bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intrinsic and tumor-induced JAK/STAT signaling regulate developmental timing by the Drosophila prothoracic gland
Authors: Cao Xueya , Pastor-Pareja José Carlos 
Published: June 2021

AbstractDevelopment involves tightly paced, reproducible sequences of events, yet it must adjust to conditions external to it, such as resource availability and organismal damage. A major mediator of damage-induced immune responses in vertebrates and insects is JAK/STAT signaling. At the same time, JAK/STAT activation by the Drosophila Upd cytokines is pleiotropically involved in normal development of multiple organs. Whether inflammatory and developmental roles of JAK/STAT intersect is unknown. Here, we show that JAK/STAT is active during development of the prothoracic gland (PG), the organ that controls metamorphosis onset through ecdysone production. Reducing JAK/STAT signaling decreased PG size and slightly advanced metamorphosis. Conversely, JAK/STAT hyperactivation, achieved through overexpression of pathway components or SUMOylation loss, caused PG hypertrophy and metamorphosis delay. Interestingly, tissue damage and tumors, known to secrete Upd cytokines, also activated JAK/STAT in the PG and delayed metamorphosis. Finally, we show that expression of transcription factor Apontic, a JAK/STAT target in the PG, recapitulates PG hypertrophy and metamorphosis delay. JAK/STAT damage signaling, therefore, regulates metamorphosis onset at least in part by coopting its developmental role in the PG.Summary statementDamage signaling from tumors mediated by JAK/STAT-activating Upd cytokines delays the Drosophila larva-pupa transition through cooption of a JAK/STAT developmental role in the prothoracic gland.
Caveolae respond to acute oxidative stress through membrane lipid peroxidation, cytosolic release of CAVIN1, and downstream regulation of NRF2
Authors: Wu Yeping , Lim Ye-Wheen , Stroud David A. , Martel Nick , Hall Thomas E. , Lo Harriet P. , Ferguson Charles , Ryan Michael T. , McMahon Kerrie-Ann , Parton Robert G. 
Published: June 2021

AbstractCaveolae have been linked to many biological functions, but their precise roles are unclear. Using quantitative whole cell proteomics of genome-edited cells, we show that the oxidative stress response is the major pathway dysregulated in cells lacking the key caveola structural protein, CAVIN1. CAVIN1 deletion compromised sensitivity to oxidative stress in cultured cells and in animals. Wound-induced accumulation of reactive oxygen species and apoptosis were suppressed in Cavin1-null zebrafish, negatively affecting regeneration. Oxidative stress triggered lipid peroxidation and induced caveolar disassembly. The resulting release of CAVIN1 from caveolae allowed direct interaction between CAVIN1 and NRF2, a key regulator of the antioxidant response, facilitating NRF2 degradation. CAVIN1-null cells with impaired negative regulation of NRF2 showed resistance to lipid peroxidation-induced ferroptosis. Thus, caveolae, via lipid peroxidation and CAVIN1 release, maintain cellular susceptibility to oxidative stress-induced cell death demonstrating a crucial role for this enigmatic organelle in cellular homeostasis and wound response.
Transcranial theta-burst stimulation of primary sensory cortex attenuates somatosensory threat memory in humans
Authors: Ojala Karita E. , Staib Matthias , Gerster Samuel , Ruff Christian C. , Bach Dominik R. 
Published: June 2021

AbstractSensory cortices are required for learning to discriminate complex stimuli that predict threat from those that predict safety in rodents. Yet, sensory cortices may not be needed to learn threat associations to simple stimuli. It is unknown whether these findings apply in humans. Here, we investigated the role of primary sensory cortex in discriminative threat conditioning with simple and complex somatosensory conditioned stimuli (CS) in healthy humans. Immediately before conditioning, participants received continuous theta-burst transcranial magnetic stimulation (cTBS) to primary somatosensory cortex either in the CS-contralateral or CS-ipsilateral hemisphere. After overnight consolidation, threat memory was attenuated in the contralateral compared to the ipsilateral group, as indicated by reduced startle eye-blink potentiation. There was no evidence for a difference between simple and complex stimuli, or that CS identification or conditioning was affected, suggesting a stronger effect of cTBS on consolidation than on initial stimulus processing. We propose that non-invasive stimulation of sensory cortex may provide a new avenue for interfering with threat memories in humans.
Fungal succession on the decomposition of three plant species from a Brazilian mangrove
Authors: Moitinho Marta A. , Chiaramonte Josiane B. , Bononi Laura , Gumiere Thiago , Melo Itamar S. , Taketani Rodrigo G. 
Published: June 2021

AbstractLeaf decomposition is the primary process in release nutrients in the dynamic mangrove habitat, supporting the ecosystem food webs. On most environments, fungi are an essential part of this process. However, due to the peculiarities of mangrove forests, this group is currently neglected. Thus, this study tests the hypothesis that fungal community display an specific succession pattern in different mangrove species. A molecular approach was employed to investigate the dynamics of the fungal community during the decomposition of three common plant species (Rhizophora mangle, Laguncularia racemosa, and Avicennia schaueriana) from the mangrove habitat located at the southeast of Brazil. Plant material was the primary driver of fungi communities but time also was marginally significant for the process, and evident changes in the fungal community during the decomposition process were observed. The five most abundant classes common to all the three plant species were Saccharomycetes, Sordariomycetes, Tremellomycetes, Eurotiomycetes, and Dothideomycetes, all belonging to the Phylum Ascomycota. Microbotryomycetes class were shared only by A. schaueriana and L. racemosa, while Agaricomycetes class were shared by L. racemosa and R. mangle. The class Glomeromycetes were shared by A. schaueriana and R. mangle. The analysis of the core microbiome showed that Saccharomycetes was the most abundant class. In the variable community, Sordariomycetes was the most abundant one, mainly in the Laguncularia racemosa plant. The results presented in this work shows a specialization of the fungal community regarding plant material during mangrove litter decomposition.
Gotree/Goalign : Toolkit and Go API to facilitate the development of phylogenetic workflows
Authors: Lemoine Frédéric , Gascuel Olivier 
Published: June 2021

ABSTRACTBesides computer intensive steps, phylogenetic analysis workflows are usually composed of many small, reccuring, but important data manipulations steps. Among these, we can find file reformatting, sequence renaming, tree re-rooting, tree comparison, bootstrap support computation, etc. These are often performed by custom scripts or by several heterogeneous tools, which may be error prone, uneasy to maintain and produce results that are challenging to reproduce. For all these reasons, the development and reuse of phylogenetic workflows is often a complex task. We identified many operations that are part of most phylogenetic analyses, and implemented them in a toolkit called Gotree/Goalign. The Gotree/Goalign toolkit implements more than 120 user-friendly commands and an API dedicated to multiple sequence alignment and phylogenetic tree manipulations. It is developed in Go, which makes executables efficient, easily installable, integrable in workflow environments, and parallelizable when possible. This toolkit is freely available on most platforms (Linux, MacOS and Windows) and most architectures (amd64, i386). Sources and binaries are available on GitHub at https://github.com/evolbioinfo/gotree, Bioconda, and DockerHub.
The mitotic checkpoint protein MAD2 delivers monoamine transporters to endocytosis
Authors: Koban Florian , Freissmuth Michael 
Published: June 2021

ABSTRACTMonoamine transporters retrieve serotonin (SERT), dopamine (DAT) and norepinephrine (NET) from the synaptic cleft. Surface levels of transporters are also regulated by internalization. Clathrin-mediated endocytosis of cargo proteins requires adaptor protein 2 (AP2), which recruits cargo to the nascent clathrin-cage. The transporter C-terminus is required for internalization but lacks an AP2-binding site. In the present work, we show that internalization of SERT and DAT relies on MAD2, a protein of the mitotic spindle assembly checkpoint (SAC). A MAD2-interaction motif in the transporter C-terminus interacts with MAD2. This binding is contingent on the closed conformation of MAD2 and allowed for the recruitment of two additional SAC proteins, BubR1 and p31COMET as well as AP2. MAD2, BubR1 and p31COMET are present in serotoninergic neurons of the dorsal raphe, corroborating a biological role of the identified interactions. Depletion of MAD2 in HEK-293 cells stably expressing SERT and DAT decreases constitutive and triggered endocytosis, respectively. Altogether, our study describes a candidate mechanism, which connects monoamine transporters to the endocytic machinery and thus supports their internalization.
Contact guidance as a consequence of coupled morphological evolution and motility of adherent cells
Authors: Ippolito Alberto , DeSimone Antonio , Deshpande Vikram S. 
Published: June 2021

AbstractAdherent cells seeded on substrates spread and evolve their morphology while simultaneously displaying motility. Phenomena such as contact guidance viz. the alignment of cells on patterned substrates, are strongly linked to the coupling of morphological evolution with motility. Here we employ a recently developed statistical thermodynamics framework for modelling the non-thermal fluctuating response of the cells to probe this coupling. This thermodynamic framework is first extended to predict temporal responses via a Langevin style model. The Langevin model is then shown to not only predict the different experimentally observed temporal scales for morphological observables such as cell area and elongation but also the interplay of morphology with motility that ultimately leads to contact guidance.Author SummaryThe evolution of cellular morphology and organization plays a crucial role in the micro-architecture of tissues and dictates their biological and mechanical functioning. Despite the importance of cellular organization in all facets of tissue biology, the fundamental question of how a cell organizes itself in an anisotropic environment is still poorly understood. We demonstrate, using a Langevin style model, that non-thermal fluctuations fuelled by nutrient exchanges between the cell and its environment are critical in allowing cells to explore their surroundings. The biochemical changes, associated with non-thermal fluctuations, drive cell motility and morphological changes and the interplay between these two emerging dynamics ultimately leads to contact guidance, a critical component for tissue morphogenesis.
Investigation of Thyroid Hormone Associated Gene-Regulatory Networks during Hepatogenesis using an Induced Pluripotent Stem Cell based Model
Authors: Ncube Audrey , Graffmann Nina , Greulich Jan , Scherer Bo , Wruck Wasco , Adjaye James 
Published: June 2021

AbstractCurrently, the only treatment of end-stage liver diseases is liver transplantation. The worldwide shortage of donor organs and the high number of patients suffering from end-stage liver diseases, require alternative treatment approaches. Therefore, the generation of hepatocyte-like cells (HLCs) derived from induced pluripotent stem cells (iPSCs) is a promising treatment option. HLCs are suitable for patient-specific drug screening, disease modeling and regenerative medicine. So far, they are immature and resemble the fetal state. In this study, we employed the combined thyroid hormones triiodo-L-thyronine (T3) and L-thyroxine (T4) to drive HLCs towards maturation. HLCs expressed the maturation markers ALBUMIN (ALB), ALPHA-1 ANTITRYPSIN (A1AT), CYTOCHROME P450 3A4 (CYP3A4) and TRANSTHYRETIN (TTR). Remarkably, stimulation with T3 and T4 slightly reduced the expression of the fetal marker CYTOCHROME P450 3A7 (CYP3A7) and had an even more pronounced effect on ALPHA-FETOPROTEIN (AFP) levels. Comparative transcriptome and associated pathways in unstimulated and T3 and T4 stimulated HLCs revealed regulated expression of numerous genes within for example the peroxisome proliferator-activated receptor (PPAR), transforming growth factor beta (TGF-β), mitogen-activated protein kinase/extracellular-signal-regulated kinase (MAPK/ERK) signaling pathways and thyroid hormone synthesis. We propose the inclusion of combined T3 andT4 in HLC differentiation protocols to enhance maturation and therefore provide additional improvement in their applications in drug screening and disease modeling.
RCaN : a software for Chance and Necessity modelling
Authors: Drouineau Hilaire , Planque Benjamin , Mullon Christian 
Published: June 2021

AbstractUncertainty is a challenge in modelling ecological systems and has been a source of misunderstandings between modelers and non-modelers. The “Chance and Necessity” (CaN) modelling approach has been proposed to address this issue, in the case of trophic network modelling. CaN modelling focuses exploring food-web trajectories that can satisfy fundamental physical and biological laws, while being compatible with observations and domain knowledge. This type of approach can facilitate discussion among actors as it promotes sharing of information and does not presuppose any knowledge of modelling practices. It is therefore suitable for participatory modelling, i.e. a modelling approach in which different actors can confront their knowledge and understanding of the marine system and of the associated uncertainties.One important ingredient to achieve participatory modelling is the availability of a modelling platform that is efficient, fast and transparent, so that all actors can understand and follow the modelling steps and choices, and can rapidly visualize and discuss the results. But, until now, there existed no software to easily perform CaN modelling. Here, we present RCaN and RCaNconstructor. Combined, these provide the first tool to build CaN models in an intuitive way that is 1) suitable within participatory frameworks, 2) transparent, 4) computationally efficient, 5) fully documented through the provision of meta-information and 6) supportive of exploratory analyses through predefined graphical functions.
Polypeptides IGF-1C and P24 synergistically promote osteogenic differentiation of bone marrow mesenchymal stem cells in vitro through the p38 and JNK signaling pathways
Authors: Ran Gaoying , Fang Wei , Zhang Lifang , Peng Yuting , Li Jiatong , Ding Xianglong , Zeng Shuguang , He Yan 
Published: June 2021

AbstractObjectivesInsulin-like growth factor-1 (IGF-1) and bone morphogenetic protein 2 (BMP-2) both promote osteogenesis of bone marrow mesenchymal stem cells (BMSCs). IGF-1C, the C domain peptide of IGF-1, and P24, a BMP-2-derived peptide, both have similar biological activities as their parent growth factors. This study aimed to investigate the effects and their mechanisms of polypeptides IGF-1C and P24 on the osteogenic differentiation of BMSCs.MethodsThe optimum concentrations of IGF-IC and P24 were explored. The effects of the two polypeptides on the proliferation and osteogenic differentiation of BMSCs were examined using the Cell Counting Kit-8(CCK-8), Alkaline phosphatase (ALP) staining, ALP activity assay, alizarin red S staining, qPCR, and western blotting. In addition, specific pathway inhibitors were utilized to explore whether p38 and JNK pathways were involved in this process.ResultsThe optimal concentrations of action were both 50 μg/ml. IGF-1C and P24 synergistically promoted the proliferation of BMSCs, increased ALP activity and the formation of calcified nodules and upregulated the mRNA and protein levels of osterix (Osx), runt-related transcription factor 2 (Runx2), and osteocalcin (Ocn), phosphorylation level of p38 and JNK proteins also improved. Inhibition of the pathways significantly reduced the activation of p38 and JNK, blocked the expression of Runx2 while inhibiting ALP activity and the formation of calcified nodules.ConclusionsThese findings suggest IGF-1C and P24 synergistically promote the osteogenesis of BMSCs through activation of p38 and JNK signal pathways.
Multiscale computer model of the spinal dorsal horn reveals changes in network processing associated with chronic pain
Authors: Medlock Laura , Sekiguchi Kazutaka , Hong Sungho , Dura-Bernal Salvador , Lytton William W , Prescott Steven A. 
Published: June 2021

AbstractPain-related sensory input is processed in the spinal dorsal horn (SDH) before being relayed to the brain. That processing profoundly influences whether stimuli are correctly or incorrectly perceived as painful. Significant advances have been made in identifying the types of excitatory and inhibitory neurons that comprise the SDH, and there is some information about how neuron types are connected, but it remains unclear how the overall circuit processes sensory input or how that processing is disrupted under chronic pain conditions. To explore SDH function, we developed a computational model of the circuit that is tightly constrained by experimental data. Our model comprises conductance-based neuron models that reproduce the characteristic firing patterns of spinal neurons. Excitatory and inhibitory neuron populations, defined by their expression of genetic markers, spiking pattern, or morphology, were synaptically connected according to available qualitative data. Using a genetic algorithm, synaptic weights were tuned to reproduce projection neuron firing rates (model output) based on primary afferent firing rates (model input) across a range of mechanical stimulus intensities. Disparate synaptic weight combinations could produce equivalent circuit function, revealing degeneracy that may underlie heterogeneous responses of different circuits to perturbations or pathological insults. To validate our model, we verified that it responded to reduction of inhibition (i.e. disinhibition) and ablation of specific neuron types in a manner consistent with experiments. Thus validated, our model offers a valuable resource for interpreting experimental results and testing hypotheses in silico to plan experiments for examining normal and pathological SDH circuit function.Significance StatementWe developed a multiscale computer model of the posterior part of spinal cord gray matter (spinal dorsal horn), involved in perception of touch and pain. The model reproduces several experimental observations and makes predictions about how specific types of spinal neurons and synapses influence projection neurons that send information to the brain. Misfiring of these projection neurons can produce anomalous sensations associated with chronic pain. Our computer model will not only assist in planning future experiments, but will also be useful for developing new pharmacotherapy for chronic pain disorders, connecting the effect of drugs acting at the molecular scale with emergent properties of neurons and circuits that shape the pain experience.
Underwater CAM photosynthesis elucidated by Isoetes genome
Authors: Wickell David , Kuo Li-Yaung , Yang Hsiao-Pei , Ashok Amra Dhabalia , Irisarri Iker , Dadras Armin , de Vries Sophie , de Vries Jan , Huang Yao-Moan , Li Zheng , Barker Michael S. , Hartwick Nolan T. , Michael Todd P. , Li Fay-Wei 
Published: June 2021

AbstractTo conserve water in arid environments, numerous plant lineages have independently evolved Crassulacean Acid Metabolism (CAM). Interestingly, Isoetes, an aquatic lycophyte, can also perform CAM as an adaptation to low CO2 availability underwater. However, little is known about the evolution of CAM in aquatic plants and the lack of genomic data has hindered comparison between aquatic and terrestrial CAM. Here, we investigated the underwater CAM in Isoetes taiwanensis by generating a high-quality genome assembly and RNA-seq time course. Despite broad similarities between CAM in Isoetes and terrestrial angiosperms, we identified several key differences. Notably, for carboxylation of PEP, Isoetes recruited the lesser-known “bacterial-type” PEPC, along with the “plant-type” exclusively used in other terrestrial CAM and C4 plants. Furthermore, we found that circadian control of key CAM pathway genes has diverged considerably in Isoetes relative to flowering plants. This suggests the existence of more evolutionary paths to CAM than previously recognized.
Toward a More Accurate 3D Atlas ofC. elegansNeurons
Authors: Skuhersky Michael , Wu Tailin , Yemini Eviatar , Boyden Edward , Tegmark Max 
Published: June 2021

AbstractDetermining cell identity in volumetric images of tagged neuronal nuclei is an ongoing challenge in contemporary neuroscience. Frequently, cell identity is determined by aligning and matching tags to an “atlas” of labeled neuronal positions and other identifying characteristics. Previous analyses of suchC. elegansdatasets have been hampered by the limited accuracy of such atlases, especially for neurons present in the ventral nerve cord, and also by time-consuming manual elements of the alignment process. We present a novel automated alignment method for sparse and incomplete point clouds of the sort resulting from typicalC. elegansfluorescence microscopy datasets. This method involves a tunable learning parameter and a kernel that enforces biologically realistic deformation. We also present a pipeline for creating alignment atlases from datasets of the recently developed NeuroPAL transgene. In combination, these advances allow us to label neurons in volumetric images with confidence much higher than previous methods. We release, to the best of our knowledge, the most completeC. elegans3D positional neuron atlas, encapsulating positional variability derived from 7 animals, for the purposes of cell-type identity prediction for myriad applications (e.g., imaging neuronal activity, gene expression, and cell-fate).
The calcifying interface in a stony coral’s primary polyp: An interplay between seawater and an extracellular calcifying space
Authors: Khalifa Gal Mor , Levy Shani , Mass Tali 
Published: June 2021

AbstractStony coral exoskeletons build the foundation to the most biologically diverse yet fragile marine ecosystems on earth, coral reefs. Understanding corals biomineralization mechanisms is therefore crucial for coral reef management and for using coral skeletons in geochemical studies. In this study, we combine in-vivo and cryo-electron microscopy with single-cell RNA-seq data to gain novel insights into the calcifying micro-environment that facilitates biomineralization in primary polyps of the stony coralStylophora pistillata. We show an intimate involvement of seawater in this micro-environment. We further document increased tissue permeability and a highly dispersed cell packing in the tissue secreting the coral skeleton (i.e. calicoblastic). We also observe an extensive filopodial network containing carbon-rich vesicles extruding from some of the calicoblastic cells. Single-cell RNA-Seq data interrogation shows that calicoblastic cells express genes involved in filopodia and vesicle structure and function. These observations provide a new conceptual framework for resolving stony corals biomineralization processes.