bluuebunny/crossref_metadata_2025_split huggingface dataset:
Promyelocytic leukemia nuclear body (PML-NB) -free intranuclear milieu facilitates development of oocytes in mice
Authors: Udagawa Osamu , Kato-Udagawa Ayaka , Hirano Seishiro 
Published: September 2021

AbstractPromyelocytic leukemia (PML) nuclear bodies (PML-NBs), a class of membrane-less organelles in cells, are involved in multiple biological activities and are present throughout cells of adult organisms. Although the oocyte nucleus is an active region for the flux of multiple non-membranous organelles, PML-NBs have been predicted to be absent from oocytes. Here, we show that the deliberate assembly of PML-NBs during oocyte growth preferentially sequestered Small Ubiquitin-related Modifier (SUMO) protein from the nucleoplasm. SUMO not only was involved in the regulation of oocyte nuclear maturation but also was committed to the response, mediated by liquid droplet formation, to multiple stressors including nucleolar stress and proteotoxic stresses. Exogenous assembly of PML-NBs in the nucleus of oocytes affected the efficiency of the response of SUMO. These observations suggest that the PML-NB-free intranuclear milieu ensures that a reserve of SUMO remains available for emergent responses in oocyte development. This work demonstrated a benefit of the PML-NB-free intranuclear milieu, namely the ability to redirect the flux of SUMO otherwise needed to control PML-NB dynamics.
NR0B2 regulation during Primary Sclerosing Cholangitis defines a metabolic and pre-malignant reprogramming of Cholangiocyte
Authors: Desterke Christophe , Feray Cyrille 
Published: September 2021

SUMMARYPrimary Sclerosing Cholangitis (PSC) is an idiopathic, cholestatic liver disease that is characterized by persistent, progressive, biliary inflammation leading to cirrhosis. These patients present higher risk for developing bile duct cancers.Biomedical text-mining related to PSC symptoms like: biliary inflammation, biliary fibrosis, biliary cholestasis was initiated to collect gene associations with this pathophysiology. The text mining work was integrated in distinct omics data such as human transcriptome of PSC liver, Farnesoid X receptor (FXR) functional liver transcriptome and liver single cell transcriptome of the Abcb4-/- model of PSC. A molecular network implicated in abnormal hepatobiliary system physiology was built and confirming a major implication of Nr0b2 and its associated nuclear receptors like FXR in a metabolic cascade that could influence immune response. TNFRSF12A/TWEAK receptor, was found up regulated in PSC liver independently of FXR regulation and TWEAK signaling is known for its implication in pre-conditioning niche of cholangiocarcinoma. NR0B2 deregulation in PSC liver was found independent of gender, age and body mass index surrogates. At single cell level, Nr0b2 up regulation was found in cholangiocytes but not in hepatocytes. In affected cholangiocytes, the cell trajectory built on Nr0b2 expression, revealed implication of several metabolic pathways for detoxification like sulfur, glutathione derivative and monocarboxylic acid metabolisms. On this cell trajectory it was discovered some molecules potentially implicated in carcinogenesis like: GSTA3, ID2 and mainly TMEM45A a transmembrane molecule from golgi apparatus considered as oncogene in several cancers. All together, these observations found in humanPSC liver and in its murine models allowed to highlight an independent deregulation of NR0B2 with a metabolic and premalignant reprogramming of cholangiocytes.
Fast wavefront shaping for two-photon brain imaging with large field of view correction
Authors: Blochet Baptiste , Akemann Walther , Gigan Sylvain , Bourdieu Laurent 
Published: September 2021

Introduction paragraphIn-vivo optical imaging with diffraction-limited resolution deep inside scattering biological tissues is obtained by non-linear fluorescence microscopy1. Active compensation of tissue-induced aberrations and light scattering through adaptive wavefront correction2,3 further extends depth penetration by restoring high resolution at large depth. However, at large depths those corrections are only valid over a very limited field of view within the angular memory effect4. To overcome this limitation, we introduce an acousto-optic light modulation technique for fluorescence imaging with simultaneous wavefront correction at pixel scan speed. Biaxial wavefront corrections are first learned by adaptive optimization at multiple locations in the image field. During image acquisition, the learned corrections are then switched on-the-fly according to the position of the excitation focus during the raster scan. The proposed microscope is applied to in-vivo transcranial neuron imaging and demonstrates correction of skull-induced aberrations and scattering across large fields of view at 40 kHz data acquisition speed.
Analysis of Rod/Cone Gap Junctions from the Reconstruction of Mouse Photoreceptor Terminals
Authors: Ishibashi Munenori , Keung Joyce , Morgans Catherine W. , Aicher Sue A. , Carroll James R. , Singer Joshua H. , Jia Li , Li Wei , Fahrenfort Iris , Ribelayga Christophe P. , Massey Stephen C. 
Published: September 2021

AbstractUsing serial blockface-scanning electron microscopy (SBF-SEM) and focused ion beam-scanning electron microscopy (FIB-SEM), combined with confocal microscopy for the gap junction protein Cx36, we reconstructed mouse photoreceptor terminals and located the gap junctions between them. An exuberant spray of fine telodendria extends from each cone pedicle (including blue cones) to contact 40-50 nearby rod spherules where Cx36 clusters were located, close to the mouth of the synaptic opening. There were approximately 50 Cx36 clusters per cone pedicle and 2-3 per rod spherule. We were unable to detect rod/rod or cone/cone coupling. Thus, rod/cone coupling accounts for nearly all gap junctions between photoreceptors. Our calculations suggest a mean of 82 Cx36 channels between a rod/cone pair of which 25% are open at rest. Rod/cone gap junctions are modulated by dopamine. Comparing our morphological calculations of maximum coupling to previous physiological results suggests that dopamine antagonists can drive rod/cone gap junctions to a surprisingly high open probability, approaching 100%.
Aging is associated with increased brain iron through brain-derived hepcidin expression
Authors: Sato Tatsuya , Shapiro Jason , Chang Hsiang-Chun , Miller Richard A. , Ardehali Hossein 
Published: September 2021

AbstractIron is an essential molecule for biological processes, but its accumulation can lead to oxidative stress and cellular death. Due to its oxidative effects, iron accumulation is implicated in the process of aging and neurodegenerative diseases. However, the mechanism for this increase in iron with aging, and whether this increase is localized to specific cellular compartment(s), are not known. Here, we measured the levels of iron in different tissues of aged mice, and demonstrate that while cytosolic non-heme iron is increased in the liver and muscle tissue, only the aged brain exhibits an increase in both the cytosolic and mitochondrial non-heme iron. This increase in brain iron is associated with elevated levels of local hepcidin mRNA and protein in the brain. We also demonstrate that the increase in hepcidin is associated with increased ubiquitination and reduced levels of the only iron exporter, feroportin-1 (FPN1). Overall, our studies provide a potential mechanism for iron accumulation in the brain through increased local expression of hepcidin, and subsequent iron accumulation due to decreased iron export. Additionally, our data support that aging is associated with mitochondrial and cytosolic iron accumulation only in the brain and not in other tissues.
Legionella pneumophila regulates host cell motility by targeting Phldb2 with a 14-3-3ζ-dependent protease effector
Authors: Song Lei , Luo Jingjing , Huang Dan , Tan Yunhao , Liu Yao , Yu Kaiwen , Zhang Yong , Liu Xiaoyun , Li Dan , Luo Zhao-Qing 
Published: September 2021

AbstractThe cytoskeleton network of eukaryotic cells is essential for diverse cellular processes, including vesicle trafficking, cell motility and immunity, thus is a common target for bacterial virulence factors. A number of effectors from the bacterial pathogen Legionella pneumophila have been shown to modulate the function of host actin cytoskeleton to construct the Legionella-containing vacuole (LCV) permissive for its intracellular replication. In this study, we identified the Dot/Icm effector Lem8 (Lpg1290) as a protease that interferes with host motility. We show that the protease activity of Lem8 is catalyzed by a Cys-His-Asp motif known to be associated with diverse biochemical activities. Intriguingly, we found that Lem8 interacts with the host regulatory protein 14-3-3ζ, which activates its protease activity. Furthermore, Lem8 undergoes self-cleavage in a process that requires 14-3-3ζ. We identified the PH domain-containing protein Phldb2 involved in cell migration as a target of Lem8 and demonstrate that Lem8 plays a role in the inhibition of host cell migration. Our results reveal a novel mechanism of inhibiting host cell motility by L. pneumophila for its virulence.
Sequestration and efflux largely account for cadmium and copper resistance in the deep sea epsilonproteobacterium, Nitratiruptor sp. SB155-2
Authors: Ares Ángela , Sakai Sanae , Sasaki Toshio , Mitarai Satoshi , Nunoura Takuro 
Published: September 2021

AbstractIn deep sea hydrothermal vent environments, metal- and metalloid-enriched fluids and sediments abound, making these habitats ideal to study metal resistance in prokaryotes. In this investigation, the architecture of the epsilonproteobacterium, Nitratiruptor sp. SB155-2 transcriptome in combination with sub-cellular analysis using scanning transmission electron microscopy and energy-dispersive X-ray spectroscopy (STEM-EDX) was examined to better understand mechanisms of tolerance for cadmium (Cd) and copper (Cu) at stress-inducing concentrations. Transcriptomic expression profiles were remarkably different in the presence of these two metals, displaying 385 (19%) and 629 (31%) genes differentially expressed (DE) in the presence of Cd and Cu, respectively, while only 7% of DE genes were shared, with genes for non-specific metal transporters and genes involved in oxidative stress-response predominating. The principal metal-specific DE pathways under Cu stress, including those involving sulfur, cysteine, and methionine, are likely required for high-affinity efflux systems, while flagella formation and chemotaxis were over-represented under Cd stress. Consistent with these differences, STEM-EDX analysis revealed that polyphosphate-like granules (pPLG), the formation of CdS particles, and the periplasmic space may be crucial for Cd sequestration. Overall, this study provides new insights regarding metal-specific adaptations of Epsilonproteobacteria to deep sea hydrothermal vent environments.Significance originality statementDeep sea hydrothermal vents are unique environments in which metals and metalloids abound. Despite being a dominant phylum in these environments, adaptations enabling Epsilonproteobacteria to thrive in metal-rich environments remain poorly understood. In this study, a combination of high-throughput, whole-transcriptome RNA-seq analysis, scanning transmission electron microscopy, and energy-dispersive X-ray spectroscopy provide a comprehensive picture of molecular and morphological adaptations controlling metal efflux and sequestration systems of this bacterium in response to cadmium and copper. Many of these responses are metal-specific.
The NDNF-like factor Nord is a Hedgehog-induced extracellular BMP modulator that regulates Drosophila wing patterning and growth
Authors: Yang Shu , Wu Xuefeng , Daoutidou Euphrosyne I. , Zhang Ya , Shimell MaryJane , Chuang Kun-Han , Peterson Aidan J. , O’Connor Michael B. , Zheng Xiaoyan 
Published: September 2021

ABSTRACTHedgehog (Hh) and bone morphogenetic proteins (BMPs) pattern the developing Drosophila wing by functioning as short- and long-range morphogens, respectively. Here, we show that a previously unknown Hh-dependent mechanism fine-tunes the activity of BMPs. Through genome-wide expression profiling of the Drosophila wing imaginal discs, we identify nord as a novel target gene of the Hh signaling pathway. Nord is related to the vertebrate Neuron Derived Neurotrophic Factor (NDNF) involved in Congenital Hypogonadotropic Hypogonadism and several types of cancer. Loss- and gain-of-function analyses implicate Nord in the regulation of wing growth and proper crossvein patterning. At the molecular level, we present biochemical evidence that Nord is a secreted BMP-binding protein and localizes to the extracellular matrix. Nord binds to Decapentaplegic (Dpp) or the heterodimer Dpp-Glass bottom boat (Gbb) to modulate their release and activity. Furthermore, we demonstrate that Nord is a dosage-depend biphasic BMP modulator, where low levels of Nord promote and high levels inhibit BMP signaling. Taken together, we propose that Hh-induced Nord expression fine tunes both the range and strength of BMP signaling in the developing Drosophila wing.One sentence summaryThe NDNF-like factor Nord is a Hedgehog-induced and extracellular-localized biphasic BMP modulator that regulates Drosophila wing patterning and growth
HTSplotter: an end-to-end data processing, analysis and visualisation tool for chemical and genetic in vitro perturbation screening
Authors: Nunes Carolina , Anckaert Jasper , De Vloed Fanny , De Wyn Jolien , Durinck Kaat , Vandesompele Jo , Speleman Frank , Vermeirssen Vanessa 
Published: September 2021

AbstractIn biomedical research, high-throughput screening is often applied as it comes with automatization, higher-efficiency, and more and faster results. High-throughput screening experiments encompass drug, drug combination, genetic perturbagen or a combination of genetic and chemical perturbagen screens. These experiments are conducted in real-time assays over time or in an endpoint assay. The data analysis consists of data cleaning and structuring, as well as further data processing and visualisation, which, due to the amount of data, can easily become laborious, time consuming and error-prone. Therefore, several tools have been developed to aid researchers in this process, but these typically focus on specific experimental set-ups and are unable to process data of several time points and genetic-chemical perturbagen screens. To meet these needs, we developed HTSplotter, available as web tool and Python module, which performs automatic data analysis and visualisation of either endpoint or real-time assays from different high-throughput screening experiments: drug, drug combination, genetic perturbagen and genetic-chemical perturbagen screens. HTSplotter implements an algorithm based on conditional statements in order to identify experiment type and controls. After appropriate data normalization, including growth rate normalization, HTSplotter executes downstream analyses such as dose-response relationship and drug synergism assessment by the Bliss independence (BI), Zero Interaction Potency (ZIP) and Highest Single Agent (HAS) methods. All results are exported as a text file and plots are saved in a PDF file. The main advantage of HTSplotter over other available tools is the automatic analysis of genetic-chemical perturbagen screens and real-time assays where growth rate and perturbagen effect results are plotted over time. In conclusion, HTSplotter allows for the automatic end-to-end data processing, analysis and visualisation of various high-throughput in vitro cell culture screens, offering major improvements in terms of versatility, efficiency and time over existing tools.
Transcriptional signatures of cell-cell interactions are dependent on cellular context
Authors: Innes Brendan T. , Bader Gary D. 
Published: September 2021

AbstractCell-cell interactions are often predicted from single-cell transcriptomics data based on observing receptor and corresponding ligand transcripts in cells. These predictions could theoretically be improved by inspecting the transcriptome of the receptor cell for evidence of gene expression changes in response to the ligand. It is commonly expected that a given receptor, in response to ligand activation, will have a characteristic downstream gene expression signature. However, this assumption has not been well tested. We used ligand perturbation data from both the high-throughput Connectivity Map resource and published transcriptomic assays of cell lines and purified cell populations to determine whether ligand signals have unique and generalizable transcriptional signatures across biological conditions. Most of the receptors we analyzed did not have such characteristic gene expression signatures – instead these signatures were highly dependent on cell type. Cell context is thus important when considering transcriptomic evidence of ligand signaling, which makes it challenging to build generalizable ligand-receptor interaction signatures to improve cell-cell interaction predictions.
A cellular and molecular atlas reveals the basis of chytrid development
Authors: Laundon Davis , Chrismas Nathan , Bird Kimberley , Thomas Seth , Mock Thomas , Cunliffe Michael 
Published: September 2021

ABSTRACTThe chytrids (phylum Chytridiomycota) are a major early-diverging fungal lineage of ecological and evolutionary importance. Despite their importance, many fundamental aspects of chytrid developmental and cell biology remain poorly understood. To address these knowledge gaps, we combined quantitative volume electron microscopy and comparative transcriptome profiling to create an ‘atlas’ of the cellular and molecular basis of the chytrid life cycle, using the model chytrid Rhizoclosmatium globosum. From our developmental atlas, we show that zoospores exhibit a specialised biological repertoire dominated by inactive ribosome aggregates, and that lipid processing is complex and dynamic throughout the cell cycle. We demonstrate that the chytrid apophysis is a distinct subcellular structure characterised by high intracellular trafficking, providing evidence for division of labour in the chytrid cell plan, and show that zoosporogenesis includes ‘animal like’ amoeboid cell morphologies resulting from endocytotic cargo transport from the interstitial maternal cytoplasm. Taken together, our results reveal insights into chytrid developmental biology and provide a basis for future investigations into early-diverging fungal cell biology.
Quantifying Intratumor Heterogeneity by Key Genes Selected using Concrete Autoencoder
Authors: Tanvir Raihanul Bari , Mamun Abdullah Al , Sobhan Masrur , Mondal Ananda Mohan 
Published: September 2021

ABSTRACTThe tumor cell population in cancer tissue has distinct molecular characteristics and exhibits different phenotypes, thus, resulting in different subpopulations. This phenomenon is known as Intratumor Heterogeneity (ITH), a major contributor to drug resistance, poor prognosis, etc. Therefore, quantifying the levels of ITH in cancer patients is essential, and many algorithms do so in different ways, using different types of omics data. DEPTH (Deviating gene Expression Profiling Tumor Heterogeneity) is the latest algorithm that uses transcriptomic data to evaluate the ITH score. It shows promising performance, has strong similarity with six other algorithms and has an advantage over two algorithms that uses the same type of data (tITH, sITH). However, it has a major drawback since it uses expression values of all the genes (∼20K genes) in quantifying ITH levels. We hypothesize that a subset of key genes is sufficient to quantify the ITH level. To prove our hypothesis, we developed a deep learning-based computational framework using unsupervised Concrete Autoencoder (CAE) to select a set of cancer-specific key genes that can be used to evaluate the ITH score. For the experiment, we used gene expression profile data of tumor cohorts of breast, kidney, and lung cancer from the TCGA repository. Using multi-run CAE, we selected three sets of key genes, each set related to breast, kidney, and lung tumor cohorts. For the three cancers stated and three molecular subtypes of lung cancer, we calculated the ITH level using all genes and key genes selected by CAE and performed a side-by-side comparison. We could reach similar conclusions for survival and prognostic outcomes based on ITH scores derived from all genes and the sets of key genes. Additionally, for subtypes of lung cancer, the comparative distribution of ITH scores derived from all and key genes remains similar. Based on these observations, it can be stated that a subset of key genes, instead of all genes, is sufficient for ITH quantification. Our results also showed that many key genes are prognostically significant, which can be used as possible therapeutic targets.
An evolutionarily ancient Fatty Acid Desaturase is required for the synthesis of hexadecatrienoic acid, which is the main source of the bioactive jasmonate inMarchantia polymorpha
Authors: Soriano Gonzalo , Kneeshaw Sophie , Jimenez-Alemán Guillermo , Zamarreño Angel M. , Franco-Zorrilla José Manuel , Rey-Stolle Valcarce Mª Fernanda , Barbas Coral , García-Mina Jose M. , Solano Roberto 
Published: September 2021

SUMMARYJasmonates are fatty acid derived hormones that regulate multiple aspects of plant development, growth and stress responses. Bioactive jasmonates, defined as the ligands of the conserved COI1 receptor, differ between vascular plants and bryophytes (using jasmonoyl-L-isoleucine; JA-Ile and dinor-12-oxo-10,15(Z)-phytodienoic acid; dn-OPDA, respectively). Whilst the biosynthetic pathways of JA-Ile in the model vascular plantArabidopsis thalianahave been elucidated, the details of dn-OPDA biosynthesis in bryophytes are still unclear. Here, we identify an ortholog ofArabidopsisFatty Acid Desaturase 5 (AtFAD5) in the model liverwortMarchantia polymorphaand show that FAD5 function is ancient and conserved between species separated by more than 450 million years of independent evolution. Similar to AtFAD5, MpFAD5 is required for the synthesis of 7Z-hexadecenoic acid. Consequently, in Mpfad5mutants the hexadecanoid pathway is blocked, dn-OPDA levels almost completely depleted and normal chloroplast development is impaired. Our results demonstrate that the main source of dn-OPDA inMarchantiais the hexadecanoid pathway and the contribution of the octadecanoid pathway, i.e. from OPDA, is minimal. Remarkably, despite extremely low levels of dn-OPDA, MpCOI1-mediated responses to wounding and insect feeding can still be activated in Mpfad5, suggesting that dn-OPDA is not the only bioactive jasmonate and COI1 ligand inMarchantia.
Library-based analysis reveals segment and length dependent characteristics of defective influenza genomes
Authors: Mendes Marisa , Russell Alistair B. 
Published: September 2021

AbstractParasitic elements of the viral population which are unable to replicate on their own yet rise to high frequencies, defective interfering particles are found in a variety of different viruses. Their presence is associated with a loss of population fitness, both through the depletion of key cellular resources and the stimulation of innate immunity. For influenza A virus, these particles contain large internal deletions in the genomic segments which encode components of the heterotrimeric polymerase. Using a library-based approach, we comprehensively profile the growth and replication of defective influenza species, demonstrating that they possess an advantage during genome replication, and that exclusion during packaging reshapes population composition in a manner consistent with their final, observed, distribution in natural populations. We find that an innate immune response is not linked to the size of a deletion; however, replication of defective segments can enhance their immunostimulatory properties. Overall, our results address several key questions in defective influenza A virus biology, and the methods we have developed to answer those questions may be broadly applied to other defective viruses.