bluuebunny/crossref_metadata_2025 huggingface dataset:
Autophagy inhibition overcomes sorafenib resistance in S45F‐mutated desmoid tumors
Authors: Braggio Danielle , Koller David , Jin Feng , Siva Nanda , Zewdu Abeba , Lopez Gonzalo , Batte Kara , Casadei Lucia , Welliver Meng , Strohecker Anne M. , Lev Dina , Pollock Raphael E.
Published: April 2019

Background

Desmoid tumors (DTs) are rare and understudied fibroblastic lesions that are frequently recurrent and locally invasive. DT patients often experience chronic pain, organ dysfunction, decrease in quality of life, and even death.

Methods

Sorafenib has emerged as a promising therapeutic strategy, which has led to the first randomized phase 3 clinical trial devoted to DTs. Concurrently, we conducted a comprehensive analysis of sorafenib efficacy in a large panel of desmoid cell strains to probe for response mechanism.

Results

We found distinctive groups of higher‐ and lower‐responder cells. Clustering the lower‐responder group, we observed that CTNNB1 mutation was determinant of outcome. Our results revealed that a lower dose of sorafenib was able to inhibit cell viability, migration, and invasion of wild‐type and T41A‐mutated DTs. Apoptosis induction was observed in those cells after treatment with sorafenib. On the other hand, the lower dose of sorafenib was not able to inhibit cell viability, migration, or invasion or to induce apoptosis in the S45F‐mutated DTs. The investigation of autophagy showed the dependency of S45F‐mutated DTs on this pathway as a part of cell survival mechanism. Significantly, when autophagy was inhibited genetically or pharmacologically in the S45F mutant cell strains, sensitivity to sorafenib was restored.

Conclusions

Our findings suggest that the response to sorafenib differs when comparing S45F‐mutated DTs and T41A‐mutated or wild‐type DTs. Furthermore, the combination of hydroxychloroquine and sorafenib enhances the antiproliferative and proapoptotic effects in S45F‐mutated DT cells, suggesting that profiling β‐catenin status could guide clinical management of desmoid patients who are considering sorafenib treatment.
Cholecystokinin immunoreactive neurons in the basolateral amygdala of the rhesus monkey (Macaca mulatta)
Authors: McDonald Alexander J. , Mascagni Franco
Published: April 2019

Several distinct subpopulations of interneurons (INs) in the amygdalar basolateral nuclear complex (BNC) of the rat can be recognized on the basis of their expression of calcium‐binding proteins and neuropeptides, including parvalbumin (PV), somatostatin (SOM), calretinin (CR), and cholecystokinin (CCK). In the rat BNC CCK is expressed in two separate IN subpopulations, termed large (CCKL) and small (CCKS). These subpopulations exhibit distinct connections indicative of discrete functional roles in the circuitry of the BNC. Although there have been several studies of PV+, SOM+, and CR+ INs in the primate BNC, there is almost no information regarding CCK+ INs in these species. Therefore, in the present study the distribution and morphology of CCK+ INs and their axon terminals in the BNC of the monkey was investigated. CCK immunoreactivity in the BNC was observed in somata and proximal dendrites of nonpyramidal neurons, as well as in axon terminals. A moderate density of CCK+ INs was found in all nuclei of the BNC. CCK+ INs in the BNC were morphologically heterogeneous, with both small and large varieties observed. All CCK+ somata gave rise to 2–4 dendrites that branched sparingly and were aspiny. CCK+ axon terminals in the BNC were found both in the neuropil and forming pericellular baskets contacting somata of pyramidal cells. In addition, many CCK+ neurons were contacted by multiple CCK+ terminals, indicative of the existence of a CCK interneuronal network. These data indicate that the morphology of CCK+ INs in the monkey is very similar to that of the rat.
Image‐Based Flow Cytometry and Angle‐Resolved Light Scattering to Define the Sickling Process
Authors: Goktas Polat , Sukharevsky Ilya O. , Larkin Sandra , Kuypers Frans A. , Yalcin Ozlem , Altintas Ayhan
Published: April 2019

Red blood cells (RBCs) from sickle cell patients exposed to a low oxygen tension reveal highly heterogeneous cell morphologies due to the polymerization of sickle hemoglobin (HbS). We show that angle‐resolved light scattering approach with the use of image‐based flow cytometry provides reliable quantitative data to define the change in morphology of large populations of RBCs from sickle cell patients when the cells are exposed for different times to low oxygen. We characterize the RBC morphological profile by means of a set of morphological and physical parameters, which includes cell shape, size, and orientation. These parameters define the cell as discocyte, sickle, elongated, as well as irregularly or abnormal RBC shaped cells, including echinocytes, holly‐leaf, and granular structures. In contrast to microscopy, quick assessment of large numbers of cells provides statistically relevant information of the dynamic process of RBC sickling in time. The use of this approach facilitates the understanding of the processes that define the propensity of sickle blood samples to change their shape, and the ensuing vaso‐occlusive events in the circulation of the patients. Moreover, it assists in the evaluation of treatments that include the use of anti‐sickling agents, gene therapy‐based hemoglobin modifications, as well as other approaches to improve the quality of life of sickle cell patients. © 2019 International Society for Advancement of Cytometry
Filling in the phylogenetic gaps: Induction, migration, and differentiation of neural crest cells in a squamate reptile, the veiled chameleon (Chamaeleo calyptratus)
Authors: Diaz Raul E. , Shylo Natalia A. , Roellig Daniela , Bronner Marianne , Trainor Paul A.
Published: April 2019

Neural crest cells comprise a migratory progenitor cell population that differentiate into cell types such as neurons and glia of the peripheral nervous system, pigment cells, hormone secreting cells in glands, and skeletal and connective tissue in the head, thus making important contributions to most tissues and organs throughout the vertebrate body. The evolutionary appearance of neural crest cells is considered synonymous with the origin of vertebrates and their subsequent diversification and radiation. While the comparative biology of neural crest cells has been studied for a century and a half beginning with their discovery by Wilhelm His in 1868, most of our understanding of their development and function has come from a small number of species. Thus, critical gaps exist in our understanding of how neural crest cells mediate evolution and development. This is particularly true with respect to squamate reptiles (lizards, snakes, amphisbaenians), which account for approximately one‐third of all living tetrapods. Here, we present veiled chameleons (Chamaeleo calyptratus) as a model system for studying neural crest cell development in squamates. Chameleons exhibit various morphological specializations associated with an arboreal lifestyle that may have been facilitated through neural crest cells acting as a conduit for evolutionary change.
Spatiotemporal prediction of wildfire size extremes with Bayesian finite sample maxima
Authors: Joseph Maxwell B. , Rossi Matthew W. , Mietkiewicz Nathan P. , Mahood Adam L. , Cattau Megan E. , St. Denis Lise Ann , Nagy R. Chelsea , Iglesias Virginia , Abatzoglou John T. , Balch Jennifer K.
Published: April 2019

Wildfires are becoming more frequent in parts of the globe, but predicting where and when wildfires occur remains difficult. To predict wildfire extremes across the contiguous United States, we integrate a 30‐yr wildfire record with meteorological and housing data in spatiotemporal Bayesian statistical models with spatially varying nonlinear effects. We compared different distributions for the number and sizes of large fires to generate a posterior predictive distribution based on finite sample maxima for extreme events (the largest fires over bounded spatiotemporal domains). A zero‐inflated negative binomial model for fire counts and a lognormal model for burned areas provided the best performance. This model attains 99% interval coverage for the number of fires and 93% coverage for fire sizes over a six year withheld data set. Dryness and air temperature strongly predict extreme wildfire probabilities. Housing density has a hump‐shaped relationship with fire occurrence, with more fires occurring at intermediate housing densities. Statistically, these drivers affect the chance of an extreme wildfire in two ways: by altering fire size distributions, and by altering fire frequency, which influences sampling from the tails of fire size distributions. We conclude that recent extremes should not be surprising, and that the contiguous United States may be on the verge of even larger wildfire extremes.
Larval and phenological traits predict insect community response to mowing regime manipulations
Authors: van Klink Roel , Menz Myles H. M. , Baur Hannes , Dosch Oliver , Kühne Isabel , Lischer Lukas , Luka Henryk , Meyer Sandro , Szikora Timea , Unternährer Debora , Arlettaz Raphaël , Humbert Jean‐Yves
Published: April 2019

For the restoration of biodiversity in agricultural grasslands, it is essential to understand how management acts as an ecological filter on the resident species. Mowing constitutes such a filter: only species that possess functional traits enabling them to withstand its consequences can persist in the community. We investigated how the timing of mowing modulates this filtering effect for insects. We predicted that two traits drive species responses. Species with larval development within the meadow vegetation will suffer more from mowing than species whose larvae develop in or on the ground, or outside the meadows, while species with a later phenology should benefit from later mowing. We conducted a five‐year experiment, replicated at 12 sites across the Swiss lowlands, applying three different mowing regimes to low‐intensity hay meadows: (1) first cut of the year not earlier than 15 June (control regime); (2) the first cut delayed until 15 July; and (3) leaving an uncut grass refuge on 10–20% of the meadow area (after earliest first cut on 15 June). Before the first cut in years 4 or 5, we sampled larvae of Lepidoptera and sawflies, and adults of moths, parasitoid wasps, wild bees, hoverflies, ground beetles, and rove beetles. Overall, before the first cut of the year, abundances of species with vegetation‐dwelling larvae were higher in meadows with delayed mowing or an uncut grass refuge, with some taxon‐specific variation. In contrast, species whose larval development is independent of the meadow vegetation showed no differences in abundance between mowing regimes. Species richness did not differ among regimes. For species with vegetation‐dwelling larvae, a fourth‐corner analysis showed an association between early phenology and the control regime. No associations were found for the other functional groups. Our results show that slight modifications of mowing regimes, easily implementable in agri‐environmental policy schemes, can boost invertebrate abundance, potentially benefitting insectivorous vertebrates.
Bio‐energetic modeling of medium‐sized cetaceans shows high sensitivity to disturbance in seasons of low resource supply
Authors: Hin Vincent , Harwood John , de Roos André M.
Published: April 2019

Understanding the full scope of human impact on wildlife populations requires a framework to assess the population‐level repercussions of nonlethal disturbance. The Population Consequences of Disturbance (PCoD) framework provides such an approach, by linking the effects of disturbance on the behavior and physiology of individuals to their population‐level consequences. Bio‐energetic models have been used as implementations of PCoD, as these integrate the behavioral and physiological state of an individual with the state of the environment, to mediate between disturbance and biological significant changes in vital rates (survival, growth, and reproduction). To assess which levels of disturbance lead to adverse effects on population growth rate requires a bio‐energetic model that covers the complete life cycle of the organism under study. In a density‐independent setting, the expected lifetime reproductive output of a single female can then be used to predict the level of disturbance that leads to population decline. Here, we present such a model for a medium‐sized cetacean, the long‐finned pilot whale (Globicephala melas). Disturbance is modeled as a yearly recurrent period of no resource feeding for the pilot whale female and her calf. Short periods of disturbance lead to the pre‐weaned death of the first one or more calves of the young female. Higher disturbance levels also affect survival of calves produced later in the life of the female, in addition to degrading female survival. The level of disturbance that leads to a negative population growth rate strongly depends on the available resources in the environment. This has important repercussion for the timing of disturbance if resource availability fluctuates seasonally. The model predicts that pilot whales can tolerate on average three times longer periods of disturbance in seasons of high resource availability, compared to disturbance happening when resources are low. Although our model is specifically parameterized for pilot whales, it provides useful insights into the general consequences of nonlethal disturbance. If appropriate data on life history and energetics are available, it can be used to provide management advice for specific species or populations.
Future changes in fire weather, spring droughts, and false springs across U.S. National Forests and Grasslands
Authors: Martinuzzi Sebastián , Allstadt Andrew J. , Pidgeon Anna M. , Flather Curtis H. , Jolly William M. , Radeloff Volker C.
Published: April 2019

Public lands provide many ecosystem services and support diverse plant and animal communities. In order to provide these benefits in the future, land managers and policy makers need information about future climate change and its potential effects. In particular, weather extremes are key drivers of wildfires, droughts, and false springs, which in turn can have large impacts on ecosystems. However, information on future changes in weather extremes on public lands is lacking. Our goal was to compare historical (1950–2005) and projected mid‐century (2041–2070) changes in weather extremes (fire weather, spring droughts, and false springs) on public lands. This case study looked at the lands managed by the U.S. Forest Service across the conterminous United States including 501 ranger district units. We analyzed downscaled projections of daily records from 19 Coupled Model Intercomparison Project 5 General Circulation Models for two climate scenarios, with either medium‐low or high CO2− equivalent concentration (RCPs 4.5 and 8.5). For each ranger district, we estimated: (1) fire potential, using the Keetch‐Byram Drought Index; (2) frequency of spring droughts, using the Standardized Precipitation Index; and (3) frequency of false springs, using the extended Spring Indices. We found that future climates could substantially alter weather conditions across Forest Service lands. Under the two climate scenarios, increases in wildfire potential, spring droughts, and false springs were projected in 32–72%, 28–29%, and 13–16% of all ranger districts, respectively. Moreover, a substantial number of ranger districts (17–30%), especially in the Southwestern, Pacific Southwest, and Rocky Mountain regions, were projected to see increases in more than one type of weather extreme, which may require special management attention. We suggest that future changes in weather extremes could threaten the ability of public lands to provide ecosystem services and ecological benefits to society. Overall, our results highlight the value of spatially‐explicit weather projections to assess future changes in key weather extremes for land managers and policy makers.
Persistence of balsam fir and black spruce populations in the mixedwood and coniferous bioclimatic domain of eastern North America
Authors: Messaoud Yassine , Goudiaby Venceslas , Bergeron Yves
Published: April 2019

The boreal ecocline (ca 49°N) between the southern mixedwood (dominated by balsam fir) and the northern coniferous bioclimatic domain (dominated by black spruce) may be explained by a northward decrease of balsam fir regeneration, explaining the gradual shift to black spruce dominance. 7,010 sample plots, with absence of major disturbances, were provided by the Quebec Ministry of Forest, Fauna, and Parks. The regeneration (sapling abundance) of balsam fir and black spruce were compared within and between the two bioclimatic domains, accounting for parental trees, main soil type (clay and till) and climate conditions, reflected by summer growing degree‐days above 5°C (GDD_5), total summer precipitation (May–August; PP_MA). Parental trees and soil type determined balsam fir and black spruce regeneration. Balsam fir and black spruce, respectively, showed higher regeneration in the mixedwood and the coniferous bioclimatic domains. Overall, higher regeneration was obtained on till for balsam fir, and on clay soils for black spruce. GDD_5 and PP_MA were beneficial for balsam fir regeneration on clay and till soils, respectively, while they were detrimental for black spruce regeneration. At a population level, balsam fir required at least 28% of parental tree basal area in the mixedwood, and 38% in the coniferous bioclimatic domains to maintain a regeneration at least equal to the mean regeneration of the whole study area. However, black spruce required 82% and 79% of parental trees basal area in the mixedwood and the coniferous domains, respectively. The northern limit of the mixedwood bioclimatic domain was attributed to a gradual decrease toward the north of balsam fir regeneration most likely due to cooler temperatures, shorter growing seasons, and decrease of the parental trees further north of this northern limit. However, balsam fir still persists above this northern limit, owing to a patchy occurrence of small parental trees populations, and good establishment substrates.
“Balancing” balancing selection? Assortative mating at the major histocompatibility complex despite molecular signatures of balancing selection
Authors: Slade Joel W. G. , Watson Matthew J. , MacDougall‐Shackleton Elizabeth A.
Published: April 2019

In vertebrate animals, genes of the major histocompatibility complex (MHC) determine the set of pathogens to which an individual's adaptive immune system can respond. MHC genes are extraordinarily polymorphic, often showing elevated nonsynonymous relative to synonymous sequence variation and sharing presumably ancient polymorphisms between lineages. These patterns likely reflect pathogen‐mediated balancing selection, for example, rare‐allele or heterozygote advantage. Such selection is often reinforced by disassortative mating at MHC. We characterized exon 2 of MHC class II, corresponding to the hypervariable peptide‐binding region, in song sparrows (Melospiza melodia). We compared nonsynonymous to synonymous sequence variation in order to identify positively selected sites; assessed evidence for trans‐species polymorphisms indicating ancient balancing selection; and compared MHC similarity of socially mated pairs to expectations under random mating. Six codons showed elevated ratios of nonsynonymous to synonymous variation, consistent with balancing selection, and we characterized several alleles similar to those occurring in at least four other avian families. Despite this evidence for historical balancing selection, mated pairs were significantly more similar at MHC than were randomly generated pairings. Nonrandom mating at MHC thus appears to partially counteract, not reinforce, pathogen‐mediated balancing selection in this system. We suggest that in systems where individual fitness does not increase monotonically with MHC diversity, assortative mating may help to avoid excessive offspring heterozygosity that could otherwise arise from long‐standing balancing selection.
Plant selection initiates alternative successional trajectories in the soil microbial community after disturbance
Authors: Duhamel Marie , Wan Joe , Bogar Laura M. , Segnitz R. Max , Duncritts Nora C. , Peay Kabir G.
Published: April 2019

Because interactions between plants and microbial organisms can influence species diversity and rates of nutrient cycling, how plants shape microbial communities is fundamental to understanding the structure of ecosystems. Despite this, the spatial and temporal scales over which plants influence microbial communities is poorly understood, particularly whether past abiotic or biotic legacies strongly constrain microbial community development. We examined biogeochemical cycling and microbial community structure in a coastal landscape where historical patterns of vegetation transition after a large fire in 1995 are well known, allowing us to account for past abiotic and biotic conditions. We found that alternative states in microbial community structure and ecosystem processes emerged under different plant species, regardless of past conditions. Greenhouse studies further demonstrated that these differences arise from direct plant selection of microbes, with selection stronger in roots compared with soils, especially for bacteria. Correlation of microbial community structure with seedling growth rates was also stronger for fungi compared to bacteria. Despite these effects, minimal overlap between seedling and field microbial communities indicates that the effects of initial plant selection are not stable; rather, plant selection initiated alternative successional trajectories after the fire. Using data from a guild where we have abundant natural history information, ectomycorrhizal fungi, we show that greenhouse communities are dominated by ruderal taxa that are also common in the field after the fire and that these ruderal fungi strongly alter spatial patterns in plant–soil feedback, enabling invasion and transformation of soils previously occupied by heterospecific plants, thus potentially acting as keystone mutualists.
Soil organic matter determines the distribution and abundance of nematodes on alluvial fans in Death Valley, California
Authors: Treonis Amy M. , Sutton Kelsey A. , Unangst Samantha K. , Wren Julia E. , Dragan Emma S. , McQueen J. Parr
Published: April 2019

Death Valley, located within the Mojave Desert of the United States, is one of the most extreme terrestrial environments on Earth. We studied free‐living soil nematode abundance and community structure in soil samples collected from alluvial fans in Death Valley between 2013 and 2018. Our objective was to establish the distribution and abundance of soil nematodes on alluvial fans with respect to soil properties, vegetation, and channels that reflect past and future water flows. The study period spanned an extreme drought for the region but also included a 2016 superbloom of spring annual plants that followed a strong El Niño event. We found that nematode communities were dominated by bacterial‐feeding species and had higher densities under shrub canopies than in adjacent interplant soils. Nematode abundance was similar between areas on alluvial fans that were channelized by past water flows and adjacent desert pavement and does not appear to be linked to how water distributes on the fans following rainfall events. Nematode abundance increased during the superbloom in soils around annual plants. Across the study period, soil organic matter content was the only soil variable measured that was significantly and positively correlated to nematode abundance. Overall, nematodes in this extreme environment are adapted to drought, but they are highly dependent on the growth and distribution of both perennial and annual plants to supply the soil organic matter that their microbial food sources rely upon.
Use, selection, and home range properties: complex patterns of individual habitat utilization
Authors: Ofstad Endre Grüner , Herfindal Ivar , Solberg Erling J. , Heim Morten , Rolandsen Christer Moe , Sæther Bernt‐Erik
Published: April 2019

Individual patterns of habitat use emerge from behavioral decisions driven by interactions between landscape characteristics and individual traits. Individual traits, such as age and sex, influence the net gain of using habitats and associated resources, and thus the relationship between size and composition of the home range. However, the pathways from individual variation in home range size and composition to habitat selection are rarely fully explored. We investigated how habitat selection in moose (Alces alces) was a result of individual traits and home range characteristics, that is, we described the pathway from home range to habitat selection. The study was conducted at two spatial scales during two contrasting seasons. Home range size and composition varied with sex, with season, and to some extent with age. Males had larger home range size, and the composition of their home ranges changed more with home range size than for females. The general trend was that moose used habitats according to availability more in winter than in summer, that is, a weaker habitat selection in winter than in summer. Sex and age explained little of the variation in habitat selection, but sex had a pronounced effect on the relationship between home range size and composition. Because habitat availability (i.e., home range composition) is a component of habitat selection, it suggests that varying habitat use partly compensates for sex‐specific differences in home range composition, which in turn results from home range settlement. Hence, although males and females showed similar habitat selection, they differed in the underlying mechanisms generating the pattern of habitat selection. These complex interactions between individual traits and environmental variation have consequences for how we understand the relationships between landscape characteristics, individual behavior, and fitness.
Pathogenic modification of plants enhances long‐distance dispersal of nonpersistently transmitted viruses to new hosts
Authors: Donnelly Ruairí , Cunniffe Nik J. , Carr John P. , Gilligan Christopher A.
Published: April 2019

Aphids spread the majority of plant viruses through nonpersistent transmission (NPT), whereby virus particles attach transiently to these insects’ probing mouthparts. Virus acquisition from infected plants and inoculation to healthy host plants is favored when aphids briefly probe plant epidermal cells. It is well established that NPT virus infection can alter plant–vector interactions, and, moreover, such pathogen modifications are found in a range of plant and animal systems. In particular, viruses can make plants more attractive to aphids but inhibit aphid settling on infected plants. It is hypothesized that this viral “reprogramming” of plants promotes virus acquisition and encourages dispersal of virus‐bearing aphids to fresh hosts. In contrast, it is hypothesized that virus‐induced biochemical changes encouraging prolonged feeding on infected hosts inhibit NPT. To understand how these virus‐induced modifications affect epidemics, we developed a modeling framework accounting for important but often neglected factors, including feeding behaviors (probing or prolonged feeding) and distinct spatial scales of transmission (as conditioned by wingless or winged aphids). Analysis of our models confirmed that when viruses inhibit aphid settling on infected plants this initially promotes virus transmission. However, initially enhanced transmission is self‐limiting because it decreases vector density. Another important finding is that virus‐induced changes encouraging settling will stimulate birth of winged aphids, which promotes epidemics of NPT viruses over greater distances. Thus our results illustrate how plant virus modifications influence epidemics by altering vector distribution, density, and even vector form. Our insights are important for understanding how pathogens in general propagate through natural plant communities and crops.
Exercise‐induced hypoalgesia is present in people with Parkinson’s disease: Two observational cross‐sectional studies
Authors: Nguy Vanessa , Barry Benjamin K. , Moloney Niamh , Hassett Leanne M. , Canning Colleen G. , Lewis Simon J. G. , Allen Natalie E.
Published: April 2019

Background

Exercise is prescribed for people with Parkinson’s disease to address motor and non‐motor impairments, including pain. Exercise‐induced hypoalgesia (i.e., an immediate reduction in pain sensitivity following exercise) is reported in the general population; however, the immediate response of pain sensitivity to exercise in people with Parkinson’s disease is unknown. The purpose of this study was to investigate if exercise‐induced hypoalgesia is present following isometric and aerobic exercise in people with Parkinson’s disease, and if so, if it varies with the dose of aerobic exercise.

Methods

Thirty people with idiopathic Parkinson’s disease and pain‐free age‐matched controls completed two observational studies evaluating the response to: (a) right arm isometric exercise; and (b) treadmill walking at low and moderate intensities. Pressure pain thresholds were measured over biceps brachii and quadriceps muscles immediately before and after exercise, with increased thresholds after exercise indicating exercise‐induced hypoalgesia.

Results

Pressure pain thresholds increased in the Parkinson’s disease group at all tested sites following all exercise bouts (e.g., isometric exercise, right bicep 29%; aerobic exercise, quadriceps, moderate intensity 8.9%, low intensity 7.1% (p ≤ 0.008)), with no effect of aerobic exercise dose (p = 0.159). Similar results were found in the control group.

Conclusions

Overall, people with Parkinson’s disease experienced an exercise‐induced hypoalgesia response similar to that of the control group, the extent of which did not vary between mild and moderate doses of aerobic exercise. Further research is warranted to investigate potential longer term benefits from exercise in the management of pain in this population.

Significance

Isometric and aerobic exercise reduces pain sensitivity in people with Parkinson’s disease. As exercise is important for people with Parkinson’s disease, these results provide assurance that people with Parkinson’s disease and pain can exercise without an immediate increase in pain sensitivity. The reduction in pain sensitivity with both modes and with low and moderate intensities of aerobic exercise suggests that people with Parkinson’s disease can safely choose the mode and intensity of exercise that best suits their needs.
Composite material for high‐temperature thermochemical energy storage using calcium hydroxide and ceramic foam
Authors: Funayama Shigehiko , Takasu Hiroki , Zamengo Massimiliano , Kariya Jun , Kim Seon Tae , Kato Yukitaka
Published: April 2019

Thermochemical energy storage using a calcium oxide/calcium hydroxide/water (CaO/Ca(OH)2/H2O) reaction system is a promising technology for thermal energy storage at high‐temperatures (400°C‐600°C). The purpose of this study is to develop a practical composite material by enhancing heat transfer through the reaction bed and mitigating problems of pure CaO/Ca(OH)2 materials, such as formation of centimeter‐scale agglomerates and change in the bulk volume during repetitive reactions. The present study focused on a novel composite material using a silicon carbide/silicon (SiC/Si) foam. In the literature, performance of thermochemical energy storage of the composite using the ceramic foam remains unclear. In this study, we evaluated the performance of the composite material (~63 g) by a 100‐W‐scale packed bed reactor. The volumetric heat output rate (for the first 5 minutes, under maximum hydration pressure) of the composite was 1.3 kW L‐bed−1, which was 1.4 times higher than that previously reported for a bed of pure Ca(OH)2 pellets. The composite material, in which the CaO/Ca(OH)2 samples were subdivided inside pores with a mean diameter of 400 μm, retained high reactivity during cycle reactions, and maintained its bulk volume. Therefore, the composite material developed in this study shows promising application for high‐temperature thermochemical energy storage.
The quantile dependence of commodity futures markets on news sentiment
Authors: Omura Akihiro , Todorova Neda
Published: April 2019

Focusing on energy commodities, industrial metals, and gold, this paper examines the degree to which commodity futures returns depend on news sentiment under various market conditions, and the structure of that dependence. We observe an asymmetric market reaction to positive and negative news sentiment, which changes in periods of financial turmoil. The quantile regression analysis shows that news sentiment's influence on the futures returns follows an upward trend at higher percentiles. This structure flattens for positive news during the global financial crisis, while the slope for the negative component steepens in backwardation periods.
Sulfatase 2 promotes generation of a spinal cord astrocyte subtype that stands out through the expression of Olig2
Authors: Ohayon David , Escalas Nathalie , Cochard Philippe , Glise Bruno , Danesin Cathy , Soula Cathy
Published: April 2019

Generation of glial cell diversity in the developing spinal cord is known to depend on spatio‐temporal patterning programs. In particular, expression of the transcription factor Olig2 in neural progenitors of the pMN domain is recognized as critical to their fate choice decision to form oligodendrocyte precursor cells (OPCs) instead of astrocyte precursors (APs). However, generating some confusion, lineage‐tracing studies of Olig2 progenitors in the spinal cord provided evidence that these progenitors also generate some astrocytes. Here, we addressed the role of the heparan sulfate‐editing enzyme Sulf2 in the control of gliogenesis and found an unanticipated function for this enzyme. At initiation of gliogenesis in mouse, Sulf2 is expressed in ventral neural progenitors of the embryonic spinal cord, including in Olig2‐expressing cells of the pMN domain. We found that sulf2 deletion, while not affecting OPC production, impairs generation of a previously unknown Olig2‐expressing pMN‐derived cell subtype that, in contrast to OPCs, does not upregulate Sox10, PDGFRα or Olig1. Instead, these cells activate expression of AP identity genes, including aldh1L1 and fgfr3 and, of note, retain Olig2 expression as they populate the spinal parenchyma at embryonic stages but also as they differentiate into mature astrocytes at postnatal stages. Thus, our study, by revealing the existence of Olig2‐expressing APs that segregate early from pMN cells under the influence of Sulf2, supports the existence of a common source of APs and OPCs in the ventral spinal cord and highlights divergent regulatory mechanism for the development of pMN‐derived OPCs and APs.
Patients’ sun practices, perceptions of skin cancer and their risk of skin cancer in rural Australia
Authors: Sideris Emily , Thomas Susan J.
Published: April 2019

Issue addressed

Skin cancer affects nearly one in three Australians. As a preventable disease there have been many public awareness campaigns targeting skin cancer knowledge and sun protection in Australia in the last 30 years to increase knowledge of the disease and how to prevent it. Despite higher incidence and mortality of skin cancer in regional Australia and adults over 65 years though, little research exists examining this high‐risk population's skin cancer knowledge and sun behaviours, with most previous research conducted in urban Australia or overseas. This study aimed to examine adults’ skin cancer knowledge, sun behaviours and demographic factors in a regional Australian town.

Methods

Cross‐sectional study design was utilised. Adult patients of a Mudgee General Practice (n = 179, 18‐89 years) completed a survey based on their skin cancer knowledge and sun behaviours. Chi‐squared tests were used to analyse responses.

Results

Poor non‐melanoma skin cancer awareness, risky sun behaviours and inadequate sun protection behaviours were found. Males and those at greatest current risk of skin cancer in Australia, those over 60 years, had the poorest skin cancer knowledge and were least likely to recognise skin cancer or use some sun protection measures.

Conclusions

Greater non‐melanoma skin cancer and sun protection education and research is needed, particularly targeting older and male Australians.

So what?

The findings suggest rural men and older Australians would benefit from more targeted campaigns and education to increase their skin cancer awareness and use of sun protection in order to minimise future skin cancer.
Perinatal and familial risk factors for soft tissue sarcomas in childhood through young adulthood: A population‐based assessment in 4 million live births
Authors: Lupo Philip J. , Luna‐Gierke Ruth E. , Chambers Tiffany M. , Tavelin Björn , Scheurer Michael E. , Melin Beatrice , Papworth Karin
Published: April 2019

Perinatal factors have been associated with soft tissue sarcomas (STS) in case‐control studies. However, (i) the contributions of factors including fetal growth remain unknown, (
ii) these factors have not been examined in cohort studies and (iii) few assessments have evaluated risk in specific STS subtypes. We sought to identify the role of perinatal and familial factors on the risk of STS in a large population‐based birth cohort. We identified 4,023,436 individuals in the Swedish Birth Registry born during 1973–2012. Subjects were linked to the Swedish Cancer Registry, where incident STS cases were identified. We evaluated perinatal and familial factors obtained from Statistics Sweden, including fetal growth, gestational age, and presence of a congenital malformation. Poisson regression was used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for associations between perinatal factors and STS overall, as well as by common subtypes. There were 673 individuals diagnosed with STS in 77.5 million person‐years of follow‐up. Having a congenital malformation was associated with STS (IRR = 1.70, 95% CI: 1.23–2.35). This association was stronger (IRR = 2.90, 95% CI: 1.25–6.71) in recent years (2000–2012). Low fetal growth was also associated with STS during the same time period (IRR = 1.86, 95% CI: 1.05–3.29). Being born preterm was associated with rhabdomyosarcoma (IRR = 1.74, 95% CI: 1.08–2.79). In our cohort study, those with congenital malformations and other adverse birth outcomes were more likely to develop a STS compared to their unaffected contemporaries. These associations may point to disrupted developmental pathways and genetic factors influencing the risk of STS.
RAB27B‐activated secretion of stem‐like tumor exosomes delivers the biomarker microRNA‐146a‐5p, which promotes tumorigenesis and associates with an immunosuppressive tumor microenvironment in colorectal cancer
Authors: Cheng Wei‐Chung , Liao Tsai‐Tsen , Lin Chun‐Chi , Yuan Lan‐Ting Emily , Lan Hsin‐Yi , Lin Hung‐Hsin , Teng Hao‐Wei , Chang Hsin‐Chuan , Lin Chi‐Hung , Yang Chih‐Yung , Huang Shih‐Ching , Jiang Jeng‐Kai , Yang Shung‐Haur , Yang Muh‐Hwa , Hwang Wei‐Lun
Published: April 2019

The dynamic cell–cell communication is essential for tissue homeostasis in normal physiological circumstances and contributes to a diversified tumor microenvironment. Although exosomes are extracellular vesicles that actively participate in cell–cell interaction by shutting cellular components, impacts of tumor exosomes in the context of cancer stemness remain elusive. Here, we expand colorectal cancer stem cells (CRCSCs) as cancer spheroids and demonstrate that the β‐catenin/Tcf‐4‐activated RAB27B expression is required for the secretion of CRCSC exosomes. In an exosomal RNA sequencing analysis, a switch of exosomal RNA species from retrotransposons to microRNAs (miRNAs) is identified upon expanding CRCSCs. miRNA‐146a‐5p (miR‐146a) is the major miRNA in CRCSC exosomes and exosomal miR‐146a promotes stem‐like properties and tumorigenicity by targeting Numb in recipient CRC cells. Among 53 CRC patients, those with abundant exosomal miR‐146a expression in serum exhibits higher miR‐146aHigh/NumbLow CRCSC traits, an increased number of tumor‐filtrating CD66(+) neutrophils and a decreased number of tumor‐infiltrating CD8(+) T cells. Our study elucidates a unique mechanism of tumor exosome‐mediated stemness expansion.
Cervical adenocarcinoma in situ: Human papillomavirus types and incidence trends in five states, 2008–2015
Authors: Cleveland Angela A. , Gargano Julia W. , Park Ina U. , Griffin Marie R. , Niccolai Linda M. , Powell Melissa , Bennett Nancy M. , Saadeh Kayla , Pemmaraju Manideepthi , Higgins Kyle , Ehlers Sara , Scahill Mary , Johnson Jones Michelle L. , Querec Troy , Markowitz Lauri E. , Unger Elizabeth R. ,   HPV‐IMPACT Working Group
Published: April 2019

Primary prevention through the use of human papillomavirus (HPV) vaccination is expected to impact both cervical intraepithelial neoplasia (CIN) and adenocarcinoma in situ (AIS). While CIN is well described, less is known about the epidemiology of AIS, a rare cervical precancer. We identified AIS and CIN grade 3 (CIN3) cases through population‐based surveillance, and analyzed data on HPV types and incidence trends overall, and among women screened for cervical cancer. From 2008 to 2015, 470 AIS and 6,587 CIN3 cases were identified. The median age of women with AIS was older than those with CIN3 (35 vs. 31 years; p < 0.01). HPV16 was the most frequently detected type in both AIS and CIN3 (57% in AIS; 58% in CIN3), whereas HPV18 was the second most common type in AIS and less common in CIN3 (38% vs. 5%; p < 0.01). AIS lesions were more likely than CIN3 lesions to be positive for high‐risk types targeted by the bivalent and quadrivalent vaccines (HPV16/18, 92% vs. 63%; p < 0.01), and 9‐valent vaccine (HPV16/18/31/33/45/52/58, 95% vs. 87%; p < 0.01). AIS incidence rates decreased significantly in the 21–24 year age group (annual percent change [APC] overall: −22.1%, 95% CI: −33.9 to −8.2; APC among screened: −16.1%, 95% CI: −28.8 to −1.2), but did not decrease significantly in any older age group. This report on the largest number of genotyped AIS cases to date suggests an important opportunity for vaccine prevention of AIS, and is the first to document a decline in AIS incidence rates among young women during the vaccine era.
Upregulation of CBP by PLY can cause permeability of blood‐brain barrier to increase meningitis
Authors: Chen Jia‐Quan , Li Nan‐Nan , Wang Bo‐Wen , Liu Xiu‐Fang , Liu Jia‐Lin , Chang Qing
Published: April 2019

Background

Streptococcus pneumoniae causes many human diseases including bacterial meningitis. Previous study proposed that pneumolysin (PLY), a cytotoxin from pneumococcus, is related to the infection across blood‐brain barrier (BBB). However, the mechanism of how PLY break through BBB remains elusive. The present study showed that PLY can increase the permeability of BBB both in vitro and in vivo in our experiments.

Results

Further we found out that PLY leads to the high expression of CERB‐binding protein (CBP) which can lead to releasing of tumor necrosis factor α then enhance apoptosis of cells which is a significant factor leading to permeabilization of BBB.

Conclusion

Our findings demonstrate that CBP plays an important role in the pneumococcus infection in the brain and could be a potential therapeutic target against pneumococcal meningitis.
Synergistic effects of hormone therapy drugs and usnic acid on hormone receptor‐positive breast and prostate cancer cells
Authors: Guney Eskiler Gamze , Eryilmaz Isil Ezgi , Yurdacan Beste , Egeli Unal , Cecener Gulsah , Tunca Berrin
Published: April 2019

The aim of this study was to investigate the combined effects of usnic acid (UA) and Tamoxifen (Tam) or Enzalutamide (Enz) on hormone receptor‐positive breast and prostate cancer (BC and PC), respectively. The antiproliferative and apoptotic effects of Tam or Enz alone and in combination with UA on MCF7 and LNCaP cancer cells were detected. The results of the WST‐1 assay indicated that UA was a promising anticancer compound that significantly enhanced the effectiveness of hormone therapy drugs compared with each drug alone (combination index < 1). In addition, the combination of UA with Tam or Enz remarkably induced more cell cycle arrest at the G0/G1 phase and apoptosis than only drug‐treated cells (P < 0.01). Consequently, our findings suggest that the combination of UA with Tam or Enz may be a potential therapeutic approach for the treatment of BC and PC and further studies are required to exploit the potential mechanisms of synergistic effects.
SNPs in LncRNA genes are associated with non‐small cell lung cancer in a Chinese population
Authors: Wang Ruoyang , Feng Nannan , Wang Yu , Gao Sumeng , Zhang Fangfang , Qian Ying , Gao Ming , Yu Herbert , Zhou Baosen , Qian Biyun
Published: April 2019

Background

It has indicated that single nuclear polymorphisms (SNPs) in the regions encoding non‐coding transcripts are associated with lung cancer susceptibility. In a previous microarray study, we identified 13 differentially expressed long non‐coding RNAs (lncRNAs) in non‐small cell lung cancer (NSCLC) and associations of SNPs in these lncRNA genes with lung cancer were unknown. We conducted a case‐control study to address this issue.

Methods

Using the TaqMan method, we genotyped 17 SNPs located in the 13 lncRNA genes in 1294 cases with NSCLC and 1729 healthy controls. Unconditional logistic regression and Cox proportional hazards regression were used to analyze the associations of these SNPs with NSCLC risk and patient survival, respectively. These analyses were also repeated in subgroups of cases and controls stratified by gender, age group, smoking status, disease stage, and histological type.

Results

We identified three SNPs associated with NSCLC risk. For SNP rs498238, CC genotype was associated with lower risk compared to TT genotype (adjusted OR = 0.33, 95%CI: 0.11‐0.97, P = 0.043). For rs16901995, CT/TT genotypes were associated with lower risk compared to CC genotype in non‐smokers (adjusted OR = 0.78, 95%CI: 0.62‐0.98, P = 0.035). Variant genotypes in rs219741 were associated with NSCLC risk in young patients, and the adjusted OR was 1.47 (95%CI: 1.03‐2.10, P = 0.033) when compared to the wild genotype. No SNPs were found to be associated with patient overall survival in the study.

Conclusion

The study suggests that some genetic polymorphisms in the lncRNA genes may influence the risk of NSCLC among Chinese.
Changes in the sense of agency: Implications for the psychotherapy of bulimia nervosa‐ A case study
Authors: Kristmannsdottir Gudrun , Keski‐Rahkonen Anna , Kuusinen Kirsti‐Liisa
Published: April 2019

A sense of agency is a transtheoretical concept that increases our understanding of important processes in psychotherapy. Agency can be described in terms of how strongly the person believes that she can have an impact on her problematic experiences and behaviors. In this case study, a patient's sense of agency in relation to symptoms of bulimia nervosa was assessed during 3 years of psychotherapy. Five distinct phases of agency in relation to eating disorder symptoms were identified: A false sense of agency or no agency at all, a weak sense of agency, a nascent sense of agency, a wavering sense of agency, and a strong sense of agency. A better understanding of patient agency can facilitate adapting approaches and methods best suited for the patient's capacity for change throughout treatment.