bluuebunny/crossref_metadata_2025_split huggingface dataset:
PDS5B inhibits cell proliferation, migration, and invasion via upregulation of LATS1 in lung cancer cells
Authors: Xu Hui , Zhou Wenjing , Zhang Fan , Wu Linhui , Li Juan , Ma Tongtong , Cao Tong , Lian Chaoqun , Xia Jun , Wang Peter , Ma Jia , Li Yuyun 
Published: July 2021

AbstractPDS5B (precocious dissociation of sisters 5B) plays a pivotal role in carcinogenesis and progression. However, the biological functions of PDS5B in lung cancer and its underlying mechanisms are not fully elucidated. In the present study, we used MTT assays, wound-healing assays, and transwell migration and invasion approach to examine the cell viability, migration, and invasion of non-small cell lung cancer (NSCLC) cells after PDS5B modulation. Moreover, we investigated the function of PDS5B overexpression in vivo. Furthermore, we detected the expression of PDS5B in tissue samples of lung cancer patients by immunohistochemical study. We found that upregulation of PDS5B repressed cell viability, migration, and invasion in NSCLC cells, whereas downregulation of PDS5B had the opposite effects. We also observed that PDS5B overexpression retarded tumor growth in nude mice. Notably, PDS5B positively regulated LATS1 expression in NSCLC cells. Strikingly, low expression of PDS5B was associated with lymph node metastasis in lung cancer patients. Our findings suggest that PDS5B might be a therapeutic target for lung cancer.
H-Ras gene takes part to the host immune response to COVID-19
Authors: Sciacchitano Salvatore , Sacconi Andrea , De Vitis Claudia , Blandino Giovanni , Piaggio Giulia , Salvati Valentina , Napoli Christian , Marchetti Paolo , Taurelli Beatrice Salimbeni , Coluzzi Flaminia , Rocco Monica , Vecchione Andrea , Anibaldi Paolo , Marcolongo Adriano , Ciliberto Gennaro , Mancini Rita , Capalbo Carlo 
Published: July 2021

AbstractRas gene family members play a relevant role in cancer, especially when they are mutated. However, they may play additional roles in other conditions beside cancer. We performed gene expression analysis using the NanoString PanCancer IO 360 panel in the peripheral blood mononuclear cell (PBMC) of six COVID-19 patients and we found that H-Ras gene was significantly upregulated, while both K-Ras and N-Ras genes were downregulated. In particular, H-Ras gene upregulation was more evident in COVID-19 patients with a more severe disease. We compared our results with those obtained by analyzing two different and independent datasets, including a total of 53 COVID-19 patients, in which the gene expression analysis was performed using the Immunology_V2 panel. Comparative analysis of the H-Ras gene expression in these patients confirmed our preliminary results. In both of them, in fact, we were able to confirm the upregulation of the expression of the H-Ras gene. The exact role of this specific upregulation of the H-Ras gene in response to SARS-CoV-2 infection and its possible role in cancer still remains to be elucidated. In conclusion, H-Ras gene participates to the host immune response to SARS-CoV-2 virus infection, especially in patients affected by the most severe form of the COVID-19.
Desmin aggrephagy in rat and human ischemic heart failure through PKCζ and GSK3β as upstream signaling pathways
Authors: Bouvet Marion , Dubois-Deruy Emilie , Turkieh Annie , Mulder Paul , Peugnet Victoriane , Chwastyniak Maggy , Beseme Olivia , Dechaumes Arthur , Amouyel Philippe , Richard Vincent , Lamblin Nicolas , Pinet Florence 
Published: July 2021

AbstractPost-translational modifications of cardiac proteins could participate to left contractile dysfunction resulting in heart failure. Using a rat model of ischemic heart failure, we showed an accumulation of phosphorylated desmin leading to toxic aggregates in cardiomyocytes, but the cellular mechanisms are unknown. The same rat model was used to decipher the kinases involved in desmin phosphorylation and the proteolytic systems present in rat and human failing hearts. We used primary cultures of neonate rat cardiomyocytes for testing specific inhibitors of kinases and for characterizing the autophagic processes able to clear desmin aggregates. We found a significant increase of active PKCζ, no modulation of ubitiquitin-proteasome system, a defect in macroautophagy, and an activation of chaperone-mediated autophagy in heart failure rats. We validated in vitro that PKCζ inhibition induced a significant decrease of GSK3β and of soluble desmin. In vitro activation of ubiquitination of proteins and of chaperone-mediated autophagy is able to decrease soluble and insoluble forms of desmin in cardiomyocytes. These data demonstrate a novel signaling pathway implicating activation of PKCζ in desmin phosphorylation associated with a defect of proteolytic systems in ischemic heart failure, leading to desmin aggrephagy. Our in vitro data demonstrated that ubiquitination of proteins and chaperone-mediated autophagy are required for eliminating desmin aggregates with the contribution of its chaperone protein, α-crystallin Β-chain. Modulation of the kinases involved under pathological conditions may help preserving desmin intermediate filaments structure and thus protect the structural integrity of contractile apparatus of cardiomyocytes by limiting desmin aggregates formation.
Platinum drugs and taxanes: can we overcome resistance?
Authors: Sazonova Elena V. , Kopeina Gelina S. , Imyanitov Evgeny N. , Zhivotovsky Boris 
Published: July 2021

AbstractCancer therapy is aimed at the elimination of tumor cells and acts via the cessation of cell proliferation and induction of cell death. Many research publications discussing the mechanisms of anticancer drugs use the terms “cell death” and “apoptosis” interchangeably, given that apoptotic pathways are the most common components of the action of targeted and cytotoxic compounds. However, there is sound evidence suggesting that other mechanisms of drug-induced cell death, such as necroptosis, ferroptosis, autophagy, etc. may significantly contribute to the fate of cancer cells. Molecular cross-talks between apoptotic and nonapoptotic death pathways underlie the successes and the failures of therapeutic interventions. Here we discuss the nuances of the antitumor action of two groups of the widely used anticancer drugs, i.e., platinum salts and taxane derivatives. The available data suggest that intelligent interference with the choice of cell death pathways may open novel opportunities for cancer treatment.
A synthetic circuit for buffering gene dosage variation between individual mammalian cells
Authors: Yang Jin , Lee Jihwan , Land Michelle A. , Lai Shujuan , Igoshin Oleg A. , St-Pierre François 
Published: July 2021

AbstractPrecise control of gene expression is critical for biological research and biotechnology. However, transient plasmid transfections in mammalian cells produce a wide distribution of copy numbers per cell, and consequently, high expression heterogeneity. Here, we report plasmid-based synthetic circuits – Equalizers – that buffer copy-number variation at the single-cell level. Equalizers couple a transcriptional negative feedback loop with post-transcriptional incoherent feedforward control. Computational modeling suggests that the combination of these two topologies enables Equalizers to operate over a wide range of plasmid copy numbers. We demonstrate experimentally that Equalizers outperform other gene dosage compensation topologies and produce as low cell-to-cell variation as chromosomally integrated genes. We also show that episome-encoded Equalizers enable the rapid generation of extrachromosomal cell lines with stable and uniform expression. Overall, Equalizers are simple and versatile devices for homogeneous gene expression and can facilitate the engineering of synthetic circuits that function reliably in every cell.
High Mountain Asian glacier response to climate revealed by multi-temporal satellite observations since the 1960s
Authors: Bhattacharya Atanu , Bolch Tobias , Mukherjee Kriti , King Owen , Menounos Brian , Kapitsa Vassiliy , Neckel Niklas , Yang Wei , Yao Tandong 
Published: July 2021

AbstractKnowledge about the long-term response of High Mountain Asian glaciers to climatic variations is paramount because of their important role in sustaining Asian river flow. Here, a satellite-based time series of glacier mass balance for seven climatically different regions across High Mountain Asia since the 1960s shows that glacier mass loss rates have persistently increased at most sites. Regional glacier mass budgets ranged from −0.40 ± 0.07 m w.e.a−1 in Central and Northern Tien Shan to −0.06 ± 0.07 m w.e.a−1 in Eastern Pamir, with considerable temporal and spatial variability. Highest rates of mass loss occurred in Central Himalaya and Northern Tien Shan after 2015 and even in regions where glaciers were previously in balance with climate, such as Eastern Pamir, mass losses prevailed in recent years. An increase in summer temperature explains the long-term trend in mass loss and now appears to drive mass loss even in regions formerly sensitive to both temperature and precipitation.
Particulate organic matter as a functional soil component for persistent soil organic carbon
Authors: Witzgall Kristina , Vidal Alix , Schubert David I. , Höschen Carmen , Schweizer Steffen A. , Buegger Franz , Pouteau Valérie , Chenu Claire , Mueller Carsten W. 
Published: July 2021

AbstractThe largest terrestrial organic carbon pool, carbon in soils, is regulated by an intricate connection between plant carbon inputs, microbial activity, and the soil matrix. This is manifested by how microorganisms, the key players in transforming plant-derived carbon into soil organic carbon, are controlled by the physical arrangement of organic and inorganic soil particles. Here we conduct an incubation of isotopically labelled litter to study effects of soil structure on the fate of litter-derived organic matter. While microbial activity and fungal growth is enhanced in the coarser-textured soil, we show that occlusion of organic matter into aggregates and formation of organo-mineral associations occur concurrently on fresh litter surfaces regardless of soil structure. These two mechanisms—the two most prominent processes contributing to the persistence of organic matter—occur directly at plant–soil interfaces, where surfaces of litter constitute a nucleus in the build-up of soil carbon persistence. We extend the notion of plant litter, i.e., particulate organic matter, from solely an easily available and labile carbon substrate, to a functional component at which persistence of soil carbon is directly determined.
Cell migration guided by long-lived spatial memory
Authors: d’Alessandro Joseph , Barbier--Chebbah Alex , Cellerin Victor , Benichou Olivier , Mège René Marc , Voituriez Raphaël , Ladoux Benoît 
Published: July 2021

AbstractLiving cells actively migrate in their environment to perform key biological functions—from unicellular organisms looking for food to single cells such as fibroblasts, leukocytes or cancer cells that can shape, patrol or invade tissues. Cell migration results from complex intracellular processes that enable cell self-propulsion, and has been shown to also integrate various chemical or physical extracellular signals. While it is established that cells can modify their environment by depositing biochemical signals or mechanically remodelling the extracellular matrix, the impact of such self-induced environmental perturbations on cell trajectories at various scales remains unexplored. Here, we show that cells can retrieve their path: by confining motile cells on 1D and 2D micropatterned surfaces, we demonstrate that they leave long-lived physicochemical footprints along their way, which determine their future path. On this basis, we argue that cell trajectories belong to the general class of self-interacting random walks, and show that self-interactions can rule large scale exploration by inducing long-lived ageing, subdiffusion and anomalous first-passage statistics. Altogether, our joint experimental and theoretical approach points to a generic coupling between motile cells and their environment, which endows cells with a spatial memory of their path and can dramatically change their space exploration.
Ultrasensitive nano-optomechanical force sensor operated at dilution temperatures
Authors: Fogliano Francesco , Besga Benjamin , Reigue Antoine , Mercier de Lépinay Laure , Heringlake Philip , Gouriou Clement , Eyraud Eric , Wernsdorfer Wolfgang , Pigeau Benjamin , Arcizet Olivier 
Published: July 2021

AbstractCooling down nanomechanical force probes is a generic strategy to enhance their sensitivities through the concomitant reduction of their thermal noise and mechanical damping rates. However, heat conduction becomes less efficient at low temperatures, which renders difficult to ensure and verify their proper thermalization. Here we implement optomechanical readout techniques operating in the photon counting regime to probe the dynamics of suspended silicon carbide nanowires in a dilution refrigerator. Readout of their vibrations is realized with sub-picowatt optical powers, in a situation where less than one photon is collected per oscillation period. We demonstrate their thermalization down to 32 ± 2 mK, reaching very large sensitivities for scanning probe force sensors, 40 zN Hz−1/2, with a sensitivity to lateral force field gradients in the fN m−1 range. This opens the road toward explorations of the mechanical and thermal conduction properties of nanoresonators at minimal excitation level, and to nanomechanical vectorial imaging of faint forces at dilution temperatures.
Four chromosome scale genomes and a pan-genome annotation to accelerate pecan tree breeding
Authors: Lovell John T. , Bentley Nolan B. , Bhattarai Gaurab , Jenkins Jerry W. , Sreedasyam Avinash , Alarcon Yanina , Bock Clive , Boston Lori Beth , Carlson Joseph , Cervantes Kimberly , Clermont Kristen , Duke Sara , Krom Nick , Kubenka Keith , Mamidi Sujan , Mattison Christopher P. , Monteros Maria J. , Pisani Cristina , Plott Christopher , Rajasekar Shanmugam , Rhein Hormat Shadgou , Rohla Charles , Song Mingzhou , Hilaire Rolston St. , Shu Shengqiang , Wells Lenny , Webber Jenell , Heerema Richard J. , Klein Patricia E. , Conner Patrick , Wang Xinwang , Grauke L. J. , Grimwood Jane , Schmutz Jeremy , Randall Jennifer J. 
Published: July 2021

AbstractGenome-enabled biotechnologies have the potential to accelerate breeding efforts in long-lived perennial crop species. Despite the transformative potential of molecular tools in pecan and other outcrossing tree species, highly heterozygous genomes, significant presence–absence gene content variation, and histories of interspecific hybridization have constrained breeding efforts. To overcome these challenges, here, we present diploid genome assemblies and annotations of four outbred pecan genotypes, including a PacBio HiFi chromosome-scale assembly of both haplotypes of the ‘Pawnee’ cultivar. Comparative analysis and pan-genome integration reveal substantial and likely adaptive interspecific genomic introgressions, including an over-retained haplotype introgressed from bitternut hickory into pecan breeding pedigrees. Further, by leveraging our pan-genome presence–absence and functional annotation database among genomes and within the two outbred haplotypes of the ‘Lakota’ genome, we identify candidate genes for pest and pathogen resistance. Combined, these analyses and resources highlight significant progress towards functional and quantitative genomics in highly diverse and outbred crops.
α-TubK40me3 is required for neuronal polarization and migration by promoting microtubule formation
Authors: Xie Xuan , Wang Shaogang , Li Mingyi , Diao Lei , Pan Xingyu , Chen Jijun , Zou Weiguo , Zhang Xu , Feng Wenfeng , Bao Lan 
Published: July 2021

AbstractTri-methylation on lysine 40 of α-tubulin (α-TubK40me3) is a recently identified post-translational modification involved in mitosis and cytokinesis. However, knowledge about α-TubK40me3 in microtubule function and post-mitotic cells remains largely incomplete. Here, we report that α-TubK40me3 is required for neuronal polarization and migration by promoting microtubule formation. α-TubK40me3 is enriched in mouse cerebral cortex during embryonic day (E)14 to E16. Knockdown of α-tubulin methyltransferase SETD2 at E14 leads to the defects in neuronal migration, which could be restored by overexpressing either a cytoplasm-localized SETD2 truncation or α-TubK40me3-mimicking mutant. Furthermore, α-TubK40me3 is preferably distributed on polymerized microtubules and potently promotes tubulin nucleation. Downregulation of α-TubK40me3 results in reduced microtubule abundance in neurites and disrupts neuronal polarization, which could be rescued by Taxol. Additionally, α-TubK40me3 is increased after losing α-tubulin K40 acetylation (α-TubK40ac) and largely rescues α-TubK40ac function. This study reveals a critical role of α-TubK40me3 in microtubule formation and neuronal development.
The role of the PZP domain of AF10 in acute leukemia driven by AF10 translocations
Authors: Klein Brianna J. , Deshpande Anagha , Cox Khan L. , Xuan Fan , Zandian Mohamad , Barbosa Karina , Khanal Sujita , Tong Qiong , Zhang Yi , Zhang Pan , Sinha Amit , Bohlander Stefan K. , Shi Xiaobing , Wen Hong , Poirier Michael G. , Deshpande Aniruddha J. , Kutateladze Tatiana G. 
Published: July 2021

AbstractChromosomal translocations of the AF10 (or MLLT10) gene are frequently found in acute leukemias. Here, we show that the PZP domain of AF10 (AF10PZP), which is consistently impaired or deleted in leukemogenic AF10 translocations, plays a critical role in blocking malignant transformation. Incorporation of functional AF10PZP into the leukemogenic CALM-AF10 fusion prevents the transforming activity of the fusion in bone marrow-derived hematopoietic stem and progenitor cells in vitro and in vivo and abrogates CALM-AF10-mediated leukemogenesis in vivo. Crystallographic, biochemical and mutagenesis studies reveal that AF10PZP binds to the nucleosome core particle through multivalent contacts with the histone H3 tail and DNA and associates with chromatin in cells, colocalizing with active methylation marks and discriminating against the repressive H3K27me3 mark. AF10PZP promotes nuclear localization of CALM-AF10 and is required for association with chromatin. Our data indicate that the disruption of AF10PZP function in the CALM-AF10 fusion directly leads to transformation, whereas the inclusion of AF10PZP downregulates Hoxa genes and reverses cellular transformation. Our findings highlight the molecular mechanism by which AF10 targets chromatin and suggest a model for the AF10PZP-dependent CALM-AF10-mediated leukemogenesis.
A neuronal ensemble encoding adaptive choice during sensory conflict in Drosophila
Authors: Sareen Preeti F. , McCurdy Li Yan , Nitabach Michael N. 
Published: July 2021

AbstractFeeding decisions are fundamental to survival, and decision making is often disrupted in disease. Here, we show that neural activity in a small population of neurons projecting to the fan-shaped body higher-order central brain region of Drosophila represents food choice during sensory conflict. We found that food deprived flies made tradeoffs between appetitive and aversive values of food. We identified an upstream neuropeptidergic and dopaminergic network that relays internal state and other decision-relevant information to a specific subset of fan-shaped body neurons. These neurons were strongly inhibited by the taste of the rejected food choice, suggesting that they encode behavioral food choice. Our findings reveal that fan-shaped body taste responses to food choices are determined not only by taste quality, but also by previous experience (including choice outcome) and hunger state, which are integrated in the fan-shaped body to encode the decision before relay to downstream motor circuits for behavioral implementation.
Enhanced regulation of prokaryotic gene expression by a eukaryotic transcriptional activator
Authors: MacDonald I. Cody , Seamons Travis R. , Emmons Jonathan C. , Javdan Shwan B. , Deans Tara L. 
Published: July 2021

AbstractExpanding the genetic toolbox for prokaryotic synthetic biology is a promising strategy for enhancing the dynamic range of gene expression and enabling new engineered applications for research and biomedicine. Here, we reverse the current trend of moving genetic parts from prokaryotes to eukaryotes and demonstrate that the activating eukaryotic transcription factor QF and its corresponding DNA-binding sequence can be moved to E. coli to introduce transcriptional activation, in addition to tight off states. We further demonstrate that the QF transcription factor can be used in genetic devices that respond to low input levels with robust and sustained output signals. Collectively, we show that eukaryotic gene regulator elements are functional in prokaryotes and establish a versatile and broadly applicable approach for constructing genetic circuits with complex functions. These genetic tools hold the potential to improve biotechnology applications for medical science and research.
Probiotics impact the antibiotic resistance gene reservoir along the human GI tract in a person-specific and antibiotic-dependent manner
Authors: Montassier Emmanuel , Valdés-Mas Rafael , Batard Eric , Zmora Niv , Dori-Bachash Mally , Suez Jotham , Elinav Eran 
Published: July 2021

AbstractAntimicrobial resistance poses a substantial threat to human health. The gut microbiome is considered a reservoir for potential spread of resistance genes from commensals to pathogens, termed the gut resistome. The impact of probiotics, commonly consumed by many in health or in conjunction with the administration of antibiotics, on the gut resistome is elusive. Reanalysis of gut metagenomes from healthy antibiotics-naïve humans supplemented with an 11-probiotic-strain preparation, allowing direct assessment of the gut resistome in situ along the gastrointestinal (GI) tract, demonstrated that probiotics reduce the number of antibiotic resistance genes exclusively in the gut of colonization-permissive individuals. In mice and in a separate cohort of humans, a course of antibiotics resulted in expansion of the lower GI tract resistome, which was mitigated by autologous faecal microbiome transplantation or during spontaneous recovery. In contrast, probiotics further exacerbated resistome expansion in the GI mucosa by supporting the bloom of strains carrying vancomycin resistance genes but not resistance genes encoded by the probiotic strains. Importantly, the aforementioned effects were not reflected in stool samples, highlighting the importance of direct sampling to analyse the effect of probiotics and antibiotics on the gut resistome. Analysing antibiotic resistance gene content in additional published clinical trials with probiotics further highlighted the importance of person-specific metagenomics-based profiling of the gut resistome using direct sampling. Collectively, these findings suggest opposing person-specific and antibiotic-dependent effects of probiotics on the resistome, whose contribution to the spread of antimicrobial resistance genes along the human GI tract merit further studies.