bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lifestyle-intervention-induced reduction of abdominal fat is reflected by a decreased circulating glycerol level and an increased HDL diameter
Authors: Beekman Marian , Schutte Bianca A.M. , van den Akker Erik B. , Noordam Raymond , Dibbets-Schneider Petra , de Geus-Oei Lioe-Fee , Deelen Joris , van de Rest Ondine , van Heemst Diana , Feskens Edith J.M. , Slagboom P. Eline 
Published: July 2019

SCOPEAbdominal obesity is one of the main modifiable risk factors of age-related cardiometabolic disease. Cardiometabolic disease risk and its associated high abdominal fat mass, high cholesterol and glucose concentrations can be reduced by a healthier lifestyle. Hence, our aim is to understand the relation between lifestyle-induced changes in body composition, and specifically abdominal fat, and accompanying changes in circulating metabolic biomarkers.Methods and resultsWe used the data from the Growing Old Together (GOTO) study, in which 164 older adults (mean age 63 years, BMI 23-35 kg/m2) changed their lifestyle during 13 weeks by 12.5% caloric restriction plus 12.5% increase in energy expenditure. We show that levels of circulating metabolic biomarkers, even after adjustment for body mass index, specifically associate with abdominal fat mass. Next, we show that the applied lifestyle intervention mainly reduces abdominal fat mass (−2.6%, SD=3.0) and that this reduction, when adjusted for general weight loss, is highly associated with decreased circulating glycerol concentrations and increased HDL diameter.ConclusionsThe lifestyle-induced reduction of abdominal fat mass is particularly associated, independent of body mass index or general weight loss, with associated with decreased circulating glycerol concentrations and increased HDL diameter.
Intraspecific genetic variation underlying postmating reproductive barriers between species in the wild tomato clade (Solanumsect.Lycopersicon)
Authors: Jewell Cathleen P , Zhang Simo , Gibson Matthew J. S. , Tovar-Méndez Alejandro , McClure Bruce , Moyle Leonie C 
Published: July 2019

AbstractA goal of speciation genetics is to understand how the genetic components underlying interspecific reproductive barriers originate within species. Unilateral incompatibility (UI) is a postmating prezygotic barrier in which pollen rejection in the female reproductive tract (style) occurs in only one direction of an interspecific cross. Natural variation in the strength of UI has been observed among populations within species in the wild tomato clade. In some cases, molecular loci underlying self-incompatibility (SI) are associated with this variation in UI, but the mechanistic connection between these intra- and inter-specific pollen rejection behaviors is poorly understood in most instances. We generated an F2population between SI and SC genotypes of a single species,Solanum pennellii, to examine the genetic basis of intraspecific variation in the strength of UI against other species, and to determine whether loci underlying SI are genetically associated with this variation. We found that F2individuals vary in the rate at which UI rejection occurs. One large effect QTL detected for this trait co-localized with the SI-determiningS-locus. Moreover, individuals that expressed S-RNase—theS-locus protein involved in SI pollen rejection—in their styles had much more rapid UI responses compared to those without S-RNase protein. Our analysis shows that intraspecific variation at mate choice loci—in this case at loci that prevent self-fertilization—can contribute to variation in the strength of interspecific isolation, including postmating prezygotic barriers. Understanding the nature of such standing variation can provide insight into the accumulation of these barriers between diverging lineages.
WITHDRAWN: Complementary functions of the mechanosensitive factorsegr1,klf2bandklf2ainstruct the endocardial program
Authors: Faggianelli-Conrozier Nathalie , Polyzou Aikaterini , Chow Renee , Roth Stéphane , Trompouki Eirini , Vermot Julien 
Published: July 2019

Withdrawal StatementThe authors would like to withdraw this manuscript because they have been unable to reproduce a key finding of the preprint showing thategr1mutants have a valve phenotype. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding authors.
Differential lipid dynamics in stocked and wild juvenile lake trout
Authors: Sorrentino Madelyn G. , Stewart Taylor R. , Marsden J. Ellen , Stockwell Jason D. 
Published: July 2019

AbstractAfter more than 40 years of stocking, lake trout (Salvelinus namaycush) in Lake Champlain have started to exhibit strong, natural recruitment. The abrupt surge in recruitment suggests a change in limiting factors such as prey availability or overwinter survival. The distribution of juvenile wild lake trout varies in relative abundance among regions of Lake Champlain. The differences suggest the prey base, or foraging success, may vary geographically within the lake. Stocked and wild lake trout may differ in their ability to use resources and in overwinter survival. One metric that can indicate differences in resources across regions is lake trout lipid content, which reflects the quality of available food and serves as an important energy reserve for overwinter survival. We quantified total lipid content of stocked and wild juvenile lake trout across spatial (lake regions) and temporal (seasonal) scales. No spatial differences in lipid content were apparent. Wild fish had greater lipid content than stocked fish. Seasonally, stocked fish showed a continuous drop in lipid content from pre-winter levels at stocking to the following autumn. Wild fish showed a cyclical summer increase in lipids following winter depletion, which plateaued by autumn. The high lipid content of hatchery lake trout may be necessary as they acclimate to foraging in the wild. Hatcheries would benefit from evaluating whether post-stocking survival could be improved by altering feeding or rearing regimes.
Lifespan-increasing drug nordihydroguaiaretic acid inhibits p300 and activates autophagy
Authors: Tezil Tugsan , Chamoli Manish , Ng Che-Ping , Simon Roman P. , Butler Victoria J. , Jung Manfred , Andersen Julie , Kao Aimee W. , Verdin Eric 
Published: July 2019

AbstractAging is characterized by the progressive loss of physiological function in all organisms. Remarkably, the aging process can be modulated by environmental modifications, including diet and small molecules. The natural compound nordihydroguaiaretic acid (NDGA) robustly increases lifespan in flies and mice, but its mechanism of action remains unclear. Here, we report that NDGA is an inhibitor of the epigenetic regulator p300. We find that NDGA inhibits p300 acetyltransferase activityin vitroand suppresses acetylation of a key p300 target in histones (i.e., H3K27) in cells. We use the cellular thermal shift assay to uniquely demonstrate NDGA binding to p300 in cells. Finally, in agreement with recent findings indicating that p300 is a potent blocker of autophagy, we show that NDGA treatment induces autophagy. These findings identify p300 as a novel target of NDGA and provide mechanistic insight into its role in longevity.
Systems-level analysis of monocyte responses in inflammatory bowel disease identifies IL-10 and IL-1 cytokine networks that regulate IL-23
Authors: Aschenbrenner Dominik , Quaranta Maria , Banerjee Soumya , Ilott Nicholas , Jansen Joanneke , Steere Boyd A. , Chen Yin-Huai , Ho Stephen , Cox Karen ,   Oxford IBD Cohort Investigators, Arancibia-Cárcamo Carolina V. , Coles Mark , Gaffney Eamonn , Travis Simon , Denson Lee A. , Kugathasan Subra , Schmitz Jochen , Powrie Fiona , Sansom Stephen , Uhlig Holm H. 
Published: July 2019

ABSTRACTBACKGROUND & AIMSDysregulated immune responses are the cause of inflammatory bowel diseases. Studies in both mice and humans suggest a central role of IL-23 producing mononuclear phagocytes in disease pathogenesis. Mechanistic insights into the regulation of IL-23 are prerequisite for select IL-23 targeting therapies as part of personalized medicine.METHODSWe performed transcriptomic analysis to investigate IL-23 expression in human mononuclear phagocytes and peripheral blood mononuclear cells. We investigated the regulation of IL-23 expression and used single-cell RNA-sequencing to derive a transcriptomic signature of hyper-inflammatory monocytes. Using gene network correlation analysis, we deconvolve this signature into components associated with homeostasis and inflammation in patient biopsy samples.RESULTSWe characterized monocyte subsets of healthy individuals and patients with inflammatory bowel disease that express IL-23. We identified auto- and paracrine sensing of IL-1α/IL-1β and IL-10 as key cytokines that control IL-23-producing monocytes. Whereas Mendelian genetic defects in IL-10 receptor signalling induced IL-23 secretion, uptake of whole bacteria induced IL-23 production via acquired IL-10 signalling resistance. We found a transcriptional signature of IL-23-producing inflammatory monocytes that predicted both disease and resistance to anti-TNF therapy and differentiated that from an IL-23-associated lymphocyte differentiation signature that was present in homeostasis and in disease.CONCLUSIONOur work identifies IL-10 and IL-1 as critical regulators of monocyte IL-23 production. We differentiate homeostatic IL-23 production from hyper-inflammation-associated IL-23 production in patients with severe ulcerating active Crohn’s disease and anti-TNF treatment non-responsiveness. Altogether, we identify subgroups of patients with inflammatory bowel disease that might benefit from IL-23p19 and/or IL-1α/IL-1β-targeting therapies upstream of IL-23.
Criticality as a determinant of integrated information Φ in human brain networks
Authors: Kim Hyoungkyu , Hudetz Anthony G. , Mashour George A. , Lee UnCheol 
Published: July 2019

AbstractIntegrated information theory (IIT) postulates that consciousness arises from the cause-effect structure of a system but the optimal network conditions for this structure have not been elucidated. In the study, we test the hypothesis that network criticality, a dynamically balanced state between a large variation of functional network configurations and a large constraint of structural network configurations, is a necessary condition for the emergence of a cause-effect structure that results in a large Φ, a surrogate of integrated information. We also hypothesized that if the brain deviates from criticality, the cause-effect structure is obscured and Φ diminishes. We tested these hypotheses with a large-scale brain network model and high-density electroencephalography (EEG) acquired during various levels of human consciousness during general anesthesia. In the modeling study, maximal criticality coincided with maximal Φ. The constraint of the structural network on the functional network is maximized in the maximal criticality. The EEG study demonstrated an explicit relationship between Φ, criticality, and level of consciousness. Functional brain network significantly correlated with structural brain network only in conscious states. The results support the hypothesis that network criticality maximizes Φ.
The human canonical core histone catalogue
Authors: Susano Pinto David Miguel , Flaus Andrew 
Published: July 2019

AbstractCore histone proteins H2A, H2B, H3, and H4 are encoded by a large family of genes distributed across the human genome. Canonical core histones contribute the majority of proteins to bulk chromatin packaging, and are encoded in 4 clusters by 65 coding genes comprising 17 for H2A, 18 for H2B, 15 for H3, and 15 for H4, along with at least 17 total pseudogenes. The canonical core histone genes display coding variation that gives rise to 11 H2A, 15 H2B, 4 H3, and 2 H4 unique protein isoforms. Although histone proteins are highly conserved overall, these isoforms represent a surprising and seldom recognised variation with amino acid identity as low as 77% between canonical histone proteins of the same type. The gene sequence and protein isoform diversity also exceeds commonly used subtype designations such as H2A.1 and H3.1, and exists in parallel with the well-known specialisation of variant histone proteins. RNA sequencing of histone transcripts shows evidence for differential expression of histone genes but the functional significance of this variation has not yet been investigated. To assist understanding of the implications of histone gene and protein diversity we have catalogued the entire human canonical core histone gene and protein complement. In order to organise this information in a robust, accessible, and accurate form, we applied software build automation tools to dynamically generate the canonical core histone repertoire based on current genome annotations and then to organise the information into a manuscript format. Automatically generated values are shown with a light grey background. Alongside recognition of the encoded protein diversity, this has led to multiple corrections to human histone annotations, reflecting the flux of the human genome as it is updated and enriched in reference databases. This dynamic manuscript approach is inspired by the aims of reproducible research and can be readily adapted to other gene families.
Lattice arrangement of myosin filaments correlates with fiber type in rat skeletal muscle
Authors: Ma Weikang , Lee Kyoung Hwan , Yang Shixin , Irving Thomas , Craig Roger 
Published: July 2019

AbstractThe thick (myosin-containing) filaments of vertebrate skeletal muscle are arranged in a hexagonal lattice, interleaved with an array of thin (actin-containing) filaments with which they interact to produce contraction. X-ray diffraction and electron microscopy have shown that there are two types of thick filament lattice. In the simple lattice, all filaments have the same orientation about their long axis, while in the super lattice, nearest neighbors have rotations differing by 60°. Tetrapods (amphibians, reptiles, birds, mammals) typically have only a super lattice, while the simple lattice is confined to fish. We have carried out X-ray diffraction and electron microscopy of the soleus (SOL) and extensor digitorum longus (EDL) muscles of the rat and found that while the EDL has a super-lattice, as expected, the SOL has a simple lattice. The EDL and SOL of the rat are unusual in being essentially pure fast and slow muscles respectively. The mixed fiber content of most tetrapod muscles and/or lattice disorder may explain why the simple lattice has not been apparent in these vertebrates before. This is supported by only weak simple lattice diffraction in the X-ray pattern of mouse SOL, which has a greater mix of fiber types than rat. We conclude that the simple lattice might be common in tetrapods. The correlation between fiber type and filament lattice arrangement suggests that the lattice arrangement may contribute to the functional properties of a muscle.SummaryThe three-dimensional arrangement of thick filaments in skeletal muscle is studied by X-ray diffraction and electron microscopy. A correlation is found between thick filament lattice type (simple or super lattice) and fiber type (fast/slow). This suggests that lattice organization contributes to muscle functional properties
S-Acylation of plant immune receptors mediates immune signaling in plasma membrane nanodomains
Authors: Chen Dongqin , Ahsan Nagib , Thelen Jay J. , Stacey Gary 
Published: July 2019

SUMMARYS-Acylation is a reversible protein post-translational modification mediated by Protein S-acyltransferases (PATs). Here, we demonstrate that three plant immune receptors P2K1 (DORN1), FLS2 and CERK1, representing three distinct families of receptor like-kinases, are S-acylated by Arabidopsis PAT5 and PAT9 on the plasma membrane (PM). Mutations in Atpat5 and Atpat9 resulted in an elevated plant immune response, increased phosphorylation and decreased degradation of FLS2, P2K1 and CERK1 during immune signaling. Mutation of key cysteine residues S-acylated in these receptors resulted in a similar phenotype as exhibited by Atpat5/Atpat9 mutant plants. The data indicate that S-acylation also controls localization of the receptors in distinct PM nanodomains and, thereby, controls the formation of specific protein-protein interactions. Our study reveals that S-acylation plays a critical role in mediating spatiotemporal dynamics of plant receptors within PM nanodomains, suggesting a key role for this modification in regulating the ability of plants in respond to external stimuli.
The Ufm1 system is upregulated by ER stress during osteogenic differentiation
Authors: Dudek Michal , Wallis Gillian A. 
Published: July 2019

AbstractObjectiveMutations in the catalytic site of the ubiquitin-fold modifier 1(UFM1)-specific peptidase 2 (UFSP2) gene have been identified to cause autosomal dominant Beukes hip dysplasia in a large multigenerational family and a novel form of autosomal dominant spondyloepimetaphyseal dysplasia in a second family. We investigated the expression of the UFSP2/UFM1 system during mouse joint development the connection to ER stress induced during osteogenic differentiation.MethodsThe pattern of expression of Ufsp2 was determined by radioactive RNA in situ hybridisation on mouse tissue sections. qPCR was used to monitor expression during in vitro osteogenic differentiation and chemically induced ER stress. Affinity purification and mass spectrometry was used for isolation and identification of Ufm1 conjugation targets. Luciferase reporter assay was used to investigate the activity of Ufm1 system genes’ promoters.ResultsWe found that Ufsp2 was predominantly expressed in the bone and secondary ossification centres of 10-day old mice. The Ufm1 system was upregulated during in vitro osteogenic differentiation and in response to chemically induced ER stress. We identified unfolded protein response elements in the upstream sequences of Uba5, Ufl1, Ufm1and Lzap. We identified putative Ufm1 conjugation targets where conjugation was increased in response to ER stress.ConclusionHigher expression of Ufsp2 in bone and secondary ossification centres as well as upregulation of components of the Ufm1system in response to ER stress suggests that the molecular pathway between the UFSP2 mutations and form of skeletal dysplasia may relate to abnormal ER stress responses during osteoblast differentiation.
Biosurfactant production maintains viability in anoxic conditions by depolarizing the membrane inBacillus subtilis
Authors: Arjes Heidi A. , Vo Lam , Dunn Caroline Marie , Willis Lisa , DeRosa Christopher A. , Fraser Cassandra L. , Kearns Daniel B. , Huang Kerwyn Casey 
Published: July 2019

SummaryThe presence or absence of oxygen in the environment is a strong effector of cellular metabolism and physiology. Like many eukaryotes and some bacteria,Bacillus subtilisis an obligate aerobe that primarily utilizes oxygen during respiration to generate ATP. Despite the importance of oxygen forB. subtilissurvival, we know little about how oxygen is consumed during growth and how populations respond to shifts in oxygen availability. Here, we find that when oxygen was depleted from stationary phase cultures ∼90% ofB. subtilis3610 cells died and lysed due to autolysin activity; the remaining cells maintained colony-forming ability. Interestingly, the domesticated 168 strain maintained a higher optical density than 3610 during oxygen depletion due to the formation of cell-wall-less protoplasts, but the remaining, rod-shaped cells were >100-fold less viable than 3610. We discovered that the higher viability in 3610 was due to its ability to produce the antibacterial compound surfactin, as surfactin addition rescued 168 viability and also increased yield in aerobic growth. We further demonstrate that surfactin strongly depolarizes theB. subtilismembrane, and that other known membrane-potential disruptors restore viability to 168. These findings highlight the importance of surfactin for survival during oxygen-depleted conditions and demonstrate that antimicrobials normally considered harmful can instead benefit cells in stressful conditions when the terminal electron acceptor in respiration is limiting.
DeLTA: Automated cell segmentation, tracking, and lineage reconstruction using deep learning
Authors: Lugagne Jean-Baptiste , Lin Haonan , Dunlop Mary J. 
Published: July 2019

AbstractMicroscopy image analysis is a major bottleneck in quantification of single-cell microscopy data, typically requiring human supervision and curation, which limit both accuracy and throughput. To address this, we developed a deep learning-based image analysis pipeline that performs segmentation, tracking, and lineage reconstruction. Our analysis focuses on time-lapse movies of Escherichia coli cells trapped in a “mother machine” microfluidic device, a scalable platform for long-term single-cell analysis that is widely used in the field. While deep learning has been applied to cell segmentation problems before, our approach is fundamentally innovative in that it also uses machine learning to perform cell tracking and lineage reconstruction. With this framework we are able to get high fidelity results (1% error rate), without human supervision. Further, the algorithm is fast, with complete analysis of a typical frame containing ∼150 cells taking <700msec. The framework is not constrained to a particular experimental set up and has the potential to generalize to time-lapse images of other organisms or different experimental configurations. These advances open the door to a myriad of applications including real-time tracking of gene expression and high throughput analysis of strain libraries at single-cell resolution.Author SummaryAutomated microscopy experiments can generate massive data sets, allowing for detailed analysis of cell physiology and properties such as gene expression. In particular, dynamic measurements of gene expression with time-lapse microscopy have proved invaluable for understanding how gene regulatory networks operate. However, image analysis remains a key bottleneck in the analysis pipeline, typically requiring human supervision and a posteriori processing. Recently, machine learning-based approaches have ushered in a new era of rapid, unsupervised image analysis. In this work, we use and repurpose the U-Net deep learning algorithm to develop an image processing pipeline that can not only accurately identify the location of cells in an image, but also track them over time as they grow and divide. As an application, we focus on multi-hour time-lapse movies of bacteria growing in a microfluidic device. Our algorithm is accurate and fast, with error rates near 1% and requiring less than a second to analyze a typical movie frame. This increase in speed and fidelity has the potential to open new experimental avenues, e.g. where images are analyzed on-the-fly so that experimental conditions can be updated in real time.
The Insulin Receptor in Astrocytes is Involved in the Entrance of Circulating Insulin into the Brain
Authors: Fernandez Ana M. , Navarrete M. , Davila Jose Carlos , Garcia-Caceres Cristina , Palenzuela Rocio , de Martin Esteban Samuel Ruiz , Mostany Ricardo , Tschöp Matthias , Gutierrez Antonia , Aleman Ignacio Torres 
Published: July 2019

AbstractCirculating insulin enters into the brain through mechanisms that are not yet entirely understood. We now report that mice lacking insulin receptors (IR) in astrocytes show reduced uptake of circulating insulin and blunted brain responses to this circulating hormone, suggesting that astrocytes form part of the cellular pathway in the entrance of circulating insulin into the brain. Since we previously showed that ablation of IR in astrocytes decreases brain glucose uptake, we conclude that astrocytic IRs regulate uptake of circulating glucose and insulin.