bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does plant –microbe’s common Inter Simple Sequence Repeat lead to a new recombination? A novel mechanism of pathogenicity
Authors: Rakhashiya Purvi M. , Bhatt Pritesh P. , Thaker Vrinda S. 
Published: January 2021

AbstractA total of eight varieties of the mango from an orchard were studied using molecular markers to understand the host-pathogen interaction. From the infected leaves of the plant, a total of the 8 bacterial pathogens (Exiguobacterium arabatum, Pseudomonas mendocina, Pantoea dispersa, Bacillus sp. Pantoea ananatis, Micrococcous luteus, Microbacterium_sp., Enterobacter cloacae) were isolated and identified. All the host varieties of mango were distinguished for the genetic diversity using the Inter Simple Sequence Repeat (ISSR) DNA markers. This set of ISSR marker primers were also used for the mango pathogens. PCR amplification of the ISSR primers showed polymorphic and monomorphic band patterns in the host plants and in their pathogens. The monomorphic band generated by PCR amplification in the host and in the pathogen, by the common primer, is selected and used for PCR hybridization technique. PCR products obtained from the host, pathogen and hybridization were cloned, sequenced and compared. A multiple sequence alignment of these sequences revealed that the product of hybridization PCR was mixture of host and pathogen sequences. On this basis, we hypothesize a possibility for the recombination of host-microbes DNA as one of the mechanisms of pathogenicity for the plant pathogens using hybrid PCR technique. The possible mechanism of recombination for plant host and its pathogen is discussed.HighlightsInter Simple Sequence Repeat markers used to (i) Fingerprint the pathogens and their host (mango) and (ii) for study of the possibilities for the recombination as mechanism of pathogenicity.
Alzheimer’s disease-associated β-Amyloid does not protect against Herpes Simplex Virus 1 brain infection
Authors: Bocharova Olga , Molesworth Kara , Pandit Narayan P. , Baskakov Ilia V. 
Published: January 2021

AbstractAlzheimer’s disease (AD) is devastating fatal neurodegenerative disease. An alternative to the amyloid cascade hypothesis is the hypothesis that a viral infection is key to the etiology of late-onset AD, with amyloid Aβ peptides playing a protective role. Contrary to previous work, in the current study the 5XFAD genotype failed to protect mice against infection with two strains of herpes simplex virus 1 (HSV-1), 17syn+ and McKrae. Moreover, the region- or cell-specific tropisms of HSV-1 were not affected by the 5XFAD genotype, arguing that host-pathogen interactions were not altered. In aged 5XFAD mice with abundant Aβ plaques, only small, statistically non-significant protection against acute HSV-1 infection was observed, yet no colocalization between HSV-1 and Aβ plaques was found. While the current study questions the antiviral role of APP or Aβ, it neither supports nor refutes the viral etiology hypothesis of late-onset AD.
The expected behaviour of random fields in high dimensions: contradictions in the results of Bansal and Peterson (2018)
Authors: Davenport Samuel , Nichols Thomas E. 
Published: January 2021

AbstractBansal and Peterson (2018) found that in simple stationary Gaussian simulations Random Field Theory incorrectly estimates the number of clusters of a Gaussian field that lie above a threshold. Their results contradict the existing literature and appear to have arisen due to errors in their code. Using reproducible code we demonstrate that in their simulations Random Field Theory correctly predicts the expected number of clusters and therefore that many of their results are invalid.
A Single Cell Atlas of Lung Development
Authors: Negretti Nicholas M. , Plosa Erin J. , Benjamin John T. , Schuler Bryce A. , Habermann A. Christian , Jetter Christopher , Gulleman Peter , Taylor Chase J. , Nichols David , Matlock Brittany K. , Guttentag Susan H. , Blackwell Timothy S. , Banovich Nicholas E. , Kropski Jonathan A. , Sucre Jennifer M. S. 
Published: January 2021

SummaryLung organogenesis requires precisely timed shifts in the spatial organization and function of parenchymal cells, especially during the later stages of lung development. To investigate the mechanisms governing lung parenchymal dynamics during development, we performed a single cell RNA sequencing (scRNA-seq) time-series yielding 92,238 epithelial, endothelial, and mesenchymal cells across 8 time points from embryonic day 12 (E12) to postnatal day 14 (P14) in mice. We combined new computational analyses with RNAin situhybridization to explore transcriptional velocity, fate likelihood prediction, and spatiotemporal localization of cell populations during the transition between the saccular and alveolar stages. We interrogated this atlas to illustrate the complexity of type 1 pneumocyte function during the saccular and alveolar stages, and we demonstrate an integrated view of the cellular dynamics during lung development.
IGFBP2 protects against pulmonary fibrosis through inhibiting P21-mediated senescence
Authors: Chiahsuan Chin , Lee John , Ravichandran Ranjith , Fleming Timothy , Wheatcroft Stephen , Kearney Mark , Bremner Ross , Mohanakumar Thalachallour , Flint David J , Sureshbabu Angara 
Published: January 2021

AbstractAccumulation of senescent cells contributes to age related diseases including idiopathic pulmonary fibrosis (IPF). Insulin-like growth factor binding proteins (IGFBPs) are evolutionarily conserved proteins that play a vital role in many biological processes. Overall, little is known about the functions of IGFBP2 in the epigenetic regulation of cellular senescence and pulmonary fibrosis. Here, we show thatIgfbp2expression was significantly downregulated at both mRNA and protein levels in a low-dose bleomycin-induced pulmonary fibrosis model of aged mice. Using the reduced representation of bisulfite sequencing technique, we demonstratedIgfbp2downregulation is attributed to DNA methylation of CpG islands in fibrotic lungs of aged mice. Furthermore,Igfbp2siRNA knockdown increased both P53 and P21 protein levels in mouse lung epithelial cells exposed to hypoxia treatment. Lentiviral mediated expression ofIgfb2decreased P21 protein levels and significantly reduced beta galactosidase activity in mouse lung epithelial cells challenged with a senescent drug (atazanavir) and hypoxia treatments. Using the RT2 Profiler PCR Array, we found that P21, PAI-1, IRF-5 and IRF-7, important regulators of senescence pathway, were significantly downregulated specifically in type-II alveolar epithelial cells (AECs) of aged human-Igfbp2transgenic mice after bleomycin challenge. Finally, transgenic expression of human-Igfbp2in type-II AECs from aged bleomycin challenged mice significantly decreased senescent associated secretory phenotype factors and also reduced extracellular matrix markers compared to aged wild-type mice challenged with bleomycin injury. Collectively, these findings reveal that epigenetic repression ofIgfbp2promotes pulmonary fibrosis and that restoring IGFBP2 in fibrotic lungs could prove effective in IPF treatment.
Genetically Engineered Mice for Combinatorial Cardiovascular Optobiology
Authors: Lee Frank K. , Lee Jane C. , Shui Bo , Reining Shaun , Jibilian Megan , Small David M. , Jones Jason S. , Allan-Rahill Nathaniel H. , Lamont Michael R.E. , Rizzo Megan A. , Tajada Sendoa , Navedo Manuel F. , Santana Luis Fernando , Nishimura Nozomi , Kotlikoff Michael. I. 
Published: January 2021

AbstractOptogenetic effectors and sensors provide a novel real-time window into complex physiological processes, enabling determination of molecular signaling processes within functioning cellular networks. However, the combination of these optical tools in mice is made practical by construction of genetic lines that are optically compatible and genetically tractable. We present a new toolbox of 21 mouse lines with lineage -specific expression of optogenetic effectors and sensors for direct biallelic combination, avoiding the multiallelic requirement of Cre recombinase -mediated DNA recombination, focusing on models relevant for cardiovascular biology. Optogenetic effectors (11 lines) or Ca2+sensors (10 lines) were selectively expressed in cardiac pacemaker cells, cardiomyocytes, vascular endothelial and smooth muscle cells, alveolar epithelial cells, lymphocytes, glia, and other cell types. Optogenetic effector and sensor function was demonstrated in numerous tissues. Arterial/arteriolar tone was modulated by optical activation of the second messengers InsP3(optoα1AR) and cAMP (optoß2AR), or Ca2+- permeant membrane channels (CatCh2) in smooth muscle (Acta2) and endothelium (Cdh5). Cardiac activation was separately controlled through activation of nodal/conducting cells or cardiac myocytes. We demonstrate combined effector and sensor function in biallelic mouse crosses: optical cardiac pacing and simultaneous cardiomyocyte Ca2+imaging in HCN4BAC-CatCh2/αMHC-GCaMP8 crosses. These experiments highlight the potential of these mice to explore cellular signalingin vivo, in complex tissue networks.
Poly (I:C)-induced maternal immune activation modifies ventral hippocampal regulation of stress reactivity: prevention by environmental enrichment
Authors: Zhao Xin , Mohammed Ruqayah , Tran Hieu , Erickson Mary , Kentner Amanda C. 
Published: January 2021

AbstractEnvironmental enrichment (EE) has been successfully implemented in human rehabilitation settings. However, the mechanisms underlying its success are not understood. Incorporating components of EE protocols into our animal models allows for the exploration of these mechanisms and their role in mitigation. Using a mouse model of maternal immune activation (MIA), the present study explored disruptions in social behavior and associated hypothalamic pituitary adrenal (HPA) axis functioning, and whether a supportive environment could prevent these effects. We show that prenatal immune activation of toll-like receptor 3, by the viral mimetic polyinosinic-polycytidylic acid (poly(I:C)), led to disrupted maternal care in that dams built poorer quality nests, an effect corrected by EE housing. Standard housed male and female MIA mice engaged in higher rates of repetitive rearing and had lower levels of social interaction, alongside sex-specific expression of several ventral hippocampal neural stress markers. Moreover, MIA males had delayed recovery of plasma corticosterone in response to a novel social encounter. Enrichment housing, likely mediated by improved maternal care, protected against these MIA-induced effects. We also evaluatedc-Fosimmunoreactivity associated with the novel social experience and found MIA to decrease neural activation in the dentate gyrus. Activation in the hypothalamus was blunted in EE housed animals, suggesting that the putative circuits modulating social behaviors may be different between standard and complex housing environments. These data demonstrate that augmentation of the environment supports parental care and offspring safety/security, which can offset effects of early health adversity by buffering HPA axis dysregulation. Our findings provide further evidence for the viability of EE interventions in maternal and pediatric settings.Highlights‐Environmental enrichment (EE) protocols are used clinically to promote rehabilitation‐Use of EE in animal models may identify mechanisms underlying clinical successes‐Maternal immune activation (MIA) decreased social engagement; this effect was blocked by EE‐MIA reducedc-Fosactivation in the dentate gyrus, while EE reduced activation in the hypothalamus, in response to social stimuli‐EE inhibited MIA-induced HPA dysregulation in ventral hippocampus
Extracellular vesicles regulate yeast growth, biofilm formation, and yeast-to-hypha differentiation inCandida albicans
Authors: Honorato Leandro , Demetrio Joana Feital , Ellis Cameron C. , Piffer Alicia , Pereira Yan , Frases Susana , de Sousa Araújo Glauber Ribeiro , Pontes Bruno , Mendes Maria Tays , Pereira Marcos Dias , Guimarães Allan J. , da Silva Natalia Martins , Vargas Gabriele , Joffe Luna , Poeta Maurizio Del , Nosanchuk Joshua D. , Zamith Daniel , dos Reis Flavia Coelho Garcia , Rodrigues Marcio L. , de Toledo Martins Sharon , Alves Lysangela Ronalte , Almeida Igor C. , Nimrichter Leonardo 
Published: January 2021

AbstractThe ability to undergo morphological changes during adaptation to distinct environments is exploited byCandida albicansand has a direct impact on virulence. In this study, we investigated the influence of fungal extracellular vesicles (EVs) during yeast growth, biofilm formation, and morphogenesis inC. albicans. Addition ofC. albicansEVs (CaEVs) to the culture medium positively affected yeast growth. Using crystal violet staining and scanning electron microscopy (SEM), we demonstrated thatCaEVs inhibited biofilm formation byC. albicans in vitro. By time-lapse microscopy and SEM, we showed thatCaEV-treatment stops filamentation promoting pseudohyphae formation with multiple sites for yeast budding. The ability ofCaEVs to regulate dimorphism was further compared to EVs isolated from differentC. albicansstrains,Saccharomyces cerevisiae, andHistoplasma capsulatum.CaEVs from distinct strains robustly inhibited yeast-to-hyphae differentiation with morphological changes occurring in less than 4 hours. A minor inhibitory effect was promoted by EVs fromS. cerevisiaeandH. capsulatumonly after 24 hours of incubation. The inhibitory effect ofCaEVs was promoted by a combination of lipid compounds identified by gas chromatography-tandem mass spectrometry analysis as sesquiterpenes, diterpenes, and fatty acids. Remarkably,CaEVs were also able to reverse filamentation, transforming hyphal growth to yeast forms. Transcriptomic analysis demonstrated that treatment withCaEVs modified the expression of more than 300 genes. The most effectively upregulated pathways were related to DNA metabolism. The downregulated genes were mostly associated with extracellular and adhesion proteins. Finally, yeast cells treated withCaEVs for 24 hours lost their agar invasive ability and were avirulent when inoculated inGalleria mellonellalarvae. In summary, our results indicate that fungal EVs can profoundly modifyC. albicansgrowth and regulate yeast-to-hypha differentiation inhibiting biofilm formation and virulence.
A single cell atlas reveals unanticipated cell type complexity inDrosophilaovaries
Authors: Slaidina Maija , Gupta Selena , Banisch Torsten , Lehmann Ruth 
Published: January 2021

AbstractOrgan function relies on the spatial organization and functional coordination of numerous cell types. TheDrosophilaovary is a widely used model system to study the cellular activities underlying organ function, including stem cell regulation, cell signaling and epithelial morphogenesis. However, the relative paucity of cell type specific reagents hinders investigation of molecular functions at the appropriate cellular resolution.Here, we used single cell RNA sequencing to characterize all cell types of the stem cell compartment and early follicles of theDrosophilaovary. We computed transcriptional signatures and identified specific markers for nine states of germ cell differentiation, and 23 somatic cell types and subtypes. We uncovered an unanticipated diversity of escort cells, the somatic cells that directly interact with differentiating germline cysts. Three escort cell subtypes reside in discrete anatomical positions, and express distinct sets of secreted and transmembrane proteins, suggesting that diverse micro-environments support the progressive differentiation of germ cells. Finally, we identified 17 follicle cell subtypes, and characterized their transcriptional profiles. Altogether, we provide a comprehensive resource of gene expression, cell type specific markers, spatial coordinates and functional predictions for 34 ovarian cell types and subtypes.
PIKfyve inhibition blocks endolysosomal escape of α-synuclein fibrils and spread of α-synuclein aggregation
Authors: See Stephanie K. , Chen Merissa , Bax Sophie , Tian Ruilin , Woerman Amanda , Tse Eric , Johnson Isabel E. , Nowotny Carlos , Muñoz Elise N. , Sengstack Janine , Southworth Daniel R. , Gestwicki Jason E. , Leonetti Manuel D. , Kampmann Martin 
Published: January 2021

ABSTRACTThe inter-cellular prion-like propagation of α-synuclein aggregation is emerging as an important mechanism driving the progression of neurodegenerative diseases including Parkinson’s disease and multiple system atrophy (MSA). To discover therapeutic strategies reducing the spread of α-synuclein aggregation, we performed a genome-wide CRISPR interference screen in a human cell-based model. We discovered that inhibiting PIKfyve dramatically reduced α-synuclein aggregation induced with both recombinant α-synuclein fibrils and fibrils isolated from MSA patient brain. While PIKfyve inhibition did not affect fibril uptake or α-synuclein clearance or secretion, it reduced α-synuclein trafficking from the early endosome to the lysosome, thereby limiting fibril escape from the lysosome and reducing the amount of fibrils that reach cytosolic α-synuclein to induce aggregation. These findings point to the endolysosomal transport of fibrils as a critical step in the propagation of α-synuclein aggregation and a potential therapeutic target.
Recovery of consolidation after sleep following experimental stroke – interaction of slow waves, spindles and GABA
Authors: Kim Jaekyung , Guo Ling , Hishinuma April , Lemke Stefan , Ramanathan Dhakshin S. , Won Seok-Joon , Ganguly Karunesh 
Published: January 2021

ABSTRACTSleep is known to be important for promoting recovery after brain injuries such as stroke. Yet, it remains unclear how such injuries affect neural processing during sleep and how to precisely enhance sleep-dependent memory processing during recovery. Using an experimental model of focal cortical stroke in rats along with long-term electrophysiological monitoring of neural firing and sleep microarchitecture, here we show that sleep-dependent neural processing is altered after stroke induction. Specifically, we found that the precise coupling of spindles to global slow- oscillations (SO), a phenomenon that is known to be important for memory consolidation, appeared to be disrupted by a pathological increase in “isolated” local delta waves. The transition from this pathological to a more physiological sleep state – with both a reduction in isolated delta waves and increased spindle coupling to SO – was associated with sustained performance gains after task training during recovery. Interestingly, post-injury sleep processing could be pushed towards a more physiological state via a pharmacological reduction of tonic GABA. Together, our results suggest that sleep processing after cortical brain injuries may be impaired due to an increase in local delta waves and that restoration of physiological processing is important for recovery of task performance.
Graph neural network based heterogeneous propagation scheme for classifying alzheimer’s disease
Authors: Byun Jiyoung , Jeong Yong 
Published: January 2021

ABSTRACTDeep learning frameworks for disease classification using neuroimaging and non-imaging information require the capability of capturing individual features as well as associative information among subjects. Graphs represent the interactions among nodes, which contain the individual features, through the edges in order to incorporate the inter-relatedness among heterogeneous data. Previous graph-based approaches for disease classification have focused on the similarities among subjects by establishing customized functions or solely based on imaging features. The purpose of this paper is to propose a novel graph-based deep learning architecture for classifying Alzheimer’s disease (AD) by combining the resting-state functional magnetic resonance imaging and demographic measures without defining any study-specific function. We used the neuroimaging data from the ADNI and OASIS databases to test the robustness of our proposed model. We combined imaging-based and non-imaging information of individuals by categorizing them into distinctive nodes to construct asubject–demographic bipartite graph. The approximate personalized propagation of neural predictions, a recently developed graph neural network model, was used to classify the AD continuum from cognitively unimpaired individuals. The results showed that our model successfully captures the heterogeneous relations among subjects and improves the quality of classification when compared with other classical and deep learning models, thus outperforming the other models.
Presynaptic NMDA receptors facilitate short-term plasticity and BDNF release at hippocampal mossy fiber synapses
Authors: Lituma Pablo J. , Kwon Hyung-Bae , Alviña Karina , Lujan Rafael , Castillo Pablo E. 
Published: January 2021

SummaryNeurotransmitter release is a highly controlled process by which synapses can critically regulate information transfer within neural circuits. While presynaptic receptors –typically activated by neurotransmitters and modulated by neuromodulators– provide a powerful way of fine-tuning synaptic function, their contribution to activity-dependent changes in transmitter release remains poorly understood. Here, we report that presynaptic NMDA receptors (preNMDARs) at mossy fiber boutons in the rodent hippocampus can be activated by physiologically relevant patterns of activity and selectively enhance short-term synaptic plasticity at mossy fiber inputs onto CA3 pyramidal cells and mossy cells, but not onto inhibitory interneurons. Moreover, preNMDARs facilitate brain-derived neurotrophic factor (BDNF) release and contribute to presynaptic calcium rise. Taken together, our results indicate that by increasing presynaptic calcium, preNMDARs fine tune mossy fiber neurotransmission and can control information transfer during dentate granule cell burst activity that normally occurin vivo.
Comparative investigation of the Diabetic foot ulcer microbiome
Authors: Saeb Amr T. M. , Tayeb Hamsa T. , Ouizi Samir , Nassar Majed S. , Alfadda Assim , Raja G. K Udaya , Mani Balavenkatesh , Youssef Amira , Alsuabeyl Mohammed S. 
Published: January 2021

AbstractBackgroundMany factors may affect wound healing in Diabetic foot ulcer, namely, microbial density, microorganisms, microbial synergy, the host immune response, and infected tissue quality.MethodologyThis study used a cross-sectional design. We assessed 38 Subjects with DFUs, 23 neuroischaimic, and 15 neuropathic, for microbiota colonizing the DFU utilizing traditional cultures and 16S gene sequencing methods. All the relevant clinical factors were collected. Wound swabs were collected for both traditional microbiological analysis, direct swab (DSM), and cultured (CM) microbiome analysis. DNA isolation, and 16SrRNA hypervariable regions were amplified. Bioinformatics analysis was performed using IonReporter Software, statistical analysis, and diversity indices were computed with vegan R-package.ResultsThe traditional microbiological method was able to detect a maximum of one or two pathogens, and, in some cases, no pathogen was detected. The total number of the observed species was 176. The number of identified species was higher in the cultured microbiome (155) than the direct swab microbiome (136). Diversity analysis indicated that biological diversity is higher in the cultured microbiome compared with the DSM. The Shannon H index was 2.75 for the cultured microbiome and 2.63 for DSM. We observed some differences in the major bacterial taxa amongst neuroischaimic and neuropathic DFU microbiomes.ConclusionsCultured microbiome is superior to both the traditional method and direct swab microbiome. The Neuroischaimic group showed higher values for the tested diversity indices than the Neuroischaimic group. Neither Cluster Analysis nor Principal Component Analysis showed apparent clustering amongst the two types of ulcers.