bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emotional contagion of pain across different social cues shares common and process-specific neural representations
Authors: Zhou Feng , Li Jialin , Zhao Weihua , Xu Lei , Zheng Xiaoxiao , Fu Meina , Yao Shuxia , Kendrick Keith M. , Wager Tor D. , Becker Benjamin 
Published: February 2020

AbstractInsular and anterior cingulate cortex activation across vicarious pain induction procedures suggests that they are core pain empathy nodes. However, pain empathic responses encompass emotional contagion as well as unspecific arousal and overlapping functional activations are not sufficient to determine shared and process-specific neural representations. We employed multivariate pattern analyses to fMRI data acquired during physical and affective vicarious pain induction and found spatially and functionally similar cross-modality (physical versus affective) whole-brain vicarious pain-predictive patterns. Further analyses consistently identified shared neural representations in the bilateral mid-insula. Mid-insula vicarious pain patterns were not sensitive to capture non-painful arousing negative stimuli but predicted self-experienced pain during thermal stimulation, suggesting process-specific representation of emotional contagion for pain. Finally, a domain-general vicarious pain pattern which predicted vicarious as well as self-experienced pain was developed. Our findings demonstrate a generalizable neural expression of vicarious pain and suggest that the mid-insula encodes emotional contagion for pain.
Caenorhabditis elegansprocesses sensory information to choose between freeloading and self-defense strategies
Authors: Schiffer Jodie , Servello Francesco , Heath William , Amrit Francis Raj Gandhi , Stumbur Stephanie , Johnsen Sean , Stanley Julian , Tam Hannah , Brennan Sarah , McGowan Natalie , Vogelaar Abigail , Xu Yuyan , Serkin William , Ghazi Arjumand , Apfeld Javier 
Published: February 2020

AbstractHydrogen peroxide is the preeminent chemical weapon that organisms use for combat. Individual cells rely on conserved defenses to prevent and repair peroxide-induced damage, but whether similar defenses might be coordinated across cells in animals remains poorly understood. Here, we identify a neuronal circuit in the nematodeCaenorhabditis elegansthat processes information perceived by two sensory neurons to control the induction of hydrogen-peroxide defenses in the organism. We found that catalases produced byEscherichia coli, the nematode’s food source, can deplete hydrogen peroxide from the local environment and thereby protect the nematodes. In the presence ofE. coli, the nematode’s neurons signal via TGFβ-insulin/IGF1 relay to target tissues to repress expression of catalases and other hydrogen-peroxide defenses. This adaptive strategy is the first example of a multicellular organism modulating its defenses when it expects to freeload from the protection provided by molecularly orthologous defenses from another species.
3D Epigenomic Characterization Reveals Insights Into Gene Regulation and Lineage Specification During Corticogenesis
Authors: Song Michael , Pebworth Mark-Phillip , Yang Xiaoyu , Abnousi Armen , Fan Changxu , Wen Jia , Rosen Jonathan D. , Choudhary Mayank NK , Cui Xiekui , Jones Ian R. , Bergenholtz Seth , Eze Ugomma C. , Juric Ivan , Li Bingkun , Maliskova Lenka , Liu Weifang , Pollen Alex A. , Li Yun , Wang Ting , Hu Ming , Kriegstein Arnold R. , Shen Yin 
Published: February 2020

AbstractLineage-specific epigenomic changes during human corticogenesis have previously remained elusive due to challenges with tissue heterogeneity and sample availability. Here, we analyze cis-regulatory chromatin interactions, open chromatin regions, and transcriptomes for radial glia, intermediate progenitor cells, excitatory neurons, and interneurons isolated from mid-gestational human brain samples. We show that chromatin looping underlies transcriptional regulation for lineage-specific genes, with transcription factor motifs, families of transposable elements, and disease-associated variants enriched at distal interacting regions in a cell type-specific manner. A subset of promoters exhibit unusually high degrees of chromatin interactivity, which we term super interactive promoters. Super interactive promoters are enriched for critical lineage-specific genes, suggesting that interactions at these loci contribute to the fine-tuning of cell type-specific transcription. Finally, we present CRISPRview, a novel approach for validating distal interacting regions in primary cells. Our study presents the first characterization of cell type-specific 3D epigenomic landscapes during human corticogenesis, advancing our understanding of gene regulation and lineage specification during human brain development.
Muscle progenitor cells are required for the regenerative response and prevention of adipogenesis after limb ischemia
Authors: Abbas Hasan , Olivere Lindsey A. , Padgett Michael E. , Schmidt Cameron A. , Gilmore Brian F. , Southerland Kevin W. , McClung Joseph M. , Kontos Christopher D. 
Published: February 2020

AbstractPeripheral artery disease (PAD) is nearly as common as coronary artery disease, but few effective treatments exist, and it is associated with significant morbidity and mortality. Although PAD studies have focused on the vascular response to ischemia, skeletal muscle cells play a critically important role in determining the phenotypic manifestation of PAD. Here, we demonstrate that genetic ablation of Pax7+muscle progenitor cells (MPCs, or satellite cells) in a murine model of hind limb ischemia (HLI) resulted in a complete absence of normal muscle regeneration following ischemic injury, despite a lack of morphological or physiological changes in resting muscle. Compared to ischemic muscle of control mice (Pax7WT), the ischemic limb of Pax7-deficient mice (Pax7Δ) was unable to generate significant force 7- or 28-days after HLI inex vivoforce measurement studies. A dramatic increase in adipose infiltration was observed 28 days after HLI in Pax7Δmice, which replaced functional muscle. To investigate the mechanism of this adipogenic change, mice with inhibition of fibro/adipogenic precursors (FAPs), another pool of MPCs, were subjected to HLI. Inhibition of FAPs decreased muscle adipose fat but increased fibrosis. MPCs cultured from mouse muscle tissue failed to form myotubesin vitrofollowing depletion of satellite cellsin vivo, and they displayed an increased propensity to differentiate into fat in adipogenic medium. Importantly, this phenotype was recapitulated in patients with critical limb ischemia (CLI), the most severe form of PAD. Skeletal muscle samples from CLI patients demonstrated an increase in adipose deposition in more ischemic regions of muscle, which corresponded with a decrease in the number of satellite cells in those regions. Collectively, these data demonstrate that Pax7+MPCs are required for normal muscle regeneration after ischemic injury, and they suggest that targeting muscle regeneration may be an important therapeutic approach to prevent muscle degeneration in PAD.
Projection of orthogonal tiling from the retina to the visual cortex
Authors: Jang Jaeson , Song Min , Kim Gwangsu , Paik Se-Bum 
Published: February 2020

AbstractIn higher mammals, the primary visual cortex (V1) is organized into diverse tuning maps of visual features such as orientation, spatial frequency and ocular dominance. The topography of these maps is observed to intersect orthogonally, implying that a developmental principle for efficient tiling of sensory modules may exist. However, it remains unclear how such a systematic relationship among cortical tuning maps could develop. Here, we show that the orthogonal organization of tuning modules already exist in retinal ganglion cell (RGC) mosaics, and that this provides a blueprint of the orthogonal organization in V1. Firstly, from the analysis of multi-electrode recording data in V1, we found that the ON-OFF subregion distance of receptive fields varies periodically across the cortical surface, strongly correlated to ocular dominance and spatial frequency in the area. Further, the ON-OFF alignment angle, that is orthogonal to the ON-OFF distance, appears to correlate with orientation tuning. These suggest that the orthogonal organization in V1 may originate from the spatial organization of the ON-OFF receptive fields in the bottom-up projections, and this scenario was tested from analysis of the RGC mosaics data in monkeys and cats. We found that the ON-OFF RGC distance and ON-OFF angle of neighbouring RGCs are organized into a topographic tiling across mosaics, analogous to the orthogonal intersection of cortical tuning maps. These findings suggest that the regularly structured ON-OFF patterns mirrored from a retina may initiate efficient tiling of functional domains in V1.HighlightsOrthogonal organization of visual tuning maps are observed in both V1 and the retinaCortical tuning maps are correlated with the profile of ON-OFF feedforward projectionsThe profile of ON-OFF receptive fields varies periodically across the V1 surfaceRegularly structured RGC patterns initiate the orthogonal tiling of sensory modules in V1
Lossless Immunocytochemistry using Photo-polymerized Hydrogel Thin-films
Authors: Lee Jeong Hyun , Santoso Aline T. , Park Emily S. , Matthews Kerryn , Duffy Simon P. , Ma Hongshen 
Published: February 2020

AbstractImmunocytochemistry (ICC), or immunofluorescence microscopy, is an essential biological technique for phenotyping cells in both research and diagnostic applications. Standard ICC methods often do not work well when the cell sample contains a small number of cells (<10,000) because of the significant cell loss that occurs during washing, staining, and centrifugation steps. Cell loss is particularly relevant when working with rare cells, such as circulating tumor cells, where such losses could significantly bias experimental outcomes. In order to eliminate cell loss in ICC protocols, we present a method to encapsulate the cell sample in a photo-polymerized hydrogel thin-film. The hydrogel thin-film is permeable to antibodies and other ICC reagents, thereby allowing the use of standard ICC protocols without modification. The cell sample is physically constrained by the hydrogel at the bottom surface of a standard (unmodified) imaging microtiter plate, thereby enabling the acquisition of high-quality micrographs regardless of the properties of the cell sample or staining reagents. Furthermore, while standard ICC requires several centrifugation steps during staining and washing, our hydrogel encapsulation method requires only a single centrifugation step. This property greatly reduces the time required to perform ICC protocols and is more compatible with robotic platforms. In this study, we show that standard ICC and Cytospin protocols are extremely lossy (>70% loss) when the sample contains less than 10,000 cells, while encapsulating the cells using a permeable hydrogel thin-film results in a lossless ICC process.
Acidification of Cytoplasmic pH inEscherichia coliProvides a Strategy to Cope with Stress and Facilitates Development of Antibiotic Resistance
Authors: Reyes-Fernández Esmeralda Z. , Schuldiner Shimon 
Published: February 2020

ABSTRACTAwareness of the problem of antimicrobial resistance (AMR) has escalated, and drug-resistant infections are named among the most urgent issues facing clinicians today. Bacteria can acquire resistance to antibiotics by a variety of mechanisms that, at times, involve changes in their metabolic status, thus altering diverse biochemical reactions, many of them pH-dependent. In this work, we found that modulation of the cytoplasmic pH (pHi) ofEscherichia coliprovides a thus far unexplored strategy to support resistance. We show here that the acidification of the cytoplasmic pH is a previously unrecognized consequence of the activation of themarRABoperon. The acidification itself contributes to the full implementation of the resistance phenotype. We measured the pHiof two resistant strains, developed in our laboratory, that carry mutations inmarRthat activate themarRABoperon. The pHiof both strains is lower than that of the wild type strain. Inactivation of themarRABresponse in both strains weakens resistance, and pHiincreases back to wild type levels. Likewise, we showed that exposure of wild type cells to weak acids that caused acidification of the cytoplasm induced a resistant phenotype, independent of themarRABresponse. We speculate that the decrease of the cytoplasmic pH brought about by activation of themarRABresponse provides a signaling mechanism that modifies metabolic pathways and serves to cope with stress and to lower metabolic costs.SIGNIFICANCEThe decreasing effectiveness of antibiotics in treating common infections has quickened in recent years, and resistance has spread worldwide. There is an urgent need to understand the mechanisms underlying acquisition and maintenance of resistance, and here we identify a novel element in the chain of events leading to a full-fledged clinically relevant state. TheEscherichia colimultiple antibiotic resistance (mar) regulon is induced by a variety of signals and modulates the activity of dozens of target genes involved in resistance to antibiotics. We report here a thus far unidentified result of this activation: acidification of the cytoplasmic pH. Manipulation of the cytoplasmic pH with weak acids and bases, independently of themarresponse, shows that the acidification significantly increases resistance.
Can routine laboratory tests discriminate 2019 novel coronavirus infected pneumonia from other community-acquired pneumonia?
Authors: Pan Yunbao , Ye Guangming , Zeng Xiantao , Liu Guohong , Zeng Xiaojiao , Jiang Xianghu , Zhao Jin , Chen Liangjun , Guo Shuang , Deng Qiaoling , Hong Xiaoyue , Yang Ying , Li Yirong , Wang Xinghuan 
Published: February 2020

AbstractBackgroundThe clinical presentation of 2019 Novel Coronavirus (2019-nCov) infected pneumonia (NCIP) resembles that of other etiologies of community-acquired pneumonia (CAP). We aimed to identify clinical laboratory features to distinguish NCIP from CAP.MethodsWe compared the ability of the hematological and biochemical features of 84 patients with NCIP at hospital admission and 316 patients with CAP. Parameters independently predictive of NCIP were calculated by multivariate logistic regression. The receiver operating characteristic (ROC) curves were generated and the area under the ROC curve (AUC) was measured to evaluate the discriminative ability.ResultsMost hematological and biochemical indexes of patients with NCIP were significantly different from patients with CAP. Nine laboratory parameters were identified to be highly predictive of a diagnosis of NCIP by multivariate analysis. The AUCs demonstrated good discriminatory ability for red cell distribution width (RDW) with an AUC of 0.88 and Hemoglobin (HGB) with an AUC of 0.82. Red blood cell (RBC), albumin (ALB), eosinophil (EO), hematocrit (HCT), alkaline phosphatase (ALP), and white blood cell (WBC) had fair discriminatory ability. Combinations of any two parameters performed better than did the RDW alone.ConclusionsRoutine laboratory examinations may be helpful for the diagnosis of NCIP. Application of laboratory tests may help to optimize the use of isolation rooms for patients when they present with unexplained febrile respiratory illnesses.
The Evolution of Mass Cell Suicide in Bacterial Warfare
Authors: Granato Elisa T. , Foster Kevin R. 
Published: February 2020

SUMMARYBehaviours that reliably cause the death of an actor are typically strongly disfavoured by natural selection, and yet many bacteria undergo cell lysis to release anti-competitor toxins [1–4]. This behaviour is most easily explained if only a few cells die to release toxins and help their clonemates, but the number of cells that actually lyse during bacterial warfare is unknown. The challenge is that one cannot distinguish cells that have undergone programmed suicide from those that were simply killed by a competitor’s toxin. We developed a two-colour fluorescence reporter assay inEscherichia colito overcome this problem. Surprisingly, this revealed conditions where nearly all cells undergo programmed lysis. Adding a DNA-damaging toxin (DNase colicin) to a focal strain causes it to engage in mass cell suicide where around 85% of cells lyse to release their own toxin. Time-lapse 3D confocal microscopy revealed that self-lysis occurs at even higher frequencies (~94%) at the interface between competing colonies. We sought to understand how such high levels of cell suicide could be favoured by natural selection. ExposingE. colithat do not perform lysis to the DNase colicin revealed that mass lysis only occurs when cells are going to die anyway from toxin exposure. From an evolutionary perspective, this renders the behaviour cost-free as these cells have zero reproductive potential. This explains how mass cell suicide can evolve, as any small benefit to surviving clonemates can lead to the strategy being favoured by natural selection. Our findings have strong parallels to the suicidal attacks of social insects [5–8], which are also performed by individuals with low reproductive potential, suggesting convergent evolution in these very different organisms.HIGHLIGHTSA novel assay can detectEscherichia coliundergoing cell suicide to release toxinsWe quantified the frequency of suicidal self-lysis during competitionsUnder some conditions, nearly all cells will self-lyse to release toxinsSelf-lysis makes evolutionary sense as cells will die anyway from competitors’ toxins
Genetic Profiling of Protein Burden and Nuclear Export Overload
Authors: Kintaka Reiko , Makanae Koji , Kato Hisaaki , Ohnuki Shinsuke , Ohya Yoshikazu , Andrews Brenda , Boone Charles , Moriya Hisao 
Published: February 2020

AbstractOverproduction (op) of proteins triggers cellular defects. One of the defined consequences of protein overproduction is the protein burden/cost, which is produced by an overloading of the protein synthesis process. However, the physiology of cells under a protein burden is not well characterized. We performed genetic profiling of protein burden by systematic analysis of genetic interactions between GFP-op, surveying both deletion mutants of nonessential genes and temperature-sensitive mutants of essential genes, in the budding yeastSaccharomyces cerevisiae. To dissect interactions specific to the protein burden, we also performed genetic profiling in cells with overproduction of triple-GFP (tGFP), and the nuclear export signal-containing tGFP (NES-tGFP). The mutants specifically interacted with GFP-op were suggestive of unexpected connections between actin-related processes like polarization and the protein burden, which was supported by morphological analysis. The tGFP-op interactions suggested that this protein probe overloads the proteasome, probably through the formation of intracellular aggregates, whereas those that interacted with NES-tGFP involved genes encoding components of the nuclear export process, providing a resource for further analysis of the protein burden and nuclear export overload.
Two alveolin network proteins are essential for the subpellicular microtubules assembly and conoid anchoring to the apical pole of matureToxoplasma gondii
Authors: Tosetti Nicolò , Dos Santos Pacheco Nicolas , Bertiaux Eloïse , Maco Bohumil , Bournonville Lorène , Hamel Virginie , Guichard Paul , Soldati-Favre Dominique 
Published: February 2020

AbstractToxoplasma gondiibelongs to the coccidian sub-group of Apicomplexa that possess an apical complex harboring a conoid, made of unique tubulin polymer fibers. This enigmatic and dynamic organelle extrudes in extracellular invasive parasites and is associated to the apical polar ring (APR), a microtubule-organizing center for the 22 subpellicular microtubules (SPMTs). The SPMTs are linked to the Inner Membrane Complex (IMC), a patchwork of flattened vesicles, via an intricate network of small filaments composed of alveolins proteins. Here, we capitalize on super-resolution techniques including stimulated emission depletion (STED) microscopy and ultrastructure expansion microscopy (U-ExM) to localize the Apical Cap protein 9 (AC9) and its close partner AC10, identified by BioID, to the alveolin network and intercalated between the SPMTs. Conditional depletion of AC9 or AC10 using the Auxin-induced Degron (AiD) system uncovered a severe loss of fitness. Parasites lacking AC9 or AC10 replicate normally but are defective in microneme secretion and hence fail to invade and egress from infected cells. Remarkably, a series of crucial apical complex proteins (MyoH, AKMT, FRM1, CPH1, ICMAP1 and RNG2) are lost in the mature parasites although they are still present in the forming daughter cells. Electron microscopy on intracellular or deoxycholate-extracted parasites revealed that the mature parasite mutants are conoidless. Closer examination of the SPMTs by U-ExM highlighted the disassembly of the SPMTs in the apical cap region that is presumably at the origin of the catastrophic loss of APR and conoid. AC9 and AC10 are two critical components of the alveolin network that ensure the integrity of the whole apical complex inT. gondiiand likely other coccidians.
Accelerated single cell seeding in relapsed multiple myeloma
Authors: Landau Heather , Yellapantula Venkata , Diamond Benjamin T. , Rustad Even H. , Maclachlan Kylee H. , Gundem Gunes , Medina-Martinez Juan , Arango Ossa Juan , Levine Max , Zhou Yangyu , Kappagantula Rajya , Baez Priscilla , Attiye Marc , Makohon-Moore Alvin , Zhang Lance , Boyle Eileen M , Ashby Cody , Blaney Patrick , Patel Minal , Zhang Yanming , Dogan Ahmet , Chung David , Giralt Sergio , Lahoud Oscar B. , Peled Jonathan U. , Scordo Michael , Shah Gunjan , Hassoun Hani , Korde Neha S. , Lesokhin Alexander M. , Lu Sydney , Mailankody Sham , Shah Urvi , Smith Eric , Hultcrantz Malin L. , Ulaner Gary A. , van Rhee Frits , Morgan Gareth , Ola Landgren C. , Papaemmanuil Elli , Iacobuzio-Donahue Christine , Maura Francesco 
Published: February 2020

AbstractThe malignant progression of multiple myeloma is characterized by the seeding of cancer cells in different anatomic sites followed by their clonal expansion. It has been demonstrated that this spatial evolution at varying anatomic sites is characterized by genomic heterogeneity. However, it is unclear whether each anatomic site at relapse reflects the expansion of pre-existing but previously undetected disease or secondary seeding from other sites. Furthermore, genomic evolution over time at spatially distinct sites of disease has not been investigated in a systematic manner.To address this, we interrogated 25 samples, by whole genome sequencing, collected at autopsy from 4 patients with relapsed multiple myeloma and demonstrated that each site had a unique evolutionary trajectory characterized by distinct single and complex structural variants and copy number changes. By analyzing the landscape of mutational signatures at these sites and for an additional set of 125 published whole exomes collected from 51 patients, we demonstrate the profound mutagenic effect of melphalan and platinum in relapsed multiple myeloma. Chemotherapy-related mutagenic processes are known to introduce hundreds of unique mutations in each surviving cancer cell. These mutations can be detectable by bulk sequencing only in cases of clonal expansion of a single cancer cell bearing the mutational signature linked to chemotherapy exposure thus representing a unique single-cell genomic barcode linked to a discrete time window in each patient’s life. We leveraged this concept to show that multiple myeloma systemic seeding is accelerated at clinical relapse and appears to be driven by the survival and subsequent expansion of a single myeloma cell following treatment with high dose melphalan therapy and autologous stem cell transplant.