bluuebunny/crossref_metadata_2025_split huggingface dataset:
Susceptibility of rat immortalized neuronal cell line Rn33B expressing equine major histocompatibility class 1 to equine herpesvirus‐1 infection is differentiation dependent
Authors: Minato Erina , Kobayashi Atsushi , Aoshima Keisuke , Fukushi Hideto , Kimura Takashi 
Published: November 2019

AbstractEquine herpesvirus‐1 (EHV‐1), which causes encephalomyelitis in horses, shows endotheliotropism in the central nervous system of horses, and generally does not infect neurons. However, little is known about the mechanism underlying the resistance of neuron to EHV‐1, due to the lack of convenient cell culture systems. In this study, we examined EHV‐1 infection in immortalized Rn33B rat neuronal cells, which differentiate into neurons when cultured under nonpermissive conditions. Because murine cell lines are resistant to EHV‐1 infections due to the lack of functional entry receptors for EHV‐1, we used an Rn33B‐derived cell line that stably expresses the equine MHC class 1 molecule, which acts as EHV‐1 entry receptor (Rn33B‐A68B2M cells). EHV‐1 infected undifferentiated Rn33B‐A68B2M cells more efficiently than differentiated cells, resulting in the production of progeny virus in the former but not in the latter. By contrast, both differentiated and undifferentiated cells infected with herpes simplex virus‐1 produced infectious viral progeny. While EHV‐1 infection induced stronger expression of IFN alpha gene in differentiated cells than in undifferentiated cells, downstream IFN responses, including phosphorylation of STAT1 (signal transducer and activator of transcription 1) and expression of IFN‐stimulated genes, were not activated regardless of whether cells were differentiated or not. These results suggest that neuronal differentiation of RN33B‐A68B2M cells reduced their susceptibility to EHV‐1, which is not due to different IFN responses. This culture system may be useful as an in vitro model for studying neuron‐specific resistance to EHV‐1, by investigating viral and host factors responsible for the difference in susceptibility between differentiated and undifferentiated cells.
The eukaryome: Diversity and role of microeukaryotic organisms associated with animal hosts
Authors: del Campo Javier , Bass David , Keeling Patrick J. 
Published: November 2019

Abstract

Awareness of the roles that host‐associated microbes play in host biology has escalated in recent years. However, microbiome studies have focused essentially on bacteria, and overall, we know little about the role of host‐associated eukaryotes outside the field of parasitology. Despite that, eukaryotes and microeukaryotes in particular are known to be common inhabitants of animals. In many cases, and/or for long periods of time, these associations are not associated with clinical signs of disease.

Unlike the study of bacterial microbiomes, the study of the microeukaryotes associated with animals has largely been restricted to visual identification or molecular targeting of particular groups. So far, since the publication of the influential Human Microbiome Project Consortium paper in 2012, few studies have been published dealing with the microeukaryotes using a high‐throughput barcoding ‘microbiome‐like’ approach in animals.

Nonetheless, microeukaryotes have an impact on the host physiology and lifestyle and also on the diversity and composition of the wider symbiotic community of bacteria and viruses. Beyond being parasites, microeukaryotes have many different roles in animals. For example, they directly interact with the host immune system in mammals; they have a key role on cellulose degradation, lignocellulose in xylophage termites and cockroaches; and they have an essential role in providing photosynthates to reef‐building corals.

Certain microeukaryotic lineages have diversified within hosts more than others. These cases of co‐evolution led to different forms of symbiosis: from mutualism (like Symbiodinium in corals or parabasalians in termites), to commensalism (Blastocystis in humans) or to strict parasitism (apicomplexans or microsporidians in a broad range of hosts). We will review the ecological context and the evolutionary mechanisms that ended up in these different symbiotic scenarios, across the taxonomic range of both symbionts and their metazoan hosts.

Host‐associated microeukaryotes have impacts at many levels, from individual animal health to ecosystems and to agroeconomy. Therefore, it is crucial to have a better understanding of their diversity and roles. Novel methodologies are being developed to access the eukaryotic fraction of the microbiome using high‐throughput methods. From ‐omics, to imaging and barcoding approaches biased against metazoans, these novel methodologies and strategies are helping us to increase and improve our knowledge of microeukaryotes in animal‐associated environments.

A free Plain Language Summary can be found within the Supporting Information of this article.
Can dynamic network modelling be used to identify adaptive microbiomes?
Authors: Garcia Joshua , Kao‐Kniffin Jenny 
Published: November 2019

Abstract

In recent times, interest has grown in understanding how microbiomes – the collection of microorganisms in a specific environment – influence the survivability or fitness of their plant and animal hosts. The profound diversity of bacterial and fungal species found in certain environments, such as soil, provides a large pool of potential microbial partners that can interact in ways that reveal patterns of associations linking host–microbiome traits developed over time. However, most microbiome sequence data are reported as a community fingerprint, without analysis of interaction networks across microbial taxa through time.

To address this knowledge gap, more robust tools are needed to account for microbiome dynamics that could signal a beneficial change to a plant or animal host. In this paper, we discuss applying mathematical tools, such as dynamic network modelling, which involves the use of longitudinal data to study system dynamics and microbiomes that identify potential alterations in microbial communities over time in response to an environmental change. In addition, we discuss the potential challenges and pitfalls of these methodologies, such as handling large amounts of sequencing data and accounting for random processes that influence community dynamics, as well as potential ways to address them.

Ultimately, we argue that components of microbial community interactions can be characterized through mathematical models to reveal insights into complex dynamics associated with a plant or animal host trait. The inclusion of interaction networks in microbiome studies could provide insights into the behaviour of complex communities in tandem with host trait modification and evolution.

A free Plain Language Summary can be found within the Supporting Information of this article.
Within‐individual trophic variability drives short‐term intraspecific trait variation in natural populations
Authors: Musseau Camille , Vincenzi Simone , Santoul Frédéric , Boulêtreau Stéphanie , Jesenšek Dusan , Crivelli Alain J. 
Published: November 2019

Abstract

Intraspecific trait variability (ITV) maintains functional diversity in populations and communities, and plays a crucial role in ecological and evolutionary processes such as trophic cascades or speciation. Furthermore, functional variation within a species and its populations can help buffer against harmful environmental changes. Trait variability within species can be observed from differences among populations, and between‐ and within individuals. In animals, ITV can be driven by ontogeny, the environment in which populations live and by within‐individual specialization or variation unrelated to growth. However, we still know little about the relative strength of these drivers in determining ITV variation in natural populations.

Here, we aimed to (a) measure the relative strength of between‐ and within‐individual effects of body size on ITV over time, and (b) disentangle the trophic changes due to ontogeny from other sources of variability, such as the environment experienced by populations and individual preferences at varying temporal and spatial scales.

We used as a model system the endangered marble trout Salmo marmoratus, a freshwater fish living in a restricted geographical area (<900 km2) that shows marked changes in diet through ontogeny. We investigated two trophic traits, trophic position and resource use, with stable isotopes (δ15N and δ13C), and followed over time 238 individually tagged marble trout from six populations to estimate the trophic changes between and within individuals through ontogeny at three different time‐scales (short term: 3 months, medium term: 1 year and long term: 2 years).

We found that the relative strength of between‐ and within‐individual effects of body size on trophic position and resource use change strongly over time. Both effects played a similar role in ITV over medium‐ and long‐term time‐scales, but within‐individual effects were significantly driving trophic variability over short‐term scales. Apart from ontogenetic shifts, individuals showed variability in trophic traits as big as the variability estimated between populations.

Overall, our results show how the relative strengths of ITV drivers change over time. This study evidences the crucial importance of considering effects of time‐scales on functional variability at individual, population and species levels.
Evidence based practice and knowledge translation: A survey of Australian occupational therapy practice with clients experiencing neurocognitive impairments
Authors: Nott Melissa T. , Barden Hannah L. H. , Chapparo Chris , Ranka Judy L. 
Published: November 2019

AbstractIntroductionThe clinical practice patterns and use of research evidence by Australian occupational therapists working with clients experiencing neurocognitive impairments has not been surveyed for nearly 10 years. This survey aimed to evaluate the current status of occupational therapy practice and evidence use and provide recommendations for ongoing evidence translation.MethodsAn online survey of occupational therapists working in Australia was conducted over four months targeting registered clinicians working with adults experiencing neurocognitive impairments.Results191 occupational therapists from a wide range of clinical practice areas, with a significant level of experience completed the survey. Functional retraining (n = 180, 94%), compensatory training (n = 173, 91%) and task/environmental modifications (n = 161, 84%) were the most commonly reported intervention techniques, while more targeted interventions such as context‐sensitive training (n = 54, 28%), positive behaviour supports (n = 42, 22%) and metacognitive strategy training (n = 37, 19%) were used less frequently. Half the respondents were aware of current research evidence and suggested a wide range of strategies supporting evidence translation. Traditional barriers of limited time, access and skills to interpret research were also reported.ConclusionConsistent with earlier surveys most occupational therapists continue to use a functional/compensatory approach to cognitive rehabilitation, with an increasing number of therapists using specialist cognitive interventions. The current challenge for occupational therapists is embedding specialist techniques into occupation‐based intervention. Knowledge translation and implementation strategies will be a critical component to achieving this.
Hypoperfusion in the posterior cingulate cortex is associated with lower bone mass density in elderly women with osteopenia and Alzheimer’s disease
Authors: Takano Yumi , Mutoh Tatsushi , Tatewaki Yasuko , Seki Toshiki , Yamamoto Shuzo , Odagiri Hayato , Arai Hiroyuki , Taki Yasuyuki 
Published: November 2019

AbstractAccelerated bone loss is closely associated with Alzheimer's disease (AD), but the relationship between bone mineral density (BMD) and imaging markers of neurodegeneration remains uncertain. We examined the effect of low bone mass (osteopenia) on regional cerebral blood flow (rCBF) in patients with AD (n = 19) and non‐demented aging (n = 12). We enrolled 31 female outpatients diagnosed with osteopenia (age ≥ 65 years) who had both a single‐photon emission computed tomography brain scan and dual‐energy X‐ray absorptiometry bone scan taken at their initial investigation. We analyzed the relationship between osteopenia (−2.5 < T‐score < −1) and rCBF in 62 cortical areas measured using the stereotactic extraction estimation analysis on single‐photon emission computed tomography (SPECT) (mean Z‐scores). We found that the mean Z‐scores of 14 cerebral subregions, most of which are often affected early in AD, were significantly lower in the AD group than the non‐demented group (P < .001). The age‐stratified multivariate regression analysis showed that the decreased rCBF in the left posterior cingulate cortex (PCC) was an independent predictor of osteopenia (r = −0.395; P = .005). BMD and rCBF in the left PCC were significantly correlated in the overall population (r = −0.54; P = .001), as well as the AD group (r = −0.514; P = .02). These imaging data suggest that osteopenia may contribute to neurodegeneration of a brain network hub associated with AD.
Rapid divergent coevolution of Sinopotamon freshwater crab genitalia facilitates a burst of species diversification
Authors: YAO Fengxin , SHI Boyang , WANG Xiaoqi , PAN Da , BAI Ming , YAN Jie , CUMBERLIDGE Neil , SUN Hongying 
Published: November 2019

AbstractOne of the most striking radiations in brachyuran evolution is the considerable morphological diversification of the external reproductive structures of primary freshwater crabs: the male first gonopod (G1) and the female vulva (FV). However, the lack of quantitative studies, especially the lack of data on female genitalia, has seriously limited our understanding of genital evolution in these lineages. Here we examined 69 species of the large Chinese potamid freshwater crab genus Sinopotamon Bott, 1967 (more than 80% of the described species). We used a landmark‐based geometric morphometric approach to analyze variation in the shape of the G1 and FV, and to compare the relative degree of variability of the genitalia with non‐reproductive structures (the third maxillipeds). We found rapid divergent evolution of the genitalia among species of Sinopotamon when compared to non‐reproductive traits. In addition, the reconstruction of ancestral groundplans, together with plotting analyses, indicated that the FV show the most rapid divergence, and that changes in FV traits correlate with changes in G1 traits. Here we provide new evidence for coevolution between the male and female external genitalia of Sinopotamon that has likely contributed to rapid divergent evolution and an associated burst of speciation in this lineage.
Activation of insulin‐like growth factor‐1 receptor confers acquired resistance to osimertinib in non‐small cell lung cancer with EGFR T790M mutation
Authors: Hayakawa Daisuke , Takahashi Fumiyuki , Mitsuishi Yoichiro , Tajima Ken , Hidayat Moulid , Winardi Wira , Ihara Hiroaki , Kanamori Koichiro , Matsumoto Naohisa , Asao Tetsuhiko , Ko Ryo , Shukuya Takehito , Takamochi Kazuya , Hayashi Takuo , Suehara Yoshiyuki , Takeda Nakamura Ikuko , Ueno Toshihide , Kohsaka Shinji , Mano Hiroyuki , Takahashi Kazuhisa 
Published: November 2019

AbstractBackgroundOsimertinib (AZD9291) is a third‐generation EGFR‐tyrosine kinase inhibitor (TKI) that selectively inhibits the activating EGFR mutation and T790M mutation, and is currently used globally to treat EGFR‐mutant non‐small cell lung cancer (NSCLC). However, acquired resistance to osimertinib is inevitable.MethodsWe established osimertinib‐resistant cells (PC9/T790M/AZDR and H1975/AZDR) derived from EGFR‐mutant NSCLC cells harboring T790M mutation, and investigated the mechanism of acquired resistance to osimertinib by whole‐exome sequencing and multiple phospho‐receptor tyrosine kinase (RTK) array. A tumor specimen from an EGFR‐mutant NSCLC patient with acquired resistance to osimertinib was also subjected to immunohistochemical analysis.ResultsWhole‐exome sequencing analysis demonstrated that genetic alterations, such as acquisition of EGFR C797S, loss of T790M mutation, MET amplification, or mutated KRAS, MEK, BRAF, PIK3CA, were not detected. Analysis of phospho‐RTK array revealed that insulin‐like growth factor‐1 receptor (IGF1R) was activated in PC9/T790M/AZDR and H1975/AZDR cells. Knockdown of IGF1R by siRNA as well as inhibition of IGF1R activation by linstinib (IGF1R inhibitor) significantly restored the sensitivity to osimertinib. Immunohistochemical analysis revealed that the expression level of phosphorylated IGF1R was higher in the tumor specimen from the EGFR‐mutant NSCLC patient with acquired resistance to osimertinib than in the specimen collected prior to the treatment.ConclusionsIGF1R activation could occur following treatment with osimertinib in EGFR‐mutant NSCLC with T790M mutation, and might be one of the mechanisms underlying osimertinib resistance. Combined treatment of osimertinib and IGF1R inhibitor might be effective in overcoming the acquired resistance to osimertinib induced by IGF1R activation.Key pointsSignificant findings of the study: Using osimertinib‐resistant cells, we found that IGF1R activation induced by osimertinib treatment in EGFR‐mutant NSCLC with T790M mutation is involved in resistance. Increased phosphorylation of IGF1R was observed in the tumor specimen from an EGFR‐mutant NSCLC patient with acquired osimertinib resistance.What this study adds: IGF1R activation might be one of the mechanisms of osimertinib resistance. A combination therapy with osimertinib and an IGF1R inhibitor might be an optimal approach for overcoming the acquired resistance to osimertinib induced by IGF1R activation.
Horizontal and vertical distribution of mosquitoes (Diptera: Culicidae) in the rainforest of Maromizaha, Madagascar: implications for pathogen transmission to humans and animals
Authors: Tantely Luciano M , Randrianambinintsoa Fano J , Woog Friederike , Raharinirina Manou R , Ratsimbazafy Jonah , Boyer Sébastien , Girod Romain 
Published: November 2019

AbstractThe horizontal and vertical distribution of mosquito species was studied in Maromizaha rainforest, Madagascar. In November 2014, horizontal distribution was studied using light traps that were placed in four habitat types, ranging from degraded forest to primary rainforest. In November to December 2016, vertical distribution was studied using light traps placed near to the ground and elevated near the canopy. From the horizontal survey, 476 adults were collected:Uranotaenia(52.10%) andCulex(35.2%) were the most abundant genera. The highest numbers of mosquitoes were observed in the rainforest edge habitat, while the highest mosquito diversity was observed within primary rainforest. From the vertical survey, 276 adults were collected:Culexwas the most abundant genus and represented 75.70% of adults caught. Mosquitoes were more abundant in traps placed near the ground than those near the canopy. The highest species diversity was observed near the canopy. The higher abundance of mosquitoes at the forest edge agrees with the role of this zone as an ecotone between intact rainforest and the nearest human habitation. Increased mosquito abundance in lower strata might heighten their contact with particular vertebrate hosts. The presence of vectors in different habitats and in varying elevations likely influences the risk of pathogen transmission between animals and humans in this rainforest.
Phenotypic characterization of testicular immune cells expressing immune checkpoint molecules in wild‐type and pituitary adenylate cyclase‐activating polypeptide‐deficient mice
Authors: Meggyes Matyas , Lajko Adrienn , Fulop Balazs Daniel , Reglodi Dora , Szereday Laszlo 
Published: November 2019

AbstractProblemPituitary adenylate cyclase‐activating polypeptide (PACAP) is a neuropeptide having several regulatory functions in the nervous system and in peripheral organs including those of the reproductive system. PACAP‐deficient male mice have several morphological, biochemical, behavioral defects and show disturbed signaling in spermatogenesis affecting fertility in PACAP KO mice. Reproductive functions such as fertility, mating, and maternal behaviors have been widely investigated, but no immune analyses are available regarding the testicular immune‐privileged environment in male PACAP‐deficient mice.Method of StudyWe performed detailed immunophenotyping of testicular immune cells and investigated the expression of TIM‐3 and PD‐1 Immune checkpoint molecules of immune cells together with the detection of galectin‐9 and perforin. We investigated the percentage of numerous immune cell populations in the testis of wild‐type and PACAP‐deficient mice.ResultsWe demonstrated a significant increase in the frequency of testicular CD8+ T cells together with the decrease in Treg cell number obtained from PACAP KO mice compared with wild‐type mice. Investigating Immune checkpoint receptors, only PD‐1 showed a significantly decreased expression in CD8+ T cells in PACAP KO mice compared with wild‐type suggesting an impaired PD‐1/PD‐L1 pathway. Regarding TIM‐3 expression, we did not find any significant difference between the investigated groups.ConclusionWe hypothesize that these local changes may result in an immune activation with disturbed testicular immunoregulation in PACAP KO mice; however, determining the exact function requires further investigations. Our data further support the view that besides a systemic immune tolerance, localized active immunosuppression is involved in the regulation of testicular immune privilege.
Is it possible to apply trial outcomes to a real‐world population? A novel approach to External Validity Analysis
Authors: Agresta Franca , Fois Romano , Garrett Claire , Rozen Genia , Polyakov Alex 
Published: November 2019

BackgroundTranslation of findings from randomised controlled trials (RCT), the foundation of evidence‐based medicine, into clinical practice requires an understanding of relationships between patient characteristics, treatment practices and outcomes. We propose a novel technique, External Validity Analysis (EVA), to evaluate applicability of findings from a large RCT, comparing baseline characteristics, interventions and outcomes between the RCT and a large clinical database.AimTo perform EVA of the findings of a randomised controlled trial (ESTHER‐1) to a population in an Australian clinic setting. To demonstrate this method, we evaluated the discordance in first cycle follicle‐stimulating hormone (FSH) exposure and outcomes between the two populations, to inform clinical practice.Materials and MethodsIn this retrospective, descriptive analysis, we compared practices and outcomes between the follitropin alfa ‘conventional’ dosing arm of the ESTHER‐1 trial and a selected comparable clinic subpopulation of patients who underwent controlled ovarian stimulation using FSH.ResultsMean FSH exposure was 34% higher in the clinic subpopulation than in the trial subpopulation, resulting in higher average ovarian response without improving the likelihood of clinical pregnancy or live birth.ConclusionsEVA allowed for the comparison of a trial population with a selected clinic population with similar characteristics. With respect to FSH consumption, this analysis revealed higher exposure to FSH in the clinic setting without a corresponding benefit. The comparison reveals population differences as well as the potential to improve clinical outcomes through a reappraisal of current practices and objectives in gonadotropin dose selection.