bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term climbing fibre activity induces transcription of microRNAs in cerebellar Purkinje cells
Authors: Barmack Neal H. , Qian Zuyuan , Yakhnitsa Vadim
Published: August 2014

Synaptic activation of central neurons is often evoked by electrical stimulation leading to post-tetanic potentiation, long-term potentiation or long-term depression. Even a brief electrical tetanus can induce changes in as many as 100 proteins. Since climbing fibre activity is often associated with cerebellar behavioural plasticity, we used horizontal optokinetic stimulation (HOKS) to naturally increase synaptic input to floccular Purkinje cells in mice for hours, not minutes, and investigated how this activity influenced the transcription of microRNAs, small non-coding nucleotides that reduce transcripts of multiple, complementary mRNAs. A single microRNA can reduce the translation of as many as 30 proteins. HOKS evoked increases in 12 microRNA transcripts in floccular Purkinje cells. One of these microRNAs, miR335, increased 18-fold after 24 h of HOKS. After HOKS stopped, miR335 transcripts decayed with a time constant of approximately 2.5 h. HOKS evoked a 28-fold increase in pri-miR335 transcripts compared with an 18-fold increase in mature miR335 transcripts, confirming that climbing fibre-evoked increases in miR335 could be attributed to increases in transcription. We used three screens to identify potential mRNA targets for miR335 transcripts: (i) nucleotide complementarity, (ii) detection of increased mRNAs following microinjection of miR335 inhibitors into the cerebellum, and (iii) detection of decreased mRNAs following HOKS. Two genes, calbindin and 14-3-3-θ, passed these screens. Transfection of N2a cells with miR335 inhibitors or precursors inversely regulated 14-3-3-θ transcripts. Immunoprecipitation of 14-3-3-θ co-immunoprecipitated PKC-γ and GABAAγ2. Knockdown of either 14-3-3-θ or PKC-γ decreased the serine phosphorylation of GABAAγ2, suggesting that 14-3-3-θ and PKC-γ under the control of miR335 homeostatically regulate the phosphorylation and insertion of GABAAγ2into the Purkinje cell post-synaptic membrane.
DNA modifications in the mammalian brain
Authors: Shin Jaehoon , Ming Guo-li , Song Hongjun
Published: August 2014

DNA methylation is a crucial epigenetic mark in mammalian development, genomic imprinting, X-inactivation, chromosomal stability and suppressing parasitic DNA elements. DNA methylation in neurons has also been suggested to play important roles for mammalian neuronal functions, and learning and memory. In this review, we first summarize recent discoveries and fundamental principles of DNA modifications in the general epigenetics field. We then describe the profiles of different DNA modifications in the mammalian brain genome. Finally, we discuss roles of DNA modifications in mammalian brain development and function.
Postnatal signalling with homeoprotein transcription factors
Authors: Prochiantz Alain , Fuchs Julia , Di Nardo Ariel A.
Published: August 2014

Homeoprotein (HP) transcription factors were originally identified for their embryonic cell-autonomous developmental functions. In this review, we discuss their postnatal and adult physiological functions based on the study of Otx2, Engrailed-1 and Engrailed-2 (collectively Engrailed). For Engrailed, we discuss its function in the cell-autonomous regulation of ventral midbrain dopaminergic neuron survival and physiology and in the non-cell-autonomous maintenance of axons. For Otx2, we describe how the protein is expressed in the choroid plexus and transported into cortical parvalbumin cells where it regulates plasticity in the visual cortex. These two examples illustrate how the understanding of HP postnatal and adult functions, including signalling functions, may lead to the identification of disease-associated genetic pathways and to the development of original therapeutic strategies.
Sporothrix
schenckii complex biology: environment and fungal pathogenicity
Authors: Téllez M. D. , Batista-Duharte A. , Portuondo D. , Quinello C. , Bonne-Hernández R. , Carlos I. Z.
Published: August 2014

Sporothrix schenckii is a complex of various species of fungus found in soils, plants, decaying vegetables and other outdoor environments. It is the aetiological agent of sporotrichosis in humans and several animals. Humans and animals can acquire the disease through traumatic inoculation of the fungus into subcutaneous tissue. Despite the importance of sporotrichosis, it being currently regarded as an emergent disease in several countries, the factors driving its increasing medical importance are still largely unknown. There have only been a few studies addressing the influence of the environment on the virulence of these pathogens. However, recent studies have demonstrated that adverse conditions in its natural habitats can trigger the expression of different virulence factors that confer survival advantages both in animal hosts and in the environment. In this review, we provide updates on the important advances in the understanding of the biology of Spor. schenckii and the modification of its virulence linked to demonstrated or putative environmental factors.
Long-read, whole-genome shotgun sequence data for five model organisms
Authors: Kim Kristi E. , Peluso Paul , Babayan Primo , Yeadon P. Jane , Yu Charles , Fisher William W. , Chin Chen-Shan , Rapicavoli Nicole , Rank David R. , Li Joachim , Catcheside David E. A. , Celniker Susan E. , Phillippy Adam M. , Bergman Casey M. , Landolin Jane M.
Published: August 2014

Single molecule, real-time (SMRT) sequencing from Pacific Biosciences is increasingly used in many areas of biological research including de novo genome assembly, structural-variant identification, haplotype phasing, mRNA isoform discovery, and base-modification analyses. High-quality, public datasets of SMRT sequences can spur development of analytic tools that can accommodate unique characteristics of SMRT data (long read lengths, lack of GC or amplification bias, and a random error profile leading to high consensus accuracy). In this paper, we describe eight high-coverage SMRT sequence datasets from five organisms (Escherichia coli, Saccharomyces cerevisiae, Neurospora crassa, Arabidopsis thaliana, and Drosophila melanogaster) that have been publicly released to the general scientific community (NCBI Sequence Read Archive ID SRP040522). Data were generated using two sequencing chemistries (P4C2 and P5C3) on the PacBio RS II instrument. The datasets reported here can be used without restriction by the research community to generate whole-genome assemblies, test new algorithms, investigate genome structure and evolution, and identify base modifications in some of the most widely-studied model systems in biological research.
Side-binding proteins modulate actin filament dynamics
Authors: Crevenna Alvaro H. , Arciniega Marcelino , Dupont Aurelie , Kowalska Kaja , Lange Oliver , Wedlich-Soldner Roland , Lamb Don C.
Published: August 2014

Actin filament dynamics govern many key physiological processes from cell motility to tissue morphogenesis. A central feature of actin dynamics is the capacity of the filament to polymerize and depolymerize at its ends in response to cellular conditions. It is currently thought that filament kinetics can be described by a single rate constant for each end. Here, using direct visualization of single actin filament elongation, we show that actin polymerization kinetics at both filament ends are strongly influenced by proteins that bind to the lateral filament surface. We also show that the less dynamic end, called the pointed-end, has a non-elongating state that dominates the observed filament kinetic asymmetry. Estimates of filament flexibility and Brownian dynamics simulations suggest that the observed kinetic diversity arises from structural alteration. Tuning filament kinetics by exploiting the natural malleability of the actin filament structure may be a ubiquitous mechanism to generate the rich variety of observed cellular actin dynamics.
Reconsolidation of a well-learned instrumental memory
Authors: Exton-McGuinness Marc T.J. , Patton Rosemary C. , Sacco Lawrence B. , Lee Jonathan L.C.
Published: August 2014

Once consolidated, memories are dynamic entities that go through phases of instability in order to be updated with new information, via a process of reconsolidation. The phenomenon of reconsolidation has been demonstrated in a wide variety of experimental paradigms. However, the memories underpinning instrumental behaviors are currently not believed to reconsolidate. We show that well-learned lever pressing in rats does undergo reconsolidation, which can be disrupted by systemic administration of the noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist (+)-5-methyl-10,11-dihydro-SH-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) when administered prior to a switch to a variable, but not fixed, ratio schedule. Disruption of reconsolidation resulted in a reduction in long-term lever pressing performance and diminished the sensitivity of behavior to contingency change. Further investigation demonstrated that expression of the reconsolidation impairment was not affected by outcome value, implying a deficit in a stimulus–response (S–R) process. The ability to disrupt the performance of well-learned instrumental behaviors is potentially of great importance in the development of reconsolidation-based clinical treatments for conditions that involve compulsive seeking behaviors.
Protein degradation by ubiquitin–proteasome system in formation and labilization of contextual conditioning memory
Authors: Sol Fustiñana María , de la Fuente Verónica , Federman Noel , Freudenthal Ramiro , Romano Arturo
Published: August 2014

The ubiquitin–proteasome system (UPS) of protein degradation has been evaluated in different forms of neural plasticity and memory. The role of UPS in such processes is controversial. Several results support the idea that the activation of this system in memory consolidation is necessary to overcome negative constrains for plasticity. In this case, the inhibition of the UPS during consolidation impairs memory. Similar results were reported for memory reconsolidation. However, in other cases, the inhibition of UPS had no effect on memory consolidation and reconsolidation but impedes the amnesic action of protein synthesis inhibition after retrieval. The last finding suggests a specific action of the UPS inhibitor on memory labilization. However, another interpretation is possible in terms of the synthesis/degradation balance of positive and negative elements in neural plasticity, as was found in the case of long-term potentiation. To evaluate these alternative interpretations, other reconsolidation-interfering drugs than translation inhibitors should be tested. Here we analyzed initially the UPS inhibitor effect in contextual conditioning in crabs. We found that UPS inhibition during consolidation impaired long-term memory. In contrast, UPS inhibition did not affect memory reconsolidation after contextual retrieval but, in fact, impeded memory labilization, blocking the action of drugs that does not affect directly the protein synthesis. To extend these finding to vertebrates, we performed similar experiments in contextual fear memory in mice. We found that the UPS inhibitor in hippocampus affected memory consolidation and blocked memory labilization after retrieval. These findings exclude alternative interpretations to the requirement of UPS in memory labilization and give evidence of this mechanism in both vertebrates and invertebrates.
Crystal structure of (E)-2-cyano-3-(12-methyl-12H-benzo[b]phenothiazin-11-yl)acrylic acid
Authors: Watanabe Motonori , Ishihara Tatsumi
Published: August 2014

In the title compound, C21H14N2O2S, a donor–acceptor type of benzo[b]phenothiazine (bpz) derivative, the thiazine ring adopts a boat conformation and the bond-angle sum at the N atom is 360.0°. The dihedral angle between the benzene ring and the naphthelene ring system fused to the thiazine ring is 32.76 (5)°. In the crystal, carboxylic-acid inversion dimers linked by pairs of O—H...O hydrogen bonds generateR22(8) loops. Aromatic π–π stacking [shortest centroid–centroid separaton = 3.5242 (13)Å] consolidates the structure and very weak C—H...O and C—H...N interactions also occur.
Crystal structure of 5-iodo-2-methyl-3-[(4-methylphenyl)sulfonyl]-1-benzofuran
Authors: Choi Hong Dae , Lee Uk
Published: August 2014

In the title compound, C16H13IO3S, the dihedral angle between the planes of the benzofuran ring system [r.m.s. deviation = 0.015 (2) Å] and the 4-methylphenyl ring is 70.35 (5)°. In the crystal, molecules are linked by pairs of π–π interactions between the furan and benzene rings, with centroid–centroid distances of 3.667 (3) and 3.701 (3) Å. The molecules stack along thea-axis direction. In addition, pairs of C—H...O hydrogen bonds between inversion-related dimers [which generateR22(10) loops] and a short I...I [3.7534 (3) Å] contact are observed.
Expression, purification and crystallization of CTB-MPR, a candidate mucosal vaccine component against HIV-1
Authors: Lee Ho-Hsien , Cherni Irene , Yu HongQi , Fromme Raimund , Doran Jeffrey D. , Grotjohann Ingo , Mittman Michele , Basu Shibom , Deb Arpan , Dörner Katerina , Aquila Andrew , Barty Anton , Boutet Sébastien , Chapman Henry N. , Doak R. Bruce , Hunter Mark S. , James Daniel , Kirian Richard A. , Kupitz Christopher , Lawrence Robert M. , Liu Haiguang , Nass Karol , Schlichting Ilme , Schmidt Kevin E. , Seibert M. Marvin , Shoeman Robert L. , Spence John C. H. , Stellato Francesco , Weierstall Uwe , Williams Garth J. , Yoon Chunhong , Wang Dingjie , Zatsepin Nadia A. , Hogue Brenda G. , Matoba Nobuyuki , Fromme Petra , Mor Tsafrir S.
Published: August 2014

CTB-MPR is a fusion protein between the B subunit of cholera toxin (CTB) and the membrane-proximal region of gp41 (MPR), the transmembrane envelope protein ofHuman immunodeficiency virus 1(HIV-1), and has previously been shown to induce the production of anti-HIV-1 antibodies with antiviral functions. To further improve the design of this candidate vaccine, X-ray crystallography experiments were performed to obtain structural information about this fusion protein. Several variants of CTB-MPR were designed, constructed and recombinantly expressed inEscherichia coli. The first variant contained a flexible GPGP linker between CTB and MPR, and yielded crystals that diffracted to a resolution of 2.3 Å, but only the CTB region was detected in the electron-density map. A second variant, in which the CTB was directly attached to MPR, was shown to destabilize pentamer formation. A third construct containing a polyalanine linker between CTB and MPR proved to stabilize the pentameric form of the protein during purification. The purification procedure was shown to produce a homogeneously pure and monodisperse sample for crystallization. Initial crystallization experiments led to pseudo-crystals which were ordered in only two dimensions and were disordered in the third dimension. Nanocrystals obtained using the same precipitant showed promising X-ray diffraction to 5 Å resolution in femtosecond nanocrystallography experiments at the Linac Coherent Light Source at the SLAC National Accelerator Laboratory. The results demonstrate the utility of femtosecond X-ray crystallography to enable structural analysis based on nano/microcrystals of a protein for which no macroscopic crystals ordered in three dimensions have been observed before.
Evidence for shifts to faster growth strategies in the new ranges of invasive alien plants
Authors: Leishman Michelle R. , Cooke Julia , Richardson David M.
Published: August 2014

Understanding the processes underlying the transition from introduction to naturalization and spread is an important goal of invasion ecology. Release from pests and pathogens in association with capacity for rapid growth is thought to confer an advantage for species in novel regions.

We assessed leaf herbivory and leaf‐level traits associated with growth strategy in the native and exotic ranges of 13 invasive plant species from 256 populations. Species were native to either the Western Cape region of South Africa, south‐western Australia or south‐eastern Australia and had been introduced to at least one of the other regions or to New Zealand. We tested for evidence of herbivore release and shifts in leaf traits between native and exotic ranges of the 13 species.

Across all species, leaf herbivory, specific leaf area and leaf area were significantly different between native and exotic ranges while there were no significant differences across the 13 species found for leaf mass, assimilation rate, dark respiration or foliar nitrogen.

Analysis at the species‐ and region‐level showed that eight out of 13 species had reduced leaf herbivory in at least one exotic region compared to its native range.

Six out of 13 species had significantly larger specific leaf area (SLA) in at least one exotic range region and five of those six species experienced reduced leaf herbivory. Increases in SLA were underpinned by increases in leaf area rather than reductions in leaf mass.

No species showed differences in the direction of trait shifts from the native range between different exotic regions. This suggests that the driver of selection on these traits in the exotic range is consistent across regions and hence is most likely to be associated with factors linked with introduction to a novel environment, such as release from leaf herbivory, rather than with particular environmental conditions.

Synthesis. These results provide evidence that introduction of a plant species into a novel environment commonly results in a reduction in the top‐down constraint imposed by herbivores on growth, allowing plants to shift towards a faster growth strategy which may result in an increase in population size and spread and consequently to invasive success.
Seasonality of precipitation interacts with exotic species to alter composition and phenology of a semi‐arid grassland
Authors: Prevéy Janet S. , Seastedt Timothy R.
Published: August 2014

While modelling efforts suggest that invasive species will track climate changes, empirical studies are few. A relevant and largely unaddressed research question is ‘How will the presence of exotic species interact with precipitation change to alter ecosystem structure and function?’

We studied the effects of changes in seasonal timing of precipitation on species composition and resource availability in a grassland community in Colorado, USA. We examined how seasonal precipitation patterns affect the abundance of historically present (native) and recently arrived (exotic) plant species, as well as soil moisture, nitrogen and above‐ground biomass. Over 4 years, we applied four precipitation treatments based on climate model predictions for the study area: winter‐wet/summer‐ambient, winter‐wet/summer‐dry, winter‐wet/summer‐wet and winter‐dry/summer‐wet.

Cover of exotic winter‐active grasses was greater in winter‐wet treatments than in control or winter‐dry treatments. Cover of native warm‐season grasses and forbs was greatest in the winter‐dry/summer‐wet treatment, and lowest in the winter‐wet/summer‐dry treatment. These results support the expectation that increased winter precipitation benefits new arrivals, whereas increased summer precipitation benefits later‐growing native plants.

Structural equation models showed that interactive effects of increased winter precipitation and increased cover of winter‐active grasses reduced growing season soil water content and species diversity. In addition, the dominant winter‐active species, Bromus tectorum, flowered and senesced earlier in plots receiving increased winter precipitation and reduced summer precipitation, suggesting that earlier growth of winter‐active grasses decreases available soil resources and impacts later‐growing native plants. Peak above‐ground biomass was lowest in the treatment receiving reduced summer precipitation, but only in years with dry springs. Plant‐available nitrogen in spring was lower in plots receiving supplemental winter precipitation, and highest in plots with reduced winter precipitation.

Synthesis. Our results indicate that altering the seasonality of precipitation can have large direct effects on plant community composition and phenology, as well as significant indirect effects, mediated through exotic species, on plant‐available resources and plant interactions.
A novel mechanism for grazing lawn formation: large herbivore‐induced modification of the plant–soil water balance
Authors: Veldhuis Michiel P. , Howison Ruth A. , Fokkema Rienk W. , Tielens Elske , Olff Han
Published: August 2014

Large herbivores play a key role in creating spatial heterogeneity through the formation of grazing lawns. Recent research suggests that the currently accepted nutrient‐based theory on the formation of these grazing lawns cannot universally explain their formation in all ecosystems where they are found.

We developed and investigated an alternative hypothesis on grazing lawn formation and maintenance based on herbivore effects on the plant–soil water balance. We propose that large herbivores change the soil water balance in grazing lawns through defoliation and soil compaction, causing a shift in vegetation composition towards a drought‐tolerant plant community.

Investigating this idea in a tropical savanna, we indeed found profound differences in grazing lawn soil properties and water balance. In particular, defoliation increased soil temperatures and potential evaporation rates while soil compaction increased bulk density and decreased water infiltration rates, especially on fine‐textured soils. Soil moisture was therefore generally much lower in grazing lawns than in adjacent bunch grass areas.

Furthermore, we found that grazing lawn species show drought‐tolerant traits, with higher leaf sodium levels, suggesting evolutionary adaptation to these herbivore‐induced dry conditions. However, leaf water potentials did not differ between grazing lawn and bunch grass species.

Synthesis. This study shows that large herbivores might form grazing lawns through previously underestimated effects on water balance. Thus, future studies on large herbivore effects on vegetation should increasingly focus on additional pathways of soil compaction and defoliation. While nutrient‐based processes driving grazing lawn formation may operate during the wet season in savannas, we suggest that water balance‐based processes are additionally important during the dry season.
The Ethics of Researching Friends: On Convenience Sampling in Qualitative Management and Organization Studies
Authors: Brewis Joanna
Published: August 2014

Scholarship on the ethical complexities resulting from friendships which develop with respondents during qualitative data collection is well established. There has also been consideration of the ethics of researching existing friends across various disciplines. But, although management and organization scholars use convenience samples of the latter kind in qualitative research, there is virtually no discussion in our field of the ethical implications. In seeking to rectify this, I draw on my experiences of a project where I gathered data from six friends on their experiences of and attitudes towards sexual relationships, motherhood and life–work ‘balance’. I discuss the reportage of what sometimes felt like confidences, the use of ex ante data, the objectification of participants and difficulties relating to respondent validation in order to highlight some of the ethical challenges in qualitative management and organizational research with friends.
The Morality of Remote Warfare: Against the Asymmetry Objection to Remote Weaponry
Authors: Schulzke Marcus
Published: August 2014

Remote weapons, such as precision-guided munitions (PGMs) and drones, regularly play an important part in contemporary military operations, but they are extremely controversial on moral grounds. Although critics of these weapons have raised a number of objections against their use, many rely on some variation of the asymmetry thesis. This is the claim that it is immoral to wage war using weapons that allocate risk asymmetrically, allowing those who use these weapons to minimise their exposure to risk while their opponents can be easily attacked. In this article, it is demonstrated that the asymmetry thesis fails as a moral objection to the use of remote weapons by exploring three different variants of the asymmetry thesis and showing that each suffers from serious limitations.
Conspiracy Theory as Political Imaginary: Blackwater in Pakistan
Authors: Iqtidar Humeira
Published: August 2014

How may one theorise conspiracy theories? The last decade has seen a mushrooming of academic interest in conspiracy theories, perhaps in response to the increased role of conspiratorial thinking in politics in the same period. Using a case study of a private security firm, Blackwater, in Pakistan, this article suggests that while most conspiracy theories may be too linear and hyper-logical to allow for historical contingency and the messy reality of political struggles, it is possible to conceive of some of them as a kind of political imaginary that places national politics within a transnational context in an age where a surfeit of information is matched only by a paucity of relevant information. While the academic literature over the last decade has tended to take the form of conspiracy theories as an important clue to their function in contemporary politics, this article argues for taking the content of conspiracy theories seriously as well. At the same time, it suggests the value of delineating more sharply the concept of ‘political imagination’.
Spoilage by Alicyclobacillus Bacteria in Juice and Beverage Products: Chemical, Physical, and Combined Control Methods
Authors: Tianli Yue , Jiangbo Zhang , Yahong Yuan
Published: August 2014

Alicyclobacillus is a genus of spoilage bacteria causing contamination of juices and other beverage products that cannot easily be contaminated by other microbes because of their high acid contents. During the last 4 decades since the first species of Alicyclobacillus was isolated in 1967, Alicyclobacillus has become a major concern to the global juice and beverage industries, and many promising methods have been developed and applied to control them. After introducing the history and general characteristics of Alicyclobacillus, as well as their heat resistance and spoilage, this review focuses on the control methods against Alicyclobacillus, including chemical and physical methods and combined methods. All these control methods show inhibitory or killing effects against Alicyclobacillus to some extent and, moreover, some of them have been put to use in the juice and beverage industries for decades and shown to be quite effective, although further developments can be achieved and new methods are constantly being established and investigated. Although it is difficult to compare the effects with one another among these methods because of the different experimental conditions in different reports, some of them, such as the treatments of nisin and high hydrostatic pressure, are well studied and proved to have extensive application prospect. The inhibitory factors, test strains and media, and especially the detailed experimental conditions and main results of these control methods are summarized here. The limitations of some methods mainly relating to the changes of products’ sensory qualities are also presented.
Traditional Fermented Foods and Beverages from a Microbiological and Nutritional Perspective: The Colombian Heritage
Authors: Chaves‐López Clemencia , Serio Annalisa , Grande‐Tovar Carlos David , Cuervo‐Mulet Raul , Delgado‐Ospina Johannes , Paparella Antonello
Published: August 2014

Fermentation has been used for preserving foods for centuries prior to the invention of pasteurization and sterilization, and every culture has a variety of fermented products as part of its diet. This paper reviews the diversity of fermented foods and beverages from Latin America; these fermented products are produced by traditional methods that exploit mixed cultures of various nonpathogenic microorganisms. Fermented foods covered in this review include maize, cassava, palm sap, sugar cane juice, cocoa, and milk. We explore the history of some Colombian fermented foods and beverages, which are today part of the tradition of some ethnic groups, and evaluate their technology, microbiology, the presence of some nutritional factors, and safety concerns. To the best of our knowledge, this is the 1st systematic review on Colombian fermented beverages and foods, and we believe that it may contribute to valorize these products that are still part of the Latin America tradition.
Interactions of Foodborne Pathogens with Free‐living Protozoa: Potential Consequences for Food Safety
Authors: Vaerewijck Mario J.M. , Baré Julie , Lambrecht Ellen , Sabbe Koen , Houf Kurt
Published: August 2014

Free‐living protozoa (FLP) are ubiquitous in natural ecosystems where they play an important role in the reduction of bacterial biomass and the regeneration of nutrients. However, it has been shown that some species such as Acanthamoeba castellanii, Acanthamoeba polyphaga, and Tetrahymena pyriformis can act as hosts of pathogenic bacteria. There is a growing concern that FLP might contribute to the maintenance of bacterial pathogens in the environment. In addition to survival and/or replication of bacterial pathogens in FLP, resistance to antimicrobial agents and increased virulence of bacteria after passage through protozoa have been reported. This review presents an overview of FLP in food‐associated environments and on foods, and discusses bacterial interactions with FLP, with focus on the foodborne pathogens Campylobacter jejuni, Salmonella spp., Escherichia coli O157:H7, and Listeria monocytogenes. The consequences of these microbial interactions to food safety are evaluated.
A Guidance Document on the Best Practices in Food Traceability
Authors: Zhang Jianrong , Bhatt Tejas
Published: August 2014

Several regulatory agencies around the world are involved in rulemaking to improve the traceability of foods. Given the complexity of the global food system, guidance on improving traceability practices across the entire food industry is a challenge. A review of the current regulations and best practices indicates that “one back, one forward” is the minimum traceability requirement. There are also no uniform requirements across different food sectors, supply chains, or countries for collection of Critical Tracking Events (CTEs) and Key Data Elements (KDEs). There is a need for standardized and harmonized requirements across all food sectors compared with developing specialized rules and mandates, including exceptions, for specific foods. This document presents food traceability best practices guidance and it addresses the unknowns and gaps in understanding and the broad applicability of a CTE–KDE framework. It applies this framework to 6 food sectors as bakery, dairy, meat and poultry, processed foods, produce, and seafood. An analysis of similarities and differences across these sectors is conducted to determine broader applicability to other foods. Fifty‐five experts from 11 countries were involved in developing this guidance. This guidance document is intended for regulatory agencies and the food industry. Regulators will find it useful in developing regulations and/or guidance applicable to most foods. Industry will find the minimum criteria that are necessary to manage a proper food traceability system, with the understanding that companies can choose to exceed the minimum level of criteria established. This guidance is intended to serve as a step toward consistent baseline requirements for food traceability.
Homeland Heroes: Migrants and Soldiers in the Neoliberal Era
Authors: Brigden Noelle Kateri , Vogt Wendy A.
Published: August 2014

This paper examines the dynamic relationship between neoliberalism and nationalism through the counterintuitive comparison of journeys travelled by US citizens as they enlist in the military and by unauthorized Central Americans as they migrate to the United States. We argue that, however different the context and content of their decisions and their lives, Central American migrants and US soldiers are both connected within a larger political economy. We complicate the idea of migrants and soldiers as purely rational economic actors, but we also reject the idea, imputed onto migrants and soldiers by neoliberal states, that they are naturally nationalistic actors. Migrants and soldiers embody a neoliberal subjectivity produced through processes of violence, capital accumulation and militarization. Yet, as we examine throughout this paper, their construction as homeland heroes within the national imaginary masks the ways their labor and their mobility serve the institutionalization of neoliberal statecraft.
Audio spectrum analysis of umbilical artery Doppler ultrasound signals applied to a clinical material
Authors: Thuring Ann , Brännström K.Jonas , Jansson Tomas , Maršál Karel
Published: August 2014

Analysis of umbilical artery flow velocity waveforms characterized by pulsatility index (PI) is used to evaluate fetoplacental circulation in high‐risk pregnancies. However, an experienced sonographer may be able to further differentiate between various timbres of Doppler audio signals. Recently, we have developed a method for objective audio signal characterization; the method has been tested in an animal model. In the present pilot study, the method was for the first time applied to human pregnancies. Doppler umbilical artery velocimetry was performed in 13 preterm fetuses before and after two doses of 12 mg betamethasone. The auditory measure defined by the frequency band where the spectral energy had dropped 15 dB from its maximum level (MAXpeak‐15 dB), increased two days after betamethasone administration (p = 0.001) parallel with a less pronounced decrease in PI (p = 0.04). The new auditory parameter MAXpeak‐15 dB reflected the changes more sensitively than the PI did.
Mode of delivery and subsequent reproductive patterns. A national follow‐up study
Authors: Fussing‐Clausen Caroline , Geirsson Reynir T. , Hansen Thomas , Rasmussen Steen , Lidegaard Øjvind , Hedegaard Morten
Published: August 2014

Objective

To investigate associations between mode of delivery and subsequent reproductive outcomes.

Design

Cohort study.

Population

Women with term singleton live births from 1987 to 2009.

Setting

Denmark, birth registration data.

Methods

Women with a first singleton delivery after 37 weeks were followed until the end of 2010, from a first birth to include subsequent live births. We used Cox's proportional hazards model stratified by parity to compare the likelihood for subsequent delivery according to mode of delivery at first and later births, estimating maternal age effects and lag time to next delivery.

Main outcome measure

Likelihood of a subsequent live‐born child by previous delivery mode.

Results

We identified 642 052 women with a first delivery. Compared with women with a non‐instrumental vaginal delivery, delivering a child by elective cesarean section implied a 23% (95% CI 0.76–0.787) decreased likelihood for subsequent delivery. Emergency cesarean section meant 16% fewer (95% CI 0.84–0.85), and vaginal instrumental delivery 4% fewer subsequent deliveries (95% CI 0.95–0.96). Hazard ratios were largely unchanged after controlling for parity and year of birth. Small age‐trends were seen, with hazard ratios affected by maternal age at birth. Delivery mode at first birth affected marginally the time lag until next birth.

Conclusions

Fecundity, measured as likelihood of a successive live‐born child, varied with mode of delivery at the first and also subsequent births. A first or later delivery by cesarean section implied decreased likelihood of subsequent delivery compared with women with a first vaginal birth.
Maternal age and serum concentration of human chorionic gonadotropin in early pregnancy
Authors: Haavaldsen Camilla , Fedorcsak Peter , Tanbo Tom , Eskild Anne
Published: August 2014

Objective

To study whether maternal age is associated with serum concentration of human chorionic gonadotropin in early pregnancy.

Design

Cross‐sectional study.

Setting

Oslo University Hospital in Oslo, Norway.

Population

All vital pregnancies in gestational week 8 conceived by in vitro fertilization between February 1996 and February 2013 (n = 4472).

Methods

Serum concentrations of human chorionic gonadotropin were measured on day 12 after embryo transfer/day 16 following ovulation induction. Trends in geometric means of human chorionic gonadotropin concentrations by maternal age group were tested by linear regression analysis. We also studied the association of maternal age (years) with log‐transformed human chorionic gonadotropin concentrations, and adjustments were made for number of embryos transferred, method of in vitro fertilization and year (period) of embryo transfer.

Main outcome measure

Serum concentration of human chorionic gonadotropin.

Results

Geometric mean concentrations of human chorionic gonadotropin decreased with increasing maternal age (p = 0.024, test for trend by weighted linear regression). Also, we estimated a significant negative association of maternal age with log‐transformed human chorionic gonadotropin concentrations (adjusted regression coefficient −0.011, standard error 0.003, p < 0.001).

Conclusions

Serum concentrations of human chorionic gonadotropin in very early pregnancy decreased with maternal age. Since human chorionic gonadotropin is synthesized in trophoblast cells only, the lower human chorionic gonadotropin concentrations in women of advanced age may reflect functional impairment or delayed proliferation of trophoblast cells in early pregnancy in these women.
B‐type natriuretic peptide measurement for early diagnosis of acute pulmonary edema during pregnancy
Authors: Seror Jeremy , Lefevre Guillaume , Berkane Nathalie , Richard Frederic , Bornes Marie , Uzan Serge , Berkane Nadia
Published: August 2014

Calcium‐channel blockers administered to pregnant women as tocolytic agents can cause acute pulmonary edema. The first signs of this severe complication can be atypical and so delay introduction of appropriate therapy. We describe three cases in whom B‐type natriuretic peptide measurements proved to be relevant in early diagnosis and monitoring of pregnant women with acute pulmonary edema. B‐type natriuretic peptide measurement in this setting could contribute to timely diagnosis and improve follow‐up.
General, but not abdominal, overweight increases odds of asthma among Norwegian adolescents: the Young‐HUNT study
Authors: Egan Kathryn B. , Ettinger Adrienne S. , DeWan Andrew T. , Holford Theodore R. , Holmen Turid Lingaas , Bracken Michael B.
Published: August 2014

Aim

The aim of this analysis was to examine the association between asthma and general and abdominal weight status, defined by age‐ and sex‐specific cut‐offs for body mass index (BMI) and waist circumference (WC) in adolescents.

Methods

Participants aged 12–19 years in the Young‐HUNT (YH) Study (YH1 1995–1997: n = 8222; YH3 2006–2008: n = 7403) completed self‐administered questionnaires in school as part of a series of cross‐sectional, population‐based studies conducted in Nord‐Trøndelag, Norway. Weight, height and WC were measured. Adjusted odds ratios (ORs) and 95% Confidence Intervals (CI) for asthma, defined by self‐reported physician diagnosis, were calculated. Potential effect modifiers evaluated included sex and pubertal development status (PDS).

Results

Asthma was reported by 11.8% of the adolescents in YH1 and 17.0% in YH3. Asthma odds significantly increased for adolescents with general (OR = 1.33; 95%CI: 1.13, 1.56), but not abdominal, overweight and increased for adolescents with general (OR = 1.34; 95%CI: 1.02, 1.75) or abdominal obesity (OR = 1.36; 95%CI: 1.16, 1.60). Underweight had no association with asthma regardless of weight assessment type, and PDS did not meaningfully influence the associations between asthma and weight.

Conclusion

Overweight and obesity both increased the odds of asthma in 12–19 year‐old Norwegians. WC did not add further information to that already provided by BMI to improve our understanding of the association between asthma and weight.
Systemic exposure of topical erythromycin in comparison to oral administration and the effect on cytochrome P450 3A4 activity
Authors: Carls Alexandra , Jedamzik Julia , Witt Lukas , Hohmann Nicolas , Burhenne Juergen , Mikus Gerd
Published: August 2014

Aims

Erythromycin is a macrolide antibiotic, which is frequently used as a topical formulation for the treatment of acne. It is also known as an inhibitor of the cytochrome P450 (CYP) isoenzyme 3A4. In this study, the systemic availability of topical erythromycin, hence the influence on the activity of CYP3A, is evaluated in comparison to orally administered erythromycin.

Methods

Sixteen healthy volunteers received consecutively topical (two applications of 800 mg) and oral erythromycin (two dose groups, 250 and 1000 mg, with n = 8) to assess erythromycin pharmacokinetics. A microdose of midazolam (3 μg orally) was used to determine the effect on CYP3A activity.

Results

After topical administration, erythromycin was detected in the plasma of every participant without causing a statistically significant alteration of CYP3A activity. After oral administration, the dose‐normalized erythromycin exposure (AUC∞) was 1335 h ng ml−1 after 250 mg and 3‐fold higher after the 1000 mg dose (4051 h ng ml−1; P < 0.01), suggesting nonlinear pharmacokinetics of erythromycin. Both oral doses inhibited CYP3A activity; midazolam clearance was decreased to 61% (250 mg) and 21% (1000 mg). The relationship between erythromycin exposure and CYP3A activity (Hill equation) revealed a 50% reduction of CYP3A activity by an erythromycin AUC∞ of 2106 h ng ml−1.

Conclusions

Topical erythromycin did not cause clinically relevant CYP3A alterations, although low systemic availability of erythromycin was observed. This supports the assumption that treatment with topical erythromycin is not critical in terms of CYP3A inhibition. Furthermore, substantial nonlinearity of erythromycin pharmacokinetics after two different oral doses was observed, possibly due to autoinhibition.
Next‐generation sequencing is a credible strategy for blood group genotyping
Authors: Fichou Yann , Audrézet Marie‐Pierre , Guéguen Paul , Le Maréchal Cédric , Férec Claude
Published: August 2014

Although several medium/high‐throughput tools have been engineered for molecular analysis of blood group genes, they usually rely on the targeting of single nucleotide polymorphisms, while other variants remain unidentified. To circumvent this limitation a strategy for genotyping blood group genes by next‐generation sequencing (NGS) was set up. Libraries consisting of exons, flanking introns and untranslated regions of 18 genes involved in 15 blood systems were generated by the Ion AmpliSeq™ Library Kit 2.0 and by fragmenting polymerase chain reaction products, normalized by two different approaches, mixed and sequenced by the Ion Torrent Personal Genome Machine (PGM™) Sequencer. In our conditions, defined to limit both intra‐ and inter‐sample variability, sequences from mixed libraries were read in a single run for a total coverage of 86·03% of the coding DNA sequences, including all loci defining the most clinically relevant antigens in all genes, except ABO. Importantly, the challenging attempt to generate gene‐specific data for the homologous genes was successful. This work, which combines two complementary approaches to generate libraries, defines technical conditions for genotyping blood group genes, illustrates that NGS is suitable for such an application and suggests that, after automation, this novel tool could be used for molecular typing at the laboratory level.
Editorial: Can neuroscience add to clinical practice?
Authors: Taylor Eric
Published: August 2014

Neuroscience is advancing rapidly, but has so far generated few applications for clinicians in mental health. Nevertheless, it is time to consider how clinical practice might evolve to use an improving technology for individual patients, and this Editorial explores this by looking at how neuroimaging may lead to objective diagnosis, help in analysing dysfunctions and discovering new treatments and guiding more established ones for child and adolescent mental health disorders.
Thyroglobulin autoantibodies switch to immunoglobulin (Ig)G1 and IgG3 subclasses and preserve their restricted epitope pattern after 131I treatment for Graves' hyperthyroidism: the activity of autoimmune disease influences subclass distribution but not epitope pattern of autoantibodies
Authors: Latrofa F , Ricci D , Montanelli L , Piaggi P , Mazzi B , Bianchi F , Brozzi F , Santini P , Fiore E , Marinò M , Tonacchera M , Vitti P
Published: August 2014

The subclass distribution of thyroglobulin autoantibodies (TgAb) is debated, whereas their epitope pattern is restricted. Radioidine (131 I) treatment for Graves' disease (GD) induces a rise in TgAb levels, but it is unknown whether it modifies subclass distribution and epitope pattern of TgAb as well. We collected sera from GD patients before 131 I treatment and 3 and 6 months thereafter. We measured total TgAb, TgAb light chains and TgAb subclasses by enzyme-linked immunosorbent assay (ELISA) in 25 patients. We characterized the TgAb epitope pattern in 30 patients by inhibiting their binding to 125-ITg by a pool of four TgAb-Fab (recognizing Tg epitope regions A, B, C and D) and to Tg in ELISA by each TgAb-Fab. Total TgAb immunoglobulin (Ig)G rose significantly (P = 0·024). TgAb κ chains did not change (P = 0·052), whereas TgAb λ chains increased significantly (P = 0·001) and persistently. We observed a significant rise in IgG1 and IgG3 levels after 131 I (P = 0·008 and P = 0·006, respectively), while IgG2 and IgG4 levels did not change. The rise of IgG1 was persistent, that of IgG3 transient. The levels of inhibition of TgAb binding to Tg by the TgAb-Fab pool were comparable. A slight, non-significant reduction of the inhibition by the immune-dominant TgAb-Fab A was observed 3 and 6 months after 131 I. We conclude that 131 I treatment for GD increases the levels of the complement-activating IgG1 and IgG3 subclasses and does not influence significantly the epitope pattern of TgAb. In autoimmune thyroid disease subclass distribution of autoantibodies is dynamic in spite of a stable epitope pattern.