bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction and stability of human Th17 cells require endogenous NOS2 and cGMP-dependent NO signaling
Authors: Obermajer Nataša , Wong Jeffrey L. , Edwards Robert P. , Chen Kong , Scott Melanie , Khader Shabaana , Kolls Jay K. , Odunsi Kunle , Billiar Timothy R. , Kalinski Pawel
Published: June 2013

Nitric oxide (NO) is a ubiquitous mediator of inflammation and immunity, involved in the pathogenesis and control of infectious diseases, autoimmunity, and cancer. We observed that the expression of nitric oxide synthase-2 (NOS2/iNOS) positively correlates with Th17 responses in patients with ovarian cancer (OvCa). Although high concentrations of exogenous NO indiscriminately suppress the proliferation and differentiation of Th1, Th2, and Th17 cells, the physiological NO concentrations produced by patients’ myeloid-derived suppressor cells (MDSCs) support the development of RORγt(Rorc)+IL-23R+IL-17+ Th17 cells. Moreover, the development of Th17 cells from naive-, memory-, or tumor-infiltrating CD4+ T cells, driven by IL-1β/IL-6/IL-23/NO-producing MDSCs or by recombinant cytokines (IL-1β/IL-6/IL-23), is associated with the induction of endogenous NOS2 and NO production, and critically depends on NOS2 activity and the canonical cyclic guanosine monophosphate (cGMP)–cGMP-dependent protein kinase (cGK) pathway of NO signaling within CD4+ T cells. Inhibition of NOS2 or cGMP–cGK signaling abolishes the de novo induction of Th17 cells and selectively suppresses IL-17 production by established Th17 cells isolated from OvCa patients. Our data indicate that, apart from its previously recognized role as an effector mediator of Th17-associated inflammation, NO is also critically required for the induction and stability of human Th17 responses, providing new targets to manipulate Th17 responses in cancer, autoimmunity, and inflammatory diseases.
Tob1 plays a critical role in the activation of encephalitogenic T cells in CNS autoimmunity
Authors: Schulze-Topphoff Ulf , Casazza Simona , Varrin-Doyer Michel , Pekarek Kara , Sobel Raymond A. , Hauser Stephen L. , Oksenberg Jorge R. , Zamvil Scott S. , Baranzini Sergio E.
Published: June 2013

Reliable biomarkers corresponding to disease progression or therapeutic responsiveness in multiple sclerosis (MS) have not been yet identified. We previously reported that low expression of the antiproliferative gene TOB1 in CD4+ T cells of individuals presenting with an initial central nervous system (CNS) demyelinating event (a clinically isolated syndrome), correlated with high risk for progression to MS. We report that experimental autoimmune encephalomyelitis (EAE) in Tob1−/− mice was associated with augmented CNS inflammation, increased infiltrating CD4+ and CD8+ T cell counts, and increased myelin-reactive Th1 and Th17 cells, with reduced numbers of regulatory T cells. Reconstitution of Rag1−/− mice with Tob1−/− CD4+ T cells recapitulated the aggressive EAE phenotype observed in Tob1−/− mice. Furthermore, severe spontaneous EAE was observed when Tob1−/− mice were crossed to myelin oligodendrocyte glycoprotein–specific T cell receptor transgenic (2D2) mice. Collectively, our results reveal a critical role for Tob1 in adaptive T cell immune responses that drive development of EAE, thus providing support for the development of Tob1 as a biomarker for demyelinating disease activity.
Shp1 regulates T cell homeostasis by limiting IL-4 signals
Authors: Johnson Dylan J. , Pao Lily I. , Dhanji Salim , Murakami Kiichi , Ohashi Pamela S. , Neel Benjamin G.
Published: June 2013

The protein-tyrosine phosphatase Shp1 is expressed ubiquitously in hematopoietic cells and is generally viewed as a negative regulatory molecule. Mutations in Ptpn6, which encodes Shp1, result in widespread inflammation and premature death, known as the motheaten (me) phenotype. Previous studies identified Shp1 as a negative regulator of TCR signaling, but the severe systemic inflammation in me mice may have confounded our understanding of Shp1 function in T cell biology. To define the T cell–intrinsic role of Shp1, we characterized mice with a T cell–specific Shp1 deletion (Shp1fl/fl CD4-cre). Surprisingly, thymocyte selection and peripheral TCR sensitivity were unaltered in the absence of Shp1. Instead, Shp1fl/fl CD4-cre mice had increased frequencies of memory phenotype T cells that expressed elevated levels of CD44. Activation of Shp1-deficient CD4+ T cells also resulted in skewing to the Th2 lineage and increased IL-4 production. After IL-4 stimulation of Shp1-deficient T cells, Stat 6 activation was sustained, leading to enhanced Th2 skewing. Accordingly, we observed elevated serum IgE in the steady state. Blocking or genetic deletion of IL-4 in the absence of Shp1 resulted in a marked reduction of the CD44hi population. Therefore, Shp1 is an essential negative regulator of IL-4 signaling in T lymphocytes.
A probabilistic version of Rosenthal’s inequality
Authors: Astashkin S. , Tikhomirov K.
Published: June 2013

We prove some probabilistic relations between sums of independent random variables and the corresponding disjoint sums, which strengthen the well-known Rosenthal inequality and its generalizations. As a consequence we extend the inequalities proved earlier by Montgomery-Smith and Junge for rearrangement invariant spaces to the quasi-normed case.
Small GTPase Rab14 down‐regulates UT‐A1 urea transport activity through enhanced clathrin‐dependent endocytosis
Authors: Su Hua , Liu Bingchen , Fröhlich Otto , Ma Heping , Sands Jeff M. , Chen Guangping
Published: June 2013

The UT‐A1 urea transporter plays an important role in the urinary concentration mechanism. However, the molecular mechanisms regarding UT‐A1 trafficking, endocytosis, and degradation are still unclear. In this study, we identified the small GTPase Rab14 as a binding partner to the C terminus of UT‐A1 in a yeast 2‐hybrid assay. Interestingly, UT‐A1 binding is preferential for the GDP‐bound inactive form of Rab14. Coinjection of Rab14 in Xenopus oocytes results in a decrease of UT‐A1 urea transport activity, suggesting that Rab14 acts as a negative regulator of UT‐A1. We subsequently found that Rab14 reduces the cell membrane expression of UT‐A1, as evidenced by cell surface biotinylation. This effect is blocked by chlor‐promazine, an inhibitor of the clathrin‐mediated endocytic pathway, but not by filipin, an inhibitor of the caveolin‐mediated endocytic pathway. In kidney, Rab14 is mainly expressed in IMCD epithelial cells with a pattern identical to UT‐A1 expression. Consistent with its role in participating in clathrin‐mediated endocytosis, Rab14 localizes in nonlipid raft microdomains and codistributes with Rab5, a marker of the clathrin‐mediated endocytic pathway. Taken together, our study suggests that Rab14, as a novel UT‐A1 partner, may have an important regulatory function for UT‐A1 urea transport activity in the kidney inner medulla.—Su, H., Liu, B., Fröhlich, O., Ma, H., Sands, J. M., Chen, G., Small GTPase Rab14 down‐regulates UT‐A1 urea transport activity through enhanced clathrin‐dependent endocytosis. FASEB J. 27, 4100–4107 (2013). www.fasebj.org
Irradiance encoding in the suprachiasmatic nuclei by rod and cone photoreceptors
Authors: van Diepen Hester C. , Ramkisoensing Ashna , Peirson Stuart N. , Foster Russell G. , Meijer Johanna H.
Published: June 2013

Light information is transmitted to the central clock of the suprachiasmatic nuclei (SCN) for daily synchronization to the external solar cycle. Essential for synchronization is the capacity of SCN neurons to respond in a sustained and irradiance‐dependent manner to light. Melanopsin has been considered to mediate this photosensory task of irradiance detection. By contrast, the contribution of the classical photoreceptors in irradiance encoding is less clear. Here we investigate the role of classical photoreceptors by in vivo electrophysiological responses in freely moving animals to specific wavelengths of light (UV, λmax 365 nm; blue, λmax 467 nm; and green, λmax 505 nm) in both melanopsin‐deficient (Opn4–/–) mice and mice lacking rods and cones (rd/rd cl). Short‐ and long‐wavelength light induced sustained irradiance‐dependent responses in congenic wild‐type mice (+19.6%). Unexpectedly, sustained responses to light persisted in Opn4–/– mice (+18.4%). These results provide unambiguous evidence that classical photoreceptors can transmit irradiance information to the SCN. In addition, at light intensities that would stimulate rod and cone photoreceptors, the SCN of rd/rd cl mice showed greatly reduced sustained responses to light (+7.8%). Collectively, our data demonstrate a role for classical photoreceptors in illuminance detection by the SCN.—van Diepen, H. C., Ramkisoensing, A., Peirson, S. N., Foster, R. G., Meijer, J. H., Irradiance encoding in the suprachiasmatic nuclei by rod and cone photoreceptors. FASEB J. 27, 4204–4212 (2013). www.fasebj.org
Modelling the effect of GRP78 on anti-oestrogen sensitivity and resistance in breast cancer
Authors: Parmar Jignesh H. , Cook Katherine L. , Shajahan-Haq Ayesha N. , Clarke Pamela A. G. , Tavassoly Iman , Clarke Robert , Tyson John J. , Baumann William T.
Published: June 2013

Understanding the origins of resistance to anti-oestrogen drugs is of critical importance to many breast cancer patients. Recent experiments show that knockdown of GRP78, a key gene in the unfolded protein response (UPR), can re-sensitize resistant cells to anti-oestrogens, and overexpression of GRP78 in sensitive cells can cause them to become resistant. These results appear to arise from the operation and interaction of three cellular systems: the UPR, autophagy and apoptosis. To determine whether our current mechanistic understanding of these systems is sufficient to explain the experimental results, we built a mathematical model of the three systems and their interactions. We show that the model is capable of reproducing previously published experimental results and some new data gathered specifically for this paper. The model provides us with a tool to better understand the interactions that bring about anti-oestrogen resistance and the effects of GRP78 on both sensitive and resistant breast cancer cells.
Towards the endgame and beyond: complexities and challenges for the elimination of infectious diseases
Authors: Klepac Petra , Metcalf C. Jessica E. , McLean Angela R. , Hampson Katie
Published: June 2013

Successful control measures have interrupted the local transmission of human infectious diseases such as measles, malaria and polio, and saved and improved billions of lives. Similarly, control efforts have massively reduced the incidence of many infectious diseases of animals, such as rabies and rinderpest, with positive benefits for human health and livelihoods across the globe. However, disease elimination has proven an elusive goal, with only one human and one animal pathogen globally eradicated. As elimination targets expand to regional and even global levels, hurdles may emerge within the endgame when infections are circulating at very low levels, turning the last mile of these public health marathons into the longest mile. In this theme issue, we bring together recurring challenges that emerge as we move towards elimination, highlighting the unanticipated consequences of particular ecologies and pathologies of infection, and approaches to their management.
Rinderpest: the veterinary perspective on eradication
Authors: Roeder Peter , Mariner Jeffrey , Kock Richard
Published: June 2013

Rinderpest was a devastating disease of livestock responsible for continent-wide famine and poverty. Centuries of veterinary advances culminated in 2011 with the UN Food and Agriculture Organization and the World Organization for Animal Health declaring global eradication of rinderpest; only the second disease to be eradicated and the greatest veterinary achievement of our time. Conventional control measures, principally mass vaccination combined with zoosanitary procedures, led to substantial declines in the incidence of rinderpest. However, during the past decades, innovative strategies were deployed for the last mile to overcome diagnostic and surveillance challenges, unanticipated variations in virus pathogenicity, circulation of disease in wildlife populations and to service remote and nomadic communities in often-unstable states. This review provides an overview of these challenges, describes how they were overcome and identifies key factors for this success.
The final stages of the global eradication of poliomyelitis
Authors: Grassly Nicholas C.
Published: June 2013

The global incidence of poliomyelitis has dropped by more than 99 per cent since the governments of the world committed to eradication in 1988. One of the three serotypes of wild poliovirus has been eradicated and the remaining two serotypes are limited to just a small number of endemic regions. However, the Global Polio Eradication Initiative (GPEI) has faced a number of challenges in eradicating the last 1 per cent of wild-virus transmission. The polio endgame has also been complicated by the recognition that vaccination with the oral poliovirus vaccine (OPV) must eventually cease because of the risk of outbreaks of vaccine-derived polioviruses. I describe the major challenges to wild poliovirus eradication, focusing on the poor immunogenicity of OPV in lower-income countries, the inherent limitations to the sensitivity and specificity of surveillance, the international spread of poliovirus and resulting outbreaks, and the potential significance of waning intestinal immunity induced by OPV. I then focus on the challenges to eradicating all polioviruses, the problem of vaccine-derived polioviruses and the risk of wild-type or vaccine-derived poliovirus re-emergence after the cessation of oral vaccination. I document the role of research in the GPEI's response to these challenges and ultimately the feasibility of achieving a world without poliomyelitis.
The elimination of fox rabies from Europe: determinants of success and lessons for the future
Authors: Freuling Conrad M. , Hampson Katie , Selhorst Thomas , Schröder Ronald , Meslin Francois X. , Mettenleiter Thomas C. , Müller Thomas
Published: June 2013

Despite perceived challenges to controlling an infectious disease in wildlife, oral rabies vaccination (ORV) of foxes has proved a remarkably successful tool and a prime example of a sophisticated strategy to eliminate disease from wildlife reservoirs. During the past three decades, the implementation of ORV programmes in 24 countries has led to the elimination of fox-mediated rabies from vast areas of Western and Central Europe. In this study, we evaluated the efficiency of 22 European ORV programmes between 1978 and 2010. During this period an area of almost 1.9 million km² was targeted at least once with vaccine baits, with control taking between 5 and 26 years depending upon the country. We examined factors influencing effort required both to control and eliminate fox rabies as well as cost-related issues of these programmes. The proportion of land area ever affected by rabies and an index capturing the size and overlap of successive ORV campaigns were identified as factors having statistically significant effects on the number of campaigns required to both control and eliminate rabies. Repeat comprehensive campaigns that are wholly overlapping much more rapidly eliminate infection and are less costly in the long term. Disproportionally greater effort is required in the final phase of an ORV programme, with a median of 11 additional campaigns required to eliminate disease once incidence has been reduced by 90 per cent. If successive ORV campaigns span the entire affected area, rabies will be eliminated more rapidly than if campaigns are implemented in a less comprehensive manner, therefore reducing ORV expenditure in the longer term. These findings should help improve the planning and implementation of ORV programmes, and facilitate future decision-making by veterinary authorities and policy-makers.
Progress towards eliminating canine rabies: policies and perspectives from Latin America and the Caribbean
Authors: Vigilato Marco Antonio Natal , Clavijo Alfonso , Knobl Terezinha , Silva Hugo Marcelo Tamayo , Cosivi Ottorino , Schneider Maria Cristina , Leanes Luis Fernando , Belotto Albino José , Espinal Marcos Antonio
Published: June 2013

Human rabies transmitted by dogs is considered a neglected disease that can be eliminated in Latin America and the Caribbean (LAC) by 2015. The aim of this paper is to discuss canine rabies policies and projections for LAC regarding current strategies for achieving this target and to critically review the political, economic and geographical factors related to the successful elimination of this deadly disease in the context of the difficulties and challenges of the region. The strong political and technical commitment to control rabies in LAC in the 1980s, started with the regional programme coordinated by the Pan American Health Organization. National and subnational programmes involve a range of strategies including mass canine vaccination with more than 51 million doses of canine vaccine produced annually, pre- and post-exposure prophylaxis, improvements in disease diagnosis and intensive surveillance. Rabies incidence in LAC has dramatically declined over the last few decades, with laboratory confirmed dog rabies cases decreasing from approximately 25 000 in 1980 to less than 300 in 2010. Dog-transmitted human rabies cases also decreased from 350 to less than 10 during the same period. Several countries have been declared free of human cases of dog-transmitted rabies, and from the 35 countries in the Americas, there is now only notification of human rabies transmitted by dogs in seven countries (Bolivia, Peru, Honduras, Haiti, Dominican Republic, Guatemala and some states in north and northeast Brazil). Here, we emphasize the importance of the political commitment in the final progression towards disease elimination. The availability of strategies for rabies control, the experience of most countries in the region and the historical ties of solidarity between countries with the support of the scientific community are evidence to affirm that the elimination of dog-transmitted rabies can be achieved in the short term. The final efforts to confront the remaining obstacles, like achieving and sustaining high vaccination coverage in communities that are most impoverished or in remote locations, are faced by countries that struggle to allocate sufficient financial and human resources for rabies control. Continent-wide cooperation is therefore required in the final efforts to secure the free status of remaining countries in the Americas, which is key to the regional elimination of human rabies transmitted by dogs.
Economic considerations for the eradication endgame
Authors: Barrett Scott
Published: June 2013

An infectious disease will be eradicated only if it is eliminated everywhere, including in the hardest-to-reach, most vaccine-wary communities. If eradication is successful, it promises a dividend in the form of avoided infections and vaccinations. However, success is never certain unless and until eradication is achieved, and claiming the dividend means bearing the possibly great risk of re-emergence. Economic analysis of eradication evaluates these risks and rewards relative to the alternative of ‘optimal control’, and also exposes the incentives for achieving and capitalizing on eradication. Eradication is a ‘game’, because some countries may be willing to eliminate the disease within their borders only if assured that all others will eliminate the disease withintheirborders. International financing is also a game, because each country would rather free ride than contribute. Finally, for diseases such as polio, capitalizing on eradication is a game, for should any country continue to vaccinate in the post-eradication era using the live-attenuated polio vaccine, the countries that stop vaccinating will be exposed to the risk of vaccine-derived polioviruses. In the framework developed in this paper, eradication is a seductive goal, its attainment fraught with peril.
Elimination of foot-and-mouth disease in South America: lessons and challenges
Authors: Naranjo José , Cosivi Ottorino
Published: June 2013

Foot-and-mouth disease (FMD) is a highly transmissible and economically devastating disease of cloven-hoofed livestock. Although vaccines are available and have been instrumental in eliminating the disease from most of the South American animal population, viral circulation still persists in some countries and areas, posing a threat to the advances of the last 60 years by the official veterinary services with considerable support of the livestock sectors. The importance of the disease for the social and economic development of the American continent led to the establishment in 1951 of the Pan American Centre for Foot-and-Mouth Disease (PANAFTOSA), which has been providing technical cooperation to countries for the elimination of the disease. The first FMD national elimination programmes were established in South America around the 1960s and 1970s. To advance the regional elimination efforts in the 1980s, countries agreed on a Plan of Action 1988–2009 of the Hemispheric Program for the Eradication of Foot-and-Mouth Disease. The Plan of Action 1988–2009 did not reach the goal of elimination from the continent; and a new Plan of Action 2011–2020 was developed in 2010 based on the experience acquired by the countries and PANAFTOSA during the past 60 years. This plan is now being implemented; several challenges are still to be overcome to ensure the elimination of FMD from the Americas by 2020, however, the goal is achievable.
Dominant bryophyte control over high‐latitude soil temperature fluctuations predicted by heat transfer traits, field moisture regime and laws of thermal insulation
Authors: Soudzilovskaia Nadejda A. , van Bodegom Peter M. , Cornelissen Johannes H.C.
Published: June 2013

Bryophytes cover large territories in cold biomes, where they control soil temperature regime, and therefore permafrost, carbon and nutrient dynamics. The mechanisms of this control remain unclear.

We quantified the dependence of soil temperature fluctuations under bryophyte mats on the interplay of bryophyte heat conductance traits, mat thickness, density and moisture regimes.

For seventeen predominant bryophytes in six typical subarctic ecosystems, we assessed in situ soil temperature dynamics under bryophyte mats in comparison with bryophyte‐removal patches and per‐species mat field moisture. In a complimentary laboratory investigation, we studied how per‐species bryophyte thermal conductivity and volumetric heat capacity depend on mat density and moisture content. Subsequently, we tested whether heat transfer through bryophyte mats could be modelled as a function of mat thickness, thermal conductivity and volumetric heat capacity, the latter two being determined by mat density and field moisture content.

Laboratory assessment revealed that bryophyte thermal conductivity and volumetric heat capacity were independent of mat density, and depended linearly on mat moisture content, but the dependencies were not species‐specific. In the field, bryophytes reduced amplitudes of soil temperature fluctuations and freeze–thaw frequency during the growing season, but not mean soil temperature. These effects differed between species and between ecosystems, being strongest in Sphagnum fuscum‐dominated dry tundra, but were well explained by bryophyte mat thickness and field moisture content as affecting thermal conductivity and volumetric heat capacity.

We suggest that reduction in soil temperature amplitudes is a generic feature in (sub) arctic ecosystems and should be considered as an important mechanism of bryophyte control on carbon and nutrient turnover. Although heat transfer through bryophyte mats differs greatly among species and ecosystems, species differences are fully explained by differences in mat thickness and moisture content and generally comply with physical laws, without deviations due to biological processes. These results imply that in global vegetation models of carbon and nutrient cycling, the heat transfer through bryophyte mats can be modelled without taking into consideration bryophyte species composition, but considering bryophyte mat depth and moisture availability only. This will allow us to enhance modelling precision through an improved representation of the soil temperature regime.
The whole‐plant compensation point as a measure of juvenile tree light requirements
Authors: Lusk Christopher H. , Jorgensen Murray. A.
Published: June 2013

Although ‘shade tolerance’ has featured prominently in the vocabulary of foresters and ecologists for a century, we have yet to agree on a standardized method for quantifying this elusive property. The ‘whole‐plant compensation point’, interpolated from stem growth measurements across a wide range of light environments, has been proposed as a simple, robust measure of species shade tolerance. Others have argued that shade tolerance is primarily a function of differential ability to survive periods of slow growth (‘suppression’), implying that measurements of survival are vital.

We measured growth of juveniles (500–1000 mm tall) of five evergreen trees over 12 months in a cool‐temperate rain forest in New Zealand, to determine whether whole‐plant compensation points predicted species differences in occupancy of understorey light environments, which were quantified using hemispherical photography.

The five species encompassed 3·5‐fold variation in whole‐plant compensation points. Compensation points of most species fell within the first quartile of the distribution of light environments occupied by juveniles; they were also correlated with low‐light mortality rates of juveniles, estimated from permanent plot data archived in the National Vegetation Survey Databank. Compensation points were also significantly positively correlated with height growth rates in high light, confirming the presence of the growth vs. shade tolerance trade‐off detected in many other forest tree assemblages.

Results show that, in temperate evergreen forests, the whole‐plant compensation point distinguishes reliably between species of differing shade tolerance. Excepting situations involving parameterization of demographic models, shade tolerance can therefore be assessed without survival measurements. However, estimating whole‐plant compensation points may prove more difficult in deciduous forests, where seasonal variation in understorey light transmission poses additional challenges.
Testing the predictions of energy allocation decisions in the evolution of life‐history trade‐offs
Authors: Skibiel Amy L. , Speakman John R. , Hood Wendy R.
Published: June 2013

Allocating a greater amount of limited resources, such as energy, to current reproduction can reduce the amount of energy available for somatic maintenance and can ultimately impair future breeding success or maternal survival (i.e. cost of reproduction hypothesis). Although there is some support for the cost of reproduction hypothesis in birds, few empirical studies of mammals have demonstrated a trade‐off between current and future reproduction. More importantly, most studies testing ultimate costs have neglected to confirm that the proximate costs of reproduction are high.

We experimentally manipulated litter size in a wild population of Columbian ground squirrels for 2 years to examine both the proximate energetic and ultimate fitness (i.e. survival and breeding) costs of reproduction. We predicted that females raising augmented litters would have the highest rates of daily energy expenditure and as a result would experience lower survival rates or future fecundity.

Females raising augmented litters weaned more pups, had the highest litter masses at weaning, and had field metabolic rates that were almost 1·5 times greater than females raising control or reduced litters. Contrary to our prediction, there were no negative impacts of greater maternal investment and higher energy expenditure on the probability of maternal survival or future reproduction.

Pups from augmented litters grew more slowly during the lactation period were smaller at weaning and had a lower probability of survival over‐winter. Thus, although females were capable of raising more young than they gave birth to without short‐term costs of reduced survival or fecundity, our observations suggest that limitations to litter size are not due to a trade‐off in the allocation of energy, but rather due to the reduced survival of offspring from larger litters.

Examining the proximate mechanisms hypothesized to underlie life‐history trade‐offs can be challenging but is critical for a comprehensive understanding of the evolution of life histories.
Defensive symbiosis in the real world – advancing ecological studies of heritable, protective bacteria in aphids and beyond
Authors: Oliver Kerry M. , Smith Andrew H. , Russell Jacob A.
Published: June 2013

Symbiotic microbes have become increasingly recognized to mediate interactions between natural enemies and their hosts. The ecologies of these symbioses, however, are poorly understood in many systems, and a predictive framework is needed to guide future studies. To achieve this, we focus on heritable, defensive microbes of insects. Our review of laboratory‐based studies identifies diverse bacterial species that have independently evolved to protect a range of insects against parasitoids, parasites, predators and pathogens. Although defensive mechanisms are typically unknown, some involve toxins or the upregulation of host immunity.

Despite substantial benefits of infection in the presence of natural enemies, the protective symbionts of insects are often found at intermediate levels in natural populations. Using a host‐centred population genetics approach made possible by the host restriction and cytoplasmic inheritance of these microbes, we propose that balancing selection plays a major role in symbiont maintenance, with protective benefits in the presence of enemies and infection costs in their absence. Other mediating factors are likely to be important, including temperature, superinfections and transmission dynamics.

While few studies have provided evidence for defence in the field, several studies have shown symbiont infection frequencies to be dynamic, varying across temporal and spatial gradients and food–plant associations. Newly presented data from our pea aphid research reveal that temporal shifts in defensive symbiont prevalence can be quite rapid, with Hamiltonella defensa showing 10–20% shifts around a seasonal average of c. 50%. Such findings contrast with more unidirectional changes seen in laboratory population cages, suggesting temporal changes in the costs and benefits of symbionts in the field.

To frame future research on defensive symbiont ecology, we briefly consider a range of studies needed to test laboratory‐ and field‐derived predictions on defensive symbiosis. Included are investigations of defensive mechanisms, symbiont‐driven co‐evolution and community‐level effects. We also consider the need for more thorough and highly resolved molecular diagnostics of natural infections, laboratory studies on functional differences between symbiont strains and species and studies on the relative costs and benefits of defenders in nature.

The emerging theme of symbiont‐mediated defence across eukaryotes suggests that knowledge of the functional mechanisms behind protection and natural symbiont dynamics could be key to understanding many of the world's antagonistic species interactions. Thus, the development of insects as a model for such studies holds promise for these organisms and beyond.
Trophic cascades: linking ungulates to shrub‐dependent birds and butterflies
Authors: J. Teichman Kristine , E. Nielsen Scott , Roland Jens
Published: June 2013

Studies demonstrating trophic cascades through the loss of top‐down regulatory processes in productive and biologically diverse terrestrial ecosystems are limited.

Elk Island National Park, Alberta and surrounding protected areas have a wide range of ungulate density due to the functional loss of top predators, management for high ungulate numbers and variable hunting pressure. This provides an ideal setting for studying the effects of hyper‐abundant ungulates on vegetation and shrub‐dependent bird and butterfly species.

To examine the cascading effects of high ungulate density, we quantified vegetation characteristics and abundances of yellow warbler Dendroica petechia and Canadian tiger swallowtail Papilio canadensis under different ungulate density in and around Elk Island National Park.

Using Structural Equation Models we found that ungulate density was inversely related to shrub cover, whereas shrub cover was positively related to yellow warbler abundance. In addition, chokecherry Prunus virginiana abundance was inversely related to browse impact but positively related to P. canadensis abundance.

These results demonstrate a cascade resulting from hyper‐abundant ungulates on yellow warblers and Canadian tiger swallowtails through reductions in shrub cover and larval host plant density. The combined effect of the functional loss of top predators and management strategies that maintain high ungulate numbers can decouple top‐down regulation of productive temperate ecosystems.
The riddle of the sands: how population dynamics explains causes of high bivalve mortality
Authors: Callaway Ruth , Burdon Daryl , Deasey Anna , Mazik Krysia , Elliott Michael
Published: June 2013

Large‐scale bivalve mortalities in estuarine and coastal habitats are a major environmental and economic concern. They may have obvious causes such as extremely cold winter temperatures, but in the absence of an apparent chain of cause and effect, a rigorous, objective approach is needed to define a probable set of factors responsible for such mortalities. This study interrogates recurrent mortalities of the cockle Cerastoderma edule L. in the Burry Inlet (South Wales, UK), where the causes of the observed die‐offs were obscure.

Spatial and temporal patterns in cockle population dynamics were analysed to determine whether mortalities were episodic or continuous, and related to cockle density. Laboratory survival experiments complemented the field studies to indicate the fitness of the cockles. The population dynamics of other species were studied to test for environmental disturbances affecting the entire benthic community.

High cockle mortalities occurred throughout the estuary in a specific cohort, namely 1‐year‐old cockles after their first winter. The mortalities did not appear to be episodic, but happened over the spring to early summer months. Cockle densities played a minor role in the decline.

The laboratory experiments showed that cockles from the Burry Inlet had higher survival rates than those collected from other areas at early life stages (0‐year class). However, by the time they reached the end of their first year (1‐year class), their survival rates declined significantly. Results suggested a physiological weakness in the cohort after the first winter.

Other benthic species did not suffer unusual mortalities.

Synthesis and applications. We emphasize that (i) interrogating patterns in population dynamics allows us to limit the number of likely causes of high bivalve mortality and generate more specific hypotheses; (ii) extending studies to other benthic species indicates the likelihood of environmental problems that affect the entire ecosystem; (iii) joined‐up field and laboratory studies suggested that probable causes of cockle mortality were primarily species‐, or even cohort‐specific, biological factors; and (iv) well‐designed monitoring systems will indicate the population dynamics of the target species on spatio‐temporal scales suitable for assessing shifts in the populations, such as unexpected extirpation.
FORUM: Sustaining ecosystem functions in a changing world: a call for an integrated approach
Authors: Tomimatsu Hiroshi , Sasaki Takehiro , Kurokawa Hiroko , Bridle Jon R. , Fontaine Colin , Kitano Jun , Stouffer Daniel B. , Vellend Mark , Bezemer T. Martijn , Fukami Tadashi , Hadly Elizabeth A. , van der Heijden Marcel G.A. , Kawata Masakado , Kéfi Sonia , Kraft Nathan J.B. , McCann Kevin S. , Mumby Peter J. , Nakashizuka Tohru , Petchey Owen L. , Romanuk Tamara N. , Suding Katharine N. , Takimoto Gaku , Urabe Jotaro , Yachi Shigeo
Published: June 2013

With ever‐increasing human pressure on ecosystems, it is critically important to predict how ecosystem functions will respond to such human‐induced perturbations. We define perturbations as either changes to abiotic environment (e.g. eutrophication, climate change) that indirectly affects biota, or direct changes to biota (e.g. species introductions). While two lines of research in ecology, biodiversity–ecosystem function (BDEF) and ecological resilience (ER) research, have addressed this issue, both fields of research have nontrivial shortcomings in their abilities to address a wide range of realistic scenarios.

We outline how an integrated research framework may foster a deeper understanding of the functional consequences of perturbations via simultaneous application of (i) process‐based mechanistic predictions using trait‐based approaches and (ii) detection of empirical patterns of functional changes along real perturbation gradients. In this context, the complexities of ecological interactions and evolutionary perspectives should be integrated into future research.

Synthesis and applications. Management of human‐impacted ecosystems can be guided most directly by understanding the response of ecosystem functions to controllable perturbations. In particular, we need to characterize the form of a wide range of perturbation–function relationships and to draw connections between those patterns and the underlying ecological processes. We anticipate that the integrated perspectives will also be helpful for managers to derive practical implications for management from academic literature.
A slippery slope: logging alters mass–abundance scaling in ecological communities
Authors: Srinivasan Umesh
Published: June 2013

Natural ecosystems face ever‐increasing anthropogenic threats from activities such as logging. It is therefore important to: (i) understand anthropogenic impacts on key community characteristics with implications for community structure and function and (ii) identify metrics with mechanistic underpinnings, providing a more functional understanding of anthropogenic impacts on biodiversity. Mass–abundance scaling is the most fundamental property of ecological communities, with implications on energy and resource partitioning and on how species and population traits translate to community structure and function.

In habitat patches representing a continuum of logging intensity, I examined the impact of logging on mass–abundance scaling in understorey bird species using mist netting and bird ringing. I used regression quantiles to estimate the slope and intercept of upper bound of the polygonal local‐scale mass–abundance relationship.

I show that this slope becomes more negative (and the intercept higher) as logging intensity increases. Logging might therefore significantly alter resource and energy partitioning among species in natural communities.

The mechanism underlying this pattern is likely to be an interaction between resource depletion, body size and density compensation. Larger species face more severe resource shortages from depleted resource availability and are expected to decline in abundance following logging, leading to more negative mass–abundance scaling. Density compensation by smaller species following large species decline can ‘push up’ the intercept of the mass–abundance relationship. This might result in both steeper slopes and higher intercepts in logged habitats.

Synthesis and applications. This study shows for the first time that anthropogenic habitat change can alter fundamental community properties such as mass–abundance scaling and that this property of ecological communities was better at detecting logging impacts than other standard community measures. Identifying key metrics that provide a functional understanding of anthropogenic impacts on biodiversity is a crucial need, for both the assessment of these impacts and the continued monitoring of habitat change. This study highlights the need to supplement commonly used community descriptions with more mechanistic measures of human impacts on biodiversity.
Against Camps' Violence: Some Voices on Italian Holding Centres
Authors: Puggioni Raffaela
Published: June 2013

The present article looks at the politics of the camp and investigates the way in which detainees claim their right to a political and meaningful life against bare life. The question I look at is whether bare life might be resisted from within camps and how this resistance should be conceptualised. How are we to judge resistance? According to the modalities through which resistance is enacted? Or according to the subjects involved in those acts? Or indeed according to (political) outcomes? This article starts by scrutinising Agamben's Homo Sacer and its understanding of camp and bare life. It claims that more attention should be given to the way in which acts of open dissent blend with coping strategies, to the point of making some dissenting acts almost imperceptible. Special attention is given to the concept of dailiness, as articulated in the work of De Certeau, Scott and Bleiker, as well as to Isin's concept of ‘acts of citizenship’ and to the way in which such acts are performed in an attempt to disrupt sovereign violence.
Implementing REDD through community‐based forest management: Lessons from Tanzania
Authors: Robinson Elizabeth J. Z. , Albers Heidi J. , Meshack Charles , Lokina Razack B.
Published: June 2013

REDD (reduced emissions from deforestation and degradation) aims to slow carbon releases caused by forest disturbance by making payments conditional on forest quality over time. Like earlier policies to slow deforestation, REDD must change the behaviour of forest degrading actors. Broadly, it can be implemented with payments to forest users in exchange for improved forest management, thus creating incentives; through payments for enforcement, thus creating disincentives; or through addressing external drivers such as urban charcoal demand. In Tanzania, community‐based forest management (CBFM), a form of participatory forest management, was chosen by the Tanzania Forest Conservation Group, a local NGO, as a model for implementing REDD pilot programmes. Payments are made to villages that have the rights to forest carbon. In exchange, the villages must demonstrably reduce deforestation at the village level. In this paper, using this pilot programme as a case study, combined with a review of the literature, we provide insights for REDD implementation in sub‐Saharan Africa. We pay particular attention to leakage, monitoring and enforcement. We suggest that implementing REDD through CBFM‐type structures can create appropriate incentives and behaviour change when the recipients of the REDD funds are also the key drivers of forest change. When external forces drive forest change, however, REDD through CBFM‐type structures becomes an enforcement programme with local communities rather than government agencies being responsible for the enforcement. That structure imposes costs on local communities, whose local authority limits the ability to address leakage outside the particular REDD village.
Role of E2F‐1 and its involving pathway in esophageal squamous cell carcinoma
Authors: Wang Wen , Shen Luyan , Sun Yu , Dong Bin , Chen Keneng
Published: June 2013

Background

Esophageal cancer is a lethal disease and the optimal therapy remains unclear. Neoadjuvant chemotherapy provides an increased chance of survival; therefore, we attempted to identify potential molecular markers that might improve evaluations of individual responses to therapy.

Methods

We recruited 109 patients with resectable esophageal squamous cell carcinoma. The patients underwent radical esophagectomy and did not receive any other perioperative treatment. Expression of E2F‐1 and molecules involved in its targeted pathways, pERK, Bim, pRb, epidermal growth factor receptor, EZH2 and pAKT, was investigated immunohistochemically.

Results

Correlations were observed between E2F‐1 and pRb expression; EZH2 expression was significantly correlated with the degree of carcinoma differentiation (P = 0.01). Stage III patients were found to have longer survival if they did not express pERK than if they did (23 months vs. 11 months, P = 0.01). Patients with E2F‐1 not expressing pRb were found to have longer survival times than those with E2F‐1 who expressed pRb (18.8 months vs. 8.6 months, P = 0.021). Similarly, stage III patients with E2F‐1 but not expressing pERK also survived longer than those expressing pERK (23.5 months vs. 3.9 months, P < 0.001).

Conclusions

A high expression of pERK was significantly associated with poor survival in patients with locally advanced esophageal cancer. Expression of a combination of molecules, rather than of individual molecules, was more predictive of disease prognosis. E2F‐1 and molecules of its targeted pathways may be candidate proteins as markers of chemosensitivity in esophageal cancer patients.
Application ofLoreau &Hector's (2001) partitioning method to complex functional traits
Authors: Grossiord Charlotte , Granier André , Gessler Arthur , Scherer‐Lorenzen Michael , Pollastrini Martina , Bonal Damien
Published: June 2013

In 2001,Loreau andHector proposed a method to calculate the effect of biodiversity on ecosystem‐level properties that distinguished selection effects (SE) from complementarity effects (CE). The approach was designed and has been widely used for the study of yield in mixed‐species situations taking into account the relative abundance of each species in ecosystem‐level yield. However, complex functional traits commonly used to integrate ecosystem‐level properties that cannot be analysed like yield data because the weighted contribution of each species is not determined by its relative abundance.

We adapted the original method by clearly identifying ecologically meaningful weighting coefficients to represent species‐specific contributions to ecosystem function.

We applied the adapted method of analysis to tree foliar carbon isotope composition in an experimental plantation in order to test the influence of species richness on plot water use efficiency (WUEplot). The appropriate weights for theWUEplotof each species are leafCO2assimilation rate.

We observed a large range ofWUEplotand biodiversity effects among plots. The absence of a significantSEonWUEplotindicated that the overall net biodiversity effect was primarily driven by aCE. The net biodiversity effect andCEwere mostly negative, suggesting that interspecific interactions resulted in a decrease in the ratio between carbon acquisition and transpiration at the ecosystem level.

The application of the method to complex components of ecosystem functioning provides important new insights into the practical and conceptual aspects of functional biodiversity research.