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Search results for: Mechanisms

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#34525475   2021/09/15 To Up

Autopsy-Based Pulmonary and Vascular Pathology: Pulmonary Endotheliitis and Multi-Organ Involvement in COVID-19 Associated Deaths.

Findings from autopsies have provided evidence on systemic microvascular damage as one of the underlying mechanisms of Coronavirus disease 2019 (CO-VID-19). The aim of this study was to correlate autopsy-based cause of death in SARS-CoV-2, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients with chest imaging and severity grade of pulmonary and systemic morphological vascular pathology.
Martina Haberecker, Esther Irene Schwarz, Peter Steiger, Karl Frontzek, Felix Scholkmann, Xiankun Zeng, Sylvia Höller, Holger Moch, Zsuzsanna Varga

1147 related Products with: Autopsy-Based Pulmonary and Vascular Pathology: Pulmonary Endotheliitis and Multi-Organ Involvement in COVID-19 Associated Deaths.



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#34525413   2021/09/08 To Up

Modelling the relationship between poor sleep and problem anger in veterans: A dynamic structural equation modelling approach.

Problem anger and poor sleep are common, particularly in military and veteran populations, but the nature of the relationship is poorly understood, and treatment approaches would benefit from improved understanding of how these constructs interact. Ecological momentary assessment (EMA) is suitable for monitoring day-to-day fluctuations in symptoms, and modelling dynamic relationships between variables.
Olivia Metcalf, Jonathon Little, Sean Cowlishaw, Tracey Varker, Hussain-Abdulah Arjmand, Meaghan O'Donnell, Andrea Phelps, Mark Hinton, Richard Bryant, Malcolm Hopwood, Alexander McFarlane, David Forbes

1092 related Products with: Modelling the relationship between poor sleep and problem anger in veterans: A dynamic structural equation modelling approach.

1100 μg48 samples

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#34525388   2021/09/12 To Up

The exposome in practice: an exploratory panel study of biomarkers of air pollutant exposure in Chinese people aged 60-69 years (China BAPE Study).

The exposome overhauls conventional environmental health impact research paradigms and provides a novel methodological framework that comprehensively addresses the complex, highly dynamic interplays of exogenous exposures, endogenous exposures, and modifiable factors in humans. Holistic assessments of the adverse health effects and systematic elucidation of the mechanisms underlying environmental exposures are major scientific challenges with widespread societal implications. However, to date, few studies have comprehensively and simultaneously measured airborne pollutant exposures and explored the associated biomarkers in susceptible healthy elderly subjects, potentially resulting in the suboptimal assessment and management of health risks. To demonstrate the exposome paradigm, we describe the rationale and design of a comprehensive biomarker and biomonitoring panel study to systematically explore the association between individual airborne exposure and adverse health outcomes. We used a combination of personal monitoring for airborne pollutants, extensive human biomonitoring, advanced omics analysis, confounding information, and statistical methods. We established an exploratory panel study of Biomarkers of Air Pollutant Exposure in Chinese people aged 60-69 years (China BAPE), which included 76 healthy residents from a representative community in Jinan City, Shandong Province. During the period between September 2018 and January 2019, we conducted prospective longitudinal monitoring with a 3-day assessment every month. This project: (1) leveraged advanced tools for personal airborne exposure monitoring (external exposures); (2) comprehensively characterized biological samples for exogenous and endogenous compounds (e.g., targeted and untargeted monitoring) and multi-omics scale measurements to explore potential biomarkers and putative toxicity pathways; and (3) systematically evaluated the relationships between personal exposure to air pollutants, and novel biomarkers of exposures and effects using exposome-wide association study approaches. These findings will contribute to our understanding of the mechanisms underlying the adverse health impacts of air pollution exposures and identify potential adverse clinical outcomes that can facilitate the development of effective prevention and targeted intervention techniques.
Song Tang, Tiantian Li, Jianlong Fang, Renjie Chen, Yu'e Cha, Yanwen Wang, Mu Zhu, Yi Zhang, Yuanyuan Chen, Yanjun Du, Tianwei Yu, David C Thompson, Krystal J Godri Pollitt, Vasilis Vasiliou, John S Ji, Haidong Kan, Junfeng Jim Zhang, Xiaoming Shi

1379 related Products with: The exposome in practice: an exploratory panel study of biomarkers of air pollutant exposure in Chinese people aged 60-69 years (China BAPE Study).

100ug100ug1 mL100 μg4 Arrays/Slide

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#34525374   // To Up

Myosin-X and talin modulate integrin activity at filopodia tips.

Filopodia assemble unique integrin-adhesion complexes to sense the extracellular matrix. However, the mechanisms of integrin regulation in filopodia are poorly defined. Here, we report that active integrins accumulate at the tip of myosin-X (MYO10)-positive filopodia, while inactive integrins are uniformly distributed. We identify talin and MYO10 as the principal integrin activators in filopodia. In addition, deletion of MYO10's FERM domain, or mutation of its β1-integrin-binding residues, reveals MYO10 as facilitating integrin activation, but not transport, in filopodia. However, MYO10's isolated FERM domain alone cannot activate integrins, potentially because of binding to both integrin tails. Finally, because a chimera construct generated by swapping MYO10-FERM by talin-FERM enables integrin activation in filopodia, our data indicate that an integrin-binding FERM domain coupled to a myosin motor is a core requirement for integrin activation in filopodia. Therefore, we propose a two-step integrin activation model in filopodia: receptor tethering by MYO10 followed by talin-mediated integrin activation.
Mitro Miihkinen, Max L B Grönloh, Ana Popović, Helena Vihinen, Eija Jokitalo, Benjamin T Goult, Johanna Ivaska, Guillaume Jacquemet

1306 related Products with: Myosin-X and talin modulate integrin activity at filopodia tips.

100 assays100ug Lyophilized1mg 100ul0.1 mg1 mg100 µg100ug100 assays100 μg1 mg

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#34525372   // To Up

The prolyl-isomerase PIN1 is essential for nuclear Lamin-B structure and function and protects heterochromatin under mechanical stress.

Chromatin organization plays a crucial role in tissue homeostasis. Heterochromatin relaxation and consequent unscheduled mobilization of transposable elements (TEs) are emerging as key contributors of aging and aging-related pathologies, including Alzheimer's disease (AD) and cancer. However, the mechanisms governing heterochromatin maintenance or its relaxation in pathological conditions remain poorly understood. Here we show that PIN1, the only phosphorylation-specific cis/trans prolyl isomerase, whose loss is associated with premature aging and AD, is essential to preserve heterochromatin. We demonstrate that this PIN1 function is conserved from Drosophila to humans and prevents TE mobilization-dependent neurodegeneration and cognitive defects. Mechanistically, PIN1 maintains nuclear type-B Lamin structure and anchoring function for heterochromatin protein 1α (HP1α). This mechanism prevents nuclear envelope alterations and heterochromatin relaxation under mechanical stress, which is a key contributor to aging-related pathologies.
Francesco Napoletano, Gloria Ferrari Bravo, Ilaria Anna Pia Voto, Aurora Santin, Lucia Celora, Elena Campaner, Clara Dezi, Arianna Bertossi, Elena Valentino, Mariangela Santorsola, Alessandra Rustighi, Valentina Fajner, Elena Maspero, Federico Ansaloni, Valeria Cancila, Cesare Fabio Valenti, Manuela Santo, Osvaldo Basilio Artimagnella, Sara Finaurini, Ubaldo Gioia, Simona Polo, Remo Sanges, Claudio Tripodo, Antonello Mallamaci, Stefano Gustincich, Fabrizio d'Adda di Fagagna, Fiamma Mantovani, Valeria Specchia, Giannino Del Sal

1129 related Products with: The prolyl-isomerase PIN1 is essential for nuclear Lamin-B structure and function and protects heterochromatin under mechanical stress.

25 mg 5 G1 LITRE100 ml0.1 ml96T0.2 mg1000 TESTS/0.65ml100 mg

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#34525371   // To Up

The transcription factor BCL11A defines distinct subsets of midbrain dopaminergic neurons.

Midbrain dopaminergic (mDA) neurons are diverse in their projection targets, effect on behavior, and susceptibility to neurodegeneration. Little is known about the molecular mechanisms establishing this diversity during development. We show that the transcription factor BCL11A is expressed in a subset of mDA neurons in the developing and adult murine brain and in a subpopulation of pluripotent-stem-cell-derived human mDA neurons. By combining intersectional labeling and viral-mediated tracing, we demonstrate that Bcl11a-expressing mDA neurons form a highly specific subcircuit within the murine dopaminergic system. In the substantia nigra, the Bcl11a-expressing mDA subset is particularly vulnerable to neurodegeneration upon α-synuclein overexpression or oxidative stress. Inactivation of Bcl11a in murine mDA neurons increases this susceptibility further, alters the distribution of mDA neurons, and results in deficits in skilled motor behavior. In summary, BCL11A defines mDA subpopulations with highly distinctive characteristics and is required for establishing and maintaining their normal physiology.
Marianna Tolve, Ayse Ulusoy, Nikolaos Patikas, K Ushna S Islam, Gabriela O Bodea, Ece Öztürk, Bianca Broske, Astrid Mentani, Antonia Wagener, Karen M J van Loo, Stefan Britsch, Pengtao Liu, Walid T Khaled, Emmanouil Metzakopian, Stephan L Baader, Donato A Di Monte, Sandra Blaess

2129 related Products with: The transcription factor BCL11A defines distinct subsets of midbrain dopaminergic neurons.

96Kit 25UG200ug9630 Reactions200ug6200ug96200ug 100ul

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#34525368   // To Up

The RNA-binding protein Musashi controls axon compartment-specific synaptic connectivity through ptp69D mRNA poly(A)-tailing.

Synaptic targeting with subcellular specificity is essential for neural circuit assembly. Developing neurons use mechanisms to curb promiscuous synaptic connections and to direct synapse formation to defined subcellular compartments. How this selectivity is achieved molecularly remains enigmatic. Here, we discover a link between mRNA poly(A)-tailing and axon collateral branch-specific synaptic connectivity within the CNS. We reveal that the RNA-binding protein Musashi binds to the mRNA encoding the receptor protein tyrosine phosphatase Ptp69D, thereby increasing poly(A) tail length and Ptp69D protein levels. This regulation specifically promotes synaptic connectivity in one axon collateral characterized by a high degree of arborization and strong synaptogenic potential. In a different compartment of the same axon, Musashi prevents ectopic synaptogenesis, revealing antagonistic, compartment-specific functions. Moreover, Musashi-dependent Ptp69D regulation controls synaptic connectivity in the olfactory circuit. Thus, Musashi differentially shapes synaptic connectivity at the level of individual subcellular compartments and within different developmental and neuron type-specific contexts.
María Landínez-Macías, Weihong Qi, Anna Bratus-Neuenschwander, Martin Müller, Olivier Urwyler

1066 related Products with: The RNA-binding protein Musashi controls axon compartment-specific synaptic connectivity through ptp69D mRNA poly(A)-tailing.

1x96 well plate100 100 ul200 96tests100 0.1 mg100 ug200 100.00 ug100ul

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#34525365   // To Up

RORα is critical for mTORC1 activity in T cell-mediated colitis.

Inflammatory bowel disease (IBD) is multi-factorial chronic intestinal inflammation driven by pathogenic T cells, among which a large portion of patients are resistant to current anti-inflammatory regimes. The mechanisms underlying colitis pathogenicity and drug resistance are not fully understood. Here, we demonstrate that RORα is highly expressed in active UC patients, particularly in those non-responsive to anti-TNF treatment. Rorα deficiency in CD4 T cells greatly reduced colitis development. Mechanistically, RORα regulated T cell infiltration in colon and inhibited T cell apoptosis. Meanwhile, genome-wide occupancy and transcriptome analysis revealed that RORα promoted mTORC1 activation. mTORC1 signaling, also hyperactivated in active UC patients, is necessary for T cell-mediated colitis. Our results thus demonstrate a crucial role of the RORα-mTORC1 axis in CD4 T cells in promoting IBD, which may be targeted in human patients.
Xinxin Chi, Wei Jin, Xue Bai, Xiaohong Zhao, Jing Shao, Jiaqi Li, Qinli Sun, Bing Su, Xiaohu Wang, Xuexian O Yang, Chen Dong

1734 related Products with: RORα is critical for mTORC1 activity in T cell-mediated colitis.

100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized1 kit100ug Lyophilized100ug Lyophilized100ug Lyophilized1 kit100ug Lyophilized100ug Lyophilized

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#34525349   // To Up

Transitions in lineage specification and gene regulatory networks in hematopoietic stem/progenitor cells over human development.

Human hematopoiesis is a dynamic process that starts in utero 18-21 days post-conception. Understanding the site- and stage-specific variation in hematopoiesis is important if we are to understand the origin of hematological disorders, many of which occur at specific points in the human lifespan. To unravel how the hematopoietic stem/progenitor cell (HSPC) compartment changes during human ontogeny and the underlying gene regulatory mechanisms, we compare 57,489 HSPCs from 5 different tissues spanning 4 developmental stages through the human lifetime. Single-cell transcriptomic analysis identifies significant site- and developmental stage-specific transitions in cellular architecture and gene regulatory networks. Hematopoietic stem cells show progression from cycling to quiescence and increased inflammatory signaling during ontogeny. We demonstrate the utility of this dataset for understanding aberrant hematopoiesis through comparison to two cancers that present at distinct time points in postnatal life-juvenile myelomonocytic leukemia, a childhood cancer, and myelofibrosis, which classically presents in older adults.
Anindita Roy, Guanlin Wang, Deena Iskander, Sorcha O'Byrne, Natalina Elliott, Jennifer O'Sullivan, Gemma Buck, Elisabeth F Heuston, Wei Xiong Wen, Alba Rodriguez Meira, Peng Hua, Anastasios Karadimitris, Adam J Mead, David M Bodine, Irene Roberts, Bethan Psaila, Supat Thongjuea

1510 related Products with: Transitions in lineage specification and gene regulatory networks in hematopoietic stem/progenitor cells over human development.

1 mg10 ug1.00 flask300 units5ug1.00 flask1.00 flask1.00 flask100 100 μg

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#34525343   2021/09/07 To Up

Social interaction is a catalyst for adult human learning in online contexts.

Human learning is highly social. Advances in technology have increasingly moved learning online, and the recent coronavirus disease 2019 (COVID-19) pandemic has accelerated this trend. Online learning can vary in terms of how "socially" the material is presented (e.g., live or recorded), but there are limited data on which is most effective, with the majority of studies conducted on children and inconclusive results on adults. Here, we examine how young adults (aged 18-35) learn information about unknown objects, systematically varying the social contingency (live versus recorded lecture) and social richness (viewing the teacher's face, hands, or slides) of the learning episodes. Recall was tested immediately and after 1 week. Experiment 1 (n = 24) showed better learning for live presentation and a full view of the teacher (hands and face). Experiment 2 (n = 27; pre-registered) replicated the live-presentation advantage. Both experiments showed an interaction between social contingency and social richness: the presence of social cues affected learning differently depending on whether teaching was interactive or not. Live social interaction with a full view of the teacher's face provided the optimal setting for learning new factual information. However, during observational learning, social cues may be more cognitively demanding and/or distracting, resulting in less learning from rich social information if there is no interactivity. We suggest that being part of a genuine social interaction catalyzes learning, possibly via mechanisms of joint attention, common ground, or (inter-)active discussion, and as such, interactive learning benefits from rich social settings..
Sara De Felice, Gabriella Vigliocco, Antonia F de C Hamilton

2056 related Products with: Social interaction is a catalyst for adult human learning in online contexts.

100 μg100 μg100 ul100ug Lyophilized100 μg 100ul100ug Lyophilized25 µg100ug Lyophilized25 µg100 μg100ug Lyophilized

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