bluuebunny/crossref_metadata_2025 huggingface dataset:
Physiology in ecological niche modeling: using zebra mussel's upper thermal tolerance to refine model predictions through Bayesian analysis
Authors: Feng Xiao , Liang Ye , Gallardo Belinda , Papeş Monica
Published: November 2019

Climate change and human‐mediated dispersal are increasingly influencing species’ geographic distributions. Ecological niche models (ENMs) are widely used in forecasting species’ distributions, but are weak in extrapolation to novel environments because they rely on available distributional data and do not incorporate mechanistic information, such as species’ physiological response to abiotic conditions. To improve accuracy of ENMs, we incorporated physiological knowledge through Bayesian analysis. In a case study of the zebra musselDreissena polymorpha, we used native and global occurrences to obtain native and global models representing narrower and broader understanding of zebra mussel’ response to temperature. We also obtained thermal limit and survival information for zebra mussel from peer‐reviewed literature and used the two types of information separately and jointly to calibrate native models. We showed that, compared to global models, native models predicted lower relative probability of presence along zebra mussel's upper thermal limit, suggesting the shortcoming of native models in predicting zebra mussel's response to warm temperature. We also found that native models showed improved prediction of relative probability of presence when thermal limit was used alone, and best approximated global models when both thermal limit and survival data were used. Our result suggests that integration of physiological knowledge enhances extrapolation of ENM in novel environments. Our modeling framework can be generalized for other species or other physiological limits and may incorporate evolutionary information (e.g. evolved thermal tolerance), thus has the potential to improve predictions of species’ invasive potential and distributional response to climate change.
Soil eutrophication shaped the composition of pollinator assemblages during the past century
Authors: Carvalheiro Luísa G. , Biesmeijer Jacobus C. , Franzén Markus , Aguirre‐Gutiérrez Jesús , Garibaldi Lucas A. , Helm Aveliina , Michez Denis , Pöyry Juha , Reemer Menno , Schweiger Oliver , Leon van den Berg , WallisDeVries Michiel F. , Kunin William E.
Published: November 2019

Atmospheric nitrogen deposition and other sources of environmental eutrophication have increased substantially over the past century worldwide, notwithstanding the recent declining trends in Europe. Despite the recognized susceptibility of plants to eutrophication, few studies evaluated how impacts propagate to consumers, such as pollinators. Here we aim to test if soil eutrophication contributes to the temporal dynamics of pollinators and their larval resources.

We used a temporally and spatially explicit historical dataset with information on species occurrences to test if soil eutrophication, and more specifically nitrogen deposition, contributes to the patterns of change of plant and pollinator richness in the Netherlands over an 80 yr period. We focus on bees and butterflies, two groups for which we have good knowledge of larval resources that allowed us to define groups of species with different nitrogen related diet preferences. For each group we estimated richness changes between different 20‐yr periods at local, regional and national scale, using analytical methods developed for analyzing richness changes based on collection data.

Our findings suggest that the impacts of soil eutrophication on plant communities propagate to higher trophic levels, but with a time‐lag. Pollinators with nitrogen‐related diet preferences were particularly affected, in turn potentially impairing the performance of pollinator‐dependent plants. Pollinator declines continued even after their focal plants started to recover. In addition, our results suggest that current levels of nitrogen deposition still have a negative impact on most groups here analyzed, constraining richness recoveries and accentuating declines.

Our results indicate that the global increase in nitrogen availability plays an important role in the ongoing pollinator decline. Consequently, species tolerances to soil nitrogen levels should be considered across all trophic levels in management plans that aim to halt biodiversity loss and enhance ecosystems services worldwide.
The sirtuin 6: An overture in skin cancer
Authors: Garcia‐Peterson Liz M. , Guzmán‐Pérez Glorimar , Krier Cassandre R. , Ahmad Nihal
Published: November 2019

In the recent past, the sirtuins have been under intense investigation for their roles in biology and disease, including cancer. The sirtuin SIRT6 is comparatively a lesser studied member of this family of seven proteins. Like certain other sirtuins, SIRT6 is emerging to have an oncogenic function as well as tumor suppressor roles in cancer. Limited studies have been conducted assessing the role and functional significance of SIRT6 in melanoma and non‐melanoma skin cancers. In this review, we have attempted to critically dissect the potential role and significance of SIRT6 in skin carcinogenesis. With limited available information to date, SIRT6 appears to have a pro‐proliferative function in non‐melanoma skin cancers (NMSCs), including squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). In addition, SIRT6 is also emerging to have an oncogenic function in melanoma. Moreover, we have provided information regarding the available SIRT6 inhibitors. Conclusively, it appears that additional comprehensive studies are needed to establish the role of SIRT6 in skin biology and skin diseases, including cancer. Further, concerted efforts are needed to characterize the stage‐specific role of SIRT6 in skin cancers.
Advancing global change biology through experimental manipulations: Where have we been and where might we go?
Authors: Hanson Paul J. , Walker Anthony P.
Published: November 2019

This commentary summarizes the publication history of Global Change Biology for works on experimental manipulations over the past 25 years and highlights a number of key publications. The retrospective summary is then followed by some thoughts on the future of experimental work as it relates to mechanistic understanding and methodological needs. Experiments for elevated CO2 atmospheres and anticipated warming scenarios which take us beyond historical analogs are suggested as future priorities. Disturbance is also highlighted as a key agent of global change. Because experiments are demanding of both personnel effort and limited fiscal resources, the allocation of experimental investments across Earth's biomes should be done in ecosystems of key importance. Uncertainty analysis and broad community consultation should be used to identify research questions and target biomes that will yield substantial gains in predictive confidence and societal relevance. A full range of methodological approaches covering small to large spatial scales will continue to be justified as a source of mechanistic understanding. Nevertheless, experiments operating at larger spatial scales encompassing organismal, edaphic, and environmental diversity of target ecosystems are favored, as they allow for the assessment of long‐term biogeochemical feedbacks enabling a full range of questions to be addressed. Such studies must also include adequate investment in measurements of key interacting variables (e.g., water and nutrient availability and budgets) to enable mechanistic understanding of responses and to interpret context dependency. Integration of ecosystem‐scale manipulations with focused process‐based manipulations, networks, and large‐scale observations will aid more complete understanding of ecosystem responses, context dependence, and the extrapolation of results. From the outset, these studies must be informed by and integrated with ecosystem models that provide quantitative predictions from their embedded mechanistic hypotheses. A true two‐way interaction between experiments and models will simultaneously increase the rate and robustness of Global Change research.
Climate‐driven shift in coral morphological structure predicts decline of juvenile reef fishes
Authors: Fontoura Luisa , Zawada Kyle J. A. , D’agata Stephanie , Álvarez‐Noriega Mariana , Baird Andrew H. , Boutros Nader , Dornelas Maria , Luiz Osmar J. , Madin Joshua S. , Maina Joseph M. , Pizarro Oscar , Torres‐Pulliza Damaris , Woods Rachael M. , Madin Elizabeth M. P.
Published: November 2019

Rapid intensification of environmental disturbances has sparked widespread decline and compositional shifts in foundation species in ecosystems worldwide. Now, an emergent challenge is to understand the consequences of shifts and losses in such habitat‐forming species for associated communities and ecosystem processes. Recently, consecutive coral bleaching events shifted the morphological makeup of habitat‐forming coral assemblages on the Great Barrier Reef (GBR). Considering the disparity of coral morphological growth forms in shelter provision for reef fishes, we investigated how shifts in the morphological structure of coral assemblages affect the abundance of juvenile and adult reef fishes. We used a temporal dataset from shallow reefs in the northern GBR to estimate coral convexity (a fine‐scale quantitative morphological trait) and two widely used coral habitat descriptors (coral cover and reef rugosity) for disentangling the effects of coral morphology on reef fish assemblages. Changes in coral convexity, rather than live coral cover or reef rugosity, disproportionately affected juvenile reef fishes when compared to adults, and explained more than 20% of juvenile decline. The magnitude of this effect varied by fish body size with juveniles of small‐bodied species showing higher vulnerability to changes in coral morphology. Our findings suggest that continued large‐scale shifts in the relative abundance of morphological groups within coral assemblages are likely to affect population replenishment and dynamics of future reef fish communities. The different responses of juvenile and adult fishes according to habitat descriptors indicate that focusing on coarse‐scale metrics alone may mask fine‐scale ecological responses that are key to understand ecosystem functioning and resilience. Nonetheless, quantifying coral morphological traits may contribute to forecasting the structure of reef fish communities on novel reef ecosystems shaped by climate change.
How corals made rocks through the ages
Authors: Drake Jeana L. , Mass Tali , Stolarski Jarosław , Von Euw Stanislas , van de Schootbrugge Bas , Falkowski Paul G.
Published: November 2019

Hard, or stony, corals make rocks that can, on geological time scales, lead to the formation of massive reefs in shallow tropical and subtropical seas. In both historical and contemporary oceans, reef‐building corals retain information about the marine environment in their skeletons, which is an organic–inorganic composite material. The elemental and isotopic composition of their skeletons is frequently used to reconstruct the environmental history of Earth's oceans over time, including temperature, pH, and salinity. Interpretation of this information requires knowledge of how the organisms formed their skeletons. The basic mechanism of formation of calcium carbonate skeleton in stony corals has been studied for decades. While some researchers consider coral skeletons as mainly passive recorders of ocean conditions, it has become increasingly clear that biological processes play key roles in the biomineralization mechanism. Understanding the role of the animal in living stony coral biomineralization and how it evolved has profound implications for interpreting environmental signatures in fossil corals to understand past ocean conditions. Here we review historical hypotheses and discuss the present understanding of how corals evolved and how their skeletons changed over geological time. We specifically explain how biological processes, particularly those occurring at the subcellular level, critically control the formation of calcium carbonate structures. We examine the different models that address the current debate including the tissue–skeleton interface, skeletal organic matrix, and biomineralization pathways. Finally, we consider how understanding the biological control of coral biomineralization is critical to informing future models of coral vulnerability to inevitable global change, particularly increasing ocean acidification.
Factors associated with high‐risk drinking in older adults: Evidence from a national survey in Japan
Authors: Midorikawa Haruhiko , Tachikawa Hirokazu , Aiba Miyuki , Arai Tetsuaki , Watanabe Taeko , Tamiya Nanako
Published: November 2019

Aim

This study aimed to clarify the association between high‐risk drinking and health outcomes (e.g. physical and psychosocial factors, including help‐seeking behavior) among older Japanese adults.

Methods

Data were obtained from the 2013 Comprehensive Survey of Living Conditions in Japan, which surveyed 295 367 households. We restricted analyses to 55 147 current drinkers. Multinomial logistic regression models were used to examine associations between alcohol consumption and various factors.

Results

Overall, 35.3% of participants were in the low‐risk group, 13.1% were in the at‐risk group and 1.0% were in the high‐risk group. Those in the at‐risk and high‐risk groups were more likely to be younger, male, employed and tobacco users. They were also more likely to report sleeping ≥9 h per night, and they were more likely to report unhealthy eating habits. Being in the high‐risk drinking group was significantly associated with being divorced (OR 1.51, 95% CI 1.11–2.05) and having poor mental health (OR 1.57, 95% CI 1.13–1.68). The high‐risk drinking group was more likely to include those who endorsed experiencing challenges without seeking aid (OR 1.87, 95% CI 1.39–2.53) or felt no need to seek aid (OR 1.39, 95% CI 1.15–1.68).

Conclusions

Being at high‐risk for drinking is associated with poorer help‐seeking behavior, suggesting a need for more aggressive outreach. Geriatr Gerontol Int 2019; 19: 1260–1267.
Immunohistochemical study of renal fibropoiesis associated with dogs naturally and experimentally infected with two different strains ofLeishmania(L.)infantum
Authors: Alves Adriano F. , Pereira Ramon A. , de Andrade Helida M. , Mosser David M. , Tafuri Wagner L.
Published: November 2019

The objectives of this work were to study some pathological aspects of kidneys obtained from dogs naturally infected withLeishmania infantumand from dogs experimentally infected with two different strains ofL infantumwith special emphasis on fibrotic process. Seventy eight specimens of paraffin‐embedded kidney fragments were collected as follows: (a) CNI group composed by 62 kidney samples of adult mongrel dogs, naturally infected withL infantum; (b) BH401 group composed by five kidney samples of adult Beagles experimentally infected withL infantumstrain MCAN BR/2002/BH401; (c) BH400 group composed by eleven kidney samples of adult Beagles experimentally infected withL infantumstrain MCAN/BR/2000/BH400, at the same dose and same route of the previous group, denominated group BH400; Control group (CC) composed by four kidney samples of adult Beagles. All animals revealed glomerular and interstitial fibropoiesis associated with different types of glomerulonephritis and chronic interstitial nephritis. Fibrosis was markedly more intense in the BH401 group, followed by animals in the CNI group. Markers for myofibroblasts (mesenchymal markers) such as alpha‐actin (α‐SMA), vimentin and the cytokine transforming growth factor beta (TGF‐β) were done by immunohistochemistry. BH401 group showed higher expression of all these markers than others. Intracellular amastigotes forms of Leishmania was mainly found in BH401. These results could be indicating that the MCAN/BR/2002/BH401 strain is a good choice for the study of renal LVC experimental model.
The Christianization of African Traditional Religions
Authors: Turaki Yusufu
Published: November 2019

In studies of the historical growth and spread of Christianity in Africa, the focus has been too much on Christianizing African social and religious institutions and structures, and not enough on African traditional religion itself, which needs to be addressed by Christianity. This article addresses the core – that is, the theology and worldview – of the African traditional religion. It argues that this core needs to be Christianized and shows how this can be done. In order to achieve this task, the article uses a new theological method, a “systematic theology” of African traditional religion, as the basis for a theological method of engagement and interaction of religions and worldview. This new method explains in practical terms how Christianity can effectively Christianize African traditional religions and worldviews.
Systematic review of negative pressure wound therapy for head and neck wounds with fistulas: Outcomes and complications
Authors: Lin Fu‐Yu , Huang Pin‐Yi , Cheng Hsu‐Tang
Published: November 2019

Fistula formation in head and neck wounds is considered one of the most challenging complications that a head and neck reconstructive surgeon may encounter. The current mainstay of treatment is aggressive surgical debridement followed by vascularised soft tissue coverage. Negative pressure wound therapy (NPWT) has been successfully used for the closure of complicated wounds for decades. This study analysed the outcomes and complications of NPWT in the management of head and neck wounds with fistulas. A systematic search of studies published between January 1966 and September 2019 was conducted using the PubMed, MEDLINE, EMBASE, and SCOPUS databases and using the following key words: “negative pressure wound therapy,” “head and neck,” and “fistula.” We included human studies with abstract and full text available. Analysed endpoints were rate of fistula closure, follow‐up duration, and complications if present. Nine retrospective case series (Level IV evidence) that collectively included 122 head and neck wounds with orocutaneous fistulas, pharyngocutaneous fistulas, and salivary contamination were examined. The number of patients included in each study ranged from 5 to 64. The mode of NPWT varied among the included studies, with most adopting a continuous pressure of −125 mm Hg. Mean durations of NPWT ranged from 3.7 to 23 days, and the reported fistula closure rate ranged from 78% to 100%. To achieve complete wound healing, six studies used additional procedures after stopping NPWT, including conventional wound dressings and vascularised tissue transfer. Information regarding follow up was provided in only three of the nine studies, where patients were followed for 5, 10, and 18 months. No serious adverse events were reported. NPWT for head and neck wounds with fistulas may be considered a safe treatment method that yields beneficial outcomes with a low risk of complications. The current data originated mainly from studies with low levels of evidence characterised by heterogeneity. Therefore, definitive recommendations based on these data cannot be offered. Additional high‐quality trials are warranted to corroborate the findings of this systematic review.
What the State Owes ‘Bastards’: A Modest Critique of Modest One‐Child Policies
Authors: Anderson Matthew Lee
Published: November 2019

This essay criticises ‘modest’ one‐child policies, which would impose sanctions upon parents who create multiple children. Specifically, this article considers what the state owes individuals who would be born (illegally) beneath restrictive procreative policies and argues that such policies would fail to show due respect to second‐ or third‐born individuals created beneath them. First, I argue that modest procreative restrictions (like sanctions) are likely to generate only modest compliance. I then suggest it is reasonable to think a one‐child policy fails to demonstrate due respect to existing second and third children. I argue that such a policy generates an undue burden on any second or third children who would be born beneath them, before concluding by considering whether the state might be able to avoid effectively reinscribing ‘bastardy’ into its law by locating responsibility for the effects of such a policy entirely on the parents, rather than on children.
The multifaceted role of CARD9 in inflammatory bowel disease
Authors: Luo Ping , Yang Zhiwen , Chen Bin , Zhong Xiaoming
Published: November 2019

Inflammatory bowel disease (IBD) involves a dysregulated immune response to the gut microbiota. Emerging evidence has demonstrated that dysfunctions in caspase recruitment domain‐containing protein 9 (CARD9) may contribute to the pathogenesis of IBD. Interestingly, an allelic series of Card9 variants have both a common predisposing and rare protective function in IBD patients. In this review, we provide mechanistic insights into the role of the CARD9 adaptor molecule in intestinal inflammation and determine a potential CARD9‐targeting therapeutic approach against IBD.
Lessons from Orgreave: Police Power and the Criminalization of Protest
Authors: Gilmore Joanna
Published: November 2019

In October 2016, the Home Secretary ruled out a public inquiry into the ‘Battle of Orgreave', arguing that ‘very few lessons’ could be learned from a review of practices of three decades ago. It was suggested that policing has undergone a progressive transformation since the 1984–5 miners’ strike, at political, legal, and operational levels. This article, in contrast, charts a significant expansion of state control over public protest since the strike, including a proliferation of public order offences and an extension of pre‐emptive policing powers. Whilst concerns have been raised about the impact of these developments on protest rights, there is an absence of socio‐legal research into the operation of public order powers in practice. In this article, I begin to fill this lacuna. Drawing on three empirical case‐studies of protesters’ experiences of arrest and the criminal justice process, I highlight the relevance of Orgreave for contemporary policing practice.
A tale of worldwide success: Behind the scenes of Carex (Cyperaceae) biogeography and diversification
Authors: Martín‐Bravo Santiago , Jiménez‐Mejías Pedro , Villaverde Tamara , Escudero Marcial , Hahn Marlene , Spalink Daniel , Roalson Eric H. , Hipp Andrew L. ,   the Global Carex Group, Benítez‐Benítez Carmen , P. Bruederle Leo , Fitzek Elisabeth , A. Ford Bruce , A. Ford Kerry , Garner Mira , Gebauer Sebastian , H. Hoffmann Matthias , Jin Xiao‐Feng , Larridon Isabel , Léveillé‐Bourret Étienne , Lu Yi‐Fei , Luceño Modesto , Maguilla Enrique , Márquez‐Corro Jose Ignacio , Míguez Mónica , Naczi Robert , A. Reznicek Anton , R. Starr Julian
Published: November 2019

The megadiverse genus Carex (c. 2000 species, Cyperaceae) has a nearly cosmopolitan distribution, displaying an inverted latitudinal richness gradient with higher species diversity in cold‐temperate areas of the Northern Hemisphere. Despite great expansion in our knowledge of the phylogenetic history of the genus and many molecular studies focusing on the biogeography of particular groups during the last few decades, a global analysis of Carex biogeography and diversification is still lacking. For this purpose, we built the hitherto most comprehensive Carex‐dated phylogeny based on three markers (ETS–ITS–matK), using a previous phylogenomic Hyb‐Seq framework, and a sampling of two‐thirds of its species and all recognized sections. Ancestral area reconstruction, biogeographic stochastic mapping, and diversification rate analyses were conducted to elucidate macroevolutionary biogeographic and diversification patterns. Our results reveal that Carex originated in the late Eocene in E Asia, where it probably remained until the synchronous diversification of its main subgeneric lineages during the late Oligocene. E Asia is supported as the cradle of Carex diversification, as well as a “museum” of extant species diversity. Subsequent “out‐of‐Asia” colonization patterns feature multiple asymmetric dispersals clustered toward present times among the Northern Hemisphere regions, with major regions acting both as source and sink (especially Asia and North America), as well as several independent colonization events of the Southern Hemisphere. We detected 13 notable diversification rate shifts during the last 10 My, including remarkable radiations in North America and New Zealand, which occurred concurrently with the late Neogene global cooling, which suggests that diversification involved the colonization of new areas and expansion into novel areas of niche space.
Firm capital dynamics in centrally cleared markets
Authors: Capponi Agostino , Cheng W. Allen , Rajan Sriram
Published: November 2019

We develop a tractable continuous time model of multifirm capital dynamics in a centrally cleared market. Our framework jointly models the strategic interactions between business operations of firms and their trading activities. We show that the endogenous allocation of firm capital between trading and operations can be recovered as the unique fixed point of a system of quadratic equations. Our model predicts that (a) there exists a convex relationship between equilibrium margins and firm capital in the cross‐section, (b) market collateral demand is positively correlated with size concentration, and (c) size concentration is expected to increase over time. Using proprietary data on bilateral credit default swap exposures, we provide evidence that the convexity prediction is both economically and statistically significant and validate our model assumption that firms hedge excess risks.
A cognitive explanation of the perceived normativity of cultural conventions
Authors: Slors Marc
Published: November 2019

I argue that cultural conventions such as social etiquette facilitate a specific (non‐Lewisian) kind of action coordination—role–interaction coordination—that is required for division of labour. Playing one's roles and coordinating them with those of others is a form of multitasking. Such multitasking is made possible on a large scale because we can offload cognition aimed at coordination onto a stable infrastructure of cultural conventions. Our natural tendency to prefer multitasking in instances where one task requires low cognitive control can thus explain our preference for and expectation of familiar cultural conventions—that is, their perceived normativity.
Using pre‐ and postexploitation samples to assess the impact of commercial whaling on the genetic characteristics of eastern North Pacific gray and humpback whales and to compare methods used to infer historic demography
Authors: Béland Stephanie L. , Frasier Brenna A. , Darling James D. , Frasier Timothy R.
Published: November 2019

Many species of whales went through recent bottlenecks due to commercial whaling. These declines were rapid and recent relative to the life spans and generation times of these species, raising questions regarding to what degree commercial whaling influenced the genetic characteristics of these populations. We analyzed mitochondrial and nuclear DNA from pre‐ and postwhaling samples from two populations that have arguably shown the greatest degree of recovery: eastern North Pacific gray and humpback whales. We also compare the performance of different methods to test for historic bottlenecks and infer past demography based on genetic data. We found substantially higher levels of genetic diversity in gray than in humpback whales (for both time periods), likely due to recent connectivity between Atlantic and Pacific gray whale populations. Other than mitochondrial diversity in humpback whales, levels of diversity were not lower in contemporary samples relative to prewhaling samples, indicating that commercial whaling had a minimal impact on metrics of genetic diversity themselves. However, it did have large impacts on the patterns of diversity, as evidenced by all coalescent‐based methods showing clear evidence of a bottleneck for both populations, whereas all but one method not based on the coalescent failed to detect a bottleneck.
Looking Forward to Cuts: A Simulation Decision Tool for Cutback Management
Authors: Brien Spencer T. , Candreva Philip J. , Hansen Stephen C. , Pizzini Mina
Published: November 2019

This study addresses managerial strategies to adapt public spending in anticipation of fiscal stress. It simulates a cutback to a federal agency, providing a decision tool that applies normative recommendations from the cutback management literature. Using agency data, we develop a menu of options that illustrate how different distributions of budget reductions affect organizational goals. We show five alternatives that consider the political, legal, and fiscal implications of the agency's responses to anticipated budgetary pressure. This simulation demonstrates that public agencies can apply existing data to generate rational and viable strategic plans for weathering fiscal stress.
Alternative Methods of Experience Rating Unemployment Insurance Employer Taxes
Authors: Miller Michael , Pavosevich Robert
Published: November 2019

For most states the methodology used for assigning Unemployment Insurance tax rates to employers arose when the program was first established in 1935. More than 80 years later, with evolving employment relationships, state systems have become outmoded. This paper critiques current experience rating methods and presents new methodologies that are much easier to operate and that improve the incentives for employers to increase employment. The proposed methods would assess taxes based on employment or payroll variation such that growing firms would have lower taxes. A simulation analysis illustrates the impact of the new methods on employer groups.
PLX3397 inhibits the accumulation of intra‐tumoral macrophages and improves bromodomain and extra‐terminal inhibitor efficacy in melanoma
Authors: Erkes Dan A. , Rosenbaum Sheera R. , Field Conroy O. , Chervoneva Inna , Villanueva Jessie , Aplin Andrew E.
Published: November 2019

Bromodomain and extra‐terminal inhibitors (BETi) delay tumor growth, in part, through tumor cell intrinsic alterations and initiation of anti‐tumor CD8+ T‐cell responses. By contrast, BETi effects on pro‐tumoral immune responses remain unclear. Here, we show that the next‐generation BETi, PLX51107, delayed tumor growth to differing degrees in Braf V600E melanoma syngeneic mouse models. These differential responses were associated with the influx of tumor‐associated macrophages during BETi treatment. Tumors that were poorly responsive to PLX51107 showed increased influx of colony‐stimulating factor‐1 receptor (CSF‐1R)‐positive tumor‐associated macrophages. We depleted CSF‐1R+ tumor‐associated macrophages with the CSF‐1R inhibitor, PLX3397, in combination with PLX51107. Treatment with PLX3397 enhanced the efficacy of PLX51107 in poorly responsive Braf V600E syngeneic melanomas in vivo. These findings suggest that tumor‐associated macrophage accumulation limits BETi efficacy and that co‐treatment with PLX3397 can improve response to PLX51107, offering a potential novel combination therapy for metastatic melanoma patients.
Identification of Protective Actions to Reduce the Vulnerability of Safety‐Critical Systems to Malevolent Intentional Acts: An Optimization‐Based Decision‐Making Approach
Authors: Wang T. R. , Pedroni N. , Zio E. , Mousseau V.
Published: November 2019

An empirical classification model based on the Majority Rule Sorting (MR‐Sort) method has been previously proposed by the authors to evaluate the vulnerability of safety‐critical systems (in particular, nuclear power plants [NPPs]) with respect to malevolent intentional acts. In this article, the model serves as the basis for an analysis aimed at determining a set of protective actions to be taken (e.g., increasing the number of monitoring devices, reducing the number of accesses to the safety‐critical system) in order to effectively reduce the level of vulnerability of the safety‐critical systems under consideration.

In particular, the problem is here tackled within an optimization framework: the set of protective actions to implement is chosen as the one minimizing the overall level of vulnerability of a group of safety‐critical systems. In this context, three different optimization approaches have been explored: (i) one single classification model is built to evaluate and minimize system vulnerability; (ii) an ensemble of compatible classification models, generated by the bootstrap method, is employed to perform a “robust” optimization, taking as reference the “worst‐case” scenario over the group of models; (iii) finally, a distribution of classification models, still obtained by bootstrap, is considered to address vulnerability reduction in a “probabilistic” fashion (i.e., by minimizing the “expected” vulnerability of a fleet of systems). The results are presented and compared with reference to a fictitious example considering NPPs as the safety‐critical systems of interest.
Tourism frontiers: Primitive accumulation, and the “Free Gifts” of (Human) nature in the South China Sea and Myanmar
Authors: Mostafanezhad Mary
Published: November 2019

One of the first industries developed in frontier regions, tourism opens new land and commodity frontiers through practices of primitive accumulation that can radically disrupt the reproduction of social relations of production. However, very little work explicitly addresses the role of tourism in frontier‐making practices. This paper brings political economy and critical geopolitics to bear on the role of tourism in the development of new land and commodity frontiers in the South China Sea and Myanmar. Geopolitical ambitions are played out under the guise of tourism development and are obscured by the assemblage of institutions, discourses, and practices (e.g., photographic surveillance, social media representations, place branding) that aid in the appropriation of the “free gifts” of not only nature, but also human nature. The state is integral to the extraction of use values of non‐human and human nature: territorialisation, dispossession, and enclosure are all fundamental to this process. Additionally, as people and places (e.g., beaches, cultural practices, ethnic identities) become legible as commodities, so too do they become alienated from the products of their labour. This paper sheds analytical light on the ways in which powerful mechanisms of the tourism industry legitimise the creative creation of new land and commodity frontiers.
Volume incompliance and transfusion are essential for transfusion‐associated circulatory overload: a novel animal model
Authors: Klanderman Robert B. , Bosboom Joachim J. , Maas Adrie A.W. , Roelofs Joris J.T.H. , de Korte Dirk , van Bruggen Robin , van Buul Jaap D. , Zuurbier Coert J. , Veelo Denise P. , Hollmann Markus W. , Vroom Margreeth B. , Juffermans Nicole P. , Geerts Bart F. , Vlaar Alexander P.J.
Published: November 2019

BACKGROUND

Transfusion‐associated circulatory overload (TACO) is the predominant complication of transfusion resulting in death. The pathophysiology is poorly understood, but inability to manage volume is associated with TACO, and observational data suggest it is different from simple cardiac overload due to fluids. We developed a two‐hit TACO animal model to assess the role of volume incompliance (“first‐hit”) and studied whether volume overload (“second‐hit”) by red blood cell (RBC) transfusion is different compared to fluids (Ringer's lactate [RL]).

MATERIALS AND METHODS

Male adult Lewis rats were stratified into a control group (no intervention) or a first hit: either myocardial infarction (MI) or acute kidney injury (AKI). Animals were randomized to a second hit of either RBC transfusion or an equal volume of RL. A clinically relevant difference was defined as an increase in left ventricular end‐diastolic pressure (ΔLVEDP) of +4.0 mm Hg between the RBC and RL groups.

RESULTS

In control animals (without first hit) LVEDP was not different between infusion groups (Δ + 1.6 mm Hg). LVEDP increased significantly more after RBCs compared to RL in animals with MI (Δ7.4 mm Hg) and AKI (Δ + 5.4 mm Hg), respectively. Volume‐incompliant rats matched clinical TACO criteria in 92% of transfused versus 25% of RL‐infused animals, with a greater increase in heart rate and significantly higher blood pressure.

CONCLUSION

To our knowledge, this is the first animal model for TACO, showing that a combination of volume incompliance and transfusion is essential for development of circulatory overload. This model allows for further testing of mechanistic factors as well as therapeutic approaches.
Whole blood: back to the future
Authors: Haley Nancy Rebecca , Hess John R.
Published: November 2019

See article on page 3468–3477, in this issue
Antibody levels to Malassezia pachydermatis and Staphylococcus pseudintermedius in atopic dogs and their relationship with lesion scores
Authors: Khantavee Nathrada , Chanthick Chanettee , Sookrung Nitat , Prapasarakul Nuvee
Published: November 2019

Background

Elevated immunoglobulin E (IgE) levels to Malassezia or Staphylococcus species in human atopic dermatitis are related to the skin severity index; a similar association has not been reported in atopic dogs.

Objectives

To investigate serum levels of allergen‐specific IgE, total specific IgG and IgG subclasses (IgG1 and IgG2) for M. pachydermatis and S. pseudintermedius, and to correlate them with the severity of dermatitis in dogs.

Animals

Serum samples were collected from dogs categorized by age and disease status. Groups 1 and 2: <3‐year‐old healthy (n = 9) and atopic dogs (n = 9), respectively; and groups 3 and 4: ≥3‐year‐old healthy (n = 11) and atopic dogs (n = 14), respectively.

Methods and materials

Antibody levels were measured by ELISA. The Canine Atopic Dermatitis Lesion Index (CADLI) was analyzed in relation to antibody levels.

Results

Specific IgE and total IgG against M. pachydermatis and S. pseudintermedius were significantly increased in atopic dogs of all ages. Although differences between atopic and healthy dogs, with regard to specific IgG1 and IgG2 levels to each microbe, varied in significance within age groups. No significant relationships were found between the CADLI and any specific immunoglobulin levels for both microbe types.

Conclusions and clinical importance

In dog skin, microbes may act as allergens triggering inflammatory responses via IgE‐ and IgG‐dependent pathway(s). The affinity of the IgG subclass produced may vary according to antigen type. Specific IgE levels may be related to clinical disease in dogs and not to skin lesion severity.
Immediate brain plasticity after one hour of brain–computer interface (BCI)
Authors: Nierhaus Till , Vidaurre Carmen , Sannelli Claudia , Mueller Klaus‐Robert , Villringer Arno
Published: November 2019

Key points

Two groups of inexperienced brain‐computer interface users underwent a purely mental EEG‐BCI session that rapidly impacted on their brain.

Modulations in structural and functional MRI were found after only 1 h of BCI training.

Two different types of BCI (based on motor imagery or visually evoked potentials) were employed and analyses showed that the brain plastic changes are spatially specific for the respective neurofeedback.

This spatial specificity promises tailored therapeutic interventions (e.g. for stroke patients).

A brain‐computer‐interface (BCI) allows humans to control computational devices using only neural signals. However, it is still an open question, whether performing BCI also impacts on the brain itself, i.e. whether brain plasticity is induced. Here, we show rapid and spatially specific signs of brain plasticity measured with functional and structural MRI after only 1 h of purely mental BCI training in BCI‐naive subjects. We employed two BCI approaches with neurofeedback based on (i) modulations of EEG rhythms by motor imagery (MI‐BCI) or (ii) event‐related potentials elicited by visually targeting flashing letters (ERP‐BCI). Before and after the BCI session we performed structural and functional MRI. For both BCI approaches we found increased T1‐weighted MR signal in the grey matter of the respective target brain regions, such as occipital/parietal areas after ERP‐BCI and precuneus and sensorimotor regions after MI‐BCI. The latter also showed increased functional connectivity and higher task‐evoked BOLD activity in the same areas. Our results demonstrate for the first time that BCI by means of targeted neurofeedback rapidly impacts on MRI measures of brain structure and function. The spatial specificity of BCI‐induced brain plasticity promises therapeutic interventions tailored to individual functional deficits, for example in patients after stroke.
Long-acting reversible contraception by effervescent microneedle patch
Authors: Li Wei , Tang Jie , Terry Richard N. , Li Song , Brunie Aurelie , Callahan Rebecca L. , Noel Richard K. , Rodríguez Carlos A. , Schwendeman Steven P. , Prausnitz Mark R.
Published: November 2019

An effervescent microneedle patch has been designed for rapid separation of drug-loaded microneedles and long-term contraception.
SCAN1-TDP1 trapping on mitochondrial DNA promotes mitochondrial dysfunction and mitophagy
Authors: Ghosh Arijit , Bhattacharjee Sangheeta , Chowdhuri Srijita Paul , Mallick Abhik , Rehman Ishita , Basu Sudipta , Das Benu Brata
Published: November 2019

Mitochondrial dysfunction promotes the etiology of neurodegenerative syndrome SCAN1.
Integrated proteogenetic analysis reveals the landscape of a mitochondrial-autophagosome synapse during PARK2-dependent mitophagy
Authors: Heo Jin-Mi , Harper Nathan J. , Paulo Joao A. , Li Mamie , Xu Qikai , Coughlin Margaret , Elledge Stephen J. , Harper J. Wade
Published: November 2019

We explore the landscape of a mitochondrial-autophagosome synapse during mitophagy using proteomics and genetic screens.
An embryonic CaVβ1 isoform promotes muscle mass maintenance via GDF5 signaling in adult mouse
Authors: Traoré Massiré , Gentil Christel , Benedetto Chiara , Hogrel Jean-Yves , De la Grange Pierre , Cadot Bruno , Benkhelifa-Ziyyat Sofia , Julien Laura , Lemaitre Mégane , Ferry Arnaud , Piétri-Rouxel France , Falcone Sestina
Published: November 2019

CaVβ1E boosts downstream growth differentiation factor 5 signaling to counteract muscle mass loss in denervated or aged mouse muscles.
Tectono-sedimentary evolution of a fossil ocean-continent transition: Tasna nappe, central Alps (SE Switzerland)
Authors: Ribes Charlotte , Petri Benoit , Ghienne Jean-François , Manatschal Gianreto , Galster Federico , Karner Garry D. , Figueredo Patricio H. , Johnson Christopher A. , Karpoff Anne-Marie
Published: November 2019

Magma-poor ocean-continent transitions at distal rifted margins record complex stratigraphic interactions engendered by extreme crustal thinning and mantle exhumation. The Tasna ocean-continent transition, exposed in the Middle Penninic Tasna nappe in eastern Switzerland, is so far the only known example where the lateral transition from continental crust to exhumed serpentinized mantle lithosphere is exposed and not overprinted by later Alpine deformation. This paper presents sedimentological, structural, and petrographical observations and detrital zircon provenance data to document: (1) the processes controlling continental hyperextension and mantle exhumation; and (2) the facies, depositional systems, sediment sources, delivery pathways, and depositional stacking patterns associated with magma-poor ocean-continent transitions. Our results show that the basement units of the Tasna ocean-continent transition are composed of prerift upper and lower crust and subcontinental mantle rocks juxtaposed as part of the continental crustal thinning process. The absence of pervasive, synrift deformation in the lower-crustal rocks indicates that the thinning was likely achieved by deformation along localized shear zones before being exhumed at the seafloor by brittle, late extensional detachment faulting and not by any form of lower-crustal flow.

The age of the first sediments deposited on the continental crust and exhumed mantle, the so-called Tonschiefer Formation, is considered to be Late Jurassic. A key observation is that the restored morpho-tectonic and sedimentary evolution of the Tasna ocean-continent transition shows the intercalation of downdip, transported platform-derived sediments and along-axis–derived siliciclastic sediments originating from the recycling of prerift sediments, local basement, and/or extra-Alpine sources.
Thermal history of the western Central Taurides fold-thrust belt: Implications for Cenozoic vertical motions of southern Central Anatolia
Authors: McPhee Peter J. , van Hinsbergen Douwe J.J. , Thomson Stuart N.
Published: November 2019

The modern physiography of central Turkey is dominated by the 1-km-high Central Anatolian Plateau and the Central Tauride mountains that form the southern plateau margin. These correspond to a Cretaceous–Eocene backarc extensional province and forearc fold-thrust belt, respectively. The extent to which the morphology of the Miocene plateau was inherited from the physiography of the Cretaceous–Eocene subduction zone that assembled the Anatolian crust has not been tested but is important if we are to isolate the signal of Miocene and younger subduction dynamics in the formation of the modern plateau margin. There is no known stratigraphic record of the post-Eocene pre-Miocene evolution of the Taurides. We therefore collected rock samples across the Taurides and used zircon (U-Th)/He (ZHe), apatite (U-Th)/He (AHe), and apatite fission-track (AFT) low-temperature thermochronometers to constrain cooling; we interpret these thermochronometers to signal erosional exhumation. We use inverse thermal modeling to aid interpretation of our results and find that: (1) thermochronometers across the Taurides were reset as a result of heating by the emplacement of the Antalya and Bozkır nappes; (2) AFT and ZHe Eocene cooling ages are related to structurally driven uplift and erosional exhumation on major thrust culminations; (3) dispersed AHe ages record low rates of Oligocene–early Miocene cooling and hence low rates of erosional exhumation; and (4) fast rates of cooling were determined for samples along the margin of the Köprüçay Basin. We interpret that early Miocene cooling is a signal of active erosion of the western Central Taurides at a time of marine sedimentation in the Mut Basin on the southern Central Taurides, and these differing histories may reflect evolution above the Antalya and Cyprus slabs. Our thermochronological data, the enigmatic development of the Antalya Basin, and thrusting within the basin may be explained as the surface expression of stepwise delamination of the Antalya slab from the Tauride hinterland to its current position below the Gulf of Antalya since early Miocene time over a distance of ∼150 km.