bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL-1-conferred gene expression pattern in ERα+ BCa and AR+ PCa cells is intrinsic to ERα− BCa and AR− PCa cells and promotes cell survival
Authors: Nawas Afshan F. , Kanchwala Mohammed , Thomas-Jardin Shayna E. , Dahl Haley , Daescu Kelly , Bautista Monica , Anunobi Vanessa , Wong Ally , Meade Rachel , Mistry Ragini , Ghatwai Nisha , Bayerl Felix , Xing Chao , Delk Nikki A. 
Published: September 2019

ABSTRACTBackgroundBreast (BCa) and prostate (PCa) cancers are hormone receptor (HR)-driven cancers. Thus, BCa and PCa patients are given therapies that reduce hormone levels or directly blocks HR activity; but most patients eventually develop treatment resistance. We have previously reported that interleukin-1 (IL-1) inflammatory cytokine downregulates ERα and AR mRNA in HR-positive (HR+) BCa and PCa cell lines, yet the cells can remain viable. Additionally, we identified pro-survival proteins and processes upregulated by IL-1 in HR+ BCa and PCa cells, that are basally high in HR− BCa and PCa cells. Therefore, we hypothesize that IL-1 confers a conserved gene expression pattern in HR+ BCa and PCa cells that mimics conserved basal gene expression patterns in HR− BCa and PCa cells to promote HR-independent survival and tumorigenicity.MethodsWe performed RNA sequencing (RNA-seq) for HR+ BCa and PCa cell lines exposed to IL-1 and for untreated HR− BCa and PCa cell lines. We confirmed expression patterns of select genes by RT-qPCR and used siRNA and/or drug inhibition to silence select genes in HR− BCa cell lines. Finally, we performed Ingenuity Pathway Analysis (IPA) to identify signaling pathways encoded by our RNA-seq data set.ResultsWe identified 350 genes in common between BCa and PCa cells that are induced or repressed by IL-1 in HR+ cells that are, respectively, basally high or low in HR− cells. Among these genes, we identified Sequestome-1 (SQSTM1/p62) and SRY (Sex-Determining Region Y)-Box 9 (SOX9) to be essential for survival of HR− BCa and PCa cell lines. Analysis of publicly available data indicates that p62 and SOX9 expression are elevated in HR-independent BCa and PCa sublines generated in vitro, suggesting that p62 and SOX9 have a role in acquired treatment resistance. We also assessed HR− cell line viability in response to the p62-targeting drug, verteporfin, and found that verteporfin is cytotoxic for HR− cell lines.ConclusionsOur 350 gene set can be used to identify novel therapeutic targets and/or biomarkers conserved among acquired (e.g. due to inflammation) or intrinsic HR-independent BCa and PCa.
Correlative three-dimensional super-resolution and block face electron microscopy of whole vitreously frozen cells
Authors: Hoffman David P. , Shtengel Gleb , Xu C. Shan , Campbell Kirby R. , Freeman Melanie , Wang Lei , Milkie Daniel E. , Pasolli H. Amalia , Iyer Nirmala , Bogovic John A. , Stabley Daniel R. , Shirinifard Abbas , Pang Song , Peale David , Schaefer Kathy , Pomp Wim , Chang Chi-Lun , Lippincott-Schwartz Jennifer , Kirchhausen Tom , Solecki David J. , Betzig Eric , Hess Harald 
Published: September 2019

AbstractLiving cells function through the spatial compartmentalization of thousands of distinct proteins serving a multitude of diverse biochemical needs. Correlative super-resolution (SR) fluorescence and electron microscopy (EM) has emerged as a pathway to directly view nanoscale protein relationships to the underlying global ultrastructure, but has traditionally suffered from tradeoffs of structure preservation, fluorescence retention, resolution, and field of view. We developed a platform for three-dimensional correlative cryogenic SR and focused ion beam milled block-face EM across entire vitreously frozen cells that addresses these issues by preserving native ultrastructure and enabling independent SR and EM workflow optimization. Application to a variety of biological systems revealed a number of unexpected protein-ultrastructure relationships and underscored the value of a comprehensive multimodal view of ultrastructural variability across whole cells.
Free Energy Principle in Human Postural Control System: Skin Stretch Feedback Reduces the Entropy
Authors: Hur Pilwon , Pan Yi-Tsen , DeBuys Christian 
Published: September 2019

ABSTRACTHuman upright standing involves an integration of multiple sensory inputs such as vision, vestibular and somatosensory systems. It has been known that sensory deficits worsen the standing balance. However, how the modulation of sensory information contributes to postural stabilization still remains an open question for researchers. The purpose of this work was to formulate the human standing postural control system in the framework of the free-energy principle, and to investigate the efficacy of the skin stretch feedback in enhancing the human standing balance. Previously, we have shown that sensory augmentation by skin stretch feedback at the fingertip could modulate the standing balance of the people with simulated sensory deficits. In this study, subjects underwent ten 30-second trials of quiet standing balance with and without skin stretch feedback. Visual and vestibular sensory deficits were simulated by having each subject close their eyes and tilt their head back. We found that sensory augmentation by velocity-based skin stretch feedback at the fingertip reduced the entropy of the standing postural sway of the people with simulated sensory deficits. This result aligns with the framework of the free energy principle which states that a self-organizing biological system at its equilibrium state tries to minimize its free energy either by updating the internal state or by correcting body movement with appropriate actions. The velocity-based skin stretch feedback at the fingertip may increase the signal-to-noise ratio of the sensory signals, which in turn enhances the accuracy of the internal states in the central nervous system. With more accurate internal states, the human postural control system can further adjust the standing posture to minimize the entropy, and thus the free energy.
Machine learning-assisted neurotoxicity prediction in human midbrain organoids
Authors: Monzel Anna S. , Hemmer Kathrin , Mukendi Tony Kaoma , Lucarelli Philippe , Rosety Isabel , Zagare Alise , Bolognin Silvia , Antony Paul , Nickels Sarah L. , Krueger Rejko , Azuaje Francisco , Schwamborn Jens C. 
Published: September 2019

AbstractA major challenge in the field of neurodegenerative diseases is the poor translation of pre-clinical models to clinical applications. The human brain is an immensely complex structure, which makes it difficult to recapitulate its development, function and disorders. In the recent years, brain organoids derived from human induced pluripotent stem cells have risen as novel tools to study neurodegenerative diseases such as Parkinson’s disease (PD). PD is a multifactorial disorder, with aging, genetics and environmental factors as key etiological elements. The majority of the PD cases are idiopathic and proposed to result from a complex interaction between genetic predisposition and environmental exposure. Consequently, the identification of potentially disease causing environmental factors is of critical importance. Organoids, as complex multi-cellular tissue proxies, are an ideal tool to study cellular response to environmental changes. However, with increasing complexity of the system, usage of quantitative tools becomes challenging. This led us to develop an automated high-content image analysis pipeline for image-based cell profiling in the organoid system. Here, we introduce a midbrain organoid system that recapitulates features of neurotoxin-induced PD, representing a platform for machine-learning-assisted prediction of neurotoxicity in high-content imaging data. This model is a valuable tool for advanced in vitro PD modeling and for the screening of putative neurotoxic compounds.
Mast cells and γδ T cells are largely dispensable for adaptive immune responses after laser-mediated epicutaneous immunization
Authors: Joubert Isabella , Kovacs Daniel , Scheiblhofer Sandra , Winter Petra , Korotchenko Evgeniia , Strandt Helen , Weiss Richard 
Published: September 2019

AbstractBackgroundThe skin resembles an attractive target for vaccination due to its accessibility and abundance of resident immune cells. Cells like γδ T cells and mast cells (MCs) are part of the first line of defence against exogenous threats. Despite being important mediators for eliciting TH2 immune responses after epithelial stress, γδ T cell and MC function still remains to be completely understood. Here, we aimed to characterize their roles in shaping adaptive immune responses after laser-mediated epicutaneous immunization (EPI).Methodsγδ T cell knock out, MC depleted, and wildtype control mice were immunized with mannan-conjugated grass pollen allergen Phl p 5 (P5-MN) by laser-mediated EPI. After 2-3 immunizations, cytokine expression, T helper polarization, and antigen-specific IgG1/IgE levels were analysed. The local cytokine/chemokine milieu after laser microporation was determined.ResultsWhile the majority of inflammatory chemokines and cytokines induced by laser treatment was not affected by the presence of γδ T cells or MCs, RANTES, was elevated in γδ T cell knock out mice, and GROα and TSLP, were significantly decreased after MC depletion. However, absence of γδ T cells or depletion of MC had no substantial effect on adaptive humoral or cellular immune responses after laser-mediated EPI, except for slightly reduced IgG1 and effector T cell levels in MC depleted mice.Conclusionsγδ T cells did not play a pivotal role in shaping the humoral and cellular adaptive immune response after laser-mediated EPI, whereas MC depletion decreased numbers of effector T cells, indicating a potential role of MCs in the activation and maturation of T cells after EPI.HighlightsLaser microporation induces an inflammatory chemokine milieu at the site of immunizationγδ T cells and mast cells contribute to the steady-state or damage-induced cytokine milieu in the skinγδ T cells and mast cells are dispensable for adaptive immunity after laser-mediated immunization
Microbiome-Gut-Brain-Axis communication influences metabolic switch in the mosquitoAnopheles culicifacies
Authors: Das De Tanwee , Sharma Punita , Tevatiya Sanjay , Chauhan Charu , Kumari Seena , Singla Deepak , Srivastava Vartika , Rani Jyoti , Hasija Yasha , Pandey Kailash C , Kajla Mayur , Dixit Rajnikant 
Published: September 2019

AbstractPeriodic ingestion of a protein-rich blood meal by adult female mosquitoes causes a drastic metabolic change in their innate physiological status, which is referred to as ‘metabolic switch. Although the down-regulation of olfactory factors is key to restrain host-attraction, how the gut ‘metabolic switch’ modulates brain functions, and resilience physiological homeostasis remains unexplored. Here, we demonstrate that the protein-rich diet induces mitochondrial function and energy metabolism, possibly shifting the brain’s engagement to manage organismal homeostasis. A dynamic expression pattern of neuro-signaling and neuro-modulatory genes in both the brain and gut indicates an optimal brain-distant organ communication. Even after decapitation, significant modulation of the neuro-modulator receptor genes as well as quantitative estimation of neurotransmitters (NTs), together confer the gut’s ability to serve as a ‘second brain’. Finally, data on comparative metagenomic analysis and altered NTs dynamics of naïve and aseptic mosquitoes provide the initial evidence that gut-endosymbionts are key modulators for the synthesis of major neuroactive molecules. Conclusively, our data establish a new conceptual understanding of microbiome-gut-brain-axis communication in mosquitoes.Abstract FigureGraphical abstractHighlightsHighly proteinaceous blood meal uptake causes gut ‘metabolic switch’ activity in mosquitoes.Gut’s calling shifts the brain’s administrative function from external communication to inter-organ management.‘Gut’, as a ‘Second brain’ plays a crucial role in the maintenance of physiological homeostasis.Metabolic switch and proliferation of symbiotic bacteria establish microbiome-gut-brain axis communication in mosquitoes.
Expert Curation of the Human and Mouse Olfactory Receptor Gene Repertoires Identifies Conserved Coding Regions Split Across Two Exons
Authors: Barnes If H. A. , Ibarra-Soria Ximena , Fitzgerald Stephen , Gonzalez Jose M. , Davidson Claire , Hardy Matthew P. , Manthravadi Deepa , Van Gerven Laura , Jorissen Mark , Zeng Zhen , Khan Mona , Mombaerts Peter , Harrow Jennifer , Logan Darren W. , Frankish Adam 
Published: September 2019

ABSTRACTOlfactory receptor (OR) genes are the largest multi-gene family in the mammalian genome, with over 850 in human and nearly 1500 genes in mouse. The expansion of the OR gene repertoire has occurred through numerous duplication events followed by diversification, resulting in a large number of highly similar paralogous genes. These characteristics have made the annotation of the complete OR gene repertoire a complex task. Most OR genes have been predicted in silico and are typically annotated as intronless coding sequences. Here we have developed an expert curation pipeline to analyse and annotate every OR gene in the human and mouse reference genomes. By combining evidence from structural features, evolutionary conservation and experimental data, we have unified the annotation of these gene families, and have systematically determined the protein-coding potential of each locus. We have defined the non-coding regions of many OR genes, enabling us to generate full-length transcript models. We found that 13 human and 41 mouse OR loci have coding sequences that are split across two exons. These split OR genes are conserved across mammals, and are expressed at the same level as protein-coding OR genes with an intronless coding region. Our findings challenge the long-standing and widespread notion that the coding region of a vertebrate OR gene is contained within a single exon.
Inter- and intraspecific differences inDrosophilacold tolerance are linked to hindgut reabsorption capacity
Authors: Andersen Mads Kuhlmann , Overgaard Johannes 
Published: September 2019

AbstractMaintaining extracellular osmotic and ionic homeostasis is crucial to maintain organismal function. In insects, hemolymph volume and ion content is regulated by the combined actions of the secretory Malpighian tubules and reabsorptive hindgut. When exposed to stressful cold, homeostasis is gradually disrupted, characterized by a debilitating increase in extracellular K+concentration (hyperkalemia). In accordance with this paradigm, studies have found a strong link between the cold tolerance of insect species and their ability to maintain ion and water homeostasis at low temperature. This is also the case for drosophilids where studies have already established how inter- and intra-specific differences in cold tolerance are linked to the secretory capacity of Malpighian tubules. However, presently there is little information on the effects of temperature on the reabsorptive capacity of the hindgut inDrosophila.To address this question we developed a novel method that allows for continued measurements of hindgut ion and fluid reabsorption inDrosophila.Firstly we demonstrate that this assay is temporally stable (> 3 hours) and that the preparation is responsive to humoral stimulation and pharmacological intervention of active and passive transport in accordance with the current insect hindgut reabsorption model. Using this method at benign (24°C) and low temperature (3°C) we investigated how cold acclimation or cold adaptation affected the thermal sensitivity of osmoregulatory function. We found that cold tolerantDrosophilaspecies and cold-acclimatedD. melanogasterare innately better at maintaining rates of fluid and Na+reabsorption at low temperature. Furthermore, cold adaptation and acclimation causes a relative reduction in K+reabsorption at low temperature. These characteristic responses of cold adapted/acclimatedDrosophilawill act to promote maintenance of ion and water homeostasis at low temperature and therefore provide further links between adaptations in osmoregulatory capacity of insects and their ability to tolerate cold exposure.
Three-dimensional characterisation of osteocyte volumes at multiple scales, and its relationship with bone biology and genome evolution in ray-finned fishes
Authors: Davesne Donald , Schmitt Armin D. , Fernandez Vincent , Benson Roger B. J. , Sanchez Sophie 
Published: September 2019

AbstractOsteocytes, cells embedded within the bone mineral matrix, inform on key aspects of vertebrate biology. In particular, a relationship between volumes of the osteocytes and bone growth and/or genome size has been proposed for several tetrapod lineages. However, the variation in osteocyte volume across different scales is poorly characterised, and mostly relies on incomplete, two-dimensional information. In this study, we propose to characterise the variation of osteocyte volumes in ray-finned fishes (Actinopterygii), a clade including more than half of modern vertebrate species in which osteocyte biology is poorly known. We use X-ray synchrotron micro computed tomography (SRμCT) to achieve a three-dimensional visualisation of osteocytes and direct measurement of their volumes. Our specimen sample is designed to characterise osteocyte variation at three scales: within a bone, between the bones of one individual and between taxa spanning actinopterygian phylogeny. At the intra-bone scale, we find that osteocytes vary noticeably in volume between zones of organised and woven bone (being larger in the latter), and across cyclical bone deposition. This is probably explained by differences in bone deposition rate, with larger osteocytes contained in bone that deposits faster. Osteocyte volumes vary from one bone to another, for unclear reasons. Finally, we find that genome size is the best explanatory variable of osteocyte volume at the inter-specific scale: actinopterygian taxa with larger genomes (polyploid taxa in particular) have larger osteocytes. Our findings corroborate previous two-dimensional observations in tetrapods, and open new perspectives for actinopterygian bone evolution, physiology and palaeogenomics.
Simulation with RADinitio Improves RADseq Experimental Design and Sheds Light on Sources of Missing Data
Authors: Rivera-Colón Angel G. , Rochette Nicolas C. , Catchen Julian M. 
Published: September 2019

AbstractRestriction-site Associated DNA sequencing (RADseq) has become a powerful and versatile tool in modern population genomics, enabling large-scale genomic analyses in otherwise inaccessible biological systems. With its widespread use, different variants on the protocol have been developed to suit specific experimental needs. Researchers face the challenge of choosing the optimal molecular and sequencing protocols for their experimental design, an often-complicated process. Strategic errors can lead to improper data generation that has reduced power to answer biological questions. Here we present RADinitio, simulation software for the selection and optimization of RADseq experiments via the generation of sequencing data that behaves similarly to empirical sources. RADinitio provides an evolutionary simulation of populations, implementation of various RADseq protocols with customizable parameters, and thorough assessment of missing data. Using the software, we test its efficacy using different RAD protocols across several organisms, highlighting the importance of protocol selection on the magnitude and quality of data acquired. Additionally, we test the effects of RAD library preparation and sequencing on allelic dropout, observing that library preparation and sequencing often contributes more to missing alleles than population-level variation.
Distinct features of human myeloid cell cytokine response profiles identify neutrophil activation by cytokines as a prognostic feature during tuberculosis and cancer1
Authors: Devlin Joseph C. , Zwack Erin E. , Tang Mei San , Li Zhi , Fenyo David , Torres Victor J. , Ruggles Kelly V. , Loke P’ng 
Published: September 2019

ABSTRACTMyeloid cells are a vital component of innate immunity and comprise of monocytes, macrophages, dendritic cells and granulocytes. How myeloid cell lineage affects activation states in response to cytokines remains poorly understood. The cytokine environment and cellular infiltrate during an inflammatory response may contain prognostic features that could predict disease outcome. Here we analyzed the transcriptional responses of human monocytes, macrophages, dendritic cells and neutrophils in response to stimulation by IFN-γ, IFN-β IFN-λ, IL-4, IL-13 and IL-10 cytokines, to better understand the heterogeneity of activation states in inflammatory conditions. This generated a myeloid cell cytokine specific response matrix that can infer representation of myeloid cells and the cytokine environment they encounter during infection and in tumors. Neutrophils were highly responsive to type 1 and type 2 cytokine stimulation but did not respond to IL-10. We identified transcripts specific to IFN-β stimulation, whereas other IFN signature genes were upregulated by both IFN-γ and IFN-β. When we used our matrix to deconvolute blood profiles from tuberculosis patients, the IFN-β specific neutrophil signature was reduced in TB patients with active disease whereas the shared response to IFN-γ and IFN-β in neutrophils was increased. When applied to glioma patients, transcripts of neutrophils exposed to IL-4 or IL-13 and monocyte responses to IFN-γ or IFN-β emerged as opposing predictors of patient survival. Hence, by dissecting how different myeloid cells respond to cytokine activation, we can delineate biological roles for myeloid cells in different cytokine environments during disease processes, especially during infection and tumor progression.
Three-dimensional label-free observation of individual bacteria upon antibiotic treatment using optical diffraction tomography
Authors: Oh Jeonghun , Ryu Jea Sung , Lee Moosung , Jung Jaehwang , Han Seung yun , Chung Hyun Jung , Park Yongkeun 
Published: September 2019

AbstractMeasuring alterations in bacteria upon antibiotic application is important for basic studies in microbiology, drug discovery, and clinical diagnosis, and disease treatment. However, imaging and 3D time-lapse response analysis of individual bacteria upon antibiotic application remain largely unexplored mainly due to limitations in imaging techniques. Here, we present a method to systematically investigate the alterations in individual bacteria in 3D and quantitatively analyze the effects of antibiotics. Using optical diffraction tomography,in-situresponses ofEscherichia coliandBacillus subtilisto various concentrations of ampicillin were investigated in a label-free and quantitative manner. The presented method reconstructs the dynamic changes in the 3D refractive-index distributions of living bacteria in response to antibiotics at sub-micrometer spatial resolution.