bluuebunny/crossref_metadata_2025 huggingface dataset:
Diffusion‐weighted magnetic resonance imaging is effective to detect ileocolonic ulcerations in Crohn's disease
Authors: Buisson A. , Hordonneau C. , Goutte M. , Boyer L. , Pereira B. , Bommelaer G.
Published: June 2015

Background

Magnetic resonance entero‐colonography enables accurate assessment of ileocolonic Crohn's disease, but the need for bowel cleansing and rectal enema limits considerably its use in daily practice.

Aim

We evaluated the accuracy of diffusion‐weighted magnetic resonance entero‐colonography with neither bowel cleansing nor rectal enema to assess endoscopic activity.

Methods

Forty‐four Crohn's disease patients underwent prospectively and consecutively diffusion‐weighted magnetic resonance entero‐colonography [with apparent diffusion coefficient (ADC) and Clermont score calculation] and ileocolonoscopy [with Crohn's Disease Endoscopic Index of Severity (CDEIS) and Simplified Endoscopic score for Crohn's Disease (SES‐CD) calculation].

Results

Mean ADC was inversely correlated with total CDEIS (ρ = −0.40; P = 0.0067) and total SES‐CD (ρ = −0.33; P = 0.032). Considering the 194 segments, ADC was inversely correlated with segmental CDEIS (−0.48; P < 0.001) and segmental SES‐CD (−0.44; P < 0.001). ADC values were lower in segments with deep ulcers (1.30 ± 0.23) or superficial ulcerations (1.75 ± 0.64) than in non‐ulcerated segments (2.15 ± 0.5) (P = 0.001). Using a receiver operating curve, we determined that segmental ADC <1.42 detected endoscopic deep ulcerations with sensitivity = 0.91 and specificity = 0.83 (Area under the curve = 0.84; P < 0.001). Segmental ADC <1.88 detected endoscopic superficial ulcerations with sensitivity = 0.64 and specificity = 0.75. The segmental ADC values decreased when the ulcerations size increased (P = 0.0001). Clermont score correlated with ileal CDEIS (0.63; P < 0.05) and ileal SES‐CD (0.58; P < 0.05). Clermont score was higher in ulcerated segments (23.3 ± 8.4) than in non‐ulcerated segments (12.4 ± 10.0) (P = 0.006) and increased with ulcers size (P = 0.012). Clermont score >18.9 detected ulcerations with sensitivity = 0.79 and specificity = 0.73.

Conclusion

Diffusion‐weighted magnetic resonance entero‐colonography using apparent diffusion coefficient and Clermont score was effective to indirectly detect endoscopic ulcerations in ileocolonic Crohn's disease.
Muscle synergies and complexity of neuromuscular control during gait in cerebral palsy
Authors: Steele Katherine M , Rozumalski Adam , Schwartz Michael H
Published: June 2015

Aim

Individuals with cerebral palsy (CP) have impaired movement due to a brain injury near birth. Understanding how neuromuscular control is altered in CP can provide insight into pathological movement. We sought to determine if individuals with CP demonstrate reduced complexity of neuromuscular control during gait compared with unimpaired individuals and if changes in control are related to functional ability.

Method

Muscle synergies during gait were retrospectively analyzed for 633 individuals (age range 3.9–70y): 549 with CP (hemiplegia, n=122; diplegia, n=266; triplegia, n=73; quadriplegia, n=88) and 84 unimpaired individuals. Synergies were calculated using non‐negative matrix factorization from surface electromyography collected during previous clinical gait analyses. Synergy complexity during gait was compared with diagnosis subtype, functional ability, and clinical examination measures.

Result

Fewer synergies were required to describe muscle activity during gait in individuals with CP compared with unimpaired individuals. Changes in synergies were related to functional impairment and clinical examination measures including selective motor control, strength, and spasticity.

Interpretation

Individuals with CP use a simplified control strategy during gait compared with unimpaired individuals. These results were similar to synergies during walking among adult stroke survivors, suggesting similar neuromuscular control strategies between these clinical populations.
FOOD PRICES, WAGES, AND WELFARE IN RURAL INDIA
Authors: Jacoby Hanan G.
Published: June 2015

With soaring food prices in recent years has come alarm about rising poverty in the developing world. Less appreciated, however, is that many of the poor in agricultural economies may benefit from higher wages. This study finds that wages for manual labor in rural India, both within and outside agriculture, rose faster in districts growing more of those crops with large producer price run‐ups over the 2004–2009 period. Based on a general equilibrium framework that accounts for such wage gains, rural households across the income spectrum are found, contrary to more conventional welfare analysis, to benefit from higher agricultural prices. (JEL Q17, Q18, F14)
Bendamustine in multiple myeloma
Authors: Gentile Massimo , Vigna Ernesto , Recchia Anna Grazia , Morabito Lucio , Mendicino Francesco , Giagnuolo Giovanna , Morabito Fortunato
Published: June 2015

The advent of high‐dose melphalan with autologous stem‐cell transplantation (ASCT), the availability of novel agents such as thalidomide, lenalidomide (immunomodulatory drugs or IMiDs) and bortezomib (proteasome inhibitor) and improvements in supportive care have allowed to increase overall survival in multiple myeloma (MM) patients; nevertheless, MM remains an incurable pathology. For this reason, newer agents are required for continued disease control. Bendamustine is an old drug rediscovered in the last decade. In fact, its unique mechanism of action with structural similarities to both alkylating agents and antimetabolities, but which is not cross‐resistant to alkylating agents, has reawakened interest in the use of this drug in the treatment of MM. Studies have proven the safety and efficacy of bendamustine administered alone or in combination with new drugs in both upfront and relapse/refractory settings of MM patients, including those with renal impairment. Moreover, bendamustine has been successfully used as conditioning for autologous stem‐cell transplantation. Finally, the use of bendamustine does not compromise peripheral blood stem‐cell collection. This drug is generally well tolerated, with the majority of adverse events being due to myelosuppression. Non‐haematological adverse events are infrequent and usually mild.
Antimicrobial resistance in bacteria from horses: Epidemiology of antimicrobial resistance
Authors: Maddox T. W. , Clegg P. D. , Williams N. J. , Pinchbeck G. L.
Published: June 2015

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections. While the epidemiology of antimicrobial resistance in bacteria from man has been studied extensively, less work has been undertaken in companion animals, particularly horses. Methicillin‐resistantStaphylococcus aureushas been identified as a cause of infections, with a low prevalence of nasal carriage by horses in the community but higher for hospitalised horses. Molecular characterisation has shown methicillin‐resistantStaphylococcus aureusstrains either to be predominantly of types associated with horses or of sequence typeST398. Antimicrobial‐resistantEscherichia coli(including multidrug‐resistant and extended spectrum β‐lactamase‐producing isolates) have caused infections and been documented in faecal carriage by horses, with many significant resistance mechanisms identified. More sporadic reports and molecular characterisation exist for resistance in other bacteria such as enterococci,Salmonella,AcinetobacterandPseudomonasspecies. Limited work has been undertaken evaluating risk factors and much of the epidemiology of antimicrobial resistance in bacteria from horses remains to be determined.
Abnormal Connectivity Within Executive Resting‐State Network in Migraine With Aura
Authors: Tessitore Alessandro , Russo Antonio , Conte Francesca , Giordano Alfonso , De Stefano Manuela , Lavorgna Luigi , Corbo Daniele , Caiazzo Giuseppina , Esposito Fabrizio , Tedeschi Gioacchino
Published: June 2015

Objective

To evaluate the executive control network connectivity integrity in patients with migraine with aura, in the interictal period, in comparison to patients with migraine without aura and healthy controls.

Methods

Using resting‐state functional magnetic resonance imaging, we compared executive control network functional connectivity in 20 patients with migraine with aura vs 20 sex and age‐matched patients with migraine without aura and 20 healthy controls, and assessed the correlation between executive control network functional connectivity and clinical features of patients with migraine. We used voxel‐based morphometry and diffusion tensor imaging to investigate potential structural or microstructural changes.

Results

Neuropsychological data revealed no significant executive dysfunction in patients with migraine. Resting‐state functional magnetic resonance imaging showed significant group differences in right middle frontal gyrus (Talairach coordinates x, y, z: +26, +2, +48) and dorsal anterior cingulate cortex (Talairach coordinates x, y, z: +6, +13, +49), indicating that these areas had a decreased component activity in both patients with migraine with and without aura when compared with healthy controls. Conversely, there were no significant differences in the executive control network functional connectivity between patients with migraine with and without aura (P < .05, cluster‐level corrected). These functional abnormalities are independent of structural and microstructural changes and did not significantly correlate with clinical parameters.

Conclusions

Our data demonstrate a disrupted executive control network functional connectivity in patients with migraine with and without aura, in the interictal period. Although this functional phenomenon is present in the absence of clinically relevant executive deficits, it may reflect a vulnerability to executive high‐demanding conditions of daily living activities in patients with migraine.
How Organizational Cognitive Neuroscience Can Deepen Understanding of Managerial Decision‐making: A Review of the Recent Literature and Future Directions
Authors: Butler Michael J.R. , O'Broin Holly L.R. , Lee Nick , Senior Carl
Published: June 2015

There is growing interest in exploring the potential links between human biology and management and organization studies, which is bringing greater attention to bear on the place of mental processes in explaining human behaviour and effectiveness. The authors define this new field as organizational cognitive neuroscience (OCN), which is in the exploratory phase of its emergence and diffusion. It is clear that there are methodological debates and issues associated with OCN research, and the aim of this paper is to illuminate these concerns, and provide a roadmap for rigorous and relevant future work in the area. To this end, the current reach of OCN is investigated by the systematic review methodology, revealing three clusters of activity, covering the fields of economics, marketing and organizational behaviour. Among these clusters, organizational behaviour seems to be an outlier, owing to its far greater variety of empirical work, which the authors argue is largely a result of the plurality of research methods that have taken root within this field. Nevertheless, all three clusters contribute to a greater understanding of the biological mechanisms that mediate choice and decision‐making. The paper concludes that OCN research has already provided important insights regarding the boundaries surrounding human freedom to act in various domains and, in turn, self‐determination to influence the workplace. However, there is much to be done, and emerging research of significant interest is highlighted.
The protein arginine methyltransferase PRMT5 regulates Aβ‐induced toxicity in human cells and Caenorhabditis elegans models of Alzheimer's disease
Authors: Quan Xin , Yue Wenhui , Luo Yunfeng , Cao Jianwei , Wang Hongyun , Wang Yue , Lu Zhongbing
Published: June 2015

The protein arginine methyltransferase 5 (PRMT5) controls cell growth and apoptosis by catalyzing mono and symmetric dimethylation of arginine residues. In human brain tissue, PRMT5 is predominantly expressed in neuronal cells. There is evidence that PRMT5 provides protection against cell death, but the impact of PRMT5 on neuronal apoptosis during the evolution of Alzheimer's disease has not been tested. In the present study, we show that PRMT5 is down‐regulated by β‐amyloid (Aβ) in primary neurons and SH‐SY5Y cells, and this is associated with the up‐regulation of the PRMT5 target protein E2F‐1. Furthermore, knockdown of PRMT5 in SH‐SY5Y cells over‐expressing the Swedish mutant form of human amyloid‐β precursor protein caused activation of E2F‐1/p53/Bax, NF‐κB, and GSK‐3β pathways, which coincided with increased apoptosis. Co‐depletion of E2F‐1 reduced the activation of p53/Bax, NF‐κB, and GSK‐3β, and limited cell apoptosis. In addition, inhibiting NF‐κB and GSK‐3β activity by specific inhibitors also attenuated cell apoptosis, suggesting that E2F‐1/NF‐κB/GSK‐3β pathways mediate for apoptosis induced by PRMT5 depletion. More importantly, knockdown of PRMT5 resulted in more paralysis in a transgenic Caenorhabditis elegans strain CL2006, indicating that PRMT5 provides protection against Aβ toxicity in vivo. Collectively, our findings identify PRMT5 as a novel regulator of Aβ toxicity and suggest that strategies aimed at activating PRMT5 in the neuron may represent a potential therapeutic approach for the prevention of Alzheimer's disease.

image

We propose the following cascade for protein arginine methyltransferase 5 (PRMT5)‐mediated neuronal death: amyloid beta (Aβ) deposition decreases PRMT5 expression in neurons, which increases E2F‐1 expression – a PRMT5 target protein – and subsequently activates GSK‐3β and NF‐κB to induce caspase‐3‐dependent neuronal apoptosis. These findings might provide a strategy for the treatment of Alzheimer's disease.
Symmetry matters
Authors: Moubayidin Laila , Østergaard Lars
Published: June 2015

The development of multicellular organisms depends on correct establishment of symmetry both at the whole‐body scale and within individual tissues and organs. Setting up planes of symmetry must rely on communication between cells that are located at a distance from each other within the organism, presumably via mobile morphogenic signals. Although symmetry in nature has fascinated scientists for centuries, it is only now that molecular data to unravel mechanisms of symmetry establishment are beginning to emerge. As an example we describe the genetic and hormonal interactions leading to an unusual bilateral‐to‐radial symmetry transition of an organ in order to promote reproduction.

Contents

Summary
985

I.
Introduction
985

II.
Bilateral and radial symmetries
986

III.
Symmetry breaking
987

IV.
Symmetry transitions
988

V.
Conclusions
989

Acknowledgements
989

References
989
The effect of lichen‐dominated biological soil crusts on growth and physiological characteristics of three plant species in a temperate desert of northwest China
Authors: Zhuang W. W. , Serpe M. , Zhang Y. M.
Published: June 2015

Biocrusts (biological soil crusts) cover open spaces between vascular plants in most arid and semi‐arid areas. Information on effects of biocrusts on seedling growth is controversial, and there is little information on their effects on plant growth and physiology. We examined impacts of biocrusts on growth and physiological characteristics of three habitat‐typical plants, Erodium oxyrhynchum, Alyssum linifolium and Hyalea pulchella, growing in the Gurbantunggut Desert, northwest China. The influence of biocrusts on plant biomass, leaf area, leaf relative water content, photosynthesis, maximum quantum efficiency of PSII (Fv/Fm), chlorophyll, osmotic solutes (soluble sugars, protein, proline) and antioxidant enzymes (superoxide dismutase, catalase, peroxidase) was investigated on sites with or without biocrust cover. Biomass, leaf area, leaf water content, photosynthesis, Fv/Fm and chlorophyll content in crusted soils were higher than in uncrusted soils during early growth and lower later in the growth period. Soluble sugars, proline and antioxidant enzyme activity were always higher in crusted than in uncrusted soils, while soluble protein content was always lower. These findings indicate that biocrusts have different effects on these three ephemeral species during growth in this desert, primarily via effects on soil moisture, and possibly on soil nutrients. The influence of biocrusts changes during plant development: in early plant growth, biocrusts had either positive or no effect on growth and physiological parameters. However, biocrusts tended to negatively influence plants during later growth. Our results provide insights to explain why previous studies have found different effects of biocrusts on vascular plant growth.
A randomized, controlled clinical trial of intravenous lipid emulsion as an adjunctive treatment for permethrin toxicosis in cats
Authors: Peacock Rachel E. , Hosgood Giselle , Swindells Katrin L. , Smart Lisa
Published: June 2015

Objective

To assess for any clinical benefit of intravenous lipid emulsion (ILE) for permethrin toxicosis in cats by comparing the progression of clinical signs of cats before and after treatment with ILE to cats treated with a saline control. To accomplish this objective, a clinical staging system for cats with permethrin toxicosis was developed and validated.

Design

Prospective, multicenter, randomized, controlled clinical trial.

Setting

University veterinary teaching hospital and 12 private veterinary emergency hospitals.

Animals

Thirty‐four client‐owned cats with permethrin toxicosis.

Interventions

A clinical staging system was designed based on abnormalities found on physical examination of cats with permethrin toxicosis. The clinical staging system had 6 stages, ranging from Stage A for cats with no abnormalities to Stage F for cats with grand mal seizures. The system was validated for intraviewer and interviewer variability. Cats in the clinical trial were randomized to receive 15 mL/kg of either intravenous 0.9% saline (control) or 20% ILE over 60 minutes. For each cat, a clinical stage was recorded at set time points before and after the randomized treatment was administered. The distribution of clinical stage stratified over time was compared across treatment groups.

Measurements and Main Results

The clinical staging system showed excellent repeatability (P = 1.0) and reliability (P = 1.0). In the clinical trial, there was a significant difference in the distribution of clinical stages over time (P < 0.001) and from presentation stage to Stage B (P = 0.006), with ILE‐treated cats (n = 20) having lower clinical stages earlier than control cats (n = 14). There was no significant difference in signalment, body weight, or supportive treatment between the groups.

Conclusions

The clinical staging system was repeatable and reliable. Clinical stages of permethrin toxicosis in ILE‐treated cats improved earlier compared to control cats, suggesting ILE may be a useful adjunctive therapy in the treatment of permethrin toxicosis in cats.
The TRPV1 channel in rodents is a major target for antinociceptive effect of the probiotic Lactobacillus reuteri DSM 17938
Authors: Perez‐Burgos Azucena , Wang Lu , McVey Neufeld Karen‐Anne , Mao Yu‐Kang , Ahmadzai Mustafa , Janssen Luke J. , Stanisz Andrew M. , Bienenstock John , Kunze Wolfgang A.
Published: June 2015

Key points

Certain probiotic bacteria have been shown to reduce distension‐dependent gut pain, but the mechanisms involved remain obscure.

Live luminal Lactobacillus reuteri (DSM 17938) and its conditioned medium dose dependently reduced jejunal spinal nerve firing evoked by distension or capsaicin, and 80% of this response was blocked by a specific TRPV1 channel antagonist or in TRPV1 knockout mice.

The specificity of DSM action on TRPV1 was further confirmed by its inhibition of capsaicin‐induced intracellular calcium increases in dorsal root ganglion neurons. Another lactobacillus with ability to reduce gut pain did not modify this response.

Prior feeding of rats with DSM inhibited the bradycardia induced by painful gastric distension.

These results offer a system for the screening of new and improved candidate bacteria that may be useful as novel therapeutic adjuncts in gut pain.

Certain bacteria exert visceral antinociceptive activity, but the mechanisms involved are not determined. Lactobacillus reuteri DSM 17938 was examined since it may be antinociceptive in children. Since transient receptor potential vanilloid 1 (TRPV1) channel activity may mediate nociceptive signals, we hypothesized that TRPV1 current is inhibited by DSM. We tested this by examining the effect of DSM on the firing frequency of spinal nerve fibres in murine jejunal mesenteric nerve bundles following serosal application of capsaicin. We also measured the effects of DSM on capsaicin‐evoked increase in intracellular Ca2+ or ionic current in dorsal root ganglion (DRG) neurons. Furthermore, we tested the in vivo antinociceptive effects of oral DSM on gastric distension in rats. Live DSM reduced the response of capsaicin‐ and distension‐evoked firing of spinal nerve action potentials (238 ± 27.5% vs. 129 ± 17%). DSM also reduced the capsaicin‐evoked TRPV1 ionic current in DRG neuronal primary culture from 83 ± 11% to 41 ± 8% of the initial response to capsaicin only. Another lactobacillus (Lactobacillus rhamnosus JB‐1) with known visceral anti‐nociceptive activity did not have these effects. DSM also inhibited capsaicin‐evoked Ca2+ increase in DRG neurons; an increase in Ca2+ fluorescence intensity ratio of 2.36 ± 0.31 evoked by capsaicin was reduced to 1.25 ± 0.04. DSM releasable products (conditioned medium) mimicked DSM inhibition of capsaicin‐evoked excitability. The TRPV1 antagonist 6‐iodonordihydrocapsaicin or the use of TRPV1 knock‐out mice revealed that TRPV1 channels mediate about 80% of the inhibitory effect of DSM on mesenteric nerve response to high intensity gut distension. Finally, feeding with DSM inhibited perception in rats of painful gastric distension. Our results identify a specific target channel for a probiotic with potential therapeutic properties.
Designer proteins produce potent HIV defense
Authors: Cohen Jon
Published: June 2015

AIDS vaccine developers mimic natural route to powerful immune responses.
Sub–10 nm polyamide nanofilms with ultrafast solvent transport for molecular separation
Authors: Karan Santanu , Jiang Zhiwei , Livingston Andrew G.
Published: June 2015

Composite membranes for filtering solvents

Much research has focused on finding membranes that can purify water or extract waste carbon dioxide. However, there is also a need for the removal of small molecules from organic liquids. Many existing processes are energy-intensive and can require large quantities of solvents. Karan
et al.
grew confined polymer layers on a patterned sacrificial support to give rippled thin films that were then placed on ceramic membranes (see the Perspective by Freger). The composite membrane showed high flux for organic solvents and good stability and was able to separate out small molecules with high efficiency.

Science
, this issue p.
1347
; see also p.
1317
Comment on “Early
Homo
at 2.8 Ma from Ledi-Geraru, Afar, Ethiopia”
Authors: Hawks John , de Ruiter Darryl J. , Berger Lee R.
Published: June 2015

Villmoare
et al
. (Reports, 20 March 2015, p. 1352) report on a hominin mandible from the Ledi-Geraru research area, Ethiopia, which they claim to be the earliest known representative of the genus
Homo
. However, certain measurements and observations for
Australopithecus sediba
mandibles presented are incorrect or are not included in critical aspects of the study. When correctly used, these data demonstrate that specimen LD 350-1 cannot be unequivocally assigned to the genus
Homo
.
Parks for science
Authors: Machlis Gary , McNutt Marcia
Published: June 2015

In March 1915, a historic conference of scientists, conservationists, and park leaders was held at the University of California, Berkeley. It helped create public support for national parks in the United States and the establishment in 1916 of the National Park Service (NPS). One hundred years later, a similar summit on the same Berkeley campus convened to examine the role of science in the next century of America's national parks. Science remains crucial to the future health of America's parks and protected areas worldwide. But national parks are also vital for science.
After the Iran deal: Multinational enrichment
Authors: Glaser Alexander , Mian Zia , von Hippel Frank
Published: June 2015

World powers should buy a stake in Iran's enrichment capacity and accept the same rules
John Forbes Nash Jr. (1928–2015)
Authors: Shubik Martin
Published: June 2015

A distinguished mathematician and Nobel laureate dies tragically
Morphological and Molecular Characterization of Exophiala polymorpha sp. nov. Isolated from Sporotrichoid Lymphocutaneous Lesions in a Patient with Myasthenia Gravis
Authors: Yong Lee K. , Wiederhold Nathan P. , Sutton Deanna A. , Sandoval-Denis Marcelo , Lindner Jonathan R. , Fan Hongxin , Sanders Carmita , Guarro Josep
Published: June 2015

Exophiala
species are capable of causing cutaneous and subcutaneous infections in immunocompromised patients. An
Exophiala
isolate was cultured from a biopsy specimen of a lesion on the forearm of a patient with myasthenia gravis. The patient also had lesions on the palm and distal aspects of the hand, which were successfully treated with a long-term course of itraconazole. A detailed morphological and molecular characterization of the isolate was undertaken. Phylogenetic analysis of the internal transcribed spacer region and portions of the β-tubulin and translation elongation factor 1-alpha genes indicated that the isolate was a novel species closely related to but genetically distinct from species within the
Exophiala spinifera
clade; the name
Exophiala polymorpha
sp. nov. is proposed. Morphologically,
E. polymorpha
most closely resembles
E. xenobiotica
but it differs in possessing phialides bearing prominent, wide collarettes, and it does not produce chlamydospores.
Fonsecaea pugnacius, a Novel Agent of Disseminated Chromoblastomycosis
Authors: de Azevedo Conceição M. P. S. , Gomes Renata R. , Vicente Vania A. , Santos Daniel W. C. L. , Marques Sirlei G. , do Nascimento Mariana M. F. , Andrade Caroline E. W. , Silva Raimunda R. , Queiroz-Telles Flávio , de Hoog G. Sybren
Published: June 2015

We report a fatal case of a chromoblastomycosis-like infection caused by a novel species of
Fonsecaea
in a 52-year-old immunocompetent Caucasian male from an area of chromoblastomycosis endemicity in Brazil. The patient had a 30-year history of slowly evolving, verrucous lesions on the right upper arm which gradually affected the entire arm, the left hemifacial area, and the nose. Subsequent dissemination to the brain was observed, which led to death of the patient. The internal transcribed spacer (ITS) and partial large subunit (LSU),
BT2
, and
CDC42
genes of the isolates recovered from skin and brain were sequenced, confirming the novelty of the species. The species is clinically unique in causing brain abscesses secondary to chromoblastomycosis lesions despite the apparent intact immunity of the patient. Histopathologic appearances were very different, showing muriform cells in skin and hyphae in brain.
Analytical Comparison of
In Vitro
-Spiked Human Serum and Plasma for PCR-Based Detection of Aspergillus fumigatus DNA: a Study by the European Aspergillus PCR Initiative
Authors: Loeffler Juergen , Mengoli Carlo , Springer Jan , Bretagne Stéphane , Cuenca-Estrella Manuel , Klingspor Lena , Lagrou Katrien , Melchers Willem J. G. , Morton C. Oliver , Barnes Rosemary A. , Donnelly J. Peter , White P. Lewis
Published: June 2015

The use of serum or plasma for
Aspergillus
PCR testing facilitates automated and standardized technology. Recommendations for serum testing are available, and while serum and plasma are regularly considered interchangeable for use in fungal diagnostics, differences in galactomannan enzyme immunoassay (GM-EIA) performance have been reported and are attributed to clot formation. Therefore, it is important to assess plasma PCR testing to determine if previous recommendations for serum are applicable and also to compare analytical performance with that of serum PCR. Molecular methods testing serum and plasma were compared through multicenter distribution of quality control panels, with additional studies to investigate the effect of clot formation and blood fractionation on DNA availability. Analytical sensitivity and time to positivity (TTP) were compared, and a regression analysis was performed to identify variables that enhanced plasma PCR performance. When testing plasma, sample volume, preextraction-to-postextraction volume ratio, PCR volume, duplicate testing, and the use of an internal control for PCR were positively associated with performance. When whole-blood samples were spiked and then fractionated, the analytical sensitivity and TTP were superior when testing plasma. Centrifugation had no effect on DNA availability, whereas the presence of clot material significantly lowered the concentration (
P
= 0.028). Technically, there are no major differences in the molecular processing of serum and plasma, but the formation of clot material potentially reduces available DNA in serum. During disease,
Aspergillus
DNA burdens in blood are often at the limits of PCR performance. Using plasma might improve performance while maintaining the methodological simplicity of serum testing.
Mutation of a Single Envelope N-Linked Glycosylation Site Enhances the Pathogenicity of Bovine Leukemia Virus
Authors: de Brogniez Alix , Bouzar Amel Baya , Jacques Jean-Rock , Cosse Jean-Philippe , Gillet Nicolas , Callebaut Isabelle , Reichert Michal , Willems Luc
Published: June 2015

Viruses have coevolved with their host to ensure efficient replication and transmission without inducing excessive pathogenicity that would indirectly impair their persistence. This is exemplified by the bovine leukemia virus (BLV) system in which lymphoproliferative disorders develop in ruminants after latency periods of several years. In principle, the equilibrium reached between the virus and its host could be disrupted by emergence of more pathogenic strains. Intriguingly but fortunately, such a hyperpathogenic BLV strain was never observed in the field or designed
in vitro
. In this study, we sought to understand the role of envelope N-linked glycosylation with the hypothesis that this posttranslational modification could either favor BLV infection by allowing viral entry or allow immune escape by using glycans as a shield. Using reverse genetics of an infectious molecular provirus, we identified a N-linked envelope glycosylation site (N230) that limits viral replication and pathogenicity. Indeed, mutation N230E unexpectedly leads to enhanced fusogenicity and protein stability.

IMPORTANCE
Infection by retroviruses requires the interaction of the viral envelope protein (SU) with a membrane-associated receptor allowing fusion and release of the viral genomic RNA into the cell. We show that N-linked glycosylation of the bovine leukemia virus (BLV) SU protein is, as expected, essential for cell infection
in vitro
. Consistently, mutation of all glycosylation sites of a BLV provirus destroys infectivity
in vivo
. However, single mutations do not significantly modify replication
in vivo
. Instead, a particular mutation at SU codon 230 increases replication and accelerates pathogenesis. This unexpected observation has important consequences in terms of disease control and managing.
Phylodynamics of Enterovirus A71-Associated Hand, Foot, and Mouth Disease in Viet Nam
Authors: Geoghegan Jemma L. , Tan Le Van , Kühnert Denise , Halpin Rebecca A. , Lin Xudong , Simenauer Ari , Akopov Asmik , Das Suman R. , Stockwell Timothy B. , Shrivastava Susmita , Ngoc Nghiem My , Uyen Le Thi Tam , Tuyen Nguyen Thi Kim , Thanh Tran Tan , Hang Vu Thi Ty , Qui Phan Tu , Hung Nguyen Thanh , Khanh Truong Huu , Thinh Le Quoc , Nhan Le Nguyen Thanh , Van Hoang Minh Tu , Viet Do Chau , Tuan Ha Manh , Viet Ho Lu , Hien Tran Tinh , Chau Nguyen Van Vinh , Thwaites Guy , Grenfell Bryan T. , Stadler Tanja , Wentworth David E. , Holmes Edward C. , Van Doorn H. Rogier
Published: June 2015

Enterovirus A71 (EV-A71) is a major cause of hand, foot, and mouth disease (HFMD) and is particularly prevalent in parts of Southeast Asia, affecting thousands of children and infants each year. Revealing the evolutionary and epidemiological dynamics of EV-A71 through time and space is central to understanding its outbreak potential. We generated the full genome sequences of 200 EV-A71 strains sampled from various locations in Viet Nam between 2011 and 2013 and used these sequence data to determine the evolutionary history and phylodynamics of EV-A71 in Viet Nam, providing estimates of the effective reproduction number (R
e
) of the infection through time. In addition, we described the phylogeography of EV-A71 throughout Southeast Asia, documenting patterns of viral gene flow. Accordingly, our analysis reveals that a rapid genogroup switch from C4 to B5 likely took place during 2012 in Viet Nam. We show that the R
e
of subgenogroup C4 decreased during the time frame of sampling, whereas that of B5 increased and remained >1 at the end of 2013, corresponding to a rise in B5 prevalence. Our study reveals that the subgenogroup B5 virus that emerged into Viet Nam is closely related to variants that were responsible for large epidemics in Malaysia and Taiwan and therefore extends our knowledge regarding its associated area of endemicity. Subgenogroup B5 evidently has the potential to cause more widespread outbreaks across Southeast Asia.

IMPORTANCE
EV-A71 is one of many viruses that cause HFMD, a common syndrome that largely affects infants and children. HFMD usually causes only mild illness with no long-term consequences. Occasionally, however, severe infection may arise, especially in very young children, causing neurological complications and even death. EV-A71 is highly contagious and is associated with the most severe HFMD cases, with large and frequent epidemics of the virus recorded worldwide. Although major advances have been made in the development of a potential EV-A71 vaccine, there is no current prevention and little is known about the patterns and dynamics of EV-A71 spread. In this study, we utilize full-length genome sequence data obtained from HFMD patients in Viet Nam, a geographical region where the disease has been endemic since 2003, to characterize the phylodynamics of this important emerging virus.
Partial Attenuation of Respiratory Syncytial Virus with a Deletion of a Small Hydrophobic Gene Is Associated with Elevated Interleukin-1β Responses
Authors: Russell Ryan F. , McDonald Jacqueline U. , Ivanova Maria , Zhong Ziyun , Bukreyev Alexander , Tregoning John S.
Published: June 2015

The small hydrophobic (SH) gene of respiratory syncytial virus (RSV), a major cause of infant hospitalization, encodes a viroporin of unknown function. SH gene knockout virus (RSV ΔSH) is partially attenuatedin vivo, but notin vitro, suggesting that the SH protein may have an immunomodulatory role. RSV ΔSH has been tested as a live attenuated vaccine in humans and cattle, and here we demonstrate that it protected against viral rechallenge in mice. We compared the immune response to infection with RSV wild type and RSV ΔSHin vivousing BALB/c mice andin vitrousing epithelial cells, neutrophils, and macrophages. Strikingly, the interleukin-1β (IL-1β) response to RSV ΔSH infection was greater than to wild-type RSV, in spite of a decreased viral load, and when IL-1β was blockedin vivo, the viral load returned to wild-type levels. A significantly greater IL-1β response to RSV ΔSH was also detectedin vitro, with higher-magnitude responses in neutrophils and macrophages than in epithelial cells. Depleting macrophages (with clodronate liposome) and neutrophils (with anti-Ly6G/1A8) demonstrated the contribution of these cells to the IL-1β responsein vivo, the first demonstration of neutrophilic IL-1β production in response to viral lung infection. In this study, we describe an increased IL-1β response to RSV ΔSH, which may explain the attenuationin vivoand supports targeting the SH gene in live attenuated vaccines.

IMPORTANCEThere is a pressing need for a vaccine for respiratory syncytial virus (RSV). A number of live attenuated RSV vaccine strains have been developed in which the small hydrophobic (SH) gene has been deleted, even though the function of the SH protein is unknown. The structure of the SH protein has recently been solved, showing it is a pore-forming protein (viroporin). Here, we demonstrate that the IL-1β response to RSV ΔSH is greater in spite of a lower viral load, which contributes to the attenuationin vivo. This potentially suggests a novel method by which viruses can evade the host response. As allPneumovirinaeand someParamyxovirinaecarry similar SH genes, this new understanding may also enable the development of live attenuated vaccines for both RSV and other members of theParamyxoviridae.
Assembly of Epstein-Barr Virus Capsid in Promyelocytic Leukemia Nuclear Bodies
Authors: Wang Wen-Hung , Kuo Chung-Wen , Chang Li-Kwan , Hung Chen-Chia , Chang Tzu-Hsuan , Liu Shih-Tung
Published: June 2015

The Epstein-Barr virus (EBV) capsid contains a major capsid protein, VCA; two minor capsid proteins, BDLF1 and BORF1; and a small capsid protein, BFRF3. During the lytic cycle, these capsid proteins are synthesized and imported into the host nucleus for capsid assembly. This study finds that EBV capsid proteins colocalize with promyelocytic leukemia (PML) nuclear bodies (NBs) in P3HR1 cells during the viral lytic cycle, appearing as nuclear speckles under a confocal laser scanning microscope. In a glutathione
S
-transferase pulldown study, we show that BORF1 interacts with PML-NBs
in vitro
. BORF1 also colocalizes with PML-NBs in EBV-negative Akata cells after transfection and is responsible for bringing VCA and the VCA-BFRF3 complex from the cytoplasm to PML-NBs in the nucleus. Furthermore, BDLF1 is dispersed throughout the cell when expressed alone but colocalizes with PML-NBs when BORF1 is also present in the cell. In addition, this study finds that knockdown of PML expression by short hairpin RNA does not influence the intracellular levels of capsid proteins but reduces the number of viral particles produced by P3HR1 cells. Together, these results demonstrate that BORF1 plays a critical role in bringing capsid proteins to PML-NBs, which may likely be the assembly sites of EBV capsids. The mechanisms elucidated in this study are critical to understanding the process of EBV capsid assembly.

IMPORTANCE
Capsid assembly is an important event during the Epstein-Barr virus (EBV) lytic cycle, as this process is required for the production of virions. In this study, confocal microscopy revealed that the EBV capsid protein BORF1 interacts with promyelocytic leukemia (PML) nuclear bodies (NBs) in the host nucleus and is responsible for transporting the other EBV capsid proteins, including VCA, BDLF1, and BFRF3, to these subnuclear locations prior to initiation of capsid assembly. This study also found that knockdown of PML expression by short hairpin RNA significantly reduces EBV capsid assembly capabilities. This enhanced understanding of capsid assembly offers potential for the development of novel antiviral strategies and therapies that can prevent the propagation and spread of EBV.
Maternal Deworming Research Study (MADRES) protocol: a double-blind, placebo-controlled randomised trial to determine the effectiveness of deworming in the immediate postpartum period
Authors: Mofid Layla S , Casapía Martín , Montresor Antonio , Rahme Elham , Fraser William D , Marquis Grace S , Vercruysse Jozef , Allen Lindsay H , Gyorkos Theresa W
Published: June 2015

Introduction

Soil-transmitted helminth infections are endemic in 114 countries worldwide, and cause the highest burden of disease among all neglected tropical diseases. The WHO includes women of reproductive age as a high-risk group for infection. The primary consequence of infection in this population is anaemia. During lactation, anaemia may contribute to reduced quality and quantity of milk, decreasing the duration of exclusive breastfeeding and lowering the age at weaning. To date, no study has investigated the effects of maternal postpartum deworming on infant or maternal health outcomes.

Methods and analysis

A single-centre, parallel, double-blind, randomised, placebo-controlled trial will be carried out in Iquitos, Peru, to assess the effectiveness of integrating single-dose 400 mg albendazole into routine maternal postpartum care. A total of 1010 mother-infant pairs will be randomised to either the intervention or control arm, following inhospital delivery and prior to discharge. Participants will be visited in their homes at 1, 6, 12 and 24 months following delivery for outcome ascertainment. The primary outcome is infant mean weight gain between birth and 6 months of age. Secondary outcomes include other infant growth indicators and morbidity, maternal soil-transmitted helminth infection and intensity, anaemia, fatigue, and breastfeeding practices. All statistical analyses will be performed on an intention-to-treat basis.

Ethics and dissemination

Research ethics board approval has been obtained from the McGill University Health Centre (Canada), the Asociación Civil Impacta Salud y Educación (Peru) and the Instituto Nacional de Salud (Peru). A data safety and monitoring committee is in place to oversee study progression and evaluate adverse events. The results of the analyses will be published in peer-reviewed journals, and presented at national and international conferences.

Trial registration number

Clinicaltrials.gov:NCT01748929.
A longitudinal study of poor performance and subclinical respiratory viral activity in Standardbred trotters
Authors: Back Helena , Penell Johanna , Pringle John , Isaksson Mats , Ronéus Nils , Treiberg Berndtsson Louise , Ståhl Karl
Published: June 2015

Introduction

While clinical respiratory disease is considered a main cause of poor performance in horses, the role of subclinical respiratory virus infections is less clear and needs further investigation.

Aims and objectives

In this descriptive longitudinal study the relationship of markers of subclinical respiratory viral activity to occurrence of poor performance in racing Standardbred trotters was investigated.

Material and methods

66 elite Standardbred trotters were followed for 13 months by nasal swabs analysed with qPCR for equine influenza virus, equine arteritis virus, equine rhinitis B virus (ERBV), equine herpesvirus type 1(EHV‐1) and equine herpesvirus type 4 (EHV‐4) and serology to equine rhinitis A virus (ERAV), ERBV, EHV‐1 and EHV‐4, as well as the acute phase protein serum amyloid A (SAA). Findings on lab analyses were subsequently assessed for possible correlations to workload performance and trainer opinion measures of poor performance.

Results

Despite occurrence of poor performance and subclinical viral activity the authors were unable to detect association neither between subclinical viral activity and poor performance, nor between SAA elevations and either viral activity or poor performance.

Conclusions

Consistent with earlier study results, antibody titres to ERBV remained high for at least a year and few horses two years or older were seronegative to either ERAV or ERBV. In absence of clinical signs, serology to common respiratory viruses appears to have little diagnostic benefit in evaluation of poor performance in young athletic horses.
Nutrients alleviate the deleterious effect of salinity on germination and early seedling growth of the psammophytic grass Elymus farctus
Authors: El-Katony Taha Mohamed , Khedr Abdel-Hamid Abdel-Fattah , Soliman Naser Gadallah
Published: June 2015

Elymus farctus L. is a perennial grass, dominating the Mediterranean coastal sands of Egypt. Germination of E. farctus seeds was monitored under the impact of NaCl levels up to 300 mmol·L−1, either in water or in nutrient solution containing nitrogen in the form of ammonium, nitrate, or ammonium nitrate. Seed germination was more salt tolerant than extension of embryonic axis, and radicle elongation was more salt tolerant than plumule elongation. NaCl applied in water sharply reduced germinability beyond a threshold of 55 mmol·L−1, but progressively inhibited embryonic axis elongation. Presence of nutrients alleviated the effect of salinity, particularly if nitrogen was in the form of nitrate. The effect of salinity on speed, uniformity, and synchrony of germination was in general modulated by the presence of nutrients. Salt-treated seeds readily recovered from stress when moved to distilled water, without a lag period, and with high speed, uniformity, and synchrony of germination but with a lower recovery percentage compared with the germination of fresh seeds in distilled water, which might point to a combination of osmotic and specific ion effects of salinity on seed germination.
Enhanced expression of Giα proteins contributes to the hyperproliferation of vascular smooth muscle cells from spontaneously hypertensive rats via MAP kinase- and PI3 kinase-independent pathways
Authors: Bou Daou Grace , Li Yuan , Anand-Srivastava Madhu B.
Published: June 2015

Vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) exhibit hyperproliferation, enhanced MAP kinase (MAPK) activity, and overexpression of Giα proteins. This study was undertaken to examine whether the overexpression of Giα proteins contributes to the hyperproliferation of VSMC of SHR through MAPK signaling. The hyperproliferation of VSMC from SHR in the absence and presence of angiotensin II was restored towards those in Wistar–Kyoto (WKY) rats levels by pertussis toxin (PT) treatment. In addition, siRNA knockdown of Giα proteins also resulted in the attenuation of hyperproliferation towards control levels. The overexpression of Giα proteins was also inhibited by MAPK and PI3 kinase (PI3K) inhibitors. In addition, the hyperproliferation and enhanced phosphorylation of ERK1/2 and Akt in VSMC from SHR were attenuated towards WKY levels by the inhibitors of MAPK, PI3K, c-Src, and antioxidants, whereas PT was unable to attenuate the enhanced phosphorylation of ERK1/2 and Akt. Furthermore, 8Br-cAMP and forskolin also attenuated the hyperproliferation of VSMC from SHR. These results suggest that the hyperproliferation of VSMC from SHR may be attributed to the enhanced expression of Giα proteins and increased activation of MAPK and PI3 kinase. However, Giα-mediated hyperproliferation may not be mediated through MAPK- and PI3 kinase-dependent pathways and may involve decreased levels of intracellular cAMP.