bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of CD4+Sub-population of Resident Cardiac Fibroblasts Linked to Myocardial Fibrosis
Authors: Siamwala Jamila H. , Pagano Francesco S. , Dubielecka Patrycja M , Zhao Alexander , Chen Sonja , Granston Haley , Sadayappan Sakthivel , Rounds Sharon , Gilbert Richard J. 
Published: February 2021

AbstractInfiltration with inflammatory T-cells and accumulation of cardiac myofibroblasts are hallmarks of cardiac fibrosis and maladaptive remodeling. The origin, identity, and functions of the resident cardiac cells involved in this process are, however, unclear. To determine the identity of cells contained in regions exhibiting fibrosis, mass cytometry profiling was performed using resident human ventricular cardiac fibroblasts and right ventricle autopsy tissues from individuals diagnosed with pulmonary hypertension and SUGEN/hypoxia rats. Results showed that a subpopulation of resident myocardial fibroblasts expresses increased levels of CD4+, a helper T-cell surface marker, in addition to mesenchymal markers in humans and rats. Characterization of the resident cardiac fibroblast subpopulation, both structurally and functionally, using transcriptome and secretome analysis of the secreted cytokines, chemokines, proteins, and metabolites, evidenced that IL-1β induces a phenotypic switch of human cardiac fibroblasts from mesenchymal to CD4+lymphoidal lineagein vitro. RNA sequencing (RNA-seq) analysis of FACS-sorted CD4-expressing cardiac fibroblasts further revealed that the transcriptome of such IL-1β-induced CD4+fibroblast population exhibited classical lymphoidal and stem cell-like signatures. Lastly, reversal of cell clustering, phosphorylation of MAPK p38 and NF-κB p65, and phenotypic switching was achieved with the administration of an IL-1R antagonist. In conclusion, we have identified a subpopulation of cardiac fibroblasts which exhibits structural and functional attributes of both mesenchymal and lymphoid cells which is induced by IL-1β-IL-1R-NFkB pathway for differentiation of cardiac fibroblast cells. These data suggest that cardiac fibroblast transdifferentiation during inflammation may form the basis for maladaptive remodeling during myocardial fibrosis.
Effects of L-Dopa, SKF-38393 and Quinpirole on exploratory, anxiety- and depressive-like behaviors in pubertal female and male mice
Authors: Moraes Muiara Aparecida , Árabe Laila Blanc , Resende Bruna Lopes , Codo Beatriz Campos , de Araújo Lima Reis Ana Luiza , de Souza Bruno Rezende 
Published: February 2021

AbstractAdolescence is a phase of substantial changes in the brain, characterized by maturational remodeling of many systems. This remodeling allows functional plasticity to adapt in a changing environment but turns this period into a neurodevelopmental vulnerable window. The dopaminergic system is under morphological and physiological changes during this phase. The disruption of its balance can lead to molecular variation and abnormal behavior - representing a risk factor for neuropsychiatric disorders. In the present study, we investigated if changes in the dopaminergic tone alter mice behavior in a receptor and sex-specific manner, specifically in the beginning of puberty period. We administered L-Dopa, SKF-38393 (D1 dopamine receptor agonist) and Quinpirole (D2 dopamine receptor agonist) and tested male and female mice motor, anxiety- and depressive-like behavior. While females displayed an impaired exploratory drive, males presented an intense depressive-like response. Our results provide insights into the function of dopaminergic development in adolescent behavior and highlight the importance of studies in this time window with male and female subjects.
Cell-to-cell heterogeneities during extrinsic apoptosis arise from cell cycle progression and transmitotic apoptosis resistance
Authors: Pollak Nadine , Lindner Aline , Imig Dirke , Kuritz Karsten , Fritze Jacques S. , Heinrich Isabel , Stadager Jannis , Eisler Stephan , Stöhr Daniela , Allgöwer Frank , Scheurich Peter , Rehm Markus 
Published: February 2021

AbstractExtrinsic apoptosis relies on TNF-family receptor activation by immune cells or receptor-activating biologics. Here, we monitored cell cycle progression at minutes resolution to relate apoptosis kinetics and cell-to-cell heterogeneities in death decisions to cell cycle phases. Interestingly, we found that cells in S phase delay TRAIL receptor-induced death in favour for mitosis, thereby passing on an apoptosis-primed state to their offspring. This translates into two distinct fates, apoptosis execution post mitosis or cell survival from inefficient apoptosis. Transmitotic resistance is linked to Mcl-1 upregulation from mid S phase onwards, which allows cells to pass through mitosis with activated caspase-8, and with cells escaping apoptosis after mitosis sustaining sublethal DNA damage. Antagonizing Mcl-1 by BH3-mimetics suppresses cell cycle-dependent delays in apoptosis, prevents apoptosis-resistant progression through mitosis and averts unwanted survival from apoptosis induction. Cell cycle progression therefore modulates signal transduction during extrinsic apoptosis, with Mcl-1 governing decision making between death, proliferation and survival from inefficient apoptosis induction. Cell cycle progression thus is a crucial process from which cell-to-cell heterogeneities in fates and treatment outcomes emerge in isogenic cell populations during extrinsic apoptosis signalling.
Calbindin regulates Kv4.1 trafficking and excitability of dentate granule cells via CaMKII-dependent phosphorylation
Authors: Kim Kyung-Ran , Jeong Hyeon-Ju , Kim Yoonsub , Lee Seung Yeon , Kim Yujin , Kim Hyun-Ji , Lee Suk-Ho , Cho Hana , Kang Jong-Sun , Ho Won-Kyung 
Published: February 2021

SummaryCalbindin, a major Ca2+buffer in dentate granule cells (GCs), plays a critical role in shaping Ca2+signals, yet how it regulates neuronal functions remains largely unknown. Here, we found that calbindin knock-out mice (CBKO) exhibited hyperexcitability in dentate GCs and impaired pattern separation, which was concurrent with reduced K+current due to downregulated surface expression of Kv4.1. Consistently, manipulation of the calbindin expression in HT22 led to changes in CaMKII activation and the level of surface localization of Kv4.1 through phosphorylation at serine 555, confirming the mechanism underlying neuronal hyperexcitability in CBKO. We also discovered that Ca2+buffering capacity was significantly reduced in the GCs of Tg2576 to the level of CBKO GCs, and this reduction was restored to normal levels by antioxidants, suggesting that calbindin is a target of oxidative stress. Our data suggest that regulation of CaMKII signaling by Ca2+buffer is crucial for neuronal excitability regulation.
Aging impairs the essential contributions of non-glial progenitors to neurorepair in the dorsal telencephalon of the KillifishN. furzeri
Authors: Van houcke Jolien , Mariën Valerie , Zandecki Caroline , Vanhunsel Sophie , Moons Lieve , Ayana Rajagopal , Seuntjens Eve , Arckens Lutgarde 
Published: February 2021

SummaryThe aging central nervous system (CNS) of mammals displays progressive limited regenerative abilities. Recovery after loss of neurons is extremely restricted in the aged brain. Many research models fall short in recapitulating mammalian aging hallmarks or have an impractically long lifespan. We established a traumatic brain injury model in the African turquoise killifish (Nothobranchius furzeri), a regeneration-competent vertebrate model that evolved to naturally age extremely fast. Stab-wound injury of the aged killifish dorsal telencephalon unveils an impaired and incomplete regeneration response when compared to young individuals. Remarkably, killifish brain regeneration is mainly supported by atypical non-glial progenitors, yet their proliferation capacity appears declined with age. We identified a high inflammatory response and glial scarring to also underlie the hampered generation of new neurons in aged fish. These primary results will pave the way for further research to unravel the factor age in relation to neurorepair, and to improve therapeutic strategies to restore the injured and/or diseased aged mammalian CNS.HighlightsAging impairs neurorepair in the killifish pallium at multiple stages of the regeneration processAtypical non-glial progenitors support the production of new neurons in the naive and injured dorsal palliumThe impaired regeneration capacity of aged killifish is characterized by a reduced reactive proliferation of these progenitors followed by a decreased generation of newborn neurons that in addition, fail to reach the injury siteExcessive inflammation and glial scarring surface as potential brakes on brain repair in the aged killifish pallium
Organotypic endothelial adhesion molecules are key forTrypanosoma bruceitropism and virulence
Authors: De Niz Mariana , Bras Daniela , Pedro Mafalda , Nascimento Ana Margarida , Franco Claudio A. , Figueiredo Luisa M. 
Published: February 2021

SummaryTrypanosoma bruceiis responsible for lethal diseases in humans and cattle in Sub-Saharan Africa. These extracellular parasites extravasate from the blood circulation into several tissues. The importance of the vasculature in tissue tropism is poorly understood. Using intravital imaging and bioluminescence, we found that gonadal white adipose tissue and pancreas are the two main parasite reservoirs. We show that reservoir establishment happens before vascular permeability is compromised, suggesting that extravasation is an active mechanism. Blocking endothelial surface adhesion molecules (E-selectin, P-selectins, or ICAM2) significantly reduced extravascular parasite load in all organs and delayed host lethality. Remarkably, blocking CD36 had a specific effect on adipose tissue tropism that was sufficient to delay lethality, suggesting that establishment of the adipose tissue reservoir is necessary for parasite virulence. This works demonstrates the importance of the vasculature in aT. bruceiinfection and identifies organ-specific adhesion molecules as key players for tissue tropism.
Ocean-wide comparisons of mesopelagic planktonic community structures
Authors: Rigonato Janaina , Budinich Marko , Murillo Alejandro A. , Brandão Manoela C. , Pierella Karlusich Juan J. , Soviadan Yawouvi Dodji , Gregory Ann C. , Endo Hisashi , Kokoszka Florian , Vik Dean , Henry Nicolas , Frémont Paul , Labadie Karine , Zayed Ahmed A. , Dimier Céline , Picheral Marc , Searson Sarah , Poulain Julie , Kandels Stefanie , Pesant Stéphane , Karsenti Eric ,   The Tara Oceans coordinators, Bork Peer , Bowler Chris , de Vargas Colomban , Eveillard Damien , Gehlen Marion , Iudicone Daniele , Lombard Fabien , Ogata Hiroyuki , Stemmann Lars , Sullivan Matthew B. , Sunagawa Shinichi , Wincker Patrick , Chaffron Samuel , Jaillon Olivier 
Published: February 2021

AbstractFor decades, marine plankton have been investigated for their capacity to modulate biogeochemical cycles and provide fishery resources. Between the sunlit (epipelagic) layer and the deep dark waters, lies a vast and heterogeneous part of the ocean: the mesopelagic zone. How plankton composition is shaped by environment has been well-explored in the epipelagic but much less in the mesopelagic ocean. Here, we conducted comparative analyses of trans-kingdom community assemblages thriving in the mesopelagic oxygen minimum zone (OMZ), mesopelagic oxic, and their epipelagic counterparts. We identified nine distinct types of intermediate water masses that correlate with variation in mesopelagic community composition. Furthermore, oxygen, NO-and particle flux together appeared as the main drivers governing these communities. Novel taxonomic signatures emerged from OMZ while a global co-occurrence network analysis showed that about 70% of the abundance of mesopelagic plankton groups is organized into three community modules. One module gathers prokaryotes, pico-eukaryotes and Nucleo-Cytoplasmic Large DNA Viruses (NCLDV) from oxic regions, and the two other modules are enriched in OMZ prokaryotes and OMZ pico-eukaryotes, respectively. We hypothesize that OMZ conditions led to a diversification of ecological niches, and thus communities, due to selective pressure from limited resources. Our study further clarifies the interplay between environmental factors in the mesopelagic oxic and OMZ, and the compositional features of communities.
3D Neuronal Mitochondrial Morphology in Axons, Dendrites, and Somata of the Aging Mouse Hippocampus
Authors: Faitg Julie , Lacefield Clay , Davey Tracey , White Kathryn , Laws Ross , Kosmidis Stylianos , Reeve Amy K , Kandel Eric R , Vincent Amy E , Picard Martin 
Published: February 2021

SummaryThe brain’s ability to process complex informations relies on the constant supply of energy through aerobic respiration by mitochondria. Neurons contain three anatomically distinct compartments – the soma, dendrites, and projecting axons – which have different energetic and biochemical requirements, as well as different mitochondrial morphologies in cultured systems. Here we apply a quantitative three-dimensional electron microscopy approach to map mitochondrial network morphology and complexity in the mouse brain. We examine three neuronal sub-compartments – the soma, dendrites, myelinated axons – in the dentate gyrus and CA1 of the mouse hippocampus, two subregions with distinct principal cell types and functions. We also establish compartment-specific differences in mitochondrial morphology across these cell types between young and old mice, highlighting differences in age-related morphological recalibrations. Overall, these data define the nature of the neuronal mitochondrial network in the mouse hippocampus, providing a foundation to examine the role of mitochondrial morpho-function in the aging brain.
Dengue Virus Alters Sialic Acid Residues Configuration in Macrophages
Authors: Serrato-Salas Javier , Cruz-Zazueta Isabel , Montiel-Hernández José Luis , González-Christen Judith 
Published: February 2021

AbstractThe activation of the innate immune response requires sialic acid residues removal. Nevertheless, it is unknown the role for these changes during the Dengue virus infection. We determine if during Dengue virus infection, the sialic acid residues alter on the macrophages. The human monocytic cell line THP-1 was differentiated into macrophages and were infected with Dengue virus. The changes in sialic acid were evaluated by lectin blot in the cellular lysate. The activity of neuraminidase was defined by RT-PCR and fluorescence assays. Macrophages infection with DENV-2 reduces α-2,6 sialic acid residues at 24 h, and α-2,3 sialic acid residues lower at 48 h in some proteins. Transcriptional profile and enzymatic activities of Neu-1 showed a narrow decrease. Sialic acid residues oscillation in varied conformations and times suggest it a role of a selective mechanism to remove these residues. The lesser participation of Neu-1 in this process could be concomitant to other similar enzymes such as sialyl-transferases, or the phenomenon requires minimal activity to have a relevant biological function.
Segmentation of the Urothelium in Optical Coherence Tomography Images with Dynamic Contrast
Authors: Xu Zhuo , Zhu Hui , Wang Hui 
Published: February 2021

AbstractSignificanceSpeckle variations induced by intracellular motion (IM) in the urothelium was observed in optical coherence tomography (OCT) images. It is feasible to use the IM as a dynamic contrast to segment the urothelium with only two sequential OCT images. This new method opens the possibility of tracking the distribution of the urothelial cells to identify the microinvasion of bladder tumors.ApproachWith fresh porcine bladder tissue, IM was analyzed by tracking speckle variations using autocorrelation function, then quantified with CONTINE algorism to identify the decorrelation time (DT) of the speckle variations. Variance analysis is conducted to show IM amplitude and distribution in the urothelium. The segmentation of the urothelium is demonstrated using tissue samples with and without significantly stretching.ResultsSignificant speckle variations induced by IM exists in the urothelium. However, the distribution of the IM is heterogeneous. The DTs are majorly distributed between 1ms to 30ms. Using the IM as a dynamic contrast, the urothelium can be accurately and exclusively segmented, even the layer structure of the bladder is invisible.ConclusionsWith fresh porcine bladders, we show that IM can be used as a dynamic contrast to exclusively segment the urothelium. This contrast may provide a new mechanism for OCT to diagnosis the invasion of urothelial cancerous cells for the better staging of bladder cancer.
Acyloxyacyl Hydrolase Regulates Microglia-Mediated Pelvic Pain Through Toll-Like Receptor-4
Authors: Rahman-Enyart Afrida , Yaggie Ryan E. , Yang Wenbin , Bollinger Justin L. , Winter Deborah R. , Schaeffer Anthony J. , Klumpp David J. 
Published: February 2021

ABSTRACTInterstitial cystitis/bladder pain syndrome (IC/BPS) is a devastating condition of chronic pelvic pain and urinary dysfunction. We have shown that mice deficient for the lipase acyloxyacyl hydrolase (AOAH) develop pelvic allodynia and exhibit symptoms and comorbidities consistent with IC/BPS, as well as gut dysbiosis. Microglia are resident immune cells of the central nervous system (CNS) that respond to changes in the gut microbiome, and studies have linked microglial activation to neuropathic pain. Additionally, microglia express toll-like receptors (TLRs), including TLR4, which are activated by microbial components. We have previously shown that AOAH-deficient mice exhibit increased gut permeability, suggesting a possible mechanism of microglial TLR4 activation via translocation of microbial products across the intestinal barrier to the brain. Here, we assessed the role of AOAH and TLR4 in microglial activation and pelvic pain. AOAH immunoreactivity co-localized with the microglial marker P2YR12 but not astrocytes, suggesting a functional role for AOAH in microglia. Pharmacologic ablation of CNS microglia with PLX5622 resulted in decreased pelvic allodynia in AOAH-deficient mice and resurgence of pelvic pain upon drug washout. Aligned with microglial activation, we observed altered cytokine abundance inAoah−/− cortex that was reduced inAoah/Tlr4−/− cortex. Consistent with our hypothesis of TLR4 activation by gut microbes, we observed microbiome-dependent activation of cultured BV2 microglial cells. Skeletal analyses revealed that AOAH-deficient mice have an activated microglia morphology in brain regions associated with neuropathic pain, independent of TLR4. Compared toAoah−/− mice,Aoah/Tlr4−/− mice exhibited decreased pelvic pain and microglial cytokine expression. Together, these findings demonstrate differential roles for AOAH and TLR4 in microglial activation and pelvic pain and thus identify novel therapeutic targets for IC/BPS.
The Aurora B gradient sustains kinetochore stability in anaphase
Authors: Papini Diana , Levasseur Mark , Higgins Jonathan M.G. 
Published: February 2021

AbstractKinetochores assemble on chromosomes in mitosis to allow microtubules to attach and bring about accurate chromosome segregation. The kinases Cyclin B-Cdk1 and Aurora B are crucial for the formation of stable kinetochores. However, the activity of these two kinases appears to decline dramatically at centromeres during anaphase onset, precisely when microtubule attachments are required to move chromosomes towards opposite poles of the dividing cell. We find that, although Aurora B leaves centromeres at anaphase, a gradient of Aurora B activity centred on the central spindle is still able to phosphorylate kinetochore substrates such as Dsn1 to modulate kinetochore stability in anaphase and to regulate kinetochore disassembly as cells enter telophase. We provide a model to explain how Aurora B co-operates with Cyclin B-Cdk1 to maintain kinetochore function in anaphase.
Use of botanical gardens as arks for conserving pollinators and plant-pollinator interactions: A case study from the US Northern Great Plains
Authors: Vilella-Arnizaut Isabela B. , Fenster Charles B. 
Published: February 2021

AbstractBotanical gardens have contributed to plant conservation through the maintenance of both living and preserved plant specimens for decades. However, there is still a large gap in the literature with regards to understanding the potential conservation value botanical gardens could provide for local pollinators. We investigated how plant-pollinator community structure and diversity may differ between botanical gardens and native habitats by sampling and comparing between two environments: a restored native grassland patch within a local botanical garden and fifteen native, remnant temperate grassland sites in the Northern Great Plains. We found pollinator diversity within the restored native grassland patch was greater than 55% of total remnant temperate grassland transects throughout the entire flowering season, while plant diversity and network community metrics between the two environments remained similar throughout, except that remnant prairies have more links (higher connectance) with pollinators than the garden patch. Overall, our findings demonstrate the promising role restored native grassland patches in botanical gardens could play as reservoirs for local pollinator communities by supporting plant-pollinator interactions comparable to those found in native habitat remnants in the same region.
Protection from lethalClostridioides difficileinfection via intraspecies competition for co-germinant
Authors: Leslie Jhansi L. , Jenior Matthew L. , Vendrov Kimberly C. , Standke Alexandra K. , Barron Madeline R. , O’Brien Tricia J. , Unverdorben Lavinia , Thaprawat Pariyamon , Bergin Ingrid L. , Schloss Patrick D. , Young Vincent B. 
Published: February 2021

AbstractClostridioides difficile,a Gram-positive, spore-forming bacterium, is the primary cause of infectious nosocomial diarrhea. Antibiotics are a major risk factor forC. difficileinfection (CDI) as they disrupt the gut microbial community, enabling increased germination of spores and growth of vegetativeC. difficile. To date the only single-species bacterial preparation that has demonstrated efficacy in reducing recurrent CDI in humans is non-toxigenicC. difficile.Using multiple infection models we determined that pre-colonization with a less virulent strain is sufficient to protect from challenge with a lethal strain ofC. difficile,surprisingly even in the absence of adaptive immunity. Additionally, we showed that protection is dependent on high levels of colonization by the less virulent strain and that it is mediated by exclusion of the invading strain. Our results suggest that reduction of amino acids, specifically glycine following colonization by the first strain ofC. difficileis sufficient to decrease germination of the second strain thereby limiting colonization by the lethal strain.ImportanceAntibiotic-associated colitis is often caused by infection with the bacteriumClostridioides difficile.In this study we found that reduction of the amino acid glycine by pre-colonization with a less virulent strain ofC. difficileis sufficient to decrease germination of a second strain. This finding demonstrates that the axis of competition for nutrients can include multiple life stages. This work is important, as it is the first to identify a possible mechanism through which pre-colonization withC. difficile, a current clinical therapy, provides protection from reinfection. Furthermore, our work suggests that targeting nutrients utilized by all life stages could be an improved strategy for bacterial therapeutics that aim to restore colonization resistance in the gut.