bluuebunny/crossref_metadata_2025_split huggingface dataset:
Data integration across conditions improves turnover number estimates and metabolic predictions
Authors: Wendering Philipp , Arend Marius , Razaghi-Moghadamkashani Zahra , Nikoloski Zoran 
Published: April 2022

AbstractTurnover numbers characterize a key property of enzymes, and their usage in constraint-based metabolic modeling is expected to increase prediction accuracy of diverse cellular phenotypes. In vivo turnover numbers can be obtained by ranking of estimates obtained by integrating reaction rate and enzyme abundance measurements from individual experiments; yet, their contribution to improving predictions of condition-specific cellular phenotypes remains elusive. Here we show that available in vitro and in vivo turnover numbers lead to poor prediction of condition-specific growth rates with protein-constrained models of Escherichia coli and Saccharomyces cerevisiae, particularly in the ultimate test scenario when protein abundances are integrated in the model. We demonstrate that in vivo estimation of turnover number by simultaneous consideration of heterogeneous physiological data leads to improved prediction of condition-specific growth rates. Moreover, the obtained estimates are more precise than the available in vivo turnover numbers. Therefore, our approach provides the means to decrease the bias of in vivo turnover numbers and paves the way towards cataloguing in vivo kcatomes of other organisms.
Functional Cell Types in the Mouse Superior Colliculus
Authors: Li Ya-tang , Meister Markus 
Published: April 2022

AbstractThe superior colliculus (SC) represents a major visual processing station in the mammalian brain that receives input from many types of retinal ganglion cells (RGCs). How many parallel channels exist in the SC, and what information does each encode? Here we recorded from mouse superficial SC neurons under a battery of visual stimuli including those used for classification of RGCs. An unsupervised clustering algorithm identified 24 functional types based on their visual responses. They fall into two groups: one that responds similarly to RGCs, and another with more diverse and specialized stimulus selectivity. The second group is dominant at greater depths, consistent with a vertical progression of signal processing in the SC. Cells of the same functional type tend to cluster near each other in anatomical space. Compared to the retina, the visual representation in the SC has lower dimensionality, consistent with a sifting process along the visual pathway.
Genomic legacies of ancient adaptation illuminate the GC-content evolution in bacterial genomes
Authors: Teng Wenkai , Liao Bin , Chen Mengyun , Shu Wensheng 
Published: April 2022

ABSTRACTIn conventional views, the bacterial adaptation is characterized by strong purifying selection as well as rapid evolution in changing environments. However, the genomic GC content varies greatly but has some degree of phylogenetic stability. Using 11,083 representative genomes, we report a phylogenetically constrained bimodal distribution of the genomic GC. Results suggest that such divergence of the genomic GC can be well explained by the DNA replication and repair (DRR) system, in which multiple pathways are observed correlated to the genomic GC. The biased conservations of various stress-related genes especially the DRR-related ones imply distinct adaptive evolution of the ancestral lineages of high or low GC clades which may be induced by major environmental changes in early evolution. Furthermore, our findings support that the mutational biases resulted from these legacies of adaptation have changed the course of adaptive evolution in bacteria thus causing great variation in the genomic GC. This study demonstrates the importance of indirect effects from natural selection which may be easily misinterpreted as neutral processes.
Collagen remodeling dictates pancreatic cancer bioenergetics and outcome through DDR1 activation or degradation
Authors: Su Hua , Yang Fei , Fu Rao , Trinh Brittney , Sun Nina , Liu Junlai , Kumar Avi , Baglieri Jacopo , Siruno Jeremy , Dozier Stephen , Nair Ajay , Filliol Aveline , Rosenthal Sara Brin , Santini Jennifer , Metallo Christian M. , Molina Anthony , Schwabe Robert F. , Lowy Andrew M. , Brenner David , Sun Beicheng , Karin Michael 
Published: April 2022

AbstractPancreatic ductal adenocarcinoma (PDAC) is a highly desmoplastic, aggressive cancer that frequently progresses by liver metastasis1. Cancer-associated fibroblasts (CAF), extracellular matrix (ECM), and type I collagen (Col I) support2–5 or restrain PDAC progression and may impede blood supply and nutrient availability6–8. The dichotomous role of the stroma in PDAC, and the mechanisms through which it influences patient survival and enables desmoplastic cancers escape nutrient limitation remain poorly understood. Here we show that matrix metalloprotease (MMP)-cleaved or intact Col I (cCol I and iCol I, respectively) exert opposing effects on PDAC bioenergetics, macropinocytosis (MP), tumor growth and liver metastasis. While cCol I activates DDR1 (discoidin domain receptor-1)-NF-κB-p62-NRF2 signaling to promote PDAC growth, iCol I triggers DDR1 degradation and restrains PDAC growth. Patients whose tumors are enriched in iCol I and low in DDR1 and NRF2 have improved median survival compared to those enriched in cCol I, DDR1 and NRF2. Inhibition of DDR1-stimulated NF-κB or mitochondrial biogenesis blocked tumorigenesis in wildtype mice but not in mice expressing MMP-resistant Col I. In summary, the diverse effects of tumor stroma on PDAC growth, metastasis, and patient survival are mediated through the Col I-DDR1-NF-κB-NRF2-mitochondrial biogenesis pathway, presenting multiple new opportunities for PDAC therapy.
The Insulin receptor regulates the persistence of mechanical nociceptive sensitization in flies and mice
Authors: Wang Yan , Lopez-Bellido Roger , Huo Xiaojiao , Kavelaars Annemieke , Galko Michael J. 
Published: April 2022

AbstractEarly phase diabetes is often accompanied by pain sensitization. In the fruit flyDrosophila, the insulin receptor (InR) regulates the persistence of injury-induced thermal nociceptive sensitization. WhetherDrosophilaInR also regulates the persistence of mechanical nociceptive sensitization remains unclear. Mice with a sensory neuron deletion of the gene encoding the Insulin receptor (Insr) show normal nociceptive baselines, however, it is not known whether deletion ofInsrin nociceptive sensory neurons leads to persistent nociceptive hypersensitivity in an inflammatory pain paradigm. In this study, we used fly and mouse nociceptive sensitization models to address these questions. In flies,InRmutants and larvae with sensory neuron-specific expression of RNAi transgenes targetingInRexhibited persistent mechanical hypersensitivity, as previously observed for the thermal sensory modality. Mice with a specific deletion of theInsrgene in NaV1.8+ nociceptive sensory neurons showed normal nociceptive thermal and mechanical baselines similar to controls. In an inflammatory paradigm, however, these mutant mice showed persistent mechanical (but not thermal) hypersensitivity, particularly in female mice. Mice with the NaV1.8+ sensory neuron specific deletion ofInsrdid not show metabolic abnormalities that would be typical of a systemic defect in insulin signaling. Our results show that some aspects of the regulation of nociceptive hypersensitivity by the Insulin receptor are shared between flies and mice and that this regulation is likely independent of metabolic effects.
epiAneufinder: identifying copy number variations from single-cell ATAC-seq data
Authors: Ramakrishnan Akshaya , Symeonidi Aikaterini , Hanel Patrick , Schubert Michael , Colomé-Tatché Maria 
Published: April 2022

AbstractSingle-cell open chromatin profiling via the single-cell Assay for Transposase-Accessible Chromatin using sequencing (scATAC-seq) assay has become a mainstream measurement of open chromatin in single-cells. Here we present a novel algorithm, epiAneufinder, that exploits the read count information from scATAC-seq data to extract genome-wide copy number variations (CNVs) for individual cells, allowing to explore the CNV heterogeneity present in a sample at the single-cell level. Using different cancer scATAC-seq datasets, we show how epiAneufinder can identify intratumor clonal heterogeneity in populations of single cells based on their CNV profiles. These profiles are concordant with the ones inferred from single-cell whole genome sequencing data for the same samples. epiAneufinder allows the addition of single-cell CNV information to scATAC-seq data, without the need of additional experiments, unlocking a layer of genomic variation which is otherwise unexplored.
Remodeling of gene regulatory networks underlying thermogenic stimuli-induced adipose beiging
Authors: Lee Seoyeon , Benvie Abigail M. , Park Hui Gyu , Spektor Roman , Harlan Blaine , Brenna J Thomas , Berry Daniel C. , Soloway Paul D. 
Published: April 2022

AbstractBeige adipocytes are induced by cold temperatures or β3-adrenergic receptor (Adrb3) agonists. They create heat through glucose and fatty acid (FA) oxidation, conferring metabolic benefits. The distinct and shared mechanisms by which these treatments induce beiging are unknown. Here, we performed single-nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq) on adipose tissue from mice exposed to cold or an Adrb3 agonist to identify cellular and chromatin accessibility dynamics during beiging. Both stimuli induce chromatin remodeling that influence vascularization and inflammation in adipose. Beige adipocytes from cold-exposed mice have increased accessibility at genes regulating glycolytic processes, whereas Adrb3 activation increases cAMP responses. While both thermogenic stimuli increase accessibility at genes regulating thermogenesis, lipogenesis, and beige adipocyte development, the kinetics and magnitudes of the changes are distinct for the two stimuli. Accessibility changes at lipogenic genes are linked to functional changes in lipid composition of adipose. Both stimuli tend to decrease the proportion of palmitic acids, a saturated FA in adipose. However, Adrb3 activation increases the proportion of monounsaturated FAs, whereas cold increases the proportion of polyunsaturated FAs. These findings reveal common and distinct mechanisms of cold and Adrb3 induced beige adipocyte biogenesis, and identify the unique functional consequences of manipulating these pathways in vivo.
Lumbar time-varying muscle synergies in trunk flexion and bending movements at different velocities
Authors: Rouchi Mahdi Bagheri , Davoudi Mehrdad , Meftahi Narges , Rashedi Ehsan , Parnianpour Mohamad , Khalaf Kinda 
Published: April 2022

AbstractPurposeAlthough the extent of which the central nervous system uses muscle synergies as a movement control strategy remains an open area of research, it is widely agreed that synergies facilitate the robustness of the neuromuscular system, allowing for effective postural control and flexible movement. This work aimed to investigate the muscle activation patterns of the trunk and time-varying muscle synergies using a novel 18-muscle 3-DOF, 3-D musculoskeletal model of the lumbar spine developed by the authors.Methods24 different biaxial trunk movements were simulated via the optimization of kinetic and kinematic measures towards obtaining the corresponding muscle activation patterns at 3 different velocities. These patterns were subsequently used to extract the principal (phasic and tonic) spatio-temporal synergies associated with the observed muscle activation patterns in the range of simulated movements.ResultsFour dominant synergies were able to explain a considerable percent (about 75%) of the variance of the simulated muscle activities. The extracted synergies were spatially tuned in the direction of the main simulated movements (flexion/extension and right/left lateral bending). The temporal patterns demonstrated gradual monotonic shifts in tonic synergies and biphasic modulatory components in phasic synergies with spatially tuned time-delays. The increase in velocity resulted in an elevated amplitude coefficient and accelerated activation of phasic synergies.ConclusionOur results suggest the plausibility of a time-varying synergies strategy in the dynamic control of trunk movement. Further work is needed to explore leveraging these concepts in various applications, such as rehabilitation and musculoskeletal biomechanics, towards providing more insight into the mechanisms underlying trunk stability and flexibility.
Motifizer: a tool for parsing high-throughput sequencing datasets and quantitative comparative analyses of transcription factor-binding sites
Authors: Khan Soumen , Bhattacharjee Abhik , Badhe Pranav , Dongaonkar Chinmay , Gaglani Yash 
Published: April 2022

AbstractBackgroundComparative analysis of Chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-seq), combined with transcriptomics data (RNA-seq), can provide critical insights into gene regulatory networks controlled by transcription factors in a given biological context. While multiple programs exist, which need to be individually installed and executed to generate such information, a user-friendly tool with low system requirements which combines the various computational processes into one package, using a docker container, is lacking.ResultsIn this study, we present a user-interactive, infrastructure-independent computational pipeline, called Motifizer, which uses open source tools for processing ChIP-Seq and RNA-seq datasets. Motifizer performs extensive analysis of raw input data, performing peak calling, de-novo motif analysis and differential gene expression analysis on ChIP and RNA-seq datasets. Additionally, Motifizer can be used for analysis and quantitative comparison of transcription factor binding sites in user defined genomic regions. Motifizer also allows easy addition and/or changes of parameters, thereby adding to the versatility of the tool.ConclusionThe Motifizer tool is an easy to use tool which uses a docker container system to install and execute ChIP-seq and RNA-seq data parsing. The Analysis module of Motifizer can be employed to identify putative targets involved in gene regulatory networks. Motifizer can be accessed by a large user base and does not require programming skill by the user. Motifizer can be locally installed from the repository (https://github.com/abhikbhattacharjee/Motifizer)
Immediate predation risk alters the relationship between potential and realised selection on male traits in the Trinidad guppy Poecilia reticulata
Authors: Glavaschi Alexandra , Cattelan Silvia , Devigili Alessandro , Pilastro Andrea 
Published: April 2022

AbstractPredation risk perception can alter mating behaviours in males and females, but the consequences for sexual selection remain underexplored. We have previously shown that in experimental populations of Trinidadian guppies Poecilia reticulata the opportunity for sexual selection (i.e. the variance in male reproductive fitness) was higher following exposure to a simulated risk of predation than in a no-risk condition. We build upon this result by exploring whether imminent predation risk affects: 1) the relationship between the opportunity for sexual selection and the actual strength of selection on male traits and 2) the traits contributing to male fitness, and he shape of selection on these traits. While predation risk increased the variance in male fitness, realised selection on traits remained unaffected. Pre- and postcopulatory traits follow complex patterns of nonlinear and correlational selection in both treatments. Differences in selection gradients deviate from predictions based on evolutionary responses to predation, the most notable being stronger selection on courtship rate under predation risk. Our results demonstrate that the operation of sexual selection can be altered by perception of an imminent predation risk and reinforce the notion that both trait-based and variance-based metrics should be employed for an informative quantification.
A paracrine circuit of IL-1β/IL-1R1 between myeloid and tumor cells drives glioblastoma progression
Authors: Chen Zhihong , Giotti Bruno , Kaluzova Milota , Herting Cameron J. , Pinero Gonzalo , Vallcorba Montse Puigdelloses , Cristea Simona , Ross James L. , Ackley James , Maximov Victor , Szulzewsky Frank , Marquez-Ropero Mar , Angione Angelo , Nichols Noah , Tsankova Nadejda , Michor Franziska , Shayakhmetov Dmitry M. , Gutmann David H. , Tsankov Alexander M. , Hambardzumyan Dolores 
Published: April 2022

SummaryMonocytes and monocyte-derived macrophages (MDM) from blood circulation infiltrate and promote glioblastoma growth. Here we discover that glioma cells induce the expression of potent pro-inflammatory cytokine IL-1β in MDM, which engages IL-1R1 in glioma cells, activates NF-κB pathway, and subsequently leads to the induction of monocyte chemoattractant proteins (MCPs). Thus, a feedforward paracrine circuit of IL-1β/IL-1R1 between the tumors and MDM creates an interdependence driving glioblastoma progression. Locally antagonizing IL-1β/IL-1R1 leads to reduced MDM infiltration, diminished tumor growth, reduced exhausted CD8+T cells, and thereby extends the survival of tumor-bearing mice. In contrast to IL-1β, IL-1a exhibits anti-tumor effects. Genetic deletion ofIl1ais associated with decreased recruitment of lymphoid cells and loss of interferon (IFN) signaling in various immune populations and subsets of malignant cells. IL-1β antagonism of IL-1β should be considered as an effective anti-glioblastoma therapy.Graphical Abstract
Genetically encoded sensors for analysing neurotransmission among synaptically-connected neurons
Authors: Shindo Yutaka , Ashida Keita , Masamoto Kazuto , Takuwa Hiroyuki , Takahashi Manami , Higuchi Makoto , Ide Ryuto , Hotta Kohji , Oka Kotaro 
Published: April 2022

ABSTRACTAnatomical connectome mapping in small areas of the nervous system as well as large-scale detection of neuronal activity patterns have been respectively achieved; however, it is still challenging to evaluate the functional connections among anatomically-connected neurons in a large-scale nervous system. We have developed a novel method to visualize neurotransmission named Split Protein HEmispheres for REconstitution (Sphere). By splitting a sensor into two fragments and expressing them in pre- and postsynaptic neurons separately, functional neurotransmitter sensors can be reconstituted only at the synapses between those neurons. We developed a Sphere-SF-iGluSnFR to measure glutamate levels, and further demonstrated that this system is functional in cultured cells, worms, and mouse brains. Moreover, this system is applicable to sensors other than glutamate, and colour variants have also been developed. This could allow for brain-wide imaging of functional synaptic transmission among particular neurons and identification of important neuronal circuits in the nervous system.
Flexible color segmentation of biological images with the R package recolorize
Authors: Weller Hannah I. , Van Belleghem Steven M. , Hiller Anna E. , Lord Nathan P. 
Published: April 2022

AbstractColor is an important source of biological information in fields ranging from disease ecology to sexual selection. Despite its importance, most metrics for color are restricted to point measurements. Methods for moving beyond point measurements rely on color maps, where every pixel in an image is assigned to one of a set of discrete color classes (color segmentation). Manual methods for color segmentation are slow and subjective, while existing automated methods often fail due to biological variation in pattern, technical variation in images, and poor scalability for batch clustering. As a result, color segmentation is the common bottleneck step for a majority of existing downstream analyses. Here we presentrecolorize, an R package for color segmentation that succeeds in many cases where existing methods fail.Recolorizehas three major components: (1) an effective two-part clustering algorithm where color distributions are binned and combined according to perceived similarity in a frequency-independent manner; (2) a toolkit for minor manual adjustments to automatic output where needed; and (3) flexible export options. This paper illustrates how to userecolorizeand compares it to existing methods, including examples where we segment formerly intractable images, and demonstrates the downstream use of methods that rely on color maps.
Structural and Preliminary Biochemical Characterization of MppQ, a PLP-Dependent Aminotransferase from Streptomyces hygroscopicus
Authors: Vuksanovic Nemanja , Serrano Dante A. , Schwabacher Alan W. , Silvaggi Nicholas R. 
Published: April 2022

AbstractMppQ is an enzyme of unknown function from Streptomyces hygroscopicus that is involved in the biosynthesis of the nonproteinogenic amino acid L-enduracididine (L-End). Since L-End is a component of several peptides showing high activity against methicillin-resistant Staphylococcus aureus (MRSA), a complete understanding of its biosynthetic pathway is of utmost importance for developing chemoenzymatic routes for syntheses of novel antibiotics. In this work, we report high-resolution X-ray crystal structures of MppQ complexed with pyridoxal-5’-phosphate (PLP) and pyridoxamine-5’-phosphate (PMP). The structure of MppQ shares a fold with known Type I PLP-dependent aminotransferases, consisting of an N-terminal extension, large domain, and a small domain. We also report the first functional characterization of MppQ, which we incubated with enzymatically produced 2-ketoenduracidine and observed conversion to L-End via mass spectroscopy. Additionally, we have observed that MppQ has a relatively high affinity for 2-ketoarginine, a shunt product in the L-End biosynthetic pathway, indicating a possible role of MppQ in increasing efficiency of L-End biosynthesis by converting 2-ketoarginine back to the starting material, L-arginine.