bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stomach serosal arteries distinguish gastric regions of the rat
Authors: Jaffey Deborah M , Chesney Logan , Powley Terry L. 
Published: February 2021

AbstractBecause the stomachin situhas few distinctive surface features and changes shape dramatically with food intake, we have used microCT imaging to (1) characterize the pattern of arteries, potential landmarks, on the stomach wall and (2) evaluate how meal-related shape changes affect the size of the different regions. The stomach receives its blood supply primarily from two pairs of vessels, the gastric and gastroepiploic arteries. Each of the three regions of the stomach is delineated by a distinctive combination of arterial fields: Thecorpus, consistent with its dynamic secretory activity and extensive mucosa, is supplied by extensive arterial trees formed by the left and right gastric arteries. These major arteries course circularly from the lesser towards the greater curvature, distally along both left and right walls of the corpus, and branch rostrally to supply the region. The muscularantrumis characterized by smaller arterial branches arising primarily from the right gastroepiploic artery that follows the distal greater curvature and secondarily from small, distally directed arteries supplied by the large vessels of the left and right gastric arteries. Theforestomach, essentially devoid of mucosal tissue and separated from the corpus by the limiting ridge, is vascularized predominantly by a network of small arteries issued from the left gastroepiploic artery coursing around the proximal greater curvature, as well as from higher order and smaller branches issued by the gastric and celiac arteries. The regions of the stomach empty at different rates, thus changing the dimensions of the organ regions non-linearly.
Cancer blues? A validated judgment bias task suggests pessimism in nude mice with tumors
Authors: Resasco A. , MacLellan A. , Ayala M. A. , Kitchenham L. , Edwards A. M. , Lam S. , Dejardin S. , Mason G. 
Published: February 2021

AbstractIn humans, affective states can bias responses to ambiguous information: a phenomenon termed judgment bias (JB). Judgment biases have great potential for assessing affective states in animals, in both animal welfare and biomedical research. New animal JB tasks require construct validation, but for laboratory mice (Mus musculus), the most common research vertebrate, a valid JB task has proved elusive. Here (Experiment 1), we demonstrate construct validity for a novel mouse JB test: an olfactory Go/Go task in which subjects dig for high- or low-value food rewards. In C57BL/6 and Balb/c mice faced with ambiguous cues, latencies to dig were sensitive to high/low welfare housing, environmentally-enriched animals responding with relative ‘optimism’ through shorter latencies. Illustrating the versatility of a validated JB task across fields of research, it further allowed us to test hypotheses about the mood-altering effects of cancer (Experiment 2). Male nude mice bearing subcutaneous lung adenocarcinomas responded more pessimistically than healthy controls to ambiguous cues. Similar effects were not seen in females, however. To our knowledge, this is the first validation of a mouse JB task and the first demonstration of pessimism in tumor-bearing animals. This task, especially if refined to improve its sensitivity, thus has great potential for investigating mouse welfare, the links between affective state and disease, depression-like states in animals, and hypotheses regarding the neurobiological mechanisms that underlie affect-mediated biases in judgment.
On the evolution of host specificity: a case study of helminths
Authors: Pfenning-Butterworth Alaina C. , Botero-Cañola Sebastian , Cressler Clayton E. 
Published: February 2021

ABSTRACTThe significant variation in host specificity exhibited by parasites has been separately linked to evolutionary history and ecological factors in specific host-parasite associations. Yet, whether there are any general patterns in the factors that shape host specificity across parasites more broadly is unknown. Here we constructed a molecular phylogeny for 249 helminth species infecting free-range mammals and find that the influence of ecological factors and evolutionary history varies across different measures of host specificity. Whereas the phylogenetic range of hosts a parasite can infect shows a strong signal of evolutionary constraint, the number of hosts a parasite infects does not. Our results shed new light on the evolution of host specificity in parasites, suggesting that phylogenetic breadth may capture the evolutionary potential of a parasite to jump between hosts, whereas the number of hosts may reflect ecological opportunity. Finally, we show parasite phylogenies can also provide an alternative perspective on zoonosis by identifying which hosts are infected by a broad phylogenetic range of parasites.
The Future is Less Concrete than the Present: A Neural Signature of the Concreteness of Prospective Thought Is Modulated by Temporal Proximity during Intertemporal Decision-Making
Authors: Lee Sangil , Parthasarathi Trishala , Cooper Nicole , Zauberman Gal , Lerman Caryn , Kable Joseph W. 
Published: February 2021

AbstractWhy do people discount future rewards? Multiple theories in psychology argue that future events are imagined less concretely than immediate events, thereby diminishing their perceived value. Here we provide neuroscientific evidence for this proposal. First, we construct a neural signature of the concreteness of prospective thought, using an fMRI dataset where the concreteness of imagined future events is orthogonal to their valence by design. Then, we apply this neural signature in two additional fMRI datasets, each using a different delay discounting task, to show that neural measures of concreteness decline as rewards are delayed farther into the future.Significance StatementPeople tend to devalue, or discount, outcomes in the future relative to those that are more immediate. This tendency is evident in people’s difficulty in making healthy food choices or saving money for retirement. Several psychological theories propose that discounting occurs because delayed outcomes are perceived less concretely that more immediate ones. Here we build a brain decoder for the concreteness of future thought and use this unobtrusive measure to show that outcomes are processed less concretely as they occur farther into the future.
GABA plays a key role in plant acclimation to a combination of high light and heat stress
Authors: Balfagón Damián , Gómez-Cadenas Aurelio , Rambla José L. , Granell Antonio , Ollas Carlos de , Mittler Ron , Zandalinas Sara I 
Published: February 2021

ABSTRACTPlants are frequently subjected to different combinations of abiotic stresses, such as high light intensity and elevated temperatures. These environmental conditions pose an important threat to agriculture production, affecting photosynthesis and decreasing yield. Metabolic responses of plants, such as alterations in carbohydrates and amino acid fluxes, play a key role in the successful acclimation of plants to different abiotic stresses, directing resources towards stress responses and suppressing growth. Here we show that the primary metabolic response ofArabidopsis thalianaplants to high light or heat stress is different than that of plants subjected to a combination of high light and heat stress. We further demonstrate that a combination of high light and heat stress results in a unique metabolic response that includes increased accumulation of sugars and amino acids, coupled with decreased levels of metabolites participating in the tricarboxylic acid (TCA) cycle. Among the amino acids exclusively accumulated during a combination of high light and heat stress, we identified the non-proteinogenic amino acid γ-aminobutyric acid (GABA). Analysis of different mutants deficient in GABA biosynthesis, in particular two independent alleles of glutamate decarboxylase 3 (gad3), reveal that GABA plays a key role in the acclimation of plants to a combination of high light and heat stress. Taken together, our findings identify a new role for GABA in regulating plant responses to stress combination.One sentence summaryThe non-proteinogenic amino acid γ-aminobutyric acid (GABA) is required for plant acclimation to a combination of high light and heat stress in Arabidopsis.
Medicago SativaDefensin 1 (MsDef1), A Natural Tumor Targeted Sensitizer for Improving Chemotherapy: Translation from Anti-Fungal Agent to Potential Anti-Cancer Agent
Authors: Pandurangi Raghu S. , Karwa Amol , Sagaram Uma Shankar , Shah Dilip 
Published: February 2021

AbstractIntroductionMsDef1, a 45-amino acid cysteine-rich peptide from the seed ofMedicago sativais an antifungal defensin small protein. It exhibits broad-spectrum antifungal activity against fungal pathogens of plants at low micromolar concentrations. The common vulnerability of fungal and cancer cells determines the utility of MsDef1 as a potential anti-tumor agent.ResultsThe solution dynamics of15N-labeled MsDef1,15N longitudinal relaxation (T1) and15N-1H Nuclear Overhauser Effect (NOE) shows that GlcCer binds at two sites on the peptide molecule, i.e., Asp36-Cys39 and amino acids between 12-20 and 33-40. MsDef1 interacts with drug resistant breast cancer MCF-7R cells, permeates GlcCer-rich plasma membrane and releases apoptotic ceramide. This results in the activation of ceramide pathway involving interaction of the peptide with intracellular thioredoxin (Trx), another tumor specific biomarker. MsDef1 oxidizes Trx through four S-S bonds and in the process, gets reduced to thiols. Oxidation of Trx is correlated with the activation of Apoptosis Stimulating Kinase 1 (ASK1) which is known to sensitize cancer cells to chemotherapeutics including front-line drug Doxorubicin. A combination of MsDef1 and Doxorubicin exhibits 5-10-fold greater apoptosisin vitroin MDR triple negative breast cancer (TNBC) cells compared to either MsDef1 or Doxorubicin alone.ConclusionAn antifungal plant defensin MsDef1 is shown to be a cell permeating peptide (CPP) for MDR cancer cells targeted to two tumor specific targets activating two cell death pathways. That makes MsDef1, potentially a tumor targeted sensitizer neoadjuvant to cancer therapy.
Fast, efficient and virus-free generation ofTRAC-replaced CAR T cells
Authors: Kath Jonas , Du Weijie , Thommandru Bernice , Turk Rolf , Amini Leila , Stein Maik , Zittel Tatiana , Martini Stefania , Ostendorf Lennard , Wilhelm Andreas , Akyüz Levent , Rehm Armin , Höpken Uta E. , Pruß Axel , Künkele Annette , Jacobi Ashley M. , Volk Hans-Dieter , Schmueck-Henneresse Michael , Reinke Petra , Wagner Dimitrios L. 
Published: February 2021

AbstractChimeric Antigen Receptor (CAR) redirected T cells are a potent treatment option for certain hematological malignancies. Recently, site-specific insertion of CARs into the T cell receptor (TCR) alpha constant (TRAC) locus using gene editing and adeno-associated viruses was shown to generate CAR T cells with improved functionality over their retrovirally transduced counterparts. However, the development of viruses for gene transfer is complex and associated with extensive costs at early clinical stages. Here, we provide an economical and virus-free method for efficient CAR insertion into theTRAClocus of primary human T cellsviaCRISPR-Cas mediated homology-directed repair (HDR). While the toxicity induced by transfected double-stranded template (donor) DNA was not fully prevented by pharmacological means, the combination of DNA-sensor inhibitors and HDR enhancers resulted in highly efficient gene editing with TCR-to-CAR replacement rates reaching up to 68%. The resulting TCR-deficient CAR T cells show antigen-specific cytotoxicity and cytokine productionin vitro. Our GMP-compatible non-viral platform technology lays the foundation for clinical trials and fast-track generation of novel CAR T cells applicable for autologous or allogeneic off-the-shelf use.
PDBrenum: a webserver and program providing Protein Data Bank files renumbered according to their UniProt sequences
Authors: Faezov Bulat , Dunbrack Roland L. 
Published: February 2021

AbstractThe Protein Data Bank (PDB) was established at Brookhaven National Laboratories in 1971 as an archive for biological macromolecular crystal structures. In early 2021, the database has more than 175,000 structures solved by X-ray crystallography, nuclear magnetic resonance, cryo-electron microscopy, and other methods. Many proteins have been studied under different conditions, including binding partners such as ligands, nucleic acids, or other proteins; mutations, and post-translational modifications, thus enabling extensive comparative structure-function studies. However, these studies are made more difficult because authors are allowed by the PDB to number the amino acids in each protein sequence in any manner they wish. This results in the same protein being numbered differently in the available PDB entries. For instance, some authors may include N-terminal signal peptides or the N-terminal methionine in the sequence numbering and others may not. In addition to the coordinates, there are many fields that contain information regarding specific residues in the sequence of each protein in the entry. Here we provide a webserver and Python3 application that fixes the PDB sequence numbering problem by replacing the author numbering with numbering derived from the corresponding UniProt sequences. We obtain this correspondence from the SIFTS database from PDBe. The server and program can take a list of PDB entries or a list of UniProt identifiers (e.g., “P04637” or “P53_HUMAN”) and provide renumbered files in mmCIF format and the legacy PDB format for both asymmetric unit files and biological assembly files provided by PDBe.AvailabilitySource code is freely available athttps://github.com/Faezov/PDBrenum. The webserver is located at:http://dunbrack3.fccc.edu/PDBrenum.Contactbulat.faezov@fccc.eduorroland.dunbrack@fccc.edu.
Metabolomics, Transcriptomics and Functional Glycomics Reveals Bladder Cancer Cells Plasticity and Enhanced Aggressiveness Facing Hypoxia and Glucose Deprivation
Authors: Peixoto Andreia , Freitas Rui , Ferreira Dylan , Relvas-Santos Marta , Paulo Paula , Cardoso Marta , Soares Janine , Gaiteiro Cristiana , Palmeira Carlos , Teixeira Filipe , Ferreira Rita , José Oliveira Maria , Silva André M. N. , Lara Santos Lúcio , Ferreira José Alexandre 
Published: February 2021

AbstractBladder cancer constitutes one of the deadliest genitourinary diseases, especially when diagnosed at late stages. These tumours harbour microenvironmental niches characterized by low levels of oxygen (hypoxia) and limited glucose supply due to poor vascularization. However, the synergic contribution of these features to disease development is poorly understood. Here, we demonstrated that cells with distinct histopathological and molecular backgrounds responded similarly to such stimuli. Cancer cells arrested proliferation, significantly increased invasive capacityin vitroand enhanced tolerance to cisplatin-based chemotherapy. Reoxygenation and access to glucose restored basal proliferation and invasion levels without triggering stress-induced apoptosis, denoting significant cellular plasticity in adapting to microenvironmental cues. Whole transcriptomics showed major molecular reprogramming, supporting main functional alterations. Metabolomics evidenced fatty acidsβ-oxidation as main bioenergetic pathway rather than anaerobic glycolysis generally adopted by hypoxic cells. Joint pathway analysis also suggested relevant alterations in mucin-typeO-glycan biosynthesis. Glycomics confirmed a major antagonization ofO-glycosylation pathways, leading to simple cell glycophenotypes characterized by the accumulation of immature short-chainO-glycans such as Tn and STn antigens at the cell surface. Glycoengineered models reflecting simple cell glycophenotypes were developed and functional studiesin vitroandin vivoshowed that Tn and STn overexpression decreased proliferation and promoted chemoresistance, reinforcing their close link with tumour aggressiveness. Collectively, we have demonstrated that hypoxia and glucose deprivation trigger more aggressive cell behaviours, in what appears to be an escape mechanism from microenvironmental stress. We propose that, altered glycosylation may be used to target these subpopulations, paving the way for precision oncology.
Probing Patterning in Microbial Consortia with picCASO: a Cellular Automaton for Spatial Organisation
Authors: Venkatraghavan Sankalpa , Anantakrishnan Sathvik , Raman Karthik 
Published: February 2021

AbstractMicrobial consortia exhibit spatial patterning across diverse environments. Since probing the self-organization of natural microbial communities is limited by their inherent complexity, synthetic models have emerged as attractive alternatives. In this study, we develop novel frameworks of bacterial communication and explore the emergent spatiotemporal organization of microbes. Specifically, we build quorum sensing-mediated models of microbial growth that are utilized to characterize the dynamics of communities from arbitrary initial configurations and establish the effectiveness of our communication strategies in coupling the growth rates of microbes. Our simulations indicate that the behavior of quorum sensing-coupled consortia can be most effectively modulated by the rates of secretion of AHLs. Such a mechanism of control enables the construction of desired relative populations of constituent species in spatially organized populations. Our models accurately recapitulate previous experiments that have investigated pattern formation in synthetic multi-cellular systems. Additionally, our software tool enables the easy implementation and analysis of our frameworks for a variety of initial configurations and simplifies the development of sophisticated gene circuits facilitating distributed computing. Overall, we demonstrate the potential of spatial organization as a tunable parameter in synthetic biology by introducing a communication paradigm based on the location and strength of coupling of microbial strains.Author SummaryInteracting microorganisms that coexist in a given environment tend to have well-defined spatial arrangements. While the emergence of such organization is seen across different microbiomes in nature, it is hitherto not well understood. Decoding the inherent spatial patterning of microbes is constrained by the complexity of their natural habitats. Here, we take advantage of synthetic models of microbial communities to study the dynamics of emergent spatial organization. Our framework of bacterial communication utilizes modular synthetic devices to couple growth rates. In addition to uncovering potential principles of spatial organization, this work enables the construction of complex genetic circuits distributed across communicating strains. Additionally, we have developed a software tool, picCASO, that streamlines the investigation of microbial systems communicating through such frameworks.
The APOBEC3A deaminase drives episodic mutagenesis in cancer cells
Authors: Petljak Mia , Chu Kevan , Dananberg Alexandra , Bergstrom Erik N. , Morgen Patrick von , Alexandrov Ludmil B. , Stratton Michael R. , Maciejowski John 
Published: February 2021

ABSTRACTThe APOBEC3 family of cytidine deaminases is widely speculated to be a major source of somatic mutations in cancer1–3. However, causal links between APOBEC3 enzymes and mutations in human cancer cells have not been established. The identity of the APOBEC3 paralog(s) that may act as prime drivers of mutagenesis and the mechanisms underlying different APOBEC3-associated mutational signatures are unknown. To directly investigate the roles of APOBEC3 enzymes in cancer mutagenesis, candidateAPOBEC3genes were deleted from cancer cell lines recently found to naturally generate APOBEC3-associated mutations in episodic bursts4. Deletion of theAPOBEC3Aparalog severely diminished the acquisition of mutations of speculative APOBEC3 origins in breast cancer and lymphoma cell lines. APOBEC3 mutational burdens were undiminished inAPOBEC3Bknockout cell lines.APOBEC3Adeletion reduced the appearance of the clustered mutation typeskataegisandomikli, which are frequently found in cancer genomes. The uracil glycosylase UNG and the translesion polymerase REV1 were found to play critical roles in the generation of mutations induced by APOBEC3A. These data represent the first evidence for a long-postulated hypothesis that APOBEC3 deaminases generate prevalent clustered and non-clustered mutational signatures in human cancer cells, identify APOBEC3A as a driver of episodic mutational bursts, and dissect the roles of the relevant enzymes in generating the associated mutations in breast cancer and B cell lymphoma cell lines.
A phosphorylation of RIPK3 kinase initiates an intracellular apoptotic pathway that promotes corpus luteum regression
Authors: Li Dianrong , Chen Jie , Guo Jia , Li Lin , Cai Gaihong , Chen She , Huang Jia , Yang Hui , Zhuang Yinhua , Wang Fengchao , Wang Xiaodong 
Published: February 2021

AbstractReceptor-interacting serine/threonine-protein kinase 3 (RIPK3) normally signals to necroptosis by phosphorylating MLKL. We report here that when the cellular RIPK3 chaperone Hsp90/CDC37 level is low, RIPK3 also signals to apoptosis. The apoptotic function of RIPK3 requires phosphorylation of the serine 165/threonine 166 sites on its kinase activation loop, resulting in inactivation of RIPK3 kinase activity while gaining the ability to recruit RIPK1, FADD, and caspase-8 to form a cytosolic caspase-activating complex, thereby triggering apoptosis. We found that PGF2αinduces RIPK3 expression in luteal granulosa cells in the ovary to cause luteal regression through this RIPK3-mediated apoptosis pathway. Mice carrying homozygous phosphorylation-resistant RIPK3 S165A/T166A knockin mutations failed to respond to PGF2αbut retained pro-necroptotic function, whereas mice with phospho-mimicking S165D/T166E homozygous knockin mutation underwent spontaneous apoptosis in multiple RIPK3-expressing tissues and died shortly after birth. Thus, RIPK3 signals to either necroptosis or apoptosis depending on its serine 165/threonine 166 phosphorylation status.
Thalamocortical axons control the cytoarchitecture of neocortical layers by area-specific supply of secretory proteins
Authors: Sato Haruka , Hatakeyama Jun , Iwasato Takuji , Araki Kimi , Yamamoto Nobuhiko , Shimamura Kenji 
Published: February 2021

AbstractNeuronal abundance and thickness of each cortical layer is specific to each area, but how this fundamental feature arises during development remains poorly understood. While some of area-specific features are controlled by intrinsic cues such as morphogens and transcription factors, the exact influence and mechanisms of action by extrinsic cues, in particular the thalamic axons, have not been fully established. Here we identify a thalamus-derived factor, VGF, which is indispensable for thalamocortical axons to maintain the proper amount of layer 4 neurons in the mouse sensory cortices. This process is prerequisite for further maturation of the primary somatosensory area, such as barrel field formation instructed by a neuronal activity-dependent mechanism. Our results also provide an insight into regionalization of brain in that highly site-specific axon projection anterogradely confers further regional complexity upon the target field through locally secreting signaling molecules from axon terminals.