bluuebunny/crossref_metadata_2025_split huggingface dataset:
Density responses of lesser-studied carnivores to habitat and management strategies in southern Tanzania’s Ruaha-Rungwa landscape
Authors: Hardouin Marie , Searle Charlotte E. , Strampelli Paolo , Smit Josephine , Dickman Amy , Lobora Alex L. , Rowcliffe J. Marcus 
Published: November 2020

AbstractCompared to emblematic large carnivores, less charismatic or smaller carnivore species often receive little conservation attention, despite facing increasing anthropogenic pressure, and their status being poorly understood across much of their range. We employed systematic camera trapping and spatially explicit capture-recapture modelling to estimate variation in population density of serval, striped hyaena and aardwolf across the mixed-use Ruaha-Rungwa landscape in southern Tanzania. Three sites were selected as representative of different habitat types, management strategies, and levels of anthropogenic pressure: Ruaha National Park’s core tourist area, dominated byAcacia-Commiphorabushlands and thickets; the Park’s miombo woodland; and the neighbouring community-run MBOMIPA Wildlife Management Area, also covered inAcacia-Commiphora.Our results show that the Park’s miombo woodlands supported a higher serval density than the core tourist area and Wildlife Management Area, with 5.56 [Standard Error = ±2.45], 3.45 [±1.04] and 2.08 [±0.74] individuals per 100 km2, respectively. This variation is likely driven by precipitation, the abundance of apex predators, and the level of anthropogenic pressure.Striped hyaena were detected only in the Wildlife Management Area and at low density (1.36 [±0.5] individuals per 100 km2), potentially due to the location of the surveyed sites at the edge of the species’ global range, high densities of sympatric competitors and anthropogenic edge effects.Finally, aardwolf were captured in both the Park’s core tourist area and the Wildlife Management Area, with a higher density in the Wildlife Management Area (13.25 [±2.48] versus 9.19 [±1.66] individuals per 100 km2), possibly as a result of lower intraguild predation and late fire outbreaks in the area surveyed.By shedding light on three understudied African carnivore species, this study highlights the importance of miombo woodland conservation and community-managed conservation, as well as the value of camera trap data to improve ecological knowledge of lesser-studied carnivores.
Liquid chalk is an antiseptic against SARS-CoV-2 and influenza A respiratory viruses
Authors: McAuley Julie L. , Deerain Joshua M. , Hammersla William , Aktepe Turgut E. , Purcell Damian J.F. , Mackenzie Jason M. 
Published: November 2020

AbstractThe COVID-19 pandemic has impacted and enforced significant restrictions within our societies, including the attendance of the public and professional athletes in gyms. Liquid chalk is a commonly used accessories in gyms and is comprised of magnesium carbonate and alcohol that quickly evaporates on the hands to leave a layer of dry chalk. We investigated whether liquid chalk is an antiseptic against highly pathogenic human viruses including, SARS-CoV-2, influenza virus and noroviruses. Chalk was applied before or after virus inoculum and recovery of infectious virus was determined to mimic the use in the gym. We observed that addition of chalk before or after virus contact lead to a significant reduction on recovery of infectious SARS-CoV-2 and influenza but had little impact on norovirus. These observations suggest that the use and application of liquid chalk can be an effective and suitable antiseptic for major sporting events, such as the Olympic Games.
Intercellular transfer of mitochondria between senescent cells through cytoskeleton-supported intercellular bridges requires mTOR and Cdc42 signalling
Authors: Walters Hannah , Cox Lynne S 
Published: November 2020

AbstractCellular senescence is a state of irreversible cell proliferation arrest induced by various stressors including telomere attrition, DNA damage and oncogene induction. While beneficial as an acute response to stress, accumulation of senescent cells with increasing age is through to contribute adversely to development of cancer and a number of other age-related diseases, including neurodegenerative diseases for which there are currently no effective disease-modifying therapies. Non-cell autonomous effects of senescent cells have been suggested to arise through the SASP, a wide variety of pro-inflammatory cytokines, chemokines and exosomes secreted by senescent cells. Here, we report an additional means of cell communication utilised by senescent cells via large numbers of membrane-bound intercellular bridges - or tunnelling nanotubes (TNTs) - containing the cytoskeletal components actin and tubulin, and which form direct physical connections between cells. We observe the presence of mitochondria in these TNTs, and show organelle transfer through the TNTs to adjacent cells. While transport of individual mitochondria along single TNTs appears unidirectional, we show by differentially labelled co-culture experiments that organelle transfer through TNTs can occur both between different cells within senescent cell populations, and also between senescent and proliferating cells. Using small molecule inhibitors, we demonstrate that senescent cell TNTs are dependent on signalling through the mTOR pathway, which we further show is mediated at least in part through downstream actin-cytoskeleton regulatory factor Cdc42. These findings have significant implications for development of senomodifying therapies, as they highlight the need to account for local direct cell-cell contacts as well as the SASP in order to treat cancer and diseases of ageing in which senescence is a key factor.
Production of nonulosonic acids in the extracellular polymeric substances of “CandidatusAccumulibacter phosphatis”
Authors: Tomás-Martínez Sergio , Kleikamp Hugo B.C. , Neu Thomas R. , Pabst Martin , Weissbrodt David G. , van Loosdrecht Mark C.M. , Lin Yuemei 
Published: November 2020

AbstractNonulosonic acids (NulOs) are a family of acidic carbohydrates with a nine-carbon backbone, which include different related structures, such as sialic acids. They have mainly been studied for their relevance in animal cells and pathogenic bacteria. Recently, sialic acids have been discovered as important compound in the extracellular matrix of virtually all microbial life and in “CandidatusAccumulibacter phosphatis”, a well-studied polyphosphate-accumulating organism, in particular. Here, bioaggregates highly enriched with these bacteria (approx. 95% based on proteomic data) were used to study the production of NulOs in an enrichment of this microorganism. Fluorescence lectin-binding analysis, enzymatic quantification, and mass spectrometry were used to analyze the different NulOs present, showing a wide distribution and variety of these carbohydrates, such as sialic acids and bacterial NulOs, in the bioaggregates. Phylogenetic analysis confirmed the potential of “Ca. Accumulibacter” to produce different types of NulOs. Proteomic analysis showed the ability of “Ca. Accumulibacter” to reutilize and reincorporate these carbohydrates. This investigation points out the importance of diverse NulOs in non-pathogenic bacteria, which are normally overlooked. Sialic acids and other NulOs should be further investigated for their role in the ecology of “Ca. Accumulibacter” in particular, and biofilms in general.Key Points“Ca.Accumulibacter” has the potential to produce a range of nonulosonic acids.Mass spectrometry and lectin binding can reveal the presence and location of nonulosonic acids.Role of nonulosonic acid in non-pathogenic bacteria needs to be studied in detail.
The effect of heat on SARS-CoV-2 viability and RNA integrity as determined by plaque assay, virus culture and real-time RT-PCR
Authors: Burton Jane , Love Hannah , Richards Kevin , Burton Christopher , Summers Sian , Pitman James , Easterbrook Linda , Davies Katherine , Spencer Peter , Killip Marian , Cane Patricia , Bruce Christine , Roberts Allen D G 
Published: November 2020

AbstractThe effect of heat on SARS-CoV-2/England/2/2020 viability was assessed by plaque assay and virus culture. Heating to 56°C and 60°C for 15, 30 and 60 minutes led to a reduction in titre of between 2.1 and 4.9 log10pfu/ml but complete inactivation was not observed. At 80°C plaques were observed after 15 and 30 minutes of heating, however after 60 minutes viable virus was only detected following virus culture. Heating to 80°C for 90 minutes and 95°C for 1 and 5 minutes resulted in no viable virus being detected. At 56°C and 60°C significant variability between replicates was observed and the titre often increased with heat-treatment time. Nucleic acids were extracted and tested by RT-PCR. Sensitivity of the RT-PCR was not compromised by heating to 56°C and 60°C. Heating to 80°C for 30 minutes or more and 95°C for 1 or 5 minutes however, resulted in an increase of at least three Ct values. This increase remained constant when different dilutions of virus underwent heat treatment. This indicates that high temperature heat inactivation of clinical samples prior to nucleic acid extraction could significantly affect the ability to detect virus in clinical samples from patients with lower viral loads by RT-PCR.
Robo recruitment of the Wave Regulatory Complex plays an essential and conserved role in midline repulsion
Authors: Chaudhari Karina , Gorla Madhavi , Chang Chao , Kania Artur , Bashaw Greg J. 
Published: November 2020

SUMMARYThe Roundabout (Robo) guidance receptor family induces axon repulsion in response to its ligand Slit by inducing local cytoskeletal changes; however, the link to the cytoskeleton and the nature of these cytoskeletal changes are unclear. Here we show that the heteropentameric Scar/Wave Regulatory Complex (WRC) which drives Arp2/3-induced branched actin polymerization, is a direct effector of Robo signaling. Biochemical evidence shows that Slit triggers WRC recruitment to the Robo receptor’s WIRS motif. InDrosophilaembryos, mutants of the WRC enhance Robol-dependent midline crossing defects. Additionally, mutating Robo1’s WIRS motif significantly reduces receptor activity in rescue assaysin vivo, and CRISPR-Cas9 mutagenesis shows that the WIRS motif is essential for endogenous Robo1 function. Finally, axon guidance assays in mouse dorsal spinal commissural axons demonstrate that the WIRS motif is also required for Robo1 repulsion in mammals. Together, our data support an essential conserved role for the WRC in commissural axon repulsion.
A fine-tuned interplay of threeA. thalianaUDP glucosyltransferases orchestrates salicylic acid homeostasis
Authors: Bauer Sibylle , Georgii Elisabeth , Lange Birgit , Maksym Rafał P. , Janowski Robert , Geist Birgit , Schäffner Anton R. 
Published: November 2020

AbstractSalicylic acid (SA) is a central signaling molecule in development and defense, therefore its levels are tightly controlled. One control mechanism is conjugation with sugar moieties by UDP glucosyltransferases (UGTs). In Arabidopsis, UGT76B1, UGT74F1, and UGT74F2 are known to glucosylate SA. We show that these are the main SA UGTs in leaves, since only marginal levels of SA glucosides were found in a triple loss-of-function mutant. Analyzing transcriptomes, metabolite levels, and phenotypes of a full combinatorial set of loss-of-function mutants, we resolved the mutual relationships and the individual roles of these enzymes in SA homeostasis. The strongest gene expression changes were observed for theugt76b1 ugt74f1double mutant, which downregulated developmental genes and most pronouncedly upregulated cell death-related genes. Among the single mutants,ugt76b1specifically exhibited increased production of reactive oxygen species, increased resistance to infection, and early senescence. Likewise, higher-order mutations confirmed the dominant role of UGT76B1 in controlling SA levels and thereby the expression of biotic stress response genes. Both UGT74F1 and UGT74F2 affectedUGT76B1expression. However, while UGT76B1 and UGT74F1 produced SA-2-O-β-glucoside, UGT74F2 did not contribute there substantially. Instead, UGT74F2 acted independently of UGT74F1, decreasing steady-state SA levels by producing salicyloyl glucose ester. Remarkably, this did not restrict defense responses. In contrast, UGT74F1 interacted with UGT76B1 in suppressing defense responses. Nevertheless, a benzothiadiazole-triggered defense scenario induced only UGT76B1, whereas UGT74F1 was linked to controlling abiotic stress responses. All three enzymes form a network that, in concert with other UGTs, regulates expression of developmental and stress-related genes.One sentence summaryThe salicylic acid glucosylating enzymes of Arabidopsis leaves are crucial for salicylic acid homeostasis and combinatorially impact defense responses and developmental processes.
In vivo optical metabolic imaging of long-chain fatty acid uptake in orthotopic models of triple negative breast cancer
Authors: Madonna Megan C. , Duer Joy E. , Lee Joyce V. , Williams Jeremy , Avsaroglu Baris , Zhu Caigang , Deutsch Riley , Wang Roujia , Crouch Brian T. , Hirschey Matthew D , Goga Andrei , Ramanujam Nirmala 
Published: November 2020

AbstractTargeting a tumor’s metabolic dependencies is a clinically actionable therapeutic approach, but identifying subtypes of tumors likely to respond remains difficult. The use of lipids as a nutrient source is of particular importance, especially in breast cancer. Imaging techniques offer the opportunity to quantify nutrient use in preclinical models to aid in the development of new drugs to restrict uptake or utilization of these nutrients. We describe a fast and dynamic approach to image fatty acid uptake in vivo, a tool relevant to study tumor metabolic reprogramming or for studying the effectiveness of drugs targeting lipid metabolism spanning beyond breast cancer and optical imaging alone. Specifically, we developed a quantitative optical approach to spatially and longitudinally map the kinetics of long-chain fatty acid uptake in in vivo murine models of breast cancer using a fluorescently labeled palmitate molecule, Bodipy FL c16. We chose intra-vital microscopy of mammary tumor windows to validate our approach in two orthotopic breast cancer models: a MYC-overexpressing transgenic triple-negative breast cancer (TNBC) model and a murine model of the 4T1 family. Following injection, Bodipy FL c16 fluorescence increased and reached its maximum after approximately 30 minutes, with the signal remaining stable during the 30-80-minute post-injection period. We used the fluorescence at 60 minutes (Bodipy60), the mid-point in the plateau region, as a summary parameter to quantify Bodipy FL c16 fluorescence in subsequent experiments. Using our imaging platform, we observed a two- to four-fold decrease in fatty acid uptake in response to the downregulation of the MYC oncogene consistent with findings from in vitro metabolic assays. In contrast, our imaging studies report an increase in fatty acid uptake with tumor aggressiveness (6NR, 4T07, and 4T1), and uptake was significantly decreased after treatment with a fatty acid transport inhibitor, perphenazine, in both normal mammary pads and in the most aggressive 4T1 tumor model. Our approach fills an important gap between in vitro assays, which provide rich metabolic information but at static time points, and imaging approaches that can visualize metabolism in whole organs, but which suffer from poor resolution.
Apicobasal surfaceome architecture encodes for polarized epithelial functionality and depends on tumor suppressor PTEN
Authors: Koetemann Anika , Wollscheid Bernd 
Published: November 2020

AbstractThe loss of apicobasal polarity during the epithelial-to-mesenchymal transition (EMT) is a hallmark of cancer and metastasis. The key feature of this polarity in epithelial cells is the subdivision of the plasma membrane into apical and basolateral domains, with each orchestrating specific intra- and extracellular functions. Epithelial transport and signaling capacities are thought to be determined largely by the quality, quantity and nanoscale organization of proteins residing in these membrane domains, the apicobasal surfaceomes. Despite its implications for cancer, drug uptake and infection, our current knowledge of how the polarized surfaceome is organized and maintained is limited. Here we used chemoproteomic surfaceome scanning to establish proteotype maps of apicobasal surfaceomes and reveal quantitative distributions of i.a. surface proteases, phosphatases and tetraspanins as potential key regulators of polarized cell functionality. We show further that tumor-suppressor PTEN regulates polarized surfaceome architecture and uncover a potential role in collective cell migration. Our differential surfaceome analysis provides a molecular framework to elucidate polarized protein networks regulating epithelial functions and PTEN-associated cancer progression.SummaryOne cell, two functionally different surfaceomes: Chemoproteomic surfaceome scanning reveals quantitative polarization of protein networks across the epithelial cell membrane and unrecognized roles of tumor suppressor PTEN in surfaceome organization associated with cancer progression.
Transient K+current explains cross-species differences in the effects of myofibroblasts on myocytes
Authors: Liu Fusheng , Wu Hou , Yang Xiaoyu , Dong Yuqin , Huang Guoyou , Genin Guy M. , Lu Tian Jian , Xu Feng 
Published: November 2020

AbstractElectrical and paracrine couplings between cardiomyocytes (CMs) and myofibroblasts (MFBs) affect both physiology and pathophysiology of cardiac tissues in a range of animal models, but relating these observations to humans is a challenge because effects vary greatly across species. To address this challenge, we developed a mathematical model for mechanoelectrical interactions between CM and MFB, considering both electrical and paracrine couplings between CMs and MFBs, with the aim of identifying the sources of cross-species variation and extrapolating animal models to predicted effects in humans. Our results revealed substantial differences across species in how these couplings modulate excitation-contraction coupling and Ca2+transients of CMs. Both classes of couplings prolong action potential and increase APD in rat CMs, but shorten action potential and decrease APD in human CMs. Electrical coupling attenuates Ca2+transients and active tension generation in human CMs, but has no significant effect on rat CMs. Paracrine coupling reduces Ca2+transients and active tension in both human and rat CM. The results suggest that the variance of functional interactions between CM and MFB in cross-species may be explained by differences in the transient outward K+currents associated with the KCND2 gene, and thus suggest potential therapeutic pathways for fibrotic cardiomyopathy.
Mitochondrial copper and phosphate transporter specificity was defined early in the evolution of eukaryotes
Authors: Zhu Xinyu , Boulet Aren , Buckley Katherine M. , Phillips Casey B. , Gammon Micah G. , Oldfather Laura E. , Moore Stanley A. , Leary Scot C. , Cobine Paul A. 
Published: November 2020

AbstractMitochondrial carrier family (MCF/SLC25) proteins are selective transporters that maintain the mitochondrial metabolome. Here we combine computational, biochemical and phenotypic approaches to understand substrate selectivity of SLC25A3. In mammals, SLC25A3 transports both copper and phosphate, yet inSaccharomyces cerevisiaethe transport of these substrates is partitioned across two paralogs: PIC2, which transports copper, and MIR1, which transports phosphate. To understand whether the ancestral state of this transporter was a single promiscuous transporter that duplicated and gained selectivity, we explored the evolutionary relationships of PIC2 and MIR1 orthologs across the eukaryotic tree of life. Phylogenetic analyses reveal that PIC2-like and MIR1-like orthologs are present in all major eukaryotic supergroups, indicating that the gene duplication that created these paralogs occurred early in eukaryotic evolution. Frequent lineage-specific gene duplications and losses suggest that substrate specificity may be evolutionarily labile. To link this phylogenetic signal to protein function and resolve the residues involved in substrate selection, we used structural modelling and site-directed mutagenesis to identify PIC2 residues involved in copper and phosphate transport activities. Based on these analyses, we generated a Leu175Ala variant of mouse SLC25A3 that retains the ability to transport copper, but not phosphate, and rescues the cytochromecoxidase defect inSLC25A3knockout cells. Taken together, this work uses an evolutionary framework to uncover amino acids involved in substrate recognition by MCF proteins responsible for copper and phosphate transport.
The G protein-Coupled Metabotropic Glutamate Receptor 1 controls neuronal macroautophagy
Authors: Donoso Maribel , Speranza Luisa , Kalinowska Magdalena , Castillo Catherine , De Sanctis Claudia , Francesconi Anna 
Published: November 2020

AbstractAutophagy is an evolutionarily conserved, highly regulated catabolic process critical to neuronal homeostasis, function and survival throughout organismal lifespan. However, the external factors and signals that control autophagy in neurons are still poorly understood. Here we report that the G protein-coupled metabotropic glutamate receptor 1 (mGlu1) contributes to control basal autophagy in the brain. Autophagy is upregulated in the brain of adult mGlu1 knockout mice and genetic deletion or pharmacological inhibition of native mGlu1 receptors enhances autophagy flux in neurons. The evolutionarily conserved adaptor protein FEZ1, identified by a genome-wide screen as mGlu1 receptor interacting partner, was found to participate in the regulation of neuronal autophagy and to be required for repression of autophagy flux by the mGlu1 receptor. Furthermore, FEZ1 appears to enable association of mGlu1 with Ulk1, a core component of the autophagy pathway. Thus, we propose that the mGlu1 receptor contributes to restrain constitutive autophagy in neurons.