bluuebunny/crossref_metadata_2025 huggingface dataset:
Non‐Anthropocentric Narrative Strategies in Recent Experimental US Fiction
Authors: Traub Courtney
Published: September 2016

This article pinpoints a genre of contemporary experimental fiction that troubles normative ethical and representational demarcations between human and nonhuman life, aggregating in ecologically posthumanist, non‐anthropocentric perspectives. After offering an overview of current ecocritical debates around humanness and naturalness in the Anthropocene, the article considers two contemporary novels from the US that employ formal devices and self‐reflexive narrative strategies to disrupt the assumed primacy of the human. Addressing problems of human‐driven environmental disruption, biodiversity, and nonhuman personhood, Mark Z. Danielewski'sOnly Revolutions() and Evan Dara'sThe Lost Scrapbook() offer concrete examples of such strategies. Simultaneously deconstructive and reconstructive, these texts excoriate reigning Western discourses about Nature while imagining less deleterious sorts of relations humans might forge with the natural nonhuman world. Moreover, while the realist narrative strategies associated with traditional “nature writing” are largely absent in these experimental texts, their attention to concrete environmental risks and ethical quandaries diverges from postmodernism's purported treatment of the natural world as a mere arena of discourse subject to perpetual deconstruction. Instead, the self‐reflexive, antitotalizing, and contingent qualities associated most frequently with literary postmodernism and poststructuralist critique serve to unseat the presumptions of classical humanism, offering alternative ways of trying to know and relate to the nonhuman world – or even suggesting thatnot knowingconstitutes an ecological ethos in itself. “Critical anthropomorphism” is a strategy and trope already present in the seminal ecological writings of Henry David Thoreau and discernible inOnly Revolutions. Rather than re‐inscribing the centrality of humanness, it imagines the extension of personhood to nonhuman life. Meanwhile, in Dara's novel, the natural world figures as both radically other from, and inextricably connected to, the human: as such, the former stands in what Caribbean poet and critic Édouard Glissant would call “opaque relationality” to the latter. An ethos of opacity thus constitutes a second, radically non‐anthropocentric narrative strategy in this experimental fiction. Narrative opacity offers decentered, contingent accounts of human interactions with the natural world rather than hierarchically ordered or taxonomically precise ones, effectively troubling the presumptions of epistemological control and stewardship over the nonhuman that dominate in traditional nature writing.
The Limits of World Literature
Authors: Holmes Christopher
Published: September 2016

This essay examines recent work on world literature theory, with a particular focus on those theorists who treat individual texts as in dialogue with the circulations of linguistic and cultural translation. I treat world literature as the theory without an object and make the counterintuitive claim that its objectlessness makes it well suited for leaving behind antiquated modes of categorizing and canonizing so‐called world texts, in order to make room for new kinds of structured thinking about the world. The essay begins with an introduction to the manifold interconnections of the new world literature, including its broad overlap with fields of globalization, translation studies, comparative literature, and postcolonialism. I position four key theorists of 21st century world literature –Emily Apter,Rebecca Walkowitz,Berthold Schoene, andDavid Palumbo‐Liu– in oppositional pairs in order to show the underlying commonality in their thinking about the value of a literature of and for the world. My entry point into the “thinking machine” of the world literature text is the concept of the limit. Far from the commonplace understanding of limit as a limitation or boundary, I argue that understanding world literature at the limit allows literary texts and theory to be read as an event of thinking that is in‐process, in‐common, and incomplete, an analogue to the necessary impossibility of knowing the world.
Holocaust Trauma and Jewish Identity across Generations in Alison Pick's Far to Go
Authors: Smith Philip
Published: September 2016

The central purpose of this paper is to outline the key concerns with regard to literature by the children and grandchildren of those Jewish individuals who lived through the Nazi killing project. This paper begins with a cross‐disciplinary survey of the issues which surround the recurring questions of Jewish identity and the right to speak on the Shoah for the second and third generation. The argument presented is that, due to the moral and logistical immensity of their subject, as well as the dominant discourse on the Holocaust, many members of the second and third generations do not feel that they are able to take ownership of, or see themselves as a part of, their family history. These themes are then explored in relation to third‐generation writer Alison Pick's novel Far to Go, looking specifically at the ways in which the novel reflects question of Jewish identity for the second and third generation.
Characterization of secreted sphingosine‐1‐phosphate lyases required for virulence and intracellular survival of Burkholderia pseudomallei
Authors: Custódio Rafael , McLean Christopher J. , Scott Andrew E. , Lowther Jonathan , Kennedy Amanda , Clarke David J. , Campopiano Dominic J. , Sarkar‐Tyson Mitali , Brown Alan R.
Published: September 2016

Sphingosine‐1‐phosphate (S1P), a bioactive sphingolipid metabolite, plays a critical role in the orchestration of immune responses. S1P levels within the mammalian host are tightly regulated, in part through the activity of S1P lyase (S1PL) which catalyses its irreversible degradation. Herein, we describe the identification and characterization of secreted S1PL orthologues encoded by the facultative intracellular bacteria Burkholderia pseudomallei and Burkholderia thailandensis. These bacterial orthologues exhibited S1PL enzymatic activity, functionally complemented an S1PL‐deficient yeast strain and conferred resistance to the antimicrobial sphingolipid D‐erythro‐sphingosine. We report that secretion of these bacterial S1PLs is pH‐dependent, and is observed during intracellular infection. S1PL‐deficient mutants displayed impaired intracellular replication in murine macrophages (associated with an inability to evade the maturing phagosome) and were significantly attenuated in murine and larval infection models. Furthermore, treatment of Burkholderia‐infected macrophages with either S1P or a selective agonist of S1P receptor 1 enhanced bacterial colocalisation with LAMP‐1 and reduced their intracellular survival. In summary, our studies confirm bacterial‐encoded S1PL as a critical virulence determinant of B. pseudomallei and B. thailandensis, further highlighting the pivotal role of S1P in host‐pathogen interactions. In addition, our data suggest that S1P pathway modulators have potential for the treatment of intracellular infection.
Indulgences: A New Appreciation for the Present Moment?
Authors: Robson Jo
Published: September 2016

With the celebration of the Extraordinary Jubilee of Mercy indulgences have once again moved to the fore of Catholic imagination, with many pilgrims availing themselves of the opportunity to pass through a Door of Mercy or ‘Holy Door’ and thereby receive the jubilee indulgence. While the practice of indulgences has experienced something of a revival in popularity during recent papacies, the precise doctrine remains largely unrehearsed and unfamiliar, simultaneously evoking strong reactions of distaste and disquiet among many as memories of medieval abuse linger on. This article sets out the precepts of the most recent authoritative teaching on indulgences, itself almost fifty years old, before exploring the theological interpretation offered by Karl Rahner and tracing its gradual and largely anonymous appropriation in papal teaching through the post‐conciliar period. With Pope Francis promoting mercy as a central theme for his papacy and ecclesial vision, the paper closes by considering how he may be proposing a further re‐appropriation of indulgences which shifts attention from their post‐mortem efficacy to their capacity to establish a Franciscan reflexivity of mercy in the contemporary church.
A SIMPLE LINEARIZATION PROCEDURE FOR OBTAINING R0 FROM INVASIVE EPIDEMIC MODELS
Authors: ROSSI MARCELO MARGON , TERNES SONIA
Published: September 2016

Plant diseases often cause yield losses in agriculture worldwide. In mathematical ecology, the concept of the basic (or basal) reproduction number, R0, has received little attention in the scientific literature related to phytopathogen transmission in plants. The spread and magnitude of outbreaks, the rate of invasion and infectivity of the etiologic agent, the contact complexities occurring among parasite and host, and its susceptibility and period of infectiousness are very important factors for epidemiological models. These mathematical models, when applied in ecology, can help to understand the spread of infections from phytopathogens (or pests) to plant hosts as well as detect potential risks of contamination or outbreaks by using the basic reproduction number in effective control strategies. In this study, the Maclaurin series concepts on the Force of Infection were applied to derive R0 expressions from generic epidemiological SIR (Susceptible‐Infected‐Removed) models. Consequently, we were able to obtain these relations from three transmission‐infection model examples. Then, once the expression of Force of Infection is known from the “infectious” problem studied, it is possible to apply this technique to formulate the R0 relation and guide practicable strategies for dispersing invasive phytopathogen controls.
Petunia hybrida PDR2 is involved in herbivore defense by controlling steroidal contents in trichomes
Authors: Sasse Joëlle , Schlegel Markus , Borghi Lorenzo , Ullrich Friederike , Lee Miyoung , Liu Guo‐Wei , Giner José‐Luis , Kayser Oliver , Bigler Laurent , Martinoia Enrico , Kretzschmar Tobias
Published: September 2016

As a first line of defense against insect herbivores many plants store high concentrations of toxic and deterrent secondary metabolites in glandular trichomes. Plant Pleiotropic Drug Resistance (PDR)‐type ABC transporters are known secondary metabolite transporters, and several have been implicated in pathogen or herbivore defense. Here, we report on Petunia hybrida PhPDR2 as a major contributor to trichome‐related chemical defense. PhPDR2 was found to localize to the plasma membrane and be predominantly expressed in multicellular glandular trichomes of leaves and stems. Down‐regulation of PhPDR2 via RNA interference (pdr2) resulted in a markedly higher susceptibility of the transgenic plants to the generalist foliage feeder Spodoptera littoralis. Untargeted screening of pdr2 trichome metabolite contents showed a significant decrease in petuniasterone and petuniolide content, compounds, which had previously been shown to act as potent toxins against various insects. Our findings suggest that PhPDR2 plays a leading role in controlling petuniasterone levels in leaves and trichomes of petunia, thus contributing to herbivory resistance.
Repigmentation patterns induced by NB‐UVB and their relationship with melanocytic migration and proliferation in vitiligo
Authors: Castanedo‐Cázares Juan Pablo , Cortés‐García Juan Diego , Fuentes‐Ahumada Cornelia , Martinez‐Rosales Karla , Torres‐Álvarez Bertha
Published: September 2016

Background/Purpose

Vitiligo is the most commonly acquired depigmentation disorder of the skin and is characterized by the destruction of melanocytes. Ultraviolet phototherapy with narrow band (UVB‐NB) induces proliferation, differentiation, maturation, and migration of melanocytes. The clinical repigmentation is featured by follicular, marginal, and diffuse patterns. The aim of this study was to observe the process involved in the melanocyte migration and proliferation among these patterns and the unresponsive lesions following UVB‐NB phototherapy. The focal adhesion kinase (FAK) and c‐KIT were used as markers of melanocyte migration and differentiation, respectively.

Methods

A total of 17 vitiligo patients under UVB‐NB therapy were selected. The patients expressed the three repigmentation patterns as well as unresponsive lesions at the conclusion of a 30‐session cycle. Skin biopsies were evaluated by immunohistochemistry and qRT‐PCR.

Results

We found an increased expression of c‐KIT in the follicular pattern compared to the diffuse pattern that was expressed predominantly of FAK. Marginal pattern expressed both proteins. The unresponsive achromic lesions showed poor expressions of both markers.

Conclusion

Proliferation was prominent in the follicular pattern, but migration was prominent in the diffuse pattern. For the marginal pattern, both dynamics were present. The absence of these markers in vitiligo lesions suggests a lack of response to UVB‐NB.
When Political Gridlock Reigns in Presidential Foreign Policy: Policy Availability and the Role of Congress
Authors: Marshall Bryan W. , Prins Brandon C.
Published: September 2016

There is an inherent connection between the party cover and policy availability theories that has been largely overlooked by the presidential use of force literature. Party cover views the president's party strength in Congress as the prominent structural source shaping presidential incentives by diffusing responsibility in foreign policy. But policy availability adds to this view by explaining how such domestic conditions shape the variety of choices (or tools) presidents have for demonstrating political leadership. Policy availability anticipates that presidential incentives to use the Constitution's Article II authority across foreign policy operations will vary depending on the president's relationship with Congress. This analysis provides insight into claims made by policy availability arguments regarding the role of Congress in explaining presidential decisions to initiate military interventions. The findings point to important differences in the effects of Congress on presidential decisions for low‐risk versus high‐risk military missions. We find that the president's ability to legislate decreases the likelihood of humanitarian interventions. In addition, we find that as the president's relationship with Congress becomes more legislatively productive, presidents seem significantly more drawn toward high‐ risk military interventions. We infer from these findings that policy availability represents a powerful motivation in the president's calculation to engage in foreign policy interventions.
Spatio‐temporal Ornstein–Uhlenbeck Processes: Theory, Simulation and Statistical Inference
Authors: Nguyen Michele , Veraart Almut E. D.
Published: September 2016

Spatio‐temporal modelling is an increasingly popular topic in Statistics. Our paper contributes to this line of research by developing the theory, simulation and inference for a spatio‐temporal Ornstein–Uhlenbeck process. We conduct detailed simulation studies and demonstrate the practical relevance of these processes in an empirical study of radiation anomaly data. Finally, we describe how predictions can be carried out in the Gaussian setting.
Absorptive Capacity as a Mediator: Innovation of Handicraft Exporters in Yogyakarta, Indonesia
Authors: Fransen Jan , Helmsing A.H.J. (Bert)
Published: September 2016

Innovation processes in emerging economies tend to differ from those in developed countries in that a larger share of firms absorb existing knowledge. The paper assesses how firms’ absorptive capacity mediates the impact of global value chains on the innovation of handicraft exports in Yogyakarta, Indonesia. The study draws three conclusions. First, the incremental innovation of craft exporters demands specific but rather mundane absorptive capacities of firms, such as language abilities and capable departments. Second, and contrary to what might be expected, the study finds that the governance modes of global value chains do not significantly affect the level of innovation. Third, a group of traders have the highest level of innovation, the highest level of absorptive capacity, and they positively affect the innovation of suppliers. Overall, the findings show that knowledge diffusion is furthered within an emerging local innovation system.
An emerging opportunistic infection: fatal astrovirus (VA1/HMO‐C) encephalitis in a pediatric stem cell transplant recipient
Authors: Lum Su Han , Turner Andrew , Guiver Malcolm , Bonney Denise , Martland Timorthy , Davies Emma , Newbould Melanie , Brown Julianne , Morfopoulou Sofia , Breuer Judith , Wynn Robert
Published: September 2016

Neuroinvasive astrovirus (VA1‐HMO‐C) is an emerging life‐threatening infection in immunocompromised hosts. We describe an 8‐month‐old child who died of VA1/HMO‐C encephalitis following bone marrow transplantation. The diagnosis was only made post‐mortem using RNA deep sequencing of the brain. Repeat analysis of the post‐mortem brain tissue using polymerase chain reaction specific primers for VA1/HMO‐C was positive. Astrovirus VA1/HMO‐C should be included in the evaluation of patients with similar encephalitis.
Reconsidering Carbon Permits Auction Mechanism: An Efficient Dynamic Model
Authors: Wang Mingrong , Wang Mingxi , Lang Lihua
Published: September 2016

One of major concerns for China and developing countries is the new international trade rule concerning carbon emissions, which one needs to know its suitable mechanism and the possible implication on China's carbon trading market. Precisely, in an emission‐and‐trade scheme, an important question is whether the auction outcome is efficient, since this is closely related with the economic costs of emissions reduction. Due to the unique features of carbon permits, existing auction mechanisms do not seem to be suitable for their distribution. Inspired by the tâtonnement process, this paper proposes a new auction mechanism for them. For both practical application and theoretical extension, the discrete and continuous situations are examined, respectively. The result shows that the proposed auction converges to Pareto optimal equilibria, and that without ties, the equilibrium is unique. For bidders, the straightforward bidding strategy is the most preferred one, in the sense that the strategy makes them avoid the risk of loss. Intuitively, the auctioneer's utility is increasing in the number of bidders, while bidders’ pay‐off is increasing in permits. To a certain extent, the proposed auction mechanism resolves the confliction between efficiency and revenue in the multi‐item auction theory, while it increases people's understanding for carbon emission auction mechanism design.
Former star surgeon's disgrace rocks Swedish science
Authors: Vogel Gretchen
Published: September 2016

Investigations into the Paolo Macchiarini scandal highlight misconduct and institutional failings.
In Iran, a shady market for papers flourishes
Authors: Stone Richard
Published: September 2016

New law would tame the practice of selling theses and research articles—if enforced.
Whatever happened to …
Authors: Leslie Mitch
Published: September 2016

Celebrity molecules promised to transform our health, but haven't always lived up to their billing.
The new harvest
Authors: Hines Pamela J. , Travis John
Published: September 2016

Translational plant science yields sustainable oils, pharmaceuticals, and proteins.
Ecological selectivity of the emerging mass extinction in the oceans
Authors: Payne Jonathan L. , Bush Andrew M. , Heim Noel A. , Knope Matthew L. , McCauley Douglas J.
Published: September 2016

To better predict the ecological and evolutionary effects of the emerging biodiversity crisis in the modern oceans, we compared the association between extinction threat and ecological traits in modern marine animals to associations observed during past extinction events using a database of 2497 marine vertebrate and mollusc genera. We find that extinction threat in the modern oceans is strongly associated with large body size, whereas past extinction events were either nonselective or preferentially removed smaller-bodied taxa. Pelagic animals were victimized more than benthic animals during previous mass extinctions but are not preferentially threatened in the modern ocean. The differential importance of large-bodied animals to ecosystem function portends greater future ecological disruption than that caused by similar levels of taxonomic loss in past mass extinction events.
Awake hippocampal reactivations project onto orthogonal neuronal assemblies
Authors: Malvache Arnaud , Reichinnek Susanne , Villette Vincent , Haimerl Caroline , Cossart Rosa
Published: September 2016

The chained activation of neuronal assemblies is thought to support major cognitive processes, including memory. In the hippocampus, this is observed during population bursts often associated with sharp-wave ripples, in the form of an ordered reactivation of neurons. However, the organization and lifetime of these assemblies remain unknown. We used calcium imaging to map patterns of synchronous neuronal activation in the CA1 region of awake mice during runs on a treadmill. The patterns were composed of the recurring activation of anatomically intermingled, but functionally orthogonal, assemblies. These assemblies reactivated discrete temporal segments of neuronal sequences observed during runs and could be stable across consecutive days. A binding of these assemblies into longer chains revealed temporally ordered replay. These modules may represent the default building blocks for encoding or retrieving experience.
The socially savvy tree
The Hidden Life of Trees What They Feel, How They Communicate
Peter Wohlleben
Greystone Books, 2016. 288 pp.
Authors: Popkin Gabriel
Published: September 2016

Anthropomorphisms abound, but science underlies a forester's reverent ode to woodland complexity
A missed opportunity for U.S. biotechnology regulation
Authors: Kuzma Jennifer
Published: September 2016

Policy options for change were not on the table
Harnessing mutation: The best of two worlds
Authors: Conticello Silvestro G. , Rada Cristina
Published: September 2016

Combining vertebrate and bacterial immunity components enables targeted mutagenesis
Induction of Robust Immune Responses in Swine by Using a Cocktail of Adenovirus-Vectored African Swine Fever Virus Antigens
Authors: Lokhandwala Shehnaz , Waghela Suryakant D. , Bray Jocelyn , Martin Cameron L. , Sangewar Neha , Charendoff Chloe , Shetti Rashmi , Ashley Clay , Chen Chang-Hsin , Berghman Luc R. , Mwangi Duncan , Dominowski Paul J. , Foss Dennis L. , Rai Sharath , Vora Shaunak , Gabbert Lindsay , Burrage Thomas G. , Brake David , Neilan John , Mwangi Waithaka
Published: September 2016

The African swine fever virus (ASFV) causes a fatal hemorrhagic disease in domestic swine, and at present no treatment or vaccine is available. Natural and gene-deleted, live attenuated strains protect against closely related virulent strains; however, they are yet to be deployed and evaluated in the field to rule out chronic persistence and a potential for reversion to virulence. Previous studies suggest that antibodies play a role in protection, but induction of cytotoxic T lymphocytes (CTLs) could be the key to complete protection. Hence, generation of an efficacious subunit vaccine depends on identification of CTL targets along with a suitable delivery method that will elicit effector CTLs capable of eliminating ASFV-infected host cells and confer long-term protection. To this end, we evaluated the safety and immunogenicity of an adenovirus-vectored ASFV (Ad-ASFV) multiantigen cocktail formulated in two different adjuvants and at two immunizing doses in swine. Immunization with the cocktail rapidly induced unprecedented ASFV antigen-specific antibody and cellular immune responses against all of the antigens. The robust antibody responses underwent rapid isotype switching within 1 week postpriming, steadily increased over a 2-month period, and underwent rapid recall upon boost. Importantly, the primed antibodies strongly recognized the parental ASFV (Georgia 2007/1) by indirect fluorescence antibody (IFA) assay and Western blotting. Significant antigen-specific gamma interferon-positive (IFN-γ+) responses were detected postpriming and postboosting. Furthermore, this study is the first to demonstrate induction of ASFV antigen-specific CTL responses in commercial swine using Ad-ASFV multiantigens. The relevance of the induced immune responses in regard to protection needs to be evaluated in a challenge study.
Evaluation of a Semiquantitative Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry Method for Rapid Antimicrobial Susceptibility Testing of Positive Blood Cultures
Authors: Jung Jette S. , Hamacher Christina , Gross Birgit , Sparbier Katrin , Lange Christoph , Kostrzewa Markus , Schubert Sören
Published: September 2016

With the increasing prevalence of multidrug-resistant Gram-negative bacteria, rapid identification of the pathogen and its individual antibiotic resistance is crucial to ensure adequate antiinfective treatment at the earliest time point. Matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry for the identification of bacteria directly from the blood culture bottle has been widely established; however, there is still an urgent need for new methods that permit rapid resistance testing. Recently, a semiquantitative MALDI-TOF mass spectrometry-based method for the prediction of antibiotic resistance was described. We evaluated this method for detecting nonsusceptibility against two β-lactam and two non-β-lactam antibiotics. A collection of 30 spiked blood cultures was tested for nonsusceptibility against gentamicin and ciprofloxacin. Furthermore, 99 patient-derived blood cultures were tested for nonsusceptibility against cefotaxime, piperacillin-tazobactam, and ciprofloxacin in parallel with MALDI-TOF mass spectrometry identification from the blood culture fluid. The assay correctly classified all isolates tested for nonsusceptibility against gentamicin and cefotaxime. One misclassification for ciprofloxacin nonsusceptibility and five misclassifications for piperacillin-tazobactam nonsusceptibility occurred. Identification of the bacterium and prediction of nonsusceptibility was possible within approximately 4 h.
Disk Diffusion Testing for Detection of Methicillin-Resistant Staphylococci: Does Moxalactam Improve upon Cefoxitin?
Authors: Bonjean Marie , Hodille Elisabeth , Dumitrescu Oana , Dupieux Céline , Nkoud Mongo Christina , Allam Camille , Beghin Mathilde , Paris Mickael , Borrel Ophelie , Chardon Hubert , Laurent Fréderic , Rasigade Jean-Philippe , Lina Gerard
Published: September 2016

Disk diffusion testing is widely used to detect methicillin resistance in staphylococci, and cefoxitin is currently considered the best marker for
mecA
-mediated methicillin resistance. In low-inoculum diffusion testing (colony suspension at 10
6
CFU/ml), the addition of moxalactam in combination with cefoxitin has been reported to improve on cefoxitin alone for the detection of methicillin-heteroresistant staphylococci. However, moxalactam is absent from EUCAST and CLSI guidelines, which use high-inoculum diffusion testing (colony suspension at 10
8
CFU/ml), calling into question the potential interest of including moxalactam in their recommendations. The inhibition zone diameters of cefoxitin and moxalactam, alone and in combination, were evaluated for concordance with
mecA
and
mecC
positivity in a large collection of clinical
Staphylococcus
isolates (611
Staphylococcus aureus
,
Staphylococcus
lugdunensis
, and
Staphylococcus saprophyticus
isolates and 307 coagulase-negative staphylococci other than
S. lugdunensis
and
S. saprophyticus
isolates, of which 22% and 53% were
mecA
-positive, respectively) and in 25
mecC
-positive
S. aureus
isolates using high-inoculum diffusion testing. Receiver operating characteristic, sensitivity, and specificity analyses indicated that the detection of
mecA
- and
mecC
-positive and negative isolates did not improve with moxalactam, either alone or in combination with cefoxitin, compared to cefoxitin alone. These findings were similar in both the
S. aureus
/
S. lugdunensis
/
S. saprophyticus
group and in the coagulase-negative staphylococci group. Our results do not support the use of moxalactam as an additional marker of methicillin resistance when testing with high-inoculum disk diffusion.
Comparison of PCR-Electrospray Ionization Mass Spectrometry with 16S rRNA PCR and Amplicon Sequencing for Detection of Bacteria in Excised Heart Valves
Authors: Peeters Bart , Herijgers Paul , Beuselinck Kurt , Peetermans Willy E. , Herregods Marie-Christin , Desmet Stefanie , Lagrou Katrien
Published: September 2016

Identification of the causative pathogen of infective endocarditis (IE) is crucial for adequate management and therapy. A broad-range PCR-electrospray ionization mass spectrometry (PCR-ESI-MS) technique was compared with broad-spectrum 16S rRNA PCR and amplicon sequencing (16S rRNA PCR) for the detection of bacterial pathogens in 40 heart valves obtained from 34 definite infective endocarditis patients according to the modified Duke criteria and six nonendocarditis patients. Concordance between the two molecular techniques was 98% for being positive or negative, 97% for concordant identification up to the genus level, and 77% for concordant identification up to the species level. Sensitivity for detecting the causative pathogen (up to the genus level) in excised heart valves was 88% for 16S rRNA PCR and 85% for PCR-ESI-MS; the specificity was 83% for both methods. The two molecular techniques were significantly more sensitive than valve culture (18%) and accurately identified bacteria in excised heart valves. In eight patients with culture-negative IE, the following results were obtained: concordant detection of
Coxiella burnetii
(
n
= 2),
Streptococcus gallolyticus
(
n
= 1),
Propionibacterium acnes
(
n
= 1), and viridans group streptococci (
n
= 1) by both molecular tests, detection of
P. acnes
by PCR-ESI-MS whereas the 16S rRNA PCR was negative (
n
= 1), and a false-negative result by both molecular techniques (
n
= 2). In one case of IE caused by viridans streptococci, PCR-ESI-MS was positive for
Enterococcus
spp. The advantages of PCR-ESI-MS compared to 16S rRNA PCR are its automated workflow and shorter turnaround times.
Expansion of Comprehensive Screening of Male Sexually Transmitted Infection Clinic Attendees with Mycoplasma genitalium and Trichomonas vaginalis Molecular Assessment: a Retrospective Analysis
Authors: Munson Erik , Wenten David , Jhansale Sheila , Schuknecht Mary Kay , Pantuso Nicki , Gerritts Joshua , Steward Aaron , Munson Kimber L. , Napierala Maureen , Hamer Deb
Published: September 2016

Of 1,493 encounters of males at a sexually transmitted infection (STI) clinic in a community with a high prevalence of STI,
Chlamydia trachomatis
was detected in 8.7% and
Neisseria gonorrhoeae
was detected in 6.6%. Additional
Trichomonas vaginalis
and
Mycoplasma genitalium
screening found 17.4% and 23.9% of the encounters, respectively, to be positive for STI. STI agents were detected in 13.7% of urine specimens; addition of pharyngeal and rectal collections to the analysis resulted in detection of STI agents in 19.0% and 23.9% of encounters, respectively. A total of 101 (23.8%) encounters of identified STI involved sole detection of
M. genitalium
. Expansion of the STI analyte panel (including
M. genitalium
) and additional specimen source sampling within a comprehensive STI screening program increase identification of male STI carriers.
Commentary: Next-Generation Epidemiology: Using Real-Time Core Genome Multilocus Sequence Typing To Support Infection Control Policy
Authors: Dekker John P. , Frank Karen M.
Published: September 2016

Multidrug-resistant bacteria are responsible for substantial morbidity and mortality worldwide. Tracking the nosocomial spread of resistant bacteria is critical to infection control. Mellmann et al. (J. Clin. Microbiol. 54:2874–2881, 2016,
http://dx.doi.org/10.1128/JCM.00790-16
) have described prospective whole-genome sequencing with core genome multilocus sequencing typing (cgMLST) analysis for real-time surveillance and have addressed the practical aspects of implementing this type of operation in the hospital setting.
Rationally Designed Vaccines Targeting the V2 Region of HIV-1 gp120 Induce a Focused, Cross-Clade-Reactive, Biologically Functional Antibody Response
Authors: Zolla-Pazner Susan , Powell Rebecca , Yahyaei Sara , Williams Constance , Jiang Xunqing , Li Wei , Lu Shan , Wang Shixia , Upadhyay Chitra , Hioe Catarina E. , Totrov Max , Kong Xiangpeng
Published: September 2016

Strong antibody (Ab) responses against V1V2 epitopes of the human immunodeficiency virus type 1 (HIV-1) gp120 envelope (Env) correlated with reduced infection rates in studies of HIV, simian-human immunodeficiency virus (SHIV), and simian immunodeficiency virus (SIV). In order to focus the Ab response on V1V2, we used six V1V2 sequences and nine scaffold proteins to construct immunogens which were tested using various immunization regimens for their ability to induce cross-reactive and biologically active V2 Abs in rabbits. A prime/boost immunization strategy was employed using gp120 DNA and various V1V2-scaffold proteins. The rabbit polyclonal Ab responses (i) were successfully focused on the V1V2 region, with weak or only transient responses to other Env epitopes, (ii) displayed broad cross-reactive binding activity with gp120s and the V1V2 regions of diverse strains from clades B, C, and E, (iii) included V2 Abs with specificities similar to those found in HIV-infected individuals, and (iv) remained detectable ≥1 year after the last boosting dose. Importantly, sera from rabbits receiving V1V2-scaffold immunogens displayed Ab-dependent cellular phagocytosis whereas sera from rabbits receiving only gp120 did not. The results represent the first fully successful example of reverse vaccinology in the HIV vaccine field with rationally designed epitope scaffold immunogens inducing Abs that recapitulate the epitope specificity and biologic activity of the human monoclonal Abs from which the immunogens were designed. Moreover, this is the first immunogenicity study using epitope-targeting, rationally designed vaccine constructs that induced an Fc-mediated activity associated with protection from infection with HIV, SIV, and SHIV.

IMPORTANCE
Novel immunogens were designed to focus the antibody response of rabbits on the V1V2 epitopes of HIV-1 gp120 since such antibodies were associated with reduced infection rates of HIV, SIV, and SHIV. The vaccine-induced antibodies were broadly cross-reactive with the V1V2 regions of HIV subtypes B, C and E and, importantly, facilitated Fc-mediated phagocytosis, an activity not induced upon immunization of rabbits with gp120. This is the first immunogenicity study of vaccine constructs that focuses the antibody response on V1V2 and induces V2-specific antibodies with the ability to mediate phagocytosis, an activity that has been associated with protection from infection with HIV, SIV, and SHIV.
Herpes Simplex Virus 1 Enters Human Keratinocytes by a Nectin-1-Dependent, Rapid Plasma Membrane Fusion Pathway That Functions at Low Temperature
Authors: Sayers Charlotte L. , Elliott Gillian
Published: September 2016

Herpes simplex virus 1 (HSV-1) infects humans through stratified epithelia that are composed primarily of keratinocytes. The route of HSV-1 entry into keratinocytes has been the subject of limited investigation, but it is proposed to involve pH-dependent endocytosis, requiring the gD-binding receptor nectin-1. Here, we have utilized the nTERT human keratinocyte cell line as a new model for dissecting the mechanism of HSV-1 entry into the host. Although immortalized, these cells nonetheless retain normal growth and differentiation properties of primary cells. Using short interfering RNA (siRNA) depletion studies, we confirm that, despite nTERT cells expressing high levels of the alternative gD receptor HVEM, HSV-1 requires nectin-1, not HVEM, to enter these cells. Strikingly, virus entry into nTERT cells occurred with unusual rapidity, such that maximum penetration was achieved within 5 min. Moreover, HSV-1 was able to enter keratinocytes but not other cell types at temperatures as low as 7°C, conditions where endocytosis was shown to be completely inhibited. Transmission electron microscopy of early entry events at both 37°C and 7°C identified numerous examples of naked virus capsids located immediately beneath the plasma membrane, with no evidence of virions in cytoplasmic vesicles. Taken together, these results imply that HSV-1 uses the nectin-1 receptor to enter human keratinocyte cells via a previously uncharacterized rapid plasma membrane fusion pathway that functions at low temperature. These studies have important implications for current understanding of the relationship between HSV-1 and its relevant
in vivo
target cell.

IMPORTANCE
The gold standard of antiviral treatment for any human virus infection is the prevention of virus entry into the host cell. In the case of HSV-1, primary infection in the human begins in the epidermis of the skin or the oral mucosa, where the virus infects keratinocytes, and it is therefore important to understand the molecular events involved in HSV-1 entry into this cell type. Nonetheless, few studies have looked specifically at entry into these relevant human cells. Our results reveal a new route for virus entry that is specific to keratinocytes, involves rapid entry, and functions at low temperatures. This may reflect the environmental conditions encountered by HSV-1 when entering its host through the skin and emphasizes the importance of studying virus-host interactions in physiologically relevant cells.
Feline Immunodeficiency Virus Vif N-Terminal Residues Selectively Counteract Feline APOBEC3s
Authors: Gu Qinyong , Zhang Zeli , Cano Ortiz Lucía , Franco Ana Cláudia , Häussinger Dieter , Münk Carsten
Published: September 2016

Feline immunodeficiency virus (FIV) Vif protein counteracts feline APOBEC3s (FcaA3s) restriction factors by inducing their proteasomal degradation. The functional domains in FIV Vif for interaction with FcaA3s are poorly understood. Here, we have identified several motifs in FIV Vif that are important for selective degradation of different FcaA3s. Cats (
Felis catus
) express three types of A3s: single-domain A3Z2, single-domain A3Z3, and double-domain A3Z2Z3. We proposed that FIV Vif would selectively interact with the Z2 and the Z3 A3s. Indeed, we identified two N-terminal Vif motifs (12LF13 and 18GG19) that specifically interacted with the FcaA3Z2 protein but not with A3Z3. In contrast, the exclusive degradation of FcaA3Z3 was regulated by a region of three residues (M24, L25, and I27). Only a FIV Vif carrying a combination of mutations from both interaction sites lost the capacity to degrade and counteract FcaA3Z2Z3. However, alterations in the specific A3s interaction sites did not affect the cellular localization of the FIV Vif protein and binding to feline A3s. Pulldown experiments demonstrated that the A3 binding region localized to FIV Vif residues 50 to 80, outside the specific A3 interaction domain. Finally, we found that the Vif sites specific to individual A3s are conserved in several FIV lineages of domestic cat and nondomestic cats, while being absent in the FIV Vif of pumas. Our data support a complex model of multiple Vif-A3 interactions in which the specific region for selective A3 counteraction is discrete from a general A3 binding domain.

IMPORTANCE
Both human immunodeficiency virus (HIV) and feline immunodeficiency virus (FIV) Vif proteins counteract their host's APOBEC3 restriction factors. However, these two Vif proteins have limited sequence homology. The molecular interaction between FIV Vif and feline APOBEC3s are not well understood. Here, we identified N-terminal FIV Vif sites that regulate the selective interaction of Vif with either feline APOBEC3Z2 or APOBEC3Z3. These specific Vif sites are conserved in several FIV lineages of domestic cat and nondomestic cats, while being absent in FIV Vif from puma. Our findings provide important insights for future experiments describing the FIV Vif interaction with feline APOBEC3s and also indicate that the conserved feline APOBEC3s interaction sites of FIV Vif allow FIV transmissions in
Felidae
.
Zinc Pyrithione Improves the Antibacterial Activity of Silver Sulfadiazine Ointment
Authors: Blanchard Catlyn , Brooks Lauren , Ebsworth-Mojica Katherine , Didione Louis , Wucher Benjamin , Dewhurst Stephen , Krysan Damian , Dunman Paul M. , Wozniak Rachel A. F.
Published: September 2016

Topical antimicrobial ointments ostensibly mitigate bacterial wound disease and reliance on systemic antibiotics. Yet studies have called into question the therapeutic benefits of several traditional topical antibacterials, accentuating the need for improved next-generation antimicrobial ointments. Yet the development of such agents consisting of a new chemical entity is a time-consuming and expensive proposition. Considering that drug combinations are a mainstay therapeutic strategy for the treatment of other therapeutic indications, one alternative approach is to improve the performance of conventional antimicrobial ointments by the addition of a well-characterized and FDA-approved agent. Here we report data that indicate that the antimicrobial properties of silver sulfadiazine ointments can be significantly improved by the addition of the antifungal zinc pyrithione, suggesting that such combinations may provide an improved therapeutic option for the topical treatment of wound infections.
Transition into and out of daylight saving time and spontaneous delivery: a population-based study
Authors: László Krisztina D , Cnattingius Sven , Janszky Imre
Published: September 2016

Objective

To investigate whether the circadian rhythm disruption following the transition into and out of daylight saving time (DST) is associated with an increased risk of spontaneous delivery.

Design

We compared the number of spontaneous deliveries in the Swedish Medical Birth Register during the week after the change to and the week after the change from DST (exposure periods) with the average number of spontaneous deliveries in the control period, defined as the week before and the week after each exposure period.

Setting

Sweden, 1993–2006.

Primary and secondary outcome measures

The primary outcomes were the weekly and the daily number of spontaneous deliveries in the exposure and the control periods. In secondary analyses we also compared the mean length of pregnancy of the women with spontaneous deliveries in the exposure and control periods.

Results

The number of deliveries during the week after the transition into or out of DST was similar to that in the comparison period (18 519 observed vs 18 434 expected in case of the spring shift and 19 073 observed vs 19 122 expected in case of the autumn shift); the corresponding incidence ratio and 95% CIs were 1.005 (0.990 to 1.019) and 0.997 (0.983 to 1.012), respectively. There were no differences in the length of gestation of the deliveries in the exposure and the control periods.

Conclusions

Our results do not support the hypothesis that a minor circadian rhythm disruption is associated with an increased short-term risk of spontaneous delivery.
Undrained monotonic and cyclic shear response and particle crushing of silica sand at low and high pressures
Authors: Hyodo Masayuki , Wu Yang , Aramaki Noritaka , Nakata Yukio
Published: September 2016

A series of undrained monotonic and cyclic triaxial tests were performed on silica sand at two initial densities and different confining pressures from 0.1 to 5 MPa to investigate their shear response and crushing behaviour. The influence of particle crushing on the undrained shear strength and pore-water pressure was examined. To clarify the evolution of particle crushing, undrained monotonic and cyclic tests were terminated at several distinctive stages and sieving analysis tests were subsequently performed on the tested specimens. In the undrained monotonic test, specimens exhibited remarkable dilation behaviour and experienced no apparent particle crushing at low confining pressures. An increase in the mean stress suppressed the dilatancy due to a faster increase of the pore-water pressure, giving rise to the occurrence of particle crushing. In the undrained cyclic test, a higher confining pressure and cyclic stress ratio resulted in a much higher relative breakage. At a specific cyclic stress ratio, the relative breakage increased as the cyclic loading progressed. The confining pressure and shear strain amplitude played a significant role in controlling the evolution of particle breakage. The correlation between the relative breakage and plastic work for specimens under isotropic consolidation, undrained monotonic, and cyclic loadings has been validated experimentally.
Nutrient loading by anadromous fishes: species-specific contributions and the effects of diversity
Authors: Twining Cornelia W. , Palkovacs Eric P. , Friedman Maya A. , Hasselman Daniel J. , Post David M.
Published: September 2016

Anadromous fishes exhibit diverse life history and functional traits. Spawning anadromous fishes bring nutrients to fresh waters, and their life history and functional traits can influence nutrient loading patterns. We asked how nutrient inputs varied across 12 species of North American anadromous fishes and how these patterns affected river-wide trends in nutrient loading. We used portfolio effect analyses to assess whether diversity stabilized or destabilized nutrient inputs to freshwater ecosystems over time. Recent decreases in body size reduced per individual nutrient loading for several key species, which in turn decreased cumulative loading. Invasion also altered nutrient loading; non-native American shad (Alosa sapidissima) now provide nearly half of the annual marine-derived nutrient inputs to the Columbia River. Counter to expectations, species diversity (richness and evenness) did not significantly increase the stability of nutrient inputs to fresh waters. Species loss in the Connecticut River increased stability, while species gain in the Columbia River decreased stability.
Inflammatory and Apoptotic Regulatory Activity of Tanshinone IIA in Helicobacter pylori-Infected Cells
Authors: Chen Guan-Yu , Shu Yu-Chieh , Chuang Duen-Yau , Wang Yuan-Chuen
Published: September 2016

Helicobacter pylori infections induce host cell inflammation and apoptosis, however, they are conflicting. Tanshinone IIA is an active compound of Salvia miltiorrhiza Bge. In this study, we investigated the regulatory effects of tanshinone IIA on H. pylori-induced inflammation and apoptosis in vitro. Tanshinone IIA treatments (13.6–54.4[Formula: see text][Formula: see text]M) significantly decreased nuclear factor kappa B (NF-kB) and mitogen-activated protein kinase (MAPK) [p-38 and C-terminal Jun-kinase 1/2 (JNK1/2)] protein expressions and inflammatory substance [cyclooxygenase-2 (COX-2), 5-lipooxygenase (5-LOX), intercellular adhesion molecule-1 (ICAM-1), reactive oxygen species (ROS), nitric oxide (NO), inducible nitric oxide synthase (iNOS), interleukin-1[Formula: see text] (IL-1[Formula: see text], IL-6, and IL-8] production in the H. pylori-infected cells. In contrast, tanshinone IIA treatments significantly increased apoptotic relevant protein [Bcl-2-associated X protein (Bax) and caspase 9] expressions and increased mitochondrial transmembrane potential ([Formula: see text] disruption, mitochondrial cytochrome [Formula: see text] (cyt [Formula: see text] release, and caspase cascades. Tanshinone IIA treatments effectively decreased H. pylori-induced inflammation and significantly promoted H. pylori-induced intrinsic apoptosis through NF-kB and MAPK (p-38 and JNK) pathways. Tanshinone IIA has great potential as a candidate to protect host cells from H. pylori-induced severe inflammation and gastric cancer.