bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence, complete genome and metabolic potentials of a phylogenetically novel cyanobacterial symbiont in the coral-killing sponge,Terpios hoshinota
Authors: Chen Yu-Hsiang , Chen Hsing-Ju , Yang Cheng-Yu , Shiu Jia-Ho , Hoh Daphne Z. , Chiang Pei-Wen , Chow Wenhua Savanna , Chen Chaolun Allen , Shih Tin-Han , Lin Szu-Hsien , Yang Chi-Ming , Reimer James Davis , Hirose Euichi , Iskandar Budhi Hascaryo , Huang Hui , Schupp Peter J. , Tan Chun Hong James , Yamashiro Hideyuki , Liao Ming-Hui , Tang Sen-Lin 
Published: February 2021

AbstractTerpios hoshinotais a ferocious, space-competing sponge that kills a variety of stony corals by overgrowth. Outbreaks of this species have led to intense coral reef damage and declines in living corals on the square kilometer scale in many geographical locations. Our large-scale 16S rRNA gene survey across three oceans revealed that the core microbiome ofT.hoshinotaincluded operational taxonomic units (OTUs) related toProchloron,Endozoicomonas,Pseudospirillum, SAR116,Magnetospira, andRuegeria. AProchloron- related OTU was the most dominant cyanobacterium inT.hoshinotain the western Pacific Ocean, South China Sea, and Indian Ocean. The complete metagenome-assembled genome of theProchloron-related cyanobacterium and our pigment analysis revealed that this bacterium had phycobiliproteins and phycobilins and lacked chlorophyllb, inconsistent with the iconic definition ofProchloron. Furthermore, the phylogenetic analyses based on 16S rRNA genes and 120 single-copy genes demonstrated that the bacterium was phylogenetically distinct toProchloron, strongly suggesting that it should be a sister taxon toProchloron; we therefore proposed this symbiotic cyanobacterium as a novel species under a new genus:CandidatusParaprochloron terpiosii. With the recovery of the complete genome, we characterized the metabolic potentials of the novel cyanobacterium in carbon and nitrogen cycling and proposed a model for the interaction betweenCa.Pp. terpiosi LD05 andT. hoshinota.In addition, comparative genomics analysis revealed thatCa.Paraprochloron andProchloronshowed distinct features in transporter systems and DNA replication.ImportanceThe finding that one species predominates cyanobacteria inT.hoshinotafrom different geographic locations indicates that this sponge andCa. Pp. terpiosi LD05 share a tight relationship. This study builds the foundation forT.hoshinota’s microbiome and paves a way for understanding the ecosystem, invasion mechanism, and causes of outbreak of this coral-killing sponge. Also, the firstProchloron-related complete genome enables us to study this bacterium with molecular approaches in the future and broadens our knowledge of the evolution of symbiotic cyanobacteria.
Functional traits of carabid beetles reveal seasonal variation in community assembly in annual crops
Authors: Marrec Ronan , Gross Nicolas , Badenhausser Isabelle , Dupeyron Aurélie , Caro Gaël , Bretagnolle Vincent , Roncoroni Marilyn , Gauffre Bertrand 
Published: February 2021

AbstractTrait-based community assembly studies have mostly been addressed along spatial gradients, and do not consider explicitly a fundamental dimension governing community assembly, the time. Nevertheless, such consideration seems particularly necessary in systems in which organisms have to face regular disturbances and rapid changes in vegetation phenology, such as in intensively managed farmlands.In this study, we aimed at understanding how the functional diversity of carabid beetle communities varied across the growing season in response to crop type. We tested three alternative hypotheses on mechanisms underlying the community assembly.We used data from a long-term monitoring conducted over nine years in an intensively-managed farmland in central western France, in a total of 625 fields. First, we measured morphological traits related to body size, dispersal mode, and resource acquisition on the 13 dominant carabid species (> 85 % of all trapped individuals) and identified three independent dimensions of functional specialization within our species pool along axes of a PCA and highlighted key traits for community assembly. Second, we evaluated the community assembly temporal dynamics and the impact of habitat filtering and niche differentiation in the different crop types with time, using linear mixed-effects models.We showed that functional species assembly of carabid beetle communities occurring in crop fields varies importantly intra-annually, with strong variations in these dynamics depending on crop type and crop phenology. Each crop acted as a filter on carabid communities for body size and resource-acquisition traits, and functional differentiation between crops increased with time. We did not find any evidence of habitat filtering on traits related to dispersal mode.Our results emphasize the major role of crop phenology but also disturbances involved by agricultural practices such as crop harvesting on changes in community assembly, likely due to seasonal and inter-annual redistributions of species in agricultural landscapes in response to such changes. The temporal dimension cannot be ignored to understand the assembly of local carabid communities in farmlands.
Differences in interactions between transmembrane domains tune the activation of metabotropic glutamate receptors
Authors: Thibado Jordana K. , Tano Jean-Yves , Lee Joon , Salas-Estrada Leslie , Provasi Davide , Strauss Alexa , Lamim Ribeiro Joao Marcelo , Xiang Guoqing , Broichhagen Johannes , Filizola Marta , Lohse Martin , Levitz Joshua 
Published: February 2021

AbstractThe metabotropic glutamate receptors (mGluRs) form a family of neuromodulatory G protein-coupled receptors that contain both a seven-helix transmembrane domain (TMD) and a large extracellular ligand-binding domain (LBD) which enables stable dimerization. While numerous studies have revealed variability across subtypes in the initial activation steps at the level of LBD dimers, an understanding of inter-TMD interaction and rearrangement remains limited. Here we use a combination of single molecule fluorescence, molecular dynamics, functional assays, and conformational sensors to reveal that distinct TMD assembly properties drive differences between mGluR subtypes. We uncover a variable region within transmembrane helix 4 (TM4) that contributes to homo- and heterodimerization in a subtype-specific manner and tunes orthosteric, allosteric and basal activation. We also confirm a critical role for a conserved inter-TM6 interface in stabilizing the active state during orthosteric or allosteric activation. Together this study informs a working model of inter-TMD rearrangement that drives mGluR function.
New lessons on TDP-43 from the killifishN. furzeri
Authors: Louka Alexandra , Bagnoli Sara , Rupert Jakob , Esapa Benjamin , Tartaglia Gian Gaetano , Cellerino Alessandro , Pastore Annalisa , Tozzini Eva Terzibasi 
Published: February 2021

AbstractFrontotemporal dementia and amyotrophic lateral sclerosis are fatal and incurable neurodegenerative diseases linked to the pathological aggregation of the TDP-43 protein. This is an essential DNA/RNA binding protein involved in transcription regulation, pre-RNA processing and RNA transport. Having suitable animal models to study the mechanisms of TDP-43 aggregation is crucial to develop treatments against disease. We have previously demonstrated that the killifishNothobranchius furzerioffers the unique advantage as a model system that it is an organism with compressed lifespan and a conserved ageing phenotype that develops within months, making this organism the available shortest-lived vertebrate with a clear ageing phenotype. Here, we show that the two paralogs of TDP-43 from the killifishN. furzerishare high sequence homology with the human protein and recapitulate its cellular and biophysical behaviour. We prove that, during ageing,N. furzeriTDP-43 spontaneously forms insoluble intracellular TDP-43 aggregates that have amyloid characteristics and colocalize with the stress granule core protein G3BP. Our results propose this organism as a valuable model of TDP-43-related pathologies and show that even minute differences between the human andN. furzeriproteins may help to shed new light onto the role of TDP-43 in RNA recognition and granule formation.
Quantifying full-length circular RNAs in cancer
Authors: Yu Ken Hung-On , Shi Christina Huan , Wang Bo , Chow Savio Ho-Chit , Chung Grace Tin-Yun , Tan Ke-En , Lim Yat-Yuen , Tsang Anna Chi-Man , Lo Kwok-Wai , Yip Kevin Y. 
Published: February 2021

AbstractCircular RNAs (circRNAs) are abundantly expressed in cancer. Their resistance to exonucleases enables them to have potentially stable interactions with different types of biomolecules. Alternative splicing can create different circRNA isoforms that have different sequences and unequal interaction potentials. The study of circRNA function thus requires knowledge of complete circRNA sequences. Here we describe psirc, a method that can identify full-length circRNA isoforms and quantify their expression levels from RNA sequencing data. We confirm the effectiveness and computational efficiency of psirc using both simulated and actual experimental data. Applying psirc on transcriptome profiles from nasopharyngeal carcinoma and normal nasopharynx samples, we discover and validate circRNA isoforms differentially expressed between the two groups. Compared to the assumed circular isoforms derived from linear transcript annotations, some of the alternatively spliced circular isoforms have 100 times higher expression and contain substantially fewer microRNA response elements, demonstrating the importance of quantifying full-length circRNA isoforms.
Footprints to Singularity: A global population model explains late 20th century slow-down and predicts peak within ten years
Authors: Bystroff Christopher 
Published: February 2021

AbstractProjections of future global human population are traditionally made using birth/death trend extrapolations, but these methods ignore limits. Expressing humanity as a K-selected species whose numbers are limited by the global carrying capacity produces a different outlook. Population data for the second millennium up to the year 1970 was fit to a hyper-exponential growth equation, where the rate constant for growth itself grows exponentially due to growth of life-saving technology. The discrepancies between the projected growth and the actual population data since 1970 are accounted for by a decrease in the global carrying capacity due to ecosystem degradation. A system dynamics model that best fits recent population numbers suggests that the global biocapacity may already have been reduced to one-half of its historical value and global carrying capacity may be at its 1965 level and falling. Simulations suggest that population may soon peak or may have already peaked. Population projections depend strongly on the unknown fragility or robustness of the Earth’s essential ecosystem services that affect agricultural production. Numbers for the 2020 global census were not available for this study.
JNK activation in TA and EDL muscle is load-dependent in rats receiving identical excitation patterns
Authors: Eftestøl Einar , Franchi Martino V. , Kasper Stephanie , Flück Martin 
Published: February 2021

ABSTACTAimAs the excitation-contraction coupling is inseparable during voluntary exercise, the relative contribution of the mechanical and neural input is poorly understood. Herein, we use a rat in-vivo strength training setup with an electrically induced standardized excitation pattern previously shown to lead to a load-dependent increase in myonuclear number and hypertrophy, to study acute effects of load per se on molecular signalling.MethodsAnaesthetized rats were subjected to unliteral identical electrically-paced contractions of the TA and EDL muscles under a high or low load for a duration of 2, 10 or 28-minutes. Muscle soluble proteins were extracted, and abundance and specific phosphorylations of FAK, mTOR, p70S6K and JNK were measured. Effects of exercise, load, muscle and exercise duration were assessed.ResultsSpecific phosphorylation of S2448-mTOR, T421/S424-p70S6K and T183/Y185-JNK was increased after 28-minutes of exercise under the high- and low-load protocol. Elevated phosphorylation of mTOR and JNK was detectable already after 2 and 10 minutes of exercise, respectively, but greatest after 28-minutes of exercise. T183/Y185-JNK and S2448-mTOR demonstrated a load-dependent increase in phosphorylation in the exercised muscles that for mTOR depended on muscle type. The abundance of all four kinases was higher in TA compared to EDL muscle. FAK and JNK abundance was reduced after 28 minutes of exercise in both the exercised and control muscle.ConclusionThe current study shows that JNK and mTOR activation is load-driven, and together with muscle-type specific mTOR and p70S6K effects it may drive muscle-type specific exercise and load-responses.
Nutritional redundancy in the human diet and its application in phenotype association studies
Authors: Wang Xu-Wen , Hu Yang , Menichetti Giulia , Grodstein Francine , Bhupathiraju Shilpa N. , Sun Qi , Zhang Xuehong , Hu Frank B. , Weiss Scott T. , Liu Yang-Yu 
Published: February 2021

AbstractStudying human dietary intake may help us identify effective measures to treat or prevent many chronic diseases whose natural histories are influenced by nutritional factors. Here, by examining five cohorts with dietary intake data collected on different time scales, we show that the food intake profile varies substantially across individuals and over time, while the nutritional intake profile appears fairly stable. We refer to this phenomenon as ‘nutritional redundancy’ and attribute it to the nested structure of the food-nutrient network. This network enables us to quantify the level of nutritional redundancy for each diet assessment of any individual. Interestingly, this nutritional redundancy measure does not strongly correlate with any classical healthy diet scores, but its performance in predicting healthy aging shows comparable strength. Moreover, after adjusting for age, we find that a high nutritional redundancy is associated with lower risks of cardiovascular disease and type 2 diabetes.
13C tracer analysis identifies extensive recycling of endogenous CO2in vivo
Authors: Duan Likun , Cooper Daniel E. , Scheidemantle Grace , Locasale Jason W. , Kirsch David G. , Liu Xiaojing 
Published: February 2021

Abstract13C tracing analysis is increasingly used to monitor cellular metabolism in vivo and in intact cells, but data interpretation is still the key element to unveil the complexity of metabolic activities. We have performed [U-13C]-glucose and [U-13C]-glutamine tracing in sarcoma-bearing mice (in vivo) and in cancer cell lines (in vitro).13C enrichment of metabolites in cultured cells and tissues was determined by liquid chromatography coupled with high-resolution mass spectrometer (LC-HRMS). As expected, citrate M+2 or M+4 is the dominant mass isotopologue in vitro. However, citrate M+1 was unexpectedly the dominant isotopologue in mice receiving [U-13C]-glucose or [U-13C]-glutamine infusion. One plausible explanation is that13CO2produced from the oxidation of13C tracers in vitro is negligible due to the dilution of HCO3-supplemented to cell culture when sodium bicarbonante is used and diffusible volume of CO2in the culture incubator, while endogenous13CO2in vivo is substantial and is fixed into the TCA cycle, purine, and serine, resulting in M+1 isotopologues. A time course study shows the generation of high abundance citrate M+1 early in plasma, which may serve as a potent non-invasive biomarker of tissue pyruvate carboxylase activity. Altogether, our results show that recycling of endogenous CO2is substantial in vivo and provides important insights into the experimental design and data interpretation of13C tracing assays.
Standing Variations Modeling Captures Inter-Individual Heterogeneity in a Deterministic Model of Prostate Cancer Response to Combination Therapy
Authors: Jain Harsh Vardhan , Sorribes Inmaculada C , Handelman Samuel K , Barnaby Johnna , Jackson Trachette L 
Published: February 2021

AbstractSipuleucel-T (Provenge) is the first live cell vaccine approved for advanced, hormonally refractive prostate cancer. However, survival benefit is modest and the optimal combination or schedule of sipuleucel-T with androgen depletion remains unknown. We employ a nonlinear dynamical systems approach to modeling the response of hormonally refractive prostate cancer to sipuleucel-T. Our mechanistic model incorporates the immune response to the cancer elicited by vaccination, and the effect of androgen depletion therapy. Because only a fraction of patients benefit from sipuleucel-T treatment, inter-individual heterogeneity is clearly crucial. Therefore, we introduce our novel approach, Standing Variations Modeling, which exploits inestimability of model parameters to capture heterogeneity in a deterministic model. We use data from mouse xenograft experiments to infer distributions on parameters critical to tumor growth and to the resultant immune response. Sampling model parameters from these distributions allows us to represent heterogeneity, both at the level of the tumor cells and the individual (mouse) being treated. Our model simulations explain the limited success of sipuleucel-T observed in practice, and predict an optimal combination regime that maximizes predicted efficacy. This approach will generalize to a range of emerging cancer immunotherapies.
Rampant tooth loss across 200 million years of frog evolution
Authors: Paluh Daniel J. , Riddell Karina , Early Catherine M. , Hantak Maggie M. , Jongsma Gregory F.M. , Keeffe Rachel M. , Magalhães Silva Fernanda , Nielsen Stuart V. , Vallejo-Pareja María Camila , Stanley Edward L. , Blackburn David C. 
Published: February 2021

AbstractTeeth have been broadly maintained across most clades of vertebrates but have been lost completely at least once in actinopterygian fishes and several times in amniotes. Using phenotypic data collected from over 500 genera via micro-computed tomography, we provide the first rigorous assessment of the evolutionary history of dentition across all major lineages of amphibians. We demonstrate that dentition is invariably present in caecilians and salamanders, but teeth have been lost completely more than 20 times in frogs, a much higher occurrence of edentulism than in any other vertebrate group. The repeated loss of teeth in anurans is associated with a specialized diet of small invertebrate prey as well as shortening of the lower jaw, but it is not correlated with a reduction in body size. Frogs provide an unparalleled opportunity for investigating the molecular and developmental mechanisms of convergent tooth loss on a large phylogenetic scale.
Drosophila STING protein has a role in lipid metabolism
Authors: Akhmetova Katarina , Balasov Maxim , Chesnokov Igor 
Published: February 2021

ABSTRACTStimulator of interferon genes (STING) plays an important role in innate immunity by controlling type I interferon response against invaded pathogens. In this work we describe a direct but previously unknown role of STING in lipid metabolism inDrosophila. Flies withSTINGdeletion are sensitive to starvation and oxidative stress, have reduced lipid storage and downregulated expression of lipid metabolism genes. We found thatDrosophilaSTING interacts with lipid synthesizing enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). ACC and FAS also interact with each other, indicating that all three proteins may be components of a large multi-enzyme complex. The deletion ofDrosophila STINGleads to disturbed ACC localization and decreased FAS enzyme activity. Together, our results demonstrate a direct role of STING in lipid metabolism inDrosophila.
Systems-Level Proteomics Evaluation of Microglia Response to Tumor-Supportive Anti-inflammatory Cytokines
Authors: Ahuja Shreya , Lazar Iulia M. 
Published: February 2021

AbstractBackgroundMicroglia safeguard the CNS against injuries and pathogens by inducing an inflammatory response. When exposed to anti-inflammatory cytokines, these cells possess the ability to switch from an inflammatory to an immunosuppressive phenotype. Cancer cells exploit this property to evade the immune system, and elicit an anti-inflammatory microenvironment that facilitates tumor attachment and growth.ObjectiveThe tumor-supportive biological processes that are activated in microglia cells in response to anti-inflammatory cytokines released from cancer cells were explored with mass spectrometry and proteomic technologies.MethodsSerum-depleted and non-depleted human microglia cells (HMC3) were treated with a cocktail of IL-4, IL-13, IL-10, TGFβ, and CCL2. The cellular protein extracts were analyzed by LC-MS/MS. Using functional annotation clustering tools, statistically significant proteins that displayed a change in abundance between cytokine-treated and non-treated cells were mapped to their biological networks and pathways.ResultsThe proteomic analysis of HMC3 cells enabled the identification of ∼10,000 proteins. Stimulation with anti-inflammatory cytokines resulted in the activation of distinct, yet integrated clusters of proteins that trigger downstream a number of tumor-promoting biological processes. The observed changes could be classified into four major categories, i.e., mitochondrial gene expression, ECM remodeling, immune response, and impaired cell cycle progression. Intracellular immune activation was mediated mainly by the transducers of MAPK, STAT, TGFβ, NFKB, and integrin signaling pathways. Abundant collagen formation along with the expression of additional receptors, matrix components, growth factors, proteases and protease inhibitors, enabled ECM remodeling processes supportive of cell-cell and cell-matrix adhesion. Overexpression of integrins and their modulators was reflective of signaling processes that correlated ECM reorganization with cytoskeletal re-arrangements supportive of cell migration. Antigen processing/presentation was represented by HLA class I histocompatibility antigens, and correlated with upregulated proteasomal subunits, and vesicular/viral transport and secretory processes. Immunosuppressive and proangiogenic chemokines were detectable in low abundance. Pronounced pro-inflammatory, chemotactic or phagocytic trends were not observed, however, the expression of certain receptors and ECM proteins indicated the presence of such capabilities.ConclusionsComprehensive proteomic profiling of HMC3 cells stimulated with anti-inflammatory cytokines revealed a microglia phenotype that provides novel insights into the tumor microenvironment-driven mechanisms that fuel cancer development in the brain.