bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconsidering Durkheim's Assessment of Tarde: Formalizing a Tardian Theory of Imitation, Contagion, and Suicide Suggestion
Authors: Abrutyn Seth , Mueller Anna S.
Published: August 2014

Emile Durkheim summarily rejected Gabriel Tarde's imitation thesis, arguing that sociology need only concern itself with social suicide rates. Over a century later, a burgeoning body of suicide research has challenged Durkheim's claim to a general theory of suicide as 4 decades worth of evidence has firmly established that (1) there is a positive association between the publicization of celebrity suicides and a spike in the aggregate suicide rate, (2) some social environments are conducive to epidemic‐like outbreaks of suicides, and (3) suicidal ideas or behavior spreads to some individuals exposed to a personal role model's suicidal behavior—for example, a friend or family member. Revisiting Tarde, the article examines why Tarde's theory deserves renewed attention, elucidates what he meant by imitation, and then formalizes his “laws” into testable theses, while suggesting future research questions that would advance the study of suicide, as well as other pathologies. Each “law” is elaborated by considering advances in contemporary social psychology as well as in light of its ability to supplement Durkheim's theory in explaining the “outlier” cases.
Fame, Social Media Use, and Ethics
Authors: Replogle Elaine
Published: August 2014

This essay addresses two journalists' very public criticism of a blog that chronicles a woman's fight with cancer. I examine the role of fame in this controversy. Are the expectations for maintaining “privacy” actually stricter for people who are not famous? How do shifting boundaries between private and public (exacerbated by social media, which allow anybody to have a “public” persona) and shifting understandings of what constitutes “fame” affect the traditional understandings of what is appropriate to share?
To Life: Optimism Bias and Technological Ties in the Face of the Worst
Authors: Cerulo Karen A.
Published: August 2014

This essay addresses a recent media controversy. Two journalists actively questioned the appropriateness of a popular blog that chronicles a young woman's fight with cancer. Elaine Replogle () unfolds the facts of this case and discusses the role of fame and status in understanding the journalists' response to the blog. Here, I extend that conversation, exploring how our culture's optimism bias, as well as the increasing importance of our technological ties, informs our understanding of both the blog and its critics.
Application of leukotriene B4 and reflectance confocal microscopy as a noninvasivein vivomodel to study the dynamics of skin inflammation
Authors: Peppelman M. , Wolberink E. A. W. , Gerritsen M.‐J. P. , van de Kerkhof P. C. M. , van Erp P. E. J.
Published: August 2014

Background

Application of leukotriene B4 (LTB4) is an establishedin vivomodel that locally induces skin inflammation. Currently in this model, a biopsy is inevitable.In vivoreflectance confocal microscopy (RCM), a noninvasive imaging technique, could overcome this limitation. To find out to what extentRCMmay be anin vivoinvestigative and diagnostic tool in neutrophilic conditions, we studied the dynamics of polymorphonuclear leukocytes (PMN) migration from dermis to stratum corneum using an establishedLTB4 model.

Methods

Leukotriene B4 was topically applied on the skin of the lower back of seven volunteers. The skin sites were evaluated byRCMfor three consecutive days with a 24 h time interval. For histological correlation, 3‐mm punch biopsies were obtained. The tissue sections were hematoxylin–eosin and immunohistochemical stained. Minimal and average epidermal thickness was measured.

Results

Reflectance confocal microscopy imaging showed highly reflective ill‐defined particles with a granular content throughout the epidermis 24 h after application ofLTB4. Over time, the appearance of these cells changed throughout the epidermis. Epidermal thickness increased over time, and the measurements based on theRCMimages corresponded very well with the histological images.

Conclusions

Reflectance confocal microscopy was able to visualizePMNmigration, accumulation, and degeneration over time in the usedLTB4 model. The noninvasive character and the possibility to obtain multiplein vivoimages from the same location over time make thatRCMin combination with this model a useful tool to study the dynamics and function ofPMNin inflammatory processes in the skin.
The novel KIR2DL3*025 allele identified in an individual from a southern Chinese Han population
Authors: Zhen J.‐X. , Wang D.‐M. , Deng Z.‐H.
Published: August 2014

The novel KIR2DL3*025 allele differs from the closest allele KIR2DL3*0010101 by a non‐synonymous mutation at CDS nt280 C>A in exon 4.
The geographic and demographic scope of shared sanitation: an analysis of national survey data from low‐ and middle‐income countries
Authors: Heijnen Marieke , Rosa Ghislaine , Fuller James , Eisenberg Joseph N. S. , Clasen Thomas
Published: August 2014

Objective

A large and growing proportion of the world's population rely on shared sanitation facilities that have historically been excluded from international targets due to concerns about acceptability, hygiene and access. In connection with a proposed change in such policy, we undertook this study to describe the prevalence and scope of households that report relying on shared sanitation and to characterise them in terms of selected socio‐economic and demographic covariates.

Methods

We extracted data from the most recent national household surveys of 84 low‐ and middle‐income countries from Demographic and Health Surveys and Multiple Indicator Cluster Surveys. We describe the prevalence of shared sanitation and explore associations between specified covariates and reliance on shared sanitation using log‐binomial regression.

Results

While household reliance on any type of shared sanitation is relatively rare in Europe (2.5%) and the Eastern Mediterranean (7.7%), it is not uncommon in the Americas (14.2%), Western Pacific (16.4%) and South‐East Asia (31.3%), and it is most prevalent in Africa (44.6%) where many shared facilities do not meet the definition of ‘improved’ even if they were not shared (17.7%). Overall, shared sanitation is more common in urban (28.6%) than in rural settings (25.9%), even after adjusting for wealth. While results vary geographically, people who rely on shared sanitation tend to be poorer, reside in urban areas and live in households with more young children and headed by people with no formal education. Data from 21 countries suggest that most sharing is with neighbours and other acquaintances (82.0%) rather than the public.

Conclusions

The determinants of shared sanitation identified from these data suggest potential confounders that may explain the apparent increased health risk from sharing and should be considered in any policy recommendation. Both geographic and demographic heterogeneity indicate the need for further research to support a change in policies.
Metabolomic analysis of platelets during storage: a comparison between apheresis‐ and buffy coat–derived platelet concentrates
Authors: Paglia Giuseppe , Sigurjónsson Ólafur E. , Rolfsson Óttar , Hansen Morten Bagge , Brynjólfsson Sigurður , Gudmundsson Sveinn , Palsson Bernhard O.
Published: August 2014

Background

Platelet concentrates (PCs) can be prepared using three methods: platelet (PLT)‐rich plasma, apheresis, and buffy coat. The aim of this study was to obtain a comprehensive data set that describes metabolism of buffy coat–derived PLTs during storage and to compare it with a previously published parallel data set obtained for apheresis‐derived PLTs.

Study Design and Methods

During storage we measured more than 150 variables in 8 PLT units, prepared by the buffy coat method. Samples were collected at seven different time points resulting in a data set containing more than 8000 measurements. This data set was obtained by combining a series of standard quality control assays to monitor the quality of stored PLTs and a deep coverage metabolomics study using liquid chromatography coupled with mass spectrometry.

Results

Stored PLTs showed a distinct metabolic transition occurring 4 days after their collection. The transition was evident in PLT produced by both production methods. Apheresis‐derived PLTs showed a clearer phenotype of PLT activation during early days of storage. The activated phenotype of apheresis PLTs was accompanied by a higher metabolic activity, especially related to glycolysis and the tricarboxylic acid cycle. Moreover, the extent of the activation differed between bags resulting in interbag variability in the storage lesion of apheresis‐prepared PLTs. This may be related to donor‐related polymorphism.

Conclusion

This study demonstrated two discrete metabolic phenotypes in stored PLTs prepared with both apheresis and buffy coat methods. PLT activation occurs during the first metabolic phenotype and might lead to a low reproducibility of the apheresis PCs.
Blood reference materials from macaques infected with variant Creutzfeldt‐Jakob disease agent
Authors: McDowell Kristy L. , Nag Nabanita , Franco Zulmarie , Bu Ming , Piccardo Pedro , Cervenak Juraj , Deslys Jean‐Philippe , Comoy Emmanuel , Asher David M. , Gregori Luisa
Published: August 2014

Background

Variant Creutzfeldt‐Jakob disease (vCJD) is a fatal neurodegenerative infection that can be transmitted by blood and blood products from donors in the latent phase of the disease. Currently, there is no validated antemortem vCJD blood screening test. Several blood tests are under development. Any useful test must be validated with disease‐relevant blood reference panels.

Study Design and Methods

To generate blood reference materials, we infected four cynomolgus macaques with macaque‐adapted vCJD brain homogenates. Blood was collected throughout the preclinical and clinical phases of infection. In parallel, equivalent blood was collected from one uninfected macaque. For each blood collection, an aliquot was stored as whole blood and the remainder was separated into components. Aliquots of plasma from terminally ill macaques were assayed for the presence of PrPTSE with the protein misfolding cyclic amplification (PMCA) method. Infectivity of the macaque brain homogenate used to infect macaques was titrated in C57BL/6 and RIII J/S inbred wild‐type mice.

Results

We sampled blood 19 times from the inoculated monkeys at various stages of the disease over a period of 29 months, generating liters of vCJD‐infected macaque blood. vCJD was confirmed in all inoculated macaques. After PMCA, PrPTSE was detected in plasma from infected monkeys, but not from uninfected animals. Both mouse models were more sensitive to infection with macaque‐adapted vCJD agent than to primary human vCJD agent.

Conclusion

The macaque vCJD blood panels generated in this study provide a unique resource to support vCJD assay development and to characterize vCJD infectivity in blood.
THE TREES, MY LUNGS: SELF PSYCHOLOGY AND THE NATURAL WORLD AT AN AMERICAN BUDDHIST CENTER
Authors: Capper Daniel
Published: August 2014

This study employs ethnographic field data to trace a dialogue between the self‐psychological concept of the self object and experiences regarding the concept of “interbeing” at a Vietnamese Buddhist monastery in the United States. The dialogue develops an understanding of human experiences with the nonhuman natural world which are tensive, liminal, and nondual. From the dialogue I find that the self object concept, when applied to this form of Buddhism, must be inclusive enough to embrace relationships with animals, stones, and other natural forms. The dialogue further delineates a self‐psychological methodology for examining religions in their interactions with natural forms.
HERE AND NOW: DISCOVERING THE SACRED WITH ENTHEOGENS
Authors: Richards William A.
Published: August 2014

Renewed research with entheogens (psychedelic substances) has been able to facilitate the occurrence of mystical forms of consciousness in healthy volunteers with a high degree of reliability. This article explores the potential significance of this development for religious scholars, especially those interested in the study of mysticism. The definition of “mystical consciousness” employed in this research is presented and differentiated from visionary/archetypal and other types of alternative mental states. The ways in which entheogens may be employed with skill and maximum safety are discussed. Implications for clarifying confusion in the study of mysticism are considered, along with suggestions for future religious research on this frontier of knowledge.
GOD, CHRIST, AND ANIMALS
Authors: Fergusson David
Published: August 2014

One of the most significant contributions to the field in recent times, David Clough's work On Animals: Volume 1, Systematic Theology, should ensure that theologies of creation, redemption, and eschatological fulfillment give proper attention to animals. In a landmark study, he draws upon resources in Scripture and tradition to present a systematic theology that is alert to the place of animals in the divine economy. Amidst his relentless criticism of all forms of anthropocentrism, however, it is asked whether some unresolved tensions emerge in relation to the traditional doctrine of God, the use of the category of the “personal” in theology, and the incarnation of the Word of God as a human creature.
Three-dimensional nanofabrication using hydrogen silsesquioxane/poly(methylmethacrylate) bilayer resists
Authors: Do Hyung Wan , Chang Jae-Byum , Berggren Karl K.
Published: August 2014

In this work, the authors developed two processes for fabricating three-dimensional (3D) nanostructures using a hydrogen silsesquioxane and poly(methylmethacrylate) bilayer resist stack. The resist stack was patterned in a single electron-beam writing step without removing the wafer. The resulting 3D nanostructures naturally achieved vertical self-alignment without the need for any intermediate alignment. Self-aligned mushroom-shaped posts and freestanding supported structures were demonstrated.
Development of a golden beam data set for the commissioning of a proton double‐scattering system in a pencil‐beam dose calculation algorithm
Authors: Slopsema R. L. , Lin L. , Flampouri S. , Yeung D. , Li Z. , McDonough J. E. , Palta J.
Published: August 2014

Purpose:

The purpose of this investigation is to determine if a single set of beam data, described by a minimal set of equations and fitting variables, can be used to commission different installations of a proton double‐scattering system in a commercial pencil‐beam dose calculation algorithm.

Methods:

The beam model parameters required to commission the pencil‐beam dose calculation algorithm (virtual and effective SAD, effective source size, and pristine‐peak energy spread) are determined for a commercial double‐scattering system. These parameters are measured in a first room and parameterized as function of proton energy and nozzle settings by fitting four analytical equations to the measured data. The combination of these equations and fitting values constitutes the golden beam data (GBD). To determine the variation in dose delivery between installations, the same dosimetric properties are measured in two additional rooms at the same facility, as well as in a single room at another facility. The difference between the room‐specific measurements and the GBD is evaluated against tolerances that guarantee the 3D dose distribution in each of the rooms matches the GBD‐based dose distribution within clinically reasonable limits. The pencil‐beam treatment‐planning algorithm is commissioned with the GBD. The three‐dimensional dose distribution in water is evaluated in the four treatment rooms and compared to the treatment‐planning calculated dose distribution.

Results:

The virtual and effective SAD measurements fall between 226 and 257 cm. The effective source size varies between 2.4 and 6.2 cm for the large‐field options, and 1.0 and 2.0 cm for the small‐field options. The pristine‐peak energy spread decreases from 1.05% at the lowest range to 0.6% at the highest. The virtual SAD as well as the effective source size can be accurately described by a linear relationship as function of the inverse of the residual energy. An additional linear correction term as function of RM‐step thickness is required for accurate parameterization of the effective SAD. The GBD energy spread is given by a linear function of the exponential of the beam energy. Except for a few outliers, the measured parameters match the GBD within the specified tolerances in all of the four rooms investigated. For a SOBP field with a range of 15 g/cm2 and an air gap of 25 cm, the maximum difference in the 80%–20% lateral penumbra between the GBD‐commissioned treatment‐planning system and measurements in any of the four rooms is 0.5 mm.

Conclusions:

The beam model parameters of the double‐scattering system can be parameterized with a limited set of equations and parameters. This GBD closely matches the measured dosimetric properties in four different rooms.
The History and Science of the Manhattan Project, Second Edition.
Authors: Mihailidis Dimitris
Published: August 2014

The History and Science of the Manhattan Project, Second Edition. Cameron Reed B., Springer‐Verlag, NY, 2014. 472 pp. Price: $39.99. ISBN 978‐3‐642‐40296‐8 (hardcover).
Incompleteness of the Hamilton-Jacobi theory
Authors: Lemos Nivaldo A.
Published: August 2014

The problem of the motion of a charged particle in an electric dipole field is used to illustrate that the Hamilton-Jacobi method does not necessarily give all solutions to the equations of motion of a mechanical system. The mathematical reason for this phenomenon is discussed. In the particular case under consideration, it is shown how to circumvent the difficulty and find the missing solutions by means of a very special limiting procedure.
Sommerfeld's elliptical atomic orbits revisited—A useful preliminary to the study of quantum mechanics
Authors: Deeney Tony , O'Sullivan Colm
Published: August 2014

The Bohr-Sommerfeld atomic model is recast in the language of wave-particle duality and it is shown that requirements equivalent to the Sommerfeld-Wilson quantisation conditions arise naturally in this context. It is suggested that treating the one-electron atom in this way provides a useful introduction for students prior to encountering the more formal analysis based on the solution of the Schrödinger equation.
Nutritional Recommendations for Water Polo
Authors: Cox Gregory R. , Mujika Iñigo , van den Hoogenband Cees-Rein
Published: August 2014

Water polo is an aquatic team sport that requires endurance, strength, power, swimming speed, agility, tactical awareness, and specific technical skills, including ball control. Unlike other team sports, few researchers have examined the nutritional habits of water polo athletes or potential dietary strategies that improve performance in water polo match play. Water polo players are typically well muscled, taller athletes; female players display higher levels of adiposity compared with their male counterparts. Positional differences exist: Center players are heavier and have higher body fat levels compared with perimeter players. Knowledge of the physical differences that exist among water polo players offers the advantage of player identification as well as individualizing nutrition strategies to optimize desired physique goals. Individual dietary counseling is warranted to ensure dietary adequacy, and in cases of physique manipulation. Performance in games and during quality workouts is likely to improve by adopting strategies that promote high carbohydrate availability, although research specific to water polo is lacking. A planned approach incorporating strategies to facilitate muscle glycogen refueling and muscle protein synthesis should be implemented following intensified training sessions and matches, particularly when short recovery times are scheduled. Although sweat losses of water polo players are less than what is reported for land-based athletes, specific knowledge allows for appropriate planning of carbohydrate intake strategies for match play and training. Postgame strategies to manage alcohol intake should be developed with input from the senior player group to minimize the negative consequences on recovery and player welfare.
Semaphorin 3A activates the guanosine triphosphatase Rab5 to promote growth cone collapse and organize callosal axon projections
Authors: Wu Kong-Yan , He Miao , Hou Qiong-Qiong , Sheng Ai-Li , Yuan Lei , Liu Fei , Liu Wen-Wen , Li Guangpu , Jiang Xing-Yu , Luo Zhen-Ge
Published: August 2014

Endocytosis contributes to axon collapse mediated by a repulsive guidance cue in the developing brain.
A Dual-Action RNA Switch for Expression
Authors: Riddihough Guy
Published: August 2014

A riboswitch is both part of, and regulates the activity of, a small noncoding regulatory RNA.
TB Sunny Side Up
Authors: Colmone Angela C.
Published: August 2014

IL-32 links the microbicidal peptide pathway with resistance to disease progression in clinical tuberculosis.
EMT by p53ψ
Authors: Gough Nancy R.
Published: August 2014

A transcriptionally inactive p53 variant promotes mesenchymal phenotypes from the mitochondria.
Comparative Systems Biology Analysis To Study the Mode of Action of the Isothiocyanate Compound Iberin on Pseudomonas aeruginosa
Authors: Tan Sean Yang-Yi , Liu Yang , Chua Song Lin , Vejborg Rebecca Munk , Jakobsen Tim Holm , Chew Su Chuen , Li Yingying , Nielsen Thomas E. , Tolker-Nielsen Tim , Yang Liang , Givskov Michael
Published: August 2014

Food is now recognized as a natural resource of novel antimicrobial agents, including those that target the virulence mechanisms of bacterial pathogens. Iberin, an isothiocyanate compound from horseradish, was recently identified as a quorum-sensing inhibitor (QSI) of the bacterial pathogen
Pseudomonas aeruginosa
. In this study, we used a comparative systems biology approach to unravel the molecular mechanisms of the effects of iberin on QS and virulence factor expression of
P. aeruginosa
. Our study shows that the two systems biology methods used (i.e., RNA sequencing and proteomics) complement each other and provide a thorough overview of the impact of iberin on
P. aeruginosa
. RNA sequencing-based transcriptomics showed that iberin inhibits the expression of the GacA-dependent small regulatory RNAs RsmY and RsmZ; this was verified by using
gfp
-based transcriptional reporter fusions with the
rsmY
or
rsmZ
promoter regions. Isobaric tags for relative and absolute quantitation (iTRAQ) proteomics showed that iberin reduces the abundance of the LadS protein, an activator of GacS. Taken together, the findings suggest that the mode of QS inhibition in iberin is through downregulation of the Gac/Rsm QS network, which in turn leads to the repression of QS-regulated virulence factors, such as pyoverdine, chitinase, and protease IV. Lastly, as expected from the observed repression of small regulatory RNA synthesis, we also show that iberin effectively reduces biofilm formation. This suggests that small regulatory RNAs might serve as potential targets in the future development of therapies against pathogens that use QS for controlling virulence factor expression and assume the biofilm mode of growth in the process of causing disease.
Differential Subcutaneous Adipose Tissue Gene Expression Patterns in a Randomized Clinical Trial of Efavirenz or Lopinavir-Ritonavir in Antiretroviral-Naive Patients
Authors: Egaña-Gorroño L. , Martínez E. , Domingo P. , Loncà M. , Escribà T. , Fontdevila J. , Vidal F. , Negredo E. , Gatell J. M. , Arnedo M.
Published: August 2014

Gene expression studies of subcutaneous adipose tissue may help to better understand the mechanisms behind body fat changes in HIV-infected patients who initiate antiretroviral therapy (ART). Here, we evaluated early changes in adipose tissue gene expression and their relationship to fat changes in ART-naive HIV-infected patients randomly assigned to initiate therapy with emtricitabine/tenofovir plus efavirenz (EFV) or ritonavir-boosted lopinavir (LPV/r). Patients had abdominal subcutaneous adipose tissue biopsies at baseline and week 16 and dual-energy-X-ray absorptiometry at baseline and weeks 16 and 48. mRNA changes of 11 genes involved in adipogenesis, lipid and glucose metabolism, mitochondrial energy, and inflammation were assessed through reverse transcription-quantitative PCR (RT-qPCR). Additionally, correlations between gene expression changes and fat changes were evaluated. Fat increased preferentially in the trunk with EFV and in the limbs with LPV/r (P< 0.05). After 16 weeks of exposure to the drug regimen, transcripts ofCEBP/A,ADIPOQ,GLUT4,LPL, andCOXIVwere significantly down-regulated in the EFV arm compared to the LPV/r arm (P< 0.05). Significant correlations were observed betweenLPLexpression change and trunk fat change at week 16 in both arms and betweenCEBP/AorCOXIVchange and trunk fat change at the same time point only in the EFV arm and not in the LPV/r arm. When combined with emtricitabine/tenofovir as standard backbone therapy, EFV and LPV/r induced differential early expression of genes involved in adipogenesis and energy metabolism. Moreover, these mRNA expression changes correlated with trunk fat change in the EFV arm. (This was a substudy of a randomized clinical trial [LIPOTAR study] registered atClinicalTrials.govunder identifier NCT00759070.)
Antiviral Effects of Artesunate on JC Polyomavirus Replication in COS-7 Cells
Authors: Sharma Biswa Nath , Marschall Manfred , Rinaldo Christine Hanssen
Published: August 2014

The human JC polyomavirus (JCPyV) causes the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). A growing number of patients with induced or acquired immunosuppression are at risk for infection, and no effective antiviral therapy is presently available. The widely used antimalarial drug artesunate has shown broad antiviral activity
in vitro
but limited clinical success. The aim of this study was to investigate the effect of artesunate on JCPyV replication
in vitro
. The permissivity for JCPyV MAD-4 was first compared in four cell lines, and the monkey kidney cell line COS-7 was selected. Artesunate caused a concentration-dependent decrease in the extracellular JCPyV DNA load 96 h postinfection, with a 50% effective concentration (EC
50
) of 2.9 μM. This effect correlated with a decreased expression of capsid protein VP1 and a reduced release of infectious viral progeny. For concentrations of <20 μM, transient reductions in cellular DNA replication and proliferation were seen, while for higher concentrations, some cytotoxicity was detected. A selective index of 16.6 was found when cytotoxicity was calculated based on cellular DNA replication in the mock-infected cells, but interestingly, cellular DNA replication in the JCPyV-infected cells was more strongly affected. In conclusion, artesunate is efficacious in inhibiting JCPyV replication at micromolar concentrations, which are achievable in plasma. The inhibition at EC
50
probably reflects an effect on cellular proteins and involves transient cytostatic effects. Our results, together with the favorable distribution of the active metabolite dihydroartemisinin to the central nervous system, suggest a potential use for artesunate in patients with PML.
Culture of the Entire Mouse To Determine whether Cultivable Borrelia burgdorferi Persists in Infected Mice Treated with a Five-Day Course of Ceftriaxone
Authors: Pavia Charles S. , Wormser Gary P.
Published: August 2014

Although controversial, it has been suggested that antibiotic treatment of laboratory animals infected with
Borrelia burgdorferi
often leads to the persistence of residual spirochetes that are claimed to be viable but noncultivable. If viable cells of
B. burgdorferi
do persist following antibiotic therapy, one possible explanation for the lack of cultivability is that too few organisms persist in any given tissue site that might be sampled and cultured. In this study, we treated SKH (hairless) mice, with
B. burgdorferi
infection of 3 months' duration, with either ceftriaxone or saline for 5 days and then cultured a suspension extract of nearly the entire mouse using a combined
in vivo
/
in vitro
culture method. All of the saline-treated (control) mice were culture positive, compared with none of the antibiotic-treated mice. Our findings further document the effectiveness of antibiotic therapy in eradicating cultivable cells of
B. burgdorferi
, irrespective of tissue or organ site.
The Subcellular Location of Ovalbumin in Plasmodium berghei Blood Stages Influences the Magnitude of T-Cell Responses
Authors: Lin Jing-Wen , Shaw Tovah N. , Annoura Takeshi , Fougère Aurélie , Bouchier Pascale , Chevalley-Maurel Séverine , Kroeze Hans , Franke-Fayard Blandine , Janse Chris J. , Couper Kevin N. , Khan Shahid M.
Published: August 2014

Model antigens are frequently introduced into pathogens to study determinants that influence T-cell responses to infections. To address whether an antigen's subcellular location influences the nature and magnitude of antigen-specific T-cell responses, we generatedPlasmodium bergheiparasites expressing the model antigen ovalbumin (OVA) either in the parasite cytoplasm or on the parasitophorous vacuole membrane (PVM). For cytosolic expression, OVA alone or conjugated to mCherry was expressed from a strong constitutive promoter (OVAhsp70orOVA::mCherryhsp70); for PVM expression, OVA was fused to HEP17/EXP1 (OVA::Hep17hep17). Unexpectedly, OVA expression inOVAhsp70parasites was very low, but when OVA was fused to mCherry (OVA::mCherryhsp70), it was highly expressed. OVA expression inOVA::Hep17hep17parasites was strong but significantly less than that inOVA::mCherryhsp70parasites. These transgenic parasites were used to examine the effects of antigen subcellular location and expression level on the development of T-cell responses during blood-stage infections. While all OVA-expressing parasites induced activation and proliferation of OVA-specific CD8+T cells (OT-I) and CD4+T cells (OT-II), the level of activation varied:OVA::Hep17hep17parasites induced significantly stronger splenic and intracerebral OT-I and OT-II responses than those ofOVA::mCherryhsp70parasites, butOVA::mCherryhsp70parasites promoted stronger OT-I and OT-II responses than those ofOVAhsp70parasites. Despite lower OVA expression levels,OVA::Hep17hep17parasites induced stronger T-cell responses than those ofOVA::mCherryhsp70parasites. These results indicate that unconjugated cytosolic OVA is not stably expressed inPlasmodiumparasites and, importantly, that its cellular location and expression level influence both the induction and magnitude of parasite-specific T-cell responses. These parasites represent useful tools for studying the development and function of antigen-specific T-cell responses during malaria infection.
MicroRNA-155 Is Required for Clearance of Streptococcus pneumoniae from the Nasopharynx
Authors: Verschoor Chris P. , Dorrington Michael G. , Novakowski Kyle E. , Kaiser Julie , Radford Katherine , Nair Parameswaran , Anipindi Varun , Kaushic Charu , Surette Michael G. , Bowdish Dawn M. E.
Published: August 2014

Pneumonia caused by
Streptococcus pneumoniae
is a major cause of death and an economic burden worldwide.
S. pneumoniae
is an intermittent colonizer of the human upper respiratory tract, and the ability to control asymptomatic colonization determines the likelihood of developing invasive disease. Recognition of
S. pneumoniae
by resident macrophages via Toll-like receptor 2 (TLR-2) and the macrophage receptor with collagenous structure (MARCO) and the presence of interleukin-17 (IL-17)-secreting CD4
+
T cells are required for macrophage recruitment and bacterial clearance. Despite the fact that the primary cellular effectors needed for bacterial clearance have been identified, much of the underlying regulatory mechanisms are unknown. Herein, we demonstrate that the small, noncoding RNA microRNA-155 (mir-155) is critical for the effective clearance of
S. pneumoniae
. Our studies show that mir-155-deficient mice maintain the ability to prevent acute invasive pneumococcal infection but have significantly higher bacterial burdens following colonization, independently of macrophage recognition by TLR-2, MARCO expression, or bactericidal capacity. The observed defects in bacterial clearance parallel reduced IL-17A and gamma interferon CD4
+
T-cell responses
in vivo
, lower IL-17A mRNA levels in the nasopharynx, and a reduced capacity to induce Th17 cell polarization. Given that knockout mice are also limited in the capacity to generate high-titer
S. pneumoniae
-specific antibodies, we conclude that mir-155 is a critical mediator of the cellular effectors needed to clear primary and secondary
S. pneumoniae
colonizations.
Differential Regulation of Proinflammatory Cytokine Expression by Mitogen-Activated Protein Kinases in Macrophages in Response to Intestinal Parasite Infection
Authors: Lim Mei Xing , Png Chin Wen , Tay Crispina Yan Bing , Teo Joshua Ding Wei , Jiao Huipeng , Lehming Norbert , Tan Kevin Shyong Wei , Zhang Yongliang
Published: August 2014

Blastocystisis a common enteric protistan parasite that can cause acute, as well as chronic, infection and is associated with irritable bowel syndrome (IBS). However, the pathogenic status ofBlastocystisinfection remains unclear. In this study, we found thatBlastocystisantigens induced abundant expression of proinflammatory cytokines, including interleukin 1β (IL-1β), IL-6, and tumor necrosis factor alpha (TNF-α), in mouse intestinal explants, in mouse colitis colon, and in macrophages. Further investigation utilizing RAW264.7 murine macrophages showed thatBlastocystistreatment in RAW264.7 macrophages induced the activation of ERK, JNK, and p38, the three major groups of mammalian mitogen-activated protein (MAP) kinases that play essential roles in the expression of proinflammatory cytokines. ERK inhibition in macrophages significantly suppressed both mRNA and protein expression of IL-6 and TNF-α and mRNA expression of IL-1β. On the other hand, JNK inhibition resulted in reductions in both c-Jun and ERK activation and significant suppression of all three proinflammatory cytokines at both the mRNA and protein levels. Inhibition of p38 suppressed only IL-6 protein expression with no effect on the expression of IL-1β and TNF-α. Furthermore, we found that serine proteases produced byBlastocystisplay an important role in the induction of ERK activation and proinflammatory cytokine expression by macrophages. Our study thus demonstrated for the first time thatBlastocystiscould induce the expression of various proinflammatory cytokines via the activation of MAP kinases and that infection withBlastocystismay contribute to the pathogenesis of inflammatory intestinal diseases through the activation of inflammatory pathways in host immune cells, such as macrophages.
A Synthetic Peptide Corresponding to the Extracellular Loop 2 Region of Claudin-4 Protects against Clostridium perfringens Enterotoxin
In Vitro
and
In Vivo
Authors: Shrestha Archana , Robertson Susan L. , Garcia Jorge , Beingasser Juliann , McClane Bruce A. , Uzal Francisco A.
Published: August 2014

Clostridium perfringens
enterotoxin (CPE) action starts when the toxin binds to claudin receptors. Claudins contain two extracellular loop domains, with the second loop (ECL-2) being slightly smaller than the first. CPE has been shown to bind to ECL-2 in receptor claudins. We recently demonstrated that Caco-2 cells (a naturally CPE-sensitive enterocyte-like cell line) can be protected from CPE-induced cytotoxicity by preincubating the enterotoxin with soluble full-length recombinant claudin-4 (
r
claudin-4), which is a CPE receptor, but not with recombinant nonreceptor claudins, such as
r
claudin-1. The current study evaluated whether a synthetic peptide corresponding to the claudin-4 ECL-2 sequence can similarly inhibit CPE action
in vitro
and
in vivo
. Significant protection of Caco-2 cells was also observed using either
r
claudin-4 or the claudin-4 ECL-2 peptide in both a preincubation assay and a coincubation assay. This inhibitory effect was specific, since
r
claudin-1 and a synthetic peptide based on the claudin-1 ECL-2 offered no protection to Caco-2 cells. However, the claudin-4 ECL-2 peptide was unable to neutralize cytotoxicity if CPE had already bound to Caco-2 cells. When the study was repeated
in vivo
using a rabbit small intestinal loop assay, preincubation or coincubation of CPE with the claudin-4 ECL-2 peptide significantly and specifically inhibited the development of CPE-induced luminal fluid accumulation and histologic lesions in rabbit small intestinal loops. No similar
in vivo
protection from CPE was afforded by the claudin-1 ECL-2 peptide. These results suggest that claudin-4 ECL-2 peptides should be further investigated for their potential therapeutic application against CPE-associated disease.
Near-Real-Time Analysis of the Phenotypic Responses of Escherichia coli to 1-Butanol Exposure Using Raman Spectroscopy
Authors: Zu Theresah N. K. , Athamneh Ahmad I. M. , Wallace Robert S. , Collakova Eva , Senger Ryan S.
Published: August 2014

Raman spectroscopy was used to study the time course of phenotypic responses of
Escherichia coli
(DH5α) to 1-butanol exposure (1.2% [vol/vol]). Raman spectroscopy is of interest for bacterial phenotyping because it can be performed (i) in near real time, (ii) with minimal sample preparation (label-free), and (iii) with minimal spectral interference from water. Traditional off-line analytical methodologies were applied to both 1-butanol-treated and control cells to draw correlations with Raman data. Here, distinct sets of Raman bands are presented that characterize phenotypic traits of
E. coli
with maximized correlation to off-line measurements. In addition, the observed time course phenotypic responses of
E. coli
to 1.2% (vol/vol) 1-butanol exposure included the following: (i) decreased saturated fatty acids levels, (ii) retention of unsaturated fatty acids and low levels of cyclopropane fatty acids, (iii) increased membrane fluidity following the initial response of increased rigidity, and (iv) no changes in total protein content or protein-derived amino acid composition. For most phenotypic traits, correlation coefficients between Raman spectroscopy and traditional off-line analytical approaches exceeded 0.75, and major trends were captured. The results suggest that near-real-time Raman spectroscopy is suitable for approximating metabolic and physiological phenotyping of bacterial cells subjected to toxic environmental conditions.
The Iho670 Fibers of Ignicoccus hospitalis Are Anchored in the Cell by a Spherical Structure Located beneath the Inner Membrane
Authors: Meyer Carolin , Heimerl Thomas , Wirth Reinhard , Klingl Andreas , Rachel Reinhard
Published: August 2014

The Iho670 fibers of the hyperthermophilic crenarchaeon of
Ignicoccus hospitalis
were shown to contain several features that indicate them as type IV pilus-like structures. The application of different visualization methods, including electron tomography and the reconstruction of a three-dimensional model, enabled a detailed description of a hitherto undescribed anchoring structure of the cell appendages. It could be identified as a spherical structure beneath the inner membrane. Furthermore, pools of the fiber protein Iho670 could be localized in the inner as well as the outer cellular membrane of
I. hospitalis
cells and in the tubes/vesicles in the intermembrane compartment by immunological methods.
Extracellular Secretion of Noncatalytic Plant Cell Wall-Binding Proteins by the Cellulolytic Thermophile Caldicellulosiruptor bescii
Authors: Yokoyama Hiroshi , Yamashita Takahiro , Morioka Riki , Ohmori Hideyuki
Published: August 2014

Caldicellulosiruptor bescii
efficiently degrades cellulose, xylan, and native grasses at high temperatures above 70°C under anaerobic conditions.
C. bescii
extracellularly secretes multidomain glycoside hydrolases along with proteins of unknown function. In this study, we analyzed the
C. bescii
proteins that bind to the cell walls of timothy grass by using mass spectrometry, and we identified four noncatalytic plant cell wall-binding proteins (PWBPs) with high pI values (9.2 to 9.6). A search of a conserved domain database showed that these proteins possess a common domain related to solute-binding proteins. In addition, 12 genes encoding PWBP-like proteins were detected in the
C. bescii
genomic sequence. To analyze the binding properties of PWBPs, recombinant PWBP57 and PWBP65, expressed in
Escherichia coli
, were prepared. The PWBPs displayed a wide range of binding specificities: they bound to cellulose, lichenan, xylan, arabinoxylan, glucuronoxylan, mannan, glucomannan, pectin, oligosaccharides, and the cell walls of timothy grass. The proteins showed the highest binding affinity for the plant cell wall, with association constant (

K
a

) values of 5.2 × 10
6
to 44 × 10
6
M
−1
among the insoluble polysaccharides tested, as measured using depletion binding isotherms. Affinity gel electrophoresis demonstrated that the proteins bound to the acidic polymer pectin most strongly among the soluble polysaccharides tested. Fluorescence microscopic analysis showed that the proteins bound preferentially to the cell wall in a section of grass leaf. Binding of noncatalytic PWBPs with high pI values might be necessary for efficient utilization of polysaccharides by
C. bescii
at high temperatures.
Holins in Bacteria, Eukaryotes, and Archaea: Multifunctional Xenologues with Potential Biotechnological and Biomedical Applications
Authors: Saier Milton H. , Reddy Bhaskara L.
Published: August 2014

Holins form pores in the cytoplasmic membranes of bacteria for the primary purpose of releasing endolysins that hydrolyze the cell wall and induce cell death. Holins are encoded within bacteriophage genomes, where they promote cell lysis for virion release, and within bacterial genomes, where they serve a diversity of potential or established functions. These include (i) release of gene transfer agents, (ii) facilitation of programs of differentiation such as those that allow sporulation and spore germination, (iii) contribution to biofilm formation, (iv) promotion of responses to stress conditions, and (v) release of toxins and other proteins. There are currently 58 recognized families of holins and putative holins with members exhibiting between 1 and 4 transmembrane α-helical spanners, but many more families have yet to be discovered. Programmed cell death in animals involves holin-like proteins such as Bax and Bak that may have evolved from bacterial holins. Holin homologues have also been identified in archaea, suggesting that these proteins are ubiquitous throughout the three domains of life. Phage-mediated cell lysis of dual-membrane Gram-negative bacteria also depends on outer membrane-disrupting “spanins” that function independently of, but in conjunction with, holins and endolysins. In this minireview, we provide an overview of their modes of action and the first comprehensive summary of the many currently recognized and postulated functions and uses of these cell lysis systems. It is anticipated that future studies will result in the elucidation of many more such functions and the development of additional applications.
The management of peanut allergy
Authors: Anagnostou Katherine , Clark Andrew
Published: August 2014

Peanut allergy is common and can be a cause of severe, life-threatening reactions. It is rarely outgrown like other food allergies such as egg and milk. Measures aiming to reduce its prevalence via maternal avoidance during pregnancy and lactation, or delayed introduction into the diet, have failed to show any benefit. Peanut allergy has a significant effect on the quality of life of sufferers and their families due to dietary and social restrictions, but mainly stemming from fear of accidental peanut ingestion. The current management consists of strict avoidance, education and provision of emergency medication. Families find avoidance challenging as peanut is hidden in various food products. Despite the fact that food labelling has improved, with a legal obligation to declare certain food allergens (including nuts) in prepacked products, it still causes confusion and does not extend to cross-contamination. In an effort to address issues of safety at school, a lot of work has been undertaken to better care for peanut-allergic children in that environment. This includes training of school staff on how to recognise and treat allergic reactions promptly. Recent developments in the management of peanut allergy, such as immunotherapy, have shown some promise as an active form of treatment, but larger studies are required to further investigate safety and efficacy.
Intraoperative angiography does not lead to increased rates of surgical site infections
Authors: Stetler William R , Wilson Thomas J , Al-Holou Wajd N , Khan Adam , Thompson B Gregory , Pandey Aditya S
Published: August 2014

Background

Intraoperative angiography (IOA) is essential in evaluating residual aneurysm following clip ligation, but it does lead to an additional procedure which increases the duration of the procedure as well as increasing room traffic. We examined whether IOA during microsurgery is a risk factor for developing cranial surgical site infection.

Materials and methods

A retrospective cohort study was performed of all patients undergoing craniotomy for aneurysm treatment between 2005 and 2012 at the University of Michigan. IOA was used at the surgeons’ discretion. The primary outcome of interest was occurrence of a surgical site infection and the secondary outcome of interest was clip repositioning following IOA. Variables including IOA were tested for their independent association with the occurrence of a surgical site infection.

Results

During the study period 676 intracranial aneurysms were treated by craniotomy; IOA was used in 104 of these cases. There were a total of 20 surgical site infections, 2 in the IOA group (1.9%) and 18 in the non-IOA group (3.1%), indicating that IOA was not a statistically significant variable for infection (p=0.50). No additional single variable measured could be shown to have a statistically significant increase in infection, and there were no direct complications related to the use of IOA (stroke, dissection, perforation).

Conclusions

IOA does not increase the risk of developing a surgical site infection. It can be conducted without exposing patients to an undue risk of infection.
Size- and morphology-dependent structural transformations in anatase TiO2 nanowires under high pressures
Authors: Dong Zhaohui , Song Yang
Published: August 2014

Titanium dioxide (TiO2) nanowires with two different dimensions (i.e., <100 nm and ∼200 nm in diameter) were synthesized and studied under high pressure up to 37 GPa by Raman spectroscopy and synchrotron X-ray diffraction. Direct anatase to baddeleyite phase transitions were observed in both samples upon compression, but with different onset pressures. The observed phase transitions are in contrast to bulk TiO2, where the anatase phase transforms to α-PbO2 phase and then the baddeleyite phase. Compressibility of the anatase and baddeleyite phases was found different than both nanocrystals and the corresponding bulk materials. Our comparative study demonstrated not only that the morphology of TiO2 nanowire substantially influences the high pressure behaviors, but dimensions play a determining role in terms of transformation pressures, phase stability regions, and compressibility.