bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defining sarcopenia: some caveats and challenges
Authors: Sanchez-Rodriguez Dolores , Marco Ester , Cruz-Jentoft Alfonso J. 
Published: December 2019

Purpose of review
To summarize the latest advances and caveats in defining sarcopenia and discuss the implications of the most recent worldwide initiatives which are trying to harmonize the definition.

Recent findings
The evolution over time of the definitions of sarcopenia is discussed, with a focus on the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) definition and the Sarcopenia Definitions and Outcomes Consortium (SDOC) conference. The EWGSOP2 and the SDOC agree on the overall concept of sarcopenia, which involves both impaired function (low muscle strength) and structural damage (low muscle mass/quality). However, physical performance is considered as a diagnostic criterion (EWGSOP), a severity grading assessment (EWGSOP2) or an outcome (SDOC) pending on the definition used. Muscle strength has been recognized as the best predictor of health outcomes. Muscle mass alone, as part of the definition of cachexia, sarcopenia and malnutrition, is a nondefining parameter. Furthermore, there is a lack of precision in measurement techniques and variability of the cut-off points in defining it.

Summary
We discuss the relationship of sarcopenia with cachexia, malnutrition and frailty, and the areas that are hampering agreement. We summarize key scientific evidence, consider future study of this nutrition-related disease and raise concern about the need for a universal definition of sarcopenia.
Enhancing the Patient Experience for Individuals Undergoing Endoscopic Procedures Using Virtual Reality
Authors: Palanica Adam , Leier McKenzie , Lee Andrew , Fossat Yan , Docktor Michael J. 
Published: December 2019

ABSTRACTThe results of medical procedures can often be difficult to translate into comprehensible and engaging information for patients. This randomized controlled trial evaluated the satisfaction and perceived value of a technology, called HealthVoyager, which creates a personalized virtual reality (VR) experience of a patient's endoscopy or colonoscopy findings in comparison to the standard practice (ie, reviewing printed reports). The platform allows gastroenterologists to create a customized VR patient report to help translate medical knowledge and procedural information to the patient. Forty‐one patients (17 HealthVoyager [test]; 24 standard practice [control]) completed a self‐report survey assessing their experience for receiving medical information. Results demonstrated that patients were significantly more satisfied in learning about their gastrointestinal condition and procedural results using HealthVoyager rather than with the standard of care. These results have implications for improving the knowledge translation of medical findings between healthcare providers and patients in various disease states and patient populations.
Linking the mitochondrial genotype to phenotype: a complex endeavour
Authors: Ghiselli Fabrizio , Milani Liliana 
Published: December 2019

Finding causal links between genotype and phenotype is a major issue in biology, even more in mitochondrial biology. First of all, mitochondria form complex networks, undergoing fission and fusion and we do not know how such dynamics influence the distribution of mtDNA variants across the mitochondrial network and how they affect the phenotype. Second, the non-Mendelian inheritance of mitochondrial genes can have sex-specific effects and the mechanism of mitochondrial inheritance is still poorly understood, so it is not clear how selection and/or drift act on mtDNA genetic variation in each generation. Third, we still do not know how mtDNA expression is regulated; there is growing evidence for a convoluted mechanism that includes RNA editing, mRNA stability/turnover, post-transcriptional and post-translational modifications. Fourth, mitochondrial activity differs across species as a result of several interacting processes such as drift, adaptation, genotype-by-environment interactions, mitonuclear coevolution and epistasis. This issue will cover several aspects of mitochondrial biology along the path from genotype to phenotype, and it is subdivided into four sections focusing on mitochondrial genetic variation, on the relationship among mitochondria, germ line and sex, on the role of mitochondria in adaptation and phenotypic plasticity, and on some future perspectives in mitochondrial research.
This article is part of the theme issue ‘Linking the mitochondrial genotype to phenotype: a complex endeavour’.
Powerhouses in the cold: mitochondrial function during thermal acclimation in montane mayflies
Authors: Havird Justin C. , Shah Alisha A. , Chicco Adam J. 
Published: December 2019

Mitochondria provide the vast majority of cellular energy available to eukaryotes. Therefore, adjustments in mitochondrial function through genetic changes in mitochondrial or nuclear-encoded genes might underlie environmental adaptation. Environmentally induced plasticity in mitochondrial function is also common, especially in response to thermal acclimation in aquatic systems. Here, we examined mitochondrial function in mayfly larvae (BaetisandDrunellaspp.) from high and low elevation mountain streams during thermal acclimation to ecologically relevant temperatures. A multi-substrate titration protocol was used to evaluate different respiratory states in isolated mitochondria, along with cytochrome oxidase and citrate synthase activities. In general, maximal mitochondrial respiratory capacity and oxidative phosphorylation coupling efficiency decreased during acclimation to higher temperatures, suggesting montane insects may be especially vulnerable to rapid climate change. Consistent with predictions of the climate variability hypothesis, mitochondria fromBaetiscollected at a low elevation site with highly variable daily and seasonal temperatures exhibited greater thermal tolerance thanBaetisfrom a high elevation site with comparatively stable temperatures. However, mitochondrial phenotypes were more resilient than whole-organism phenotypes in the face of thermal stress. These results highlight the complex relationships between mitochondrial and organismal genotypes, phenotypes and environmental adaptation.This article is part of the theme issue ‘Linking the mitochondrial genotype to phenotype: a complex endeavour’.
Manipulating and elucidating mitochondrial gene expression with engineered proteins
Authors: Wallis Christopher P. , Scott Louis H. , Filipovska Aleksandra , Rackham Oliver 
Published: December 2019

Many conventional, modern genome engineering tools cannot be used to study mitochondrial genetics due to the unusual structure and physiology of the mitochondrial genome. Here, we review a number of newly developed, synthetic biology-based approaches for altering levels of mutant mammalian mitochondrial DNA and mitochondrial RNAs, including transcription activator-like effector nucleases, zinc finger nucleases and engineered RNA-binding proteins. These approaches allow researchers to manipulate and visualize mitochondrial processes and may provide future therapeutics.This article is part of the theme issue ‘Linking the mitochondrial genotype to phenotype: a complex endeavour’.
Mapping and editing animal mitochondrial genomes: can we overcome the challenges?
Authors: Klucnika Anna , Ma Hansong 
Published: December 2019

The animal mitochondrial genome, although small, can have a big impact on health and disease. Non-pathogenic sequence variation among mitochondrial DNA (mtDNA) haplotypes influences traits including fertility, healthspan and lifespan, whereas pathogenic mutations are linked to incurable mitochondrial diseases and other complex conditions like ageing, diabetes, cancer and neurodegeneration. However, we know very little about how mtDNA genetic variation contributes to phenotypic differences. Infrequent recombination, the multicopy nature and nucleic acid-impenetrable membranes present significant challenges that hamper our ability to precisely map mtDNA variants responsible for traits, and to genetically modify mtDNA so that we can isolate specific mutants and characterize their biochemical and physiological consequences. Here, we summarize the past struggles and efforts in developing systems to map and edit mtDNA. We also assess the future of performing forward and reverse genetic studies on animal mitochondrial genomes.This article is part of the theme issue ‘Linking the mitochondrial genotype to phenotype: a complex endeavour’.
Topology-driven protein-protein interaction network analysis detects genetic sub-networks regulating reproductive capacity
Authors: Kumar Tarun , Blondel Leo , Extavour Cassandra G. 
Published: December 2019

AbstractUnderstanding the genetic regulation of organ structure is a fundamental problem in developmental biology. Here, we use egg-producing structures of insect ovaries, called ovarioles, to deduce systems-level gene regulatory relationships from quantitative functional genetic analysis. We previously showed that Hippo signalling, a conserved regulator of animal organ size, regulates ovariole number inDrosophila melanogaster. To comprehensively determine how Hippo signalling interacts with other pathways in this regulation, we screened all known signalling pathway genes, and identified Hpo-dependent and Hpo-independent signalling requirements. Network analysis of known protein-protein interactions among screen results identified independent gene regulatory sub-networks regulating one or both of ovariole number and egg laying. These sub-networks predict involvement of previously uncharacterised genes with higher accuracy than the original candidate screen. This shows that network analysis combining functional genetic and large-scale interaction data can predict function of novel genes regulating development.
Machine Learning Predicts New Anti-CRISPR Proteins
Authors: Eitzinger Simon , Asif Amina , Watters Kyle E. , Iavarone Anthony T. , Knott Gavin J. , Doudna Jennifer A. , Afsar Minhas Fayyaz ul Amir 
Published: December 2019

ABSTRACTThe increasing use of CRISPR-Cas9 in medicine, agriculture and synthetic biology has accelerated the drive to discover new CRISPR-Cas inhibitors as potential mechanisms of control for gene editing applications. Many such anti-CRISPRs have been found in mobile genetic elements that disable the CRISPR-Cas adaptive immune system. However, comparing all currently known anti-CRISPRs does not reveal a shared set of properties that can be used for facile bioinformatic identification of new anti-CRISPR families. Here, we describe AcRanker, a machine learning based method for identifying new potential anti-CRISPRs directly from proteomes using protein sequence information only. Using a training set of known anti-CRISPRs, we built a model based on XGBoost ranking and extensively benchmarked it through non-redundant cross-validation and external validation. We then applied AcRanker to predict candidate anti-CRISPRs from self-targeting bacterial genomes and discovered two previously unknown anti-CRISPRs: AcrllA16 (ML1) and AcrIIA17 (ML8). We show that AcrIIA16 strongly inhibits Streptococcus iniae Cas9 (SinCas9) and weakly inhibits Streptococcus pyogenes Cas9 (SpyCas9). We also show that AcrIIA17 inhibits both SpyCas9 and SauCas9 with low potency. The addition of AcRanker to the anti-CRISPR discovery toolkit allows researchers to directly rank potential anti-CRISPR candidate genes for increased speed in testing and validation of new anti-CRISPRs. A web server implementation for AcRanker is available online at http://acranker.pythonanywhere.com/.
Discovery of functional gene markers of bacteria for monitoring hydrocarbon pollution in the marine environment - a metatranscriptomics approach
Authors: Knapik Kamila , Bagi Andrea , Krolicka Adriana , Baussant Thierry 
Published: December 2019

AbstractThe use of natural marine bacteria as “oil sensors” for the detection of pollution events can be suggested as a novel way of monitoring oil occurrence at sea. Nucleic acid-based devices generically called genosensors are emerging as potentially promising tools forin situdetection of specific microbial marker genes suited for that purpose. Functional marker genes are particularly interesting as targets for oil-related genosensing but their identification remains a challenge. Here, seawater samples, collected in tanks with oil addition mimicking a realistic oil spill scenario, were filtered and archived by the Environmental Sample Processor (ESP), a fully robotized genosensor, and the samples were then used for post-retrieval metatranscriptomic analysis. After extraction, RNA from ESP-archived samples at start, day 4 and day 7 of the experiment was used for sequencing. Metatranscriptomics revealed that several KEGG pathways were significantly enriched in samples exposed to oil. However, these pathways were highly expressed also in the non-oil-exposed water samples, most likely as a result of the release of natural organic matter from decaying phytoplankton. Temporary peaks of aliphatic alcohol and aldehyde dehydrogenases and monoaromatic ring-degrading enzymes (e.g.ben,box, anddmpclusters) were observed on day 4 in both control and oil tanks. Few alkane 1-monooxygenase genes were upregulated on oil, mostly transcribed by familiesPorticoccaceaeandRhodobacteraceae, together with aromatic ring-hydroxylating dioxygenases, mostly transcribed byRhodobacteraceae. Few transcripts from obligate hydrocarbonoclastic genera ofAlcanivorax,OleispiraandCycloclasticus, were significantly enriched in the oil-treated tank in comparison to control, and these were mostly transporters and genes involved in nitrogen and phosphorous acquisition. This study highlights the importance of seasonality,i.e., phytoplankton occurrence and senescence leading to organic compound release which can be used preferentially by bacteria over oil compounds, delaying the latter process. As a result, such seasonal effect can reduce the sensitivity of genosensing tools employing bacterial functional genes to sense oil. A better understanding of the use of natural organic matter by bacteria involved in oil-biodegradation is needed to develop an array of functional markers enabling the rapid and specificin situdetection of anthropogenic pollution.
Mechanisms underlying higher order interactions: from quantitative definitions to ecological processes
Authors: Kleinhesselink Andrew R. , Kraft Nathan J.B. , Levine Jonathan M. 
Published: December 2019

AbstractWhen species simultaneously compete with two or more species of competitor, higher order interactions (HOIs) can lead to emergent properties not present when species interact in isolated pairs. In order to extend ecological theory to multi-competitor communities, ecologists must develop a practical and general definition for HOIs that can be applied to a wide range of competition models. In this paper we propose a definition for HOIs and outline a set of criteria for testing whether a model has or does not have HOIs. These criteria are valuable for empirical ecologists in need of clarity when discussing HOIs in empirical data. We also provide thorough discussion of how our definition compares with previous definitions of HOIs and interaction modification in the literature. In the second part of the paper we demonstrate the steps required for a rigorous test of HOIs in empirical data. To do this we simulate resource competition between three annual plant species which differ in phenology. We then fit phenomenological competition models to the outcome of simulated competition and use these to test for the presence of HOIs. In our simulations, we find the strength of HOIs varies with phenology: species that grow later experience stronger HOIs than earlier growing species. Our simulation shows how HOIs could emerge in ecosystems where resource availability and individual size change rapidly throughout the course of the growing season and where there are differences in the timing of resource acquisition between competitors.
Three complete genome sequences of Penguin megrivirus from ornithogenic soil, Adelie penguin and Weddell seal of Antarctica
Authors: Aasdev Ashutosh , Mishra Anamika , Nair Manoj , Pawar Satyam D , Dubey Chandan K , Bhatia Sandeep , Dastidar Prabir G , Singh Vijendra Pal , Raut Ashwin Ashok 
Published: December 2019

AbstractWe report the complete genome sequences of Penguin megriviruses from three different sources from Antarctica namely feces of Adelie penguin, feces of Weddell seal and ornithogenic soil. Phylogenetic analysis indicates the prevalence of very similar viruses in different sources of Antarctic environment. These genome sequences aid to understand the evolution of megriviruses in Antarctic ecology and reveal their place in global megrivirus phylogeny.
The Collaborative Cross Graphical Genome
Authors: Su Hang , Chen Ziwei , Rao Jaytheert , Najarian Maya , Shorter John , Pardo Manuel de Villena Fernando , McMillan Leonard 
Published: December 2019

AbstractThe mouse reference is one of the most widely used and accurately assembled mammalian genomes, and is the foundation for a wide range of bioinformatics and genetics tools. However, it represents the genomic organization of a single inbred mouse strain. Recently, inexpensive and fast genome sequencing has enabled the assembly of other common mouse strains at a quality approaching that of the reference. However, using these alternative assemblies in standard genomics analysis pipelines presents significant challenges. It has been suggested that a pangenome reference assembly, which incorporates multiple genomes into a single representation, are the path forward, but there are few standards for, or instances of practical pangenome representations suitable for large eukaryotic genomes. We present a pragmatic graph-based pangenome representation as a genomic resource for the widely-used recombinant-inbred mouse genetic reference population known as the Collaborative Cross (CC) and its eight founder genomes. Our pangenome representation leverages existing standards for genomic sequence representations with backward-compatible extensions to describe graph topology and genome-specific annotations along paths. It packs 83 mouse genomes (8 founders + 75 CC strains) into a single graph representation that captures important notions relating genomes such as identity-by-descent and highly variable genomic regions. The introduction of special anchor nodes with sequence content provides a valid coordinate framework that divides large eukaryotic genomes into homologous segments and addresses most of the graph-based position reference issues. Parallel edges between anchors place variants within a context that facilitates orthogonal genome comparison and visualization. Furthermore, our graph structure allows annotations to be placed in multiple genomic contexts and simplifies their maintenance as the assembly improves. The CC reference pangenome provides an open framework for new tool chain development and analysis.
Conditioning a collective avoidance response in rummy-nose tetra
Authors: Lecheval Valentin , Hemelrijk Charlotte K. , Theraulaz Guy 
Published: December 2019

AbstractWe develop an experimental method to induce controlled and local perturbations in a group of fish. Using the paradigm of the shuttle box we condition aversive escape reactions in groups of rummy-nose tetra (Hemigrammus rhodostomus) in response to a green light. Our experiments suggest that aversive conditioning can (i) be used successfully in this schooling species, (ii) trigger collective escape reactions and (iii) be transferred from the training set-up to a new environment. These results are discussed in the context of propagation of information among group members in reaction to external stimuli such as perturbations mimicking sudden changes in the environment, e.g. predator attack.
Mechanistic models of signaling pathways deconvolute the functional landscape of glioblastoma at single cell resolution
Authors: Falco Matías M. , Peña-Chilet María , Loucera Carlos , Hidalgo Marta R. , Dopazo Joaquín 
Published: December 2019

AbstractThe rapid development of single cell RNA-sequencing (scRNA-seq) technologies is revealing an unexpectedly large degree of heterogeneity in gene expression levels across the different cells that compose the same tissue sample. However, little is known on the functional consequences of this heterogeneity and the contribution of individual cell-fate decisions to the collective behavior of the tissues these cells are part of. Mechanistic models of signaling pathways have already proven to be useful tools for understanding relevant aspects of cell functionality. Here we propose to use this mechanistic modeling strategy to deconvolute the complexity of the functional behavior of a tissue by dissecting it into the individual functional landscapes of its component cells by using a single-cell RNA-seq experiment of glioblastoma cells. This mechanistic modeling analysis revealed a high degree of heterogeneity at the scale of signaling circuits, suggesting the existence of a complex functional landscape at single cell level. Different clusters of neoplastic glioblastoma cells have been characterized according to their differences in signaling circuit activity profiles, which only partly overlap with the conventional glioblastoma subtype classification. The activity of signaling circuits that trigger cell functionalities which can easily be assimilated to cancer hallmarks reveals different functional strategies with different degrees of aggressiveness followed by any of the clusters.In addition, mechanistic modeling allows simulating the effect of interventions on the components of the signaling circuits, such as drug inhibitions. Thus, effects of drug inhibitions at single cell level can be dissected, revealing for the first time the mechanisms that individual cells use to avoid the effect of a targeted therapy which explain why and how a small proportion of cells display, in fact, different degrees of resistance to the treatment. The results presented here strongly suggest that mechanistic modeling at single cell level not only allows uncovering the molecular mechanisms of the tumor progression but also can predict the success of a treatment and can contribute to a better definition of therapeutic targets in the future.
Glutamine Deprivation Regulates the Origin and Function of Cancer Cell Exosomes
Authors: Fan Shih-Jung , Kroeger Benjamin , Marie Pauline P. , Bridges Esther M. , Mason John D. , McCormick Kristie , Zois Christos , Sheldon Helen , Alham Nasullah Khalid , Johnson Errin , Ellis Matthew , Stefana M. Irina , Mendes Cláudia C. , Wainwright S. Mark , Cunningham Christopher , Hamdy Freddie C. , Morris John F. , Harris Adrian L. , Wilson Clive , Goberdhan Deborah C. I. 
Published: December 2019

SUMMARYExosomes are secreted extracellular vesicles (EVs) carrying diverse cargos, which can modulate recipient cell behaviour. They are thought to derive from intraluminal vesicles formed in late endosomal multivesicular bodies (MVBs). An alternate exosome formation mechanism, which is conserved from fly to human, is described here, with exosomes carrying unique cargos, including the GTPase Rab11, generated in Rab11-positive recycling endosomal MVBs. Release of these exosomes from cancer cells is increased by reducing Akt/mechanistic Target of Rapamycin (mTORC1) signalling or depleting the key metabolic substrate glutamine, which diverts membrane flux through recycling endosomes. The resulting vesicles promote tumour cell proliferation and turnover, and modulate blood vessel networks in xenograft mouse modelsin vivo. Their growth-promoting activity, which is also observedin vitro, is Rab11a-dependent, involves ERK-MAPK-signalling and is inhibited by antibodies against Amphiregulin, an EGFR ligand concentrated on these vesicles. Therefore, glutamine depletion or mTORC1 inhibition stimulates release of Rab11a-exosomes with pro-tumorigenic functions, which we propose promote stress-induced tumour adaptation.