of developing a dynamic transmission model for measles and rubella to support analyses of future immunization policy options, we assessed the model inputs required to reproduce past behavior and to provide some confidence about model performance at the national level. We reviewed the data available from the World Health Organization (WHO) and existing measles and rubella literature for evidence of historical reported routine and supplemental immunization activities and reported cases and outbreaks. We constructed model input profiles for 180 WHO member states and three other areas to support disease transmission model development and calibration. The profiles demonstrate the significant variability in immunization strategies used historically by regions and member states and the epidemiological implications of these historical choices. The profiles provide a historical perspective on measles and rubella immunization globally at the national level, and they may help immunization program managers identify existing immunity and/or knowledge gaps.
Resisted adduction in hip neutral is a superior provocation test to assess adductor longus pain: An experimental pain study
Authors: Drew M. K. , Palsson T. S. , Izumi M. , Hirata R. P. , Lovell G. , Chiarelli P. , Osmotherly P. G. , Graven‐Nielsen T.
Published: August 2015

The criterion of long‐standing groin pain diagnoses in athletes usually relies on palpation and clinical tests. An experimental pain model was developed to examine the clinical tests under standardized conditions. Pain was induced by hypertonic saline injected into the proximal adductor longus (AL) tendon or rectus femoris (RF) tendon in 15 healthy male participants. Isotonic saline was injected contralaterally as a control. Pain intensity was assessed on a visual analog scale (VAS). Resisted hip adduction at three different angles and trunk flexion were completed before, during, and after injections. Pain provocation in the presence of experimental pain was recorded as a true positive compared with pain provocation in the non‐pain conditions. Similar peak VAS scores were found after hypertonic saline injections into the AL and RF and both induced higher VAS scores than isotonic saline (P < 0.01). Adduction at 0° had the greatest positive likelihood ratio (+LR = 2.8, 95%CI: 1.09–7.32) with 45° (−LR = 0.0, 95%CI: 0.00–1.90) and 90° (−LR = 0.0, 95%CI: 0.00–0.94) having the lowest negative LR. This study indicates that the 0° hip adduction test resisted at the ankles optimizes the diagnostic procedure without compromising diagnostic capacity to identify experimental groin pain. Validation in clinical populations is warranted.
Molecules, morphology and Mimeoma scarabs: evolutionary and taxonomic implications for a palm‐associated scarab group
Authors: MOORE MATTHEW R. , BEZA‐BEZA CRISTIAN F. , WICKELL DAVID A. , BECK JAMES B. , JAMESON MARY L.
Published: August 2015

Cyclocephaline scarabs, the second largest tribe of rhinoceros beetles, are important pollinators of early‐diverging angiosperm families in the tropics. The evolutionary history of cyclocephaline genera is poorly resolved and several genera are thought to be nonmonophyletic. We assess the monophyly of Mimeoma Casey, a group of Neotropical palm‐feeding scarabs, and its relationship to Cyclocephala with a phylogenetic analysis of 2899 bp of DNA sequence data and 18 morphological characters. All five species of Mimeoma were included in analyses along with species of Cyclocephala Dejean, Dyscinetus Harold and Tomarus Erichson as outgroup taxa. Nearly complete 28S, 12S and CO1 data were collected from 26 of 29 specimens, of which 16 samples were pinned, museum specimens. 28S data strongly support a nonmonophyletic Mimeoma; mitochondrial data (CO1 and 12S) suggest that Mimeoma species are nested within an apical clade of other Cyclocephala species; combined molecular and morphological data identify two strongly supported clades of Mimeoma species but do not support their sister relationship. Combined data show that Mimeoma species are nested within Cyclocephala, thus rendering Cyclocephala paraphyletic. Mimeoma is synonymized within Cyclocephala resulting in the following new combinations: Cyclocephala acuta Arrow n.comb., Cyclocephala englemani (Ratcliffe) n.comb., Cyclocephala maculata Burmeister n.comb., Cyclocephala nigra (Endrödi) n.comb. and Cyclocephala signatoides Höhne n.comb. Our results demonstrate that pinned, museum specimens can be used to obtain DNA sequence data (particularly high‐copy gene regions) for evolutionary studies, and provide the first empirical support that host‐plant associations within cyclocephaline scarab clades are conserved at the plant family‐level.
Hyperspectral Remote Sensing Classifications: A Perspective Survey
Authors: Chutia D , Bhattacharyya D K , Sarma K K , Kalita R , Sudhakar S
Published: August 2015

Classification of hyperspectral remote sensing data is more challenging than multispectral remote sensing data because of the enormous amount of information available in the many spectral bands. During the last few decades, significant efforts have been made to investigate the effectiveness of the traditional multispectral classification approaches on hyperspectral data. Formerly extensively established conventional classification methods have been dominated by the advanced classification approaches and many pre‐processing techniques have been developed and incorporated in hyperspectral classification. A perspective survey of hyperspectral remote sensing classification approaches is presented here. It comprehensively highlights the taxonomy of major classification approaches reported during the last two decades and describes an experimental evaluation of a few major classification algorithms. Recent advancements in the development of classification approaches are also emphasized with a set of guidelines for achieving better classification performances.
Experience with anidulafungin in patients with allogeneic hematopoietic stem cell transplantation and graft‐versus‐host disease
Authors: Yáñez L. , Insunza A. , Ibarrondo P. , de Miguel C. , Bermúdez A. , Colorado M. , López‐Duarte M. , Richard C. , Conde E.
Published: August 2015

Background

It is well known that both acute and chronic graft‐versus‐host disease (GVHD) are associated with invasive fungal disease (IFD). Because the galactomannan antigen diagnostic test has low specificity and sensitivity outside of the neutropenic period, many institutions use posaconazole or voriconazole for IFD prophylaxis during GVHD treatment. Moreover, several factors, mainly hepatic impairment, can limit the use of extended spectrum azoles, both in prophylaxis or treatment.

Methods

We retrospectively analyzed 25 patients with allogeneic hematopoietic stem cell transplantation (HSCT) and GVHD – grade III–IV acute GHVD (n = 15), progressive chronic GVHD (n = 7), and “overlap” GVHD (n = 3) – who received intravenous anidulafungin (200 mg on day 1, followed by 100 mg once daily). If necessary, anidulafungin treatment was followed by oral administration of 200 mg voriconazole twice a day or 200 mg posaconazole 3 times daily until patients were considered not at risk for IFD.

Results

Twenty‐one patients (85%) received anidulafungin as prophylaxis and 5 patients (15%) received it as treatment. Median duration of intravenous anidulafungin administration was 8 days (range 6–17). Seven patients (28%) presented mild adverse effects, with no significant interactions with calcineurin inhibitors. Sequentially, 4 patients received voriconazole and 6 posaconazole. Two patients (8%) developed IFD after anidulafungin withdrawal: 1 with Candida albicans and the other with Mucor, 8 and 5 days after withdrawal, respectively.

Conclusions

Our results are of interest owing to the absence of data in the literature on anidulafungin use in HSCT patients with GVHD, and suggest that anidulafungin, because of its spectrum, pharmacological profile, low toxicity, and absence of interactions with immunosuppressants, could be a drug of choice in this setting.
Diagnostic performance of fluorescent light‐emitting diode microscopy for tuberculous lymphadenitis in a high‐burden setting
Authors: Abdissa Ketema , Tadesse Mulualem , Abdella Kedir , Bekele Alemayehu , Bezabih Mesele , Abebe Gemeda
Published: August 2015

Objective

Diagnosis of tuberculous lymphadenitis using fine‐needle aspiration cytology is a simple and safe but low‐specificity method, whereas conventional smear microscopy has variable sensitivity due to low bacterial load. We evaluated the diagnostic performance of fluorescent light‐emitting diode (LED) microscopy on routinely collected fine‐needle aspirates from tuberculous lymphadenitis presumptive cases.

Methods

Fine‐needle aspirates were collected from patients clinically suspected of having tuberculous lymphadenitis as part of routine diagnosis. Smear preparation was performed from the aspirate and processed for cytology, conventional Ziehl–Neelsen and LED microscopy. The remaining aspirate was processed for culture on Lowenstein–Jensen media. Capilia TB‐Neo test was used to differentiate M. tuberculosis complex from non‐tuberculous mycobacteria.

Result

A total of 144 tuberculous lymphadenitis presumptive cases were included. 66.7% (96/144) were positive for M. tuberculosis complex on culture. Only one isolate was identified as non‐tuberculous mycobacteria. The detection rates of Ziehl–Neelsen and LED microscopy were 18.8% (27/144) and 34% (49/144), respectively. As compared to culture, sensitivity was 25.0% [95% CI: 16.3–33.7] for Ziehl–Neelsen microscopy and 45.8% [95% CI: 35.9–55.8] for LED microscopy. The specificity was 93.8% [95% CI: 86.9–100] for Ziehl–Neelsen microscopy and 89.6% [95% CI: 80.9–98.2] for LED microscopy. LED microscopy showed a statistically significant increase in sensitivity and similar specificity compared to Ziehl–Neelsen microscopy. Mean reading time of positive slides was 2.62 min/slide for Ziehl–Neelsen and 1.60 min/slide for LED microscopy. Cytology showed sensitivity of 82.3% and specificity of 54.2%. LED microscopy detected TB bacilli in 33.3% of cases cytologically classified as suppurative abscess.

Conclusion

The LED microscopy for tuberculous lymphadenitis had significantly higher sensitivity and shorter screening time than Ziehl–Neelsen microscopy. Use of LED microscopy among cases classified as suppurative abscess on fine‐needle aspirate cytology improves evidence‐based diagnosis of presumptive tuberculous lymphadenitis cases. Moreover, LED microscopy could be considered as an alternative approach in settings where fine‐needle aspirate cytology is impractical.
Oral glucocorticoid pulse therapy for induction of treatment of canine pemphigus foliaceus – a comparative study
Authors: Bizikova Petra , Olivry Thierry
Published: August 2015

Background

The management of canine pemphigus foliaceus (PF) often requires long‐term immunosuppressive treatment that is often associated with unacceptable adverse effects. High‐dose glucocorticoid pulse therapy, an alternative protocole used for pemphigus in people, has been shown to provide rapid improvement in dogs with pemphigus foliaceus and vulgaris.

Objectives

To further identify the benefit of pulse therapy for management of canine PF, we compared the outcomes of oral glucocorticoid pulse and traditional therapies during the first 3 months of disease management.

Animals

Dogs were allocated based on their oral glucocorticoid regimen during the first 12 weeks of PF management into the ‘traditional’ (20 dogs) or the ‘pulse’ (18 dogs) treatment groups.

Results

The proportion of dogs achieving complete remission (CR) during the first 12 weeks of treatment was significantly higher for the ‘pulse’ (61%) than for the ‘traditional’ group (15%; P = 0.0063). The maximal oral glucocorticoid dosage given to dogs from the ‘traditional’ group was significantly higher (median: 3.2 mg/kg) than that given between pulses to dogs from the other group (median: 1.1 mg/kg; P < 0.0001). There was no significant difference between groups in the time needed to achieve CR, the proportion of dogs requiring adjuvant immunosuppressive treatment or in the proportion of dogs experiencing severe adverse drug reactions.

Conclusions and clinical importance

These results suggest several benefits associated with oral glucocorticoid pulse therapy, such as a higher proportion of dogs achieving CR during the first 3 months, a lower average maximal oral glucocorticoid dosage given between pulses and minimal adverse drug events.
Outcome of Donor Cats After Unilateral Nephrectomy as Part of a Clinical Kidney Transplant Program
Authors: Danielson Kelson C. , Hardie Robert J. , McAnulty Jonathan F.
Published: August 2015

Objective

To compare 1) complications between 2 ureteral harvest techniques (ureteral papilla harvest [UPH] and ureteral transection [UT]); 2) to investigate the prevalence of kidney failure in a population of kidney donors; and 3) to evaluate owner satisfaction with commercially sourced cats adopted after kidney donation.

Study Design

Retrospective case series.

Animals

Cats (n = 72) that had unilateral nephrectomy for kidney donation.

Methods

Medical records were reviewed and information on short‐ and long‐term complications and evidence of kidney failure was recorded. Clients were interviewed by telephone to ascertain their satisfaction with the adopted donor cats as pets.

Results

Seventy‐two cats had unilateral nephrectomy. Forty‐two owners were able to be contacted for survey data. Twenty‐eight cats had complete medical records including serum BUN, creatinine, and urine specific gravity. For these 28 cats, mean age at nephrectomy was 1.9 years (median, 1.1 years; range, 0.5–9.3 years) and mean age at follow‐up was 6.8 years (median, 5.1 years; range, 1.0–18.7 years). There was no difference in major or minor complication rates between UPH and UT techniques. Kidney failure occurred in 17.8% of cats. All owners were satisfied with the adopted donor cats, which were obtained from commercial facilities.

Conclusions

UPH is a safe technique in cats being used for kidney donation. Commercially sourced cats make suitable pets after kidney donation. The prevalence of kidney failure in the donor population appears to be higher than that in the general population, but definitive conclusions cannot be made based on this study. Further, prospective study is needed to identify the true prevalence of kidney failure in cats after unilateral nephrectomy.
Adverbial relative clauses in world Englishes
Authors: SUÁREZ‐GÓMEZ CRISTINA
Published: August 2015

This paper investigates adverbial relative clauses in world Englishes, in particular relative clauses expressing place (the place where), time (the time when), manner (the way in which) and reason (the reason why). Using data from the ICE corpora, it compares the varieties spoken in India, Hong‐Kong and Singapore. In particular we consider: (i) the meaning expressed by the relative clause; (ii) the nominal antecedent, both its meaning and form; and (iii) the relative word used to introduce the relative clause (adverbial relative word,wh‐ pronoun,thatand zero). An examination of these issues reveals distinguishing features in the distribution of relative words that are related to the different constructions, to the specific postcolonial varieties that have been developed in the different countries and, finally, to the interaction between the superstrate and the different substrate languages.
Three-Dimensional Printing Based Hybrid Manufacturing of Microfluidic Devices
Authors: Alapan Yunus , Hasan Muhammad Noman , Shen Richang , Gurkan Umut A.
Published: August 2015

Microfluidic platforms offer revolutionary and practical solutions to challenging problems in biology and medicine. Even though traditional micro/nanofabrication technologies expedited the emergence of the microfluidics field, recent advances in advanced additive manufacturing hold significant potential for single-step, stand-alone microfluidic device fabrication. One such technology, which holds a significant promise for next generation microsystem fabrication is three-dimensional (3D) printing. Presently, building 3D printed stand-alone microfluidic devices with fully embedded microchannels for applications in biology and medicine has the following challenges: (i) limitations in achievable design complexity, (ii) need for a wider variety of transparent materials, (iii) limited z-resolution, (iv) absence of extremely smooth surface finish, and (v) limitations in precision fabrication of hollow and void sections with extremely high surface area to volume ratio. We developed a new way to fabricate stand-alone microfluidic devices with integrated manifolds and embedded microchannels by utilizing a 3D printing and laser micromachined lamination based hybrid manufacturing approach. In this new fabrication method, we exploit the minimized fabrication steps enabled by 3D printing, and reduced assembly complexities facilitated by laser micromachined lamination method. The new hybrid fabrication method enables key features for advanced microfluidic system architecture: (i) increased design complexity in 3D, (ii) improved control over microflow behavior in all three directions and in multiple layers, (iii) transverse multilayer flow and precisely integrated flow distribution, and (iv) enhanced transparency for high resolution imaging and analysis. Hybrid manufacturing approaches hold great potential in advancing microfluidic device fabrication in terms of standardization, fast production, and user-independent manufacturing.
Boiling Under Hele-Shaw Flow Conditions: The Occurrence of Viscous Fingering
Authors: Reinker Felix , Kapitz Marek , aus der Wiesche Stefan
Published: August 2015

Boiling and bubble dynamics were experimentally investigated in a Hele-Shaw flow cell using pure water at atmospheric pressure as the working fluid. The resulting vapor bubble shapes were recorded by means of a high-speed camera for several plate spacings and heating power levels. It was found that viscous fingering phenomena of vapor bubbles occurred only under very special boiling conditions and cell parameters. The evaporation front velocity was identified as a major parameter for the onset of viscous fingering. The observed basic viscous fingering dynamics was in reasonable agreement with theoretical analyses. In addition to that classical viscous large fingering, small-scale evaporation instability was observed leading to microscopic roughening of accelerating evaporation fronts. This instability might be explicitly related to evaporative heat and mass transfer effects across the fast-moving phase interface.
Design of an Improved Turbine Rim-Seal
Authors: Scobie James A. , Teuber Roy , Sheng Li Yan , Sangan Carl M. , Wilson Michael , Lock Gary D.
Published: August 2015

Rim seals are fitted in gas turbines at the periphery of the wheel-space formed between rotor disks and their adjacent casings. These seals, also called platform overlap seals, reduce the ingress of hot gases which can limit the life of highly stressed components in the engine. This paper describes the development of a new, patented rim-seal concept showing improved performance relative to a reference engine design, using unsteady Reynolds-averaged Navier–Stokes (URANS) computations of a turbine stage at engine conditions. The computational fluid dynamics (CFD) study was limited to a small number of purge-flow rates due to computational time and cost, and the computations were validated experimentally at a lower rotational Reynolds number and in conditions under incompressible flow. The new rim seal features a stator-side angel wing and two buffer cavities between outer and inner seals: the angel-wing promotes a counter-rotating vortex to reduce the effect of the ingress on the stator; the two buffer cavities are shown to attenuate the circumferential pressure asymmetries of the fluid ingested from the mainstream annulus. Rotor disk pumping is exploited to reduce the sealing flow rate required to prevent ingress, with the rotor boundary layer also providing protective cooling. Measurements of gas concentration and swirl ratio, determined from static and total pressure, were used to assess the performance of the new seal concept relative to a benchmark generic seal. The radial variation of concentration through the seal was measured in the experiments and these data captured the improvements due to the intermediate buffer cavities predicted by the CFD. This successful design approach is a potent combination of insight provided by computation, and the flexibility and expedience provided by experiment.
Bacterial response to different surface chemistries fabricated by plasma polymerization on electrospun nanofibers
Authors: Abrigo Martina , Kingshott Peter , McArthur Sally L.
Published: August 2015

Control over bacterial attachment and proliferation onto nanofibrous materials constitutes a major challenge for a variety of applications, including filtration membranes, protective clothing, wound dressings, and tissue engineering scaffolds. To develop effective devices, the interactions that occur between bacteria and nanofibers with different morphological and physicochemical properties need to be investigated. This paper explores the influence of fiber surface chemistry on bacterial behavior. Different chemical functionalities were generated on the surface of electrospun polystyrene nanofibers through plasma polymerization of four monomers (acrylic acid, allylamine, 1,7-octadiene, and 1,8-cineole). The interactions of Escherichia coli with the surface modified fibers were investigated through a combination of scanning electron microscopy and confocal laser scanning microscopy. Fiber wettability, surface charge, and chemistry were found to affect the ability of bacterial cells to attach and proliferate throughout the nanofiber meshes. The highest proportion of viable cells attachment occurred on the hydrophilic amine rich coating, followed by the hydrophobic octadiene. The acrylic acid coating rich in carboxyl groups showed a significantly lower attraction of bacterial cells. The 1,8-cineole retained the antibacterial activity of the monomer, resulting with a high proportion of dead isolated cells attached onto the fibers. Results showed that the surface chemistry properties of nanofibrous membranes can be strategically tuned to control bacterial behavior.
3D chemical characterization of frozen hydrated hydrogels using ToF-SIMS with argon cluster sputter depth profiling
Authors: Taylor Michael , Scurr David , Lutolf Matthias , Buttery Lee , Zelzer Mischa , Alexander Morgan
Published: August 2015

Hydrogels have been used extensively in bioengineering as artificial cell culture supports. Investigation of the interrelationship between cellular response to the hydrogel and its chemistry ideally requires methods that allow characterization without labels and can map species in three-dimensional to follow biomolecules adsorbed to, and absorbed into, the open structure before and during culture. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) has the potential to be utilized for through thickness characterization of hydrogels. The authors have established a simple sample preparation procedure to successfully achieve analysis of frozen hydrated hydrogels using ToF-SIMS without the need for dry glove box entry equipment. They demonstrate this on a poly(2-hydroxyethyl methacrylate) (pHEMA) film where a model protein (lysozyme) is incorporated using two methods to demonstrate how protein distribution can be determined. A comparison of lysozyme incorporation is made between the situation where the protein is present in a polymer dip coating solution and where lysozyme is in an aqueous medium in which the film is incubated. It is shown that protonated water clusters H(H2O)n+ where n = 5–11 that are indicative of ice are detected through the entire thickness of the pHEMA. The lysozyme distribution through the pHEMA hydrogel films can be determined using the intensity of a characteristic amino acid secondary ion fragment.
Capability of pure water calibrated time-of-flight sensors for the determination of speed of sound in seawater
Authors: von Rohden Christoph , Fehres Felix , Rudtsch Steffen
Published: August 2015

Results from a laboratory investigation of commercial time-of-flight sensors designed for oceanographic in situ speed-of-sound measurements are presented. An older analog model and three modern digital units were calibrated in pure water in the temperature range of 1 °C to 50 °C. The speed of sound (w) was measured in salt solutions of varying concentration (NaCl, MgCl2, Na2SO4) and in samples of original and diluted North Atlantic seawater at atmospheric pressure. A high reproducibility of the time-of-flight readings was found, resulting in sound speed standard deviations in pure water between 0.033 m s−1 and 0.015 m s−1, depending on the individual instruments. This depicts the potential of the time-of-flight method. However, although simultaneously calibrated, the measurements revealed systematic speed-of-sound differences between the different sensors which exceeded the reproducibility by about 1 order of magnitude. As the cause of these deviations could not be determined within this study, this exhibits a constraint for the uncertainty of measurements in seawater relative to pure water. In comparison with recent equations this has been estimated at 0.3 m s−1 (200 ppm) in original seawater. In seawater at temperatures >40 °C and in diluted seawater the results indicate relevant differences from the recent Thermodynamic Equation of Seawater–2010 equation of state.
Higher-level linguistic categories dominate lower-level acoustics in lexical tone processing
Authors: Zhao T. Christina , Kuhl Patricia K.
Published: August 2015

Native tonal-language speakers exhibit reduced sensitivity to lexical tone differences within, compared to across, categories (higher-level linguistic category influence). Yet, sensitivity is enhanced among musically trained, non-tonal-language-speaking individuals (lower-level acoustics processing influence). The current study investigated the relative contribution of higher- and lower-level influences when both are present. Seventeen Mandarin musicians completed music pitch and lexical tone discrimination tasks. Similar to English musicians [Zhao and Kuhl (2015). J. Acoust. Soc. Am. 137(3), 1452–1463], Mandarin musicians' overall sensitivity to lexical tone differences was associated with music pitch score, suggesting lower-level contributions. However, the musician's sensitivities to lexical tone pairs along a continuum were similar to Mandarin non-musicians, reflecting dominant higher-level influences.
Alzheimer’s and Parkinson’s diseases: The prion concept in relation to assembled Aβ, tau, and α-synuclein
Authors: Goedert Michel
Published: August 2015

Converging paradigms in neurodegeneration

Parkinson's disease and Alzheimer's disease are progressive neurodegenerative diseases with increasing prevalence in our aging populations. Recent evidence suggests that some of the molecular mechanisms involved in the pathology of these diseases have similarities to those observed in infectious prion diseases such as bovine spongiform encephalopathy (mad cow disease). Goedert reviews how the spread of a variety of pathological protein aggregates is involved in neurodegenerative disease.

Science
, this issue p.
10.1126/science.1255555
Brazil looks to project scientific power on the Atlantic
Authors: Escobar Herton
Published: August 2015

New world-class research vessel to do double duty in mineral prospecting.
The dimming of NEON
Authors: Mervis Jeffrey
Published: August 2015

NSF shrinks major U.S. ecology project.
Adaptive synergy between catechol and lysine promotes wet adhesion by surface salt displacement
Authors: Maier Greg P. , Rapp Michael V. , Waite J. Herbert , Israelachvili Jacob N. , Butler Alison
Published: August 2015

Keeping it sticky when wet

Some biological molecules are remarkably sticky, even to surfaces submerged in water. Mussel adhesion, for example, is based on the overproduction of dihydroxyphenylalanine (DOPA) and proteins with a high abundance of cationic amine residues such as lysine. Using bacterial iron chelators consisting of paired DOPA and lysine groups as analogs for the mussel proteins, Maier
et al.
show that these two functional groups synergistically enhance interfacial adhesion (see the Perspective by Wilker). The lysine appears to displace hydrated cations from the surface, thus giving a dry patch for better adhesion.

Science
, this issue p.
628
; see also p.
582
Efficient hot-electron transfer by a plasmon-induced interfacial charge-transfer transition
Authors: Wu K. , Chen J. , McBride J. R. , Lian T.
Published: August 2015

Improving electron harvesting

Small metal nanostructures generate electrons from light by creating surface plasmons, which can transfer “hot electrons” to a semiconductor. The efficiency of this process, however, is often low because of electron-electron scattering. Wu
et al.
demonstrate a pathway that allows the plasmon to directly excite an electron in a strongly coupled semiconductor acceptor (see the Perspective by Kale). Cadmiun selenide nanorods bearing gold nanoparticles on their ends strongly damped plasmons via interfacial electron transfer with a quantum efficiency exceeding 24%.

Science
, this issue p.
632
; see also p.
587
Identity crisis

The Man Who Wasn't There

Investigations into the Strange New Science of the Self
Anil Ananthaswamy
Dutton, 2015. 317 pp.
Authors: Vikbladh Oliver
Published: August 2015

A scientific exploration of our sense of self.
Built infrastructure is essential
Authors: Muller Mike , Biswas Asit , Martin-Hurtado Roberto , Tortajada Cecilia
Published: August 2015

Built water infrastructure supported the evolution of all human societies and will remain an integral part of socioeconomic development and modernization. Some postindustrial societies not only seek to “preserve” existing aquatic ecosystems in their otherwise transformed landscapes but also insist that others do the same. They suggest that “green infrastructure” can provide “equivalent or similar benefits to conventional (built) ‘gray’ water infrastructure” (

1

).
The field guide, rebooted
Map of Life
iOS/Android compatible, 2015. http://mol.org
Authors: Goldsmith Gregory R.
Published: August 2015

Identifying species in the field? There's an app for that.
Expanding the optogenetics toolkit
Authors: Berndt Andre , Deisseroth Karl
Published: August 2015

A naturally occurring channel for inhibitory optogenetics is discovered

[Also see Report by

Govorunova
et al.

]
Too noisy for toddlers
Authors: Bhatti Pamela
Published: August 2015

Excessive background noise may affect speech perception and language development in toddlers.
Laboratory Investigation of the First Case of Botulism Caused by Clostridium butyricum Type E Toxin in the United States
Authors: Dykes Janet K. , Lúquez Carolina , Raphael Brian H. , McCroskey Loretta , Maslanka Susan E.
Published: August 2015

We report here the laboratory investigation of the first known case of botulism in the United States caused by
Clostridium butyricum
type E. This investigation demonstrates the importance of extensive microbiological examination of specimens, which resulted in the isolation of this organism.
Application of Isothermal Amplification Techniques for Identification of Madurella mycetomatis, the Prevalent Agent of Human Mycetoma
Authors: Ahmed Sarah A. , van de Sande Wendy W. J. , Desnos-Ollivier Marie , Fahal Ahmed H. , Mhmoud Najwa A. , de Hoog G. S.
Published: August 2015

Appropriate diagnosis and treatment of eumycetoma may vary significantly depending on the causative agent. To date, the most common fungus causing mycetoma worldwide is
Madurella mycetomatis
. This species fails to express any recognizable morphological characteristics, and reliable identification can therefore only be achieved with the application of molecular techniques. Recombinase polymerase amplification (RPA) and loop-mediated isothermal amplification (LAMP) are proposed as alternatives to phenotypic methods. Species-specific primers were developed to target the ribosomal DNA (rDNA) internal transcribed spacer (ITS) region of
M. mycetomatis
. Both isothermal amplification techniques showed high specificity and sufficient sensitivity to amplify fungal DNA and proved to be appropriate for detection of
M. mycetomatis
. Diagnostic performance of the techniques was assessed in comparison to conventional PCR using biopsy specimens from eumycetoma patients. RPA is reliable and easy to operate and has the potential to be implemented in areas where mycetoma is endemic. The techniques may be expanded to detect fungal DNA from environmental samples.
Lab-on-Chip-Based Platform for Fast Molecular Diagnosis of Multidrug-Resistant Tuberculosis
Authors: Cabibbe Andrea M. , Miotto Paolo , Moure Raquel , Alcaide Fernando , Feuerriegel Silke , Pozzi Gianni , Nikolayevskyy Vladislav , Drobniewski Francis , Niemann Stefan , Reither Klaus , Cirillo Daniela M.
Published: August 2015

We evaluated the performance of the molecular lab-on-chip-based VerePLEX Biosystem for detection of multidrug-resistant tuberculosis (MDR-TB), obtaining a diagnostic accuracy of more than 97.8% compared to sequencing and MTBDR
plus
assay for
Mycobacterium tuberculosis
complex and rifampin and isoniazid resistance detection on clinical isolates and smear-positive specimens. The speed, user-friendly interface, and versatility make it suitable for routine laboratory use.
Hemagglutinin-Neuraminidase Balance Influences the Virulence Phenotype of a Recombinant H5N3 Influenza A Virus Possessing a Polybasic HA
0
Cleavage Site
Authors: Diederich Sandra , Berhane Yohannes , Embury-Hyatt Carissa , Hisanaga Tamiko , Handel Katherine , Cottam-Birt Colleen , Ranadheera Charlene , Kobasa Darwyn , Pasick John
Published: August 2015

Although a polybasic HA
0
cleavage site is considered the dominant virulence determinant for highly pathogenic avian influenza (HPAI) H5 and H7 viruses, naturally occurring virus isolates possessing a polybasic HA
0
cleavage site have been identified that are low pathogenic in chickens. In this study, we generated a reassortant H5N3 virus that possessed the hemagglutinin (HA) gene from H5N1 HPAI A/swan/Germany/R65/2006 and the remaining gene segments from low pathogenic A/chicken/British Columbia/CN0006/2004 (H7N3). Despite possessing the HA
0
cleavage site GERRRKKR/GLF, this rH5N3 virus exhibited a low pathogenic phenotype in chickens. Although rH5N3-inoculated birds replicated and shed virus and seroconverted, transmission to naive contacts did not occur. To determine whether this virus could evolve into a HPAI form, it underwent six serial passages in chickens. A progressive increase in virulence was observed with the virus from passage number six being highly transmissible. Whole-genome sequencing demonstrated the fixation of 12 nonsynonymous mutations involving all eight gene segments during passaging. One of these involved the catalytic site of the neuraminidase (NA; R293K) and is associated with decreased neuraminidase activity and resistance to oseltamivir. Although introducing the R293K mutation into the original low-pathogenicity rH5N3 increased its virulence, transmission to naive contact birds was inefficient, suggesting that one or more of the remaining changes that had accumulated in the passage number six virus also play an important role in transmissibility. Our findings show that the functional linkage and balance between HA and NA proteins contributes to expression of the HPAI phenotype.

IMPORTANCE
To date, the contribution that hemagglutinin-neuraminidase balance can have on the expression of a highly pathogenic avian influenza virus phenotype has not been thoroughly examined. Reassortment, which can result in new hemagglutinin-neuraminidase combinations, may have unpredictable effects on virulence and transmission characteristics of a virus. Our data show the importance of the neuraminidase in complementing a polybasic HA
0
cleavage site. Furthermore, it demonstrates that adaptive changes selected for during the course of virus evolution can result in unexpected traits such as antiviral drug resistance.
Neuraminidase of Influenza A Virus Binds Lysosome-Associated Membrane Proteins Directly and Induces Lysosome Rupture
Authors: Ju Xiangwu , Yan Yiwu , Liu Qiang , Li Ning , Sheng Miaomiao , Zhang Lifang , Li Xiao , Liang Zhu , Huang Fengming , Liu Kangtai , Zhao Yan , Zhang Yanxu , Zou Zhen , Du Jianchao , Zhong Ying , Zhou Huandi , Yang Peng , Lu Huijun , Tian Mingyao , Li Dangsheng , Zhang Jianming , Jin Ningyi , Jiang Chengyu
Published: August 2015

As a recycling center, lysosomes are filled with numerous acid hydrolase enzymes that break down waste materials and invading pathogens. Recently, lysosomal cell death has been defined as “lysosomal membrane permeabilization and the consequent leakage of lysosome contents into cytosol.” Here, we show that the neuraminidase (NA) of H5N1 influenza A virus markedly deglycosylates and degrades lysosome-associated membrane proteins (LAMPs; the most abundant membrane proteins of lysosome), which induces lysosomal rupture, and finally leads to cell death of alveolar epithelial carcinoma A549 cells and human tracheal epithelial cells. The NA inhibitors peramivir and zanamivir could effectively block the deglycosylation of LAMPs, inhibit the virus cell entry, and prevent cell death induced by the H5N1 influenza virus. The NA of seasonal H1N1 virus, however, does not share these characteristics. Our findings not only reveal a novel role of NA in the early stage of the H5N1 influenza virus life cycle but also elucidate the molecular mechanism of lysosomal rupture crucial for influenza virus induced cell death.

IMPORTANCE
The integrity of lysosomes is vital for maintaining cell homeostasis, cellular defense and clearance of invading pathogens. This study shows that the H5N1 influenza virus could induce lysosomal rupture through deglycosylating lysosome-associated membrane proteins (LAMPs) mediated by the neuraminidase activity of NA protein. NA inhibitors such as peramivir and zanamivir could inhibit the deglycosylation of LAMPs and protect lysosomes, which also further interferes with the H5N1 influenza virus infection at early stage of life cycle. This work is significant because it presents new concepts for NA's function, as well as for influenza inhibitors' mechanism of action, and could partially explain the high mortality and high viral load after H5N1 virus infection in human beings and why NA inhibitors have more potent therapeutic effects for lethal avian influenza virus infections at early stage.
Importation and Recombination Are Responsible for the Latest Emergence of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus in China
Authors: Zhao Kuan , Ye Chao , Chang Xiao-Bo , Jiang Cheng-Gang , Wang Shu-Jie , Cai Xue-Hui , Tong Guang-Zhi , Tian Zhi-Jun , Shi Mang , An Tong-Qing
Published: August 2015

In China, a majority of the highly pathogenic porcine reproductive and respiratory syndrome (HP-PRRSV) strains were seeded by the 2006 outbreak. However, the most recently emerged (2013-2014) HP-PRRSV strain has a very different genetic background. It is a NADC30-like PRRSV strain recently introduced from North America that has undergone genetic exchange with the classic HP-PRRSV strains in China. Subsequent isolation and characterization of this variant suggest high pathogenicity, so it merits special attention in control and vaccine strategies.
Constitutive Activation of Interleukin-13/STAT6 Contributes to Kaposi's Sarcoma-Associated Herpesvirus-Related Primary Effusion Lymphoma Cell Proliferation and Survival
Authors: Wang Chong , Zhu Caixia , Wei Fang , Zhang Liming , Mo Xiaohui , Feng Yanling , Xu Jianqing , Yuan Zhenghong , Robertson Erle , Cai Qiliang
Published: August 2015

Activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway has been associated with numerous human malignancies, including primary effusion lymphomas (PELs). PEL, a cancerous proliferation of B cells, is caused by Kaposi's sarcoma-associated herpesvirus (KSHV). Previously we identified constitutive phosphorylation of STAT6 on tyrosine 641 (p-STAT6
C
) in PEL cell lines BC3 and BCBL1; however, the molecular mechanism leading to this activation remains unclear. Here we demonstrate that STAT6 activation tightly correlates with interleukin-13 (IL-13) secretion, JAK1/2 tyrosine phosphorylation, and reduced expression of SHP1 due to KSHV infection. Moreover, p-STAT6
C
and reduction of SHP1 were also observed in KS patient tissue. Notably, blockade of IL-13 by antibody neutralization dramatically inhibits PEL cell proliferation and survival. Taken together, these results suggest that IL-13/STAT6 signaling is modulated by KSHV to promote host cell proliferation and viral pathogenesis.

IMPORTANCE
STAT6 is a member of signal transducer and activator of transcription (STAT) family, whose activation is linked to KSHV-associated cancers. The mechanism through which STAT6 is modulated by KSHV remains unclear. In this study, we demonstrated that constitutive activation of STAT6 in KSHV-associated PEL cells results from interleukin-13 (IL-13) secretion and reduced expression of SHP1. Importantly, we also found that depletion of IL-13 reduces PEL cell growth and survival. This discovery provides new insight that IL-13/STAT6 plays an essential role in KSHV pathogenesis.
Topography of the Human Papillomavirus Minor Capsid Protein L2 during Vesicular Trafficking of Infectious Entry
Authors: DiGiuseppe Stephen , Keiffer Timothy R. , Bienkowska-Haba Malgorzata , Luszczek Wioleta , Guion Lucile G. M. , Müller Martin , Sapp Martin
Published: August 2015

The human papillomavirus (HPV) capsid is composed of the major capsid protein L1 and the minor capsid protein L2. During entry, the HPV capsid undergoes numerous conformational changes that result in endosomal uptake and subsequent trafficking of the L2 protein in complex with the viral DNA to the
trans
-Golgi network. To facilitate this transport, the L2 protein harbors a number of putative motifs that, if capable of direct interaction, would interact with cytosolic host cell factors. These data imply that a portion of L2 becomes cytosolic during infection. Using a low concentration of digitonin to selectively permeabilize the plasma membrane of infected cells, we mapped the topography of the L2 protein during infection. We observed that epitopes within amino acid residues 64 to 81 and 163 to 170 and a C-terminal tag of HPV16 L2 are exposed on the cytosolic side of intracellular membranes, whereas an epitope within residues 20 to 38, which are upstream of a putative transmembrane region, is luminal. Corroborating these findings, we also found that L2 protein is sensitive to trypsin digestion during infection. These data demonstrate that the majority of the L2 protein becomes accessible on the cytosolic side of intracellular membranes in order to interact with cytosolic factors to facilitate vesicular trafficking.

IMPORTANCE
In order to complete infectious entry, nonenveloped viruses have to pass cellular membranes. This is often achieved through the viral capsid protein associating with or integrating into intracellular membrane. Here, we determine the topography of HPV L2 protein in the endocytic vesicular compartment, suggesting that L2 becomes a transmembrane protein with a short luminal portion and with the majority facing the cytosolic side for interaction with host cell transport factors.
A Druggable Pocket at the Nucleocapsid/Phosphoprotein Interaction Site of Human Respiratory Syncytial Virus
Authors: Ouizougun-Oubari Mohamed , Pereira Nelson , Tarus Bogdan , Galloux Marie , Lassoued Safa , Fix Jenna , Tortorici M. Alejandra , Hoos Sylviane , Baron Bruno , England Patrick , Desmaële Didier , Couvreur Patrick , Bontems François , Rey Félix A. , Eléouët Jean-François , Sizun Christina , Slama-Schwok Anny , Duquerroy Stéphane
Published: August 2015

Presently, respiratory syncytial virus (RSV), the main cause of severe respiratory infections in infants, cannot be treated efficiently with antivirals. However, its RNA-dependent polymerase complex offers potential targets for RSV-specific drugs. This includes the recognition of its template, the ribonucleoprotein complex (RNP), consisting of genomic RNA encapsidated by the RSV nucleoprotein, N. This recognition proceeds via interaction between the phosphoprotein P, which is the main polymerase cofactor, and N. The determinant role of the C terminus of P, and more particularly of the last residue, F241, in RNP binding and viral RNA synthesis has been assessed previously. Here, we provide detailed structural insight into this crucial interaction for RSV polymerase activity. We solved the crystallographic structures of complexes between the N-terminal domain of N (N-NTD) and C-terminal peptides of P and characterized binding by biophysical approaches. Our results provide a rationale for the pivotal role of F241, which inserts into a well-defined N-NTD pocket. This primary binding site is completed by transient contacts with upstream P residues outside the pocket. Based on the structural information of the N-NTD:P complex, we identified inhibitors of this interaction, selected by
in silico
screening of small compounds, that efficiently bind to N and compete with P
in vitro
. One of the compounds displayed inhibitory activity on RSV replication, thereby strengthening the relevance of N-NTD for structure-based design of RSV-specific antivirals.

IMPORTANCE
Respiratory syncytial virus (RSV) is a widespread pathogen that is a leading cause of acute lower respiratory infections in infants worldwide. RSV cannot be treated efficiently with antivirals, and no vaccine is presently available, with the development of pediatric vaccines being particularly challenging. Therefore, there is a need for new therapeutic strategies that specifically target RSV. The interaction between the RSV phosphoprotein P and the ribonucleoprotein complex is critical for viral replication. In this study, we identified the main structural determinants of this interaction, and we used them to screen potential inhibitors
in silico
. We found a family of molecules that were efficient competitors of P
in vitro
and showed inhibitory activity on RSV replication in cellular assays. These compounds provide a basis for a pharmacophore model that must be improved but that holds promises for the design of new RSV-specific antivirals.