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- Yang, D. P., et al.
(författare)
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Nociceptor neurons direct goblet cells via a CGRP-RAMP1 axis to drive mucus production and gut barrier protection
- 2022
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Ingår i: Cell. - : Elsevier BV. - 0092-8674. ; 185:22
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Tidskriftsartikel (refereegranskat)abstract
- Neuroepithelial crosstalk is critical for gut physiology. However, the mechanisms by which sensory neurons communicate with epithelial cells to mediate gut barrier protection at homeostasis and during inflammation are not well understood. Here, we find that Nav1.8+CGRP+ nociceptor neurons are juxtaposed with and signal to intestinal goblet cells to drive mucus secretion and gut protection. Nociceptor ablation led to decreased mucus thickness and dysbiosis, while chemogenetic nociceptor activation or capsaicin treatment induced mucus growth. Mouse and human goblet cells expressed Ramp1, receptor for the neuropeptide CGRP. Nociceptors signal via the CGRP-Ramp1 pathway to induce rapid goblet cell emptying and mucus secretion. Notably, commensal microbes activated nociceptors to control homeostatic CGRP release. In the absence of nociceptors or epithelial Ramp1, mice showed increased epithelial stress and susceptibility to colitis. Conversely, CGRP administration protected nociceptor-ablated mice against colitis. Our findings demon-strate a neuron-goblet cell axis that orchestrates gut mucosal barrier protection.
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| 4. |
- Chodankar, N. R., et al.
(författare)
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Solution-free self-assembled growth of ordered tricopper phosphide for efficient and stable hybrid supercapacitor
- 2021
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Ingår i: Energy Storage Materials. - : Elsevier B.V.. - 2405-8289 .- 2405-8297. ; 39, s. 194-202
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Tidskriftsartikel (refereegranskat)abstract
- Herein, a solution-free dry strategy for the growth of self-assembled ordered tricopper phosphide (Cu3P) nanorod arrays is developed and the product is employed as a high-energy, stable positive electrode for a solid-state hybrid supercapacitor (HSC). The ordered Cu3P nanorod arrays grown on the copper foam deliver an excellent specific capacity of 664 mA h/g with an energy efficiency of 88% at 6 A/g and an ultra-long cycling stability over 15,000 continuous charge–discharge cycles. These electrochemical features are attributed to the ordered growth of the Cu3P nanorod arrays, which offers a large number of accessible electroactive sites, a reduced number of ion transfer paths, and reversible redox activity. The potential of the Cu3P nanorod arrays is further explored by engineering solid-state HSCs in which the nanorods are paired with an activated carbon-based negative electrode. The constructed cell is shown to convey a specific energy of 76.85 Wh/kg at a specific power of 1,125 W/kg and an 88% capacitance retention over 15,000 cycles. Moreover, the superior energy storing and delivery capacity of the cell is demonstrated by an energy efficiency of around 65%. The versatile solution-free dry strategies developed here pave the way towards engineering a range of electrode materials for next-generation energy storage systems. © 2021 Elsevier B.V.
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| 5. |
- Daelman, Bo, et al.
(författare)
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Frailty and cognitive function in middle-aged and older adults with congenital heart disease
- 2024
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Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 83:12, s. 1149-1159
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Tidskriftsartikel (refereegranskat)abstract
- Background: Life expectancy of patients with congenital heart disease (CHD) has increased rapidly, resulting in a growing and aging population. Recent studies have shown that older people with CHD have higher morbidity, health care use, and mortality. To maintain longevity and quality of life, understanding their evolving medical and psychosocial challenges is essential.Objectives: The authors describe the frailty and cognitive profile of middle-aged and older adults with CHD to identify predictor variables and to explore the relationship with hospital admissions and outpatient visits.Methods: Using a cross-sectional, multicentric design, we included 814 patients aged ≥40 years from 11 countries. Frailty phenotype was determined using the Fried method. Cognitive function was assessed by the Montreal Cognitive Assessment.Results: In this sample, 52.3% of patients were assessed as robust, 41.9% as prefrail, and 5.8% as frail; 38.8% had cognitive dysfunction. Multinomial regression showed that frailty was associated with older age, female sex, higher physiologic class, and comorbidities. Counterintuitively, patients with mild heart defects were more likely than those with complex lesions to be prefrail. Patients from middle-income countries displayed more prefrailty than those from higher-income countries. Logistic regression demonstrated that cognitive dysfunction was related to older age, comorbidities, and lower country-level income.Conclusions: Approximately one-half of included patients were (pre-)frail, and more than one-third experienced cognitive impairment. Frailty and cognitive dysfunction were identified in patients with mild CHD, indicating that these concerns extend beyond severe CHD. Assessing frailty and cognition routinely could offer valuable insights into this aging population.
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| 7. |
- Halvorsen, Matthew, et al.
(författare)
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Increased burden of ultra-rare structural variants localizing to boundaries of topologically associated domains in schizophrenia
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 11:1, s. 1842-
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Tidskriftsartikel (refereegranskat)abstract
- Despite considerable progress in schizophrenia genetics, most findings have been for large rare structural variants and common variants in well-imputed regions with few genes implicated from exome sequencing. Whole genome sequencing (WGS) can potentially provide a more complete enumeration of etiological genetic variation apart from the exome and regions of high linkage disequilibrium. We analyze high-coverage WGS data from 1162 Swedish schizophrenia cases and 936 ancestry-matched population controls. Our main objective is to evaluate the contribution to schizophrenia etiology from a variety of genetic variants accessible to WGS but not by previous technologies. Our results suggest that ultra-rare structural variants that affect the boundaries of topologically associated domains (TADs) increase risk for schizophrenia. Alterations in TAD boundaries may lead to dysregulation of gene expression. Future mechanistic studies will be needed to determine the precise functional effects of these variants on biology.
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| 8. |
- Jung, Sung-Jun, 1987, et al.
(författare)
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Expression level of Sec62 modulates membrane insertion of marginally hydrophobic segments
- 2022
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Ingår i: Biochimica Et Biophysica Acta-Biomembranes. - : Elsevier BV. - 0005-2736. ; 1864:12
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Tidskriftsartikel (refereegranskat)abstract
- In the endoplasmic reticulum (ER) membrane, transmembrane (TM) domain insertion occurs through the Sec61 channel with its auxiliary components, including Sec62. Sec62 interacts with the Sec61 channel and is located on the front side of the Sec61 lateral gate, an entry site for TM domains to the lipid bilayer. Overexpression of Sec62 led to a growth defect in yeast, and we investigated its effects on protein translocation and membrane insertion by pulse labeling of Sec62 client proteins. Our data show that the insertion efficiency of marginally hydrophobic TM segments is reduced upon Sec62 overexpression. This result suggests a potential regulatory role of Sec62 as a gatekeeper of the lateral gate, thereby modulating the insertion threshold of TM segments.
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| 9. |
- Rowland, B, et al.
(författare)
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THUNDER: A reference-free deconvolution method to infer cell type proportions from bulk Hi-C data
- 2022
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 18:3, s. e1010102-
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Tidskriftsartikel (refereegranskat)abstract
- Hi-C data provide population averaged estimates of three-dimensional chromatin contacts across cell types and states in bulk samples. Effective analysis of Hi-C data entails controlling for the potential confounding factor of differential cell type proportions across heterogeneous bulk samples. We propose a novel unsupervised deconvolution method for inferring cell type composition from bulk Hi-C data, the Two-step Hi-c UNsupervised DEconvolution appRoach (THUNDER). We conducted extensive simulations to test THUNDER based on combining two published single-cell Hi-C (scHi-C) datasets. THUNDER more accurately estimates the underlying cell type proportions compared to reference-free methods (e.g., TOAST, and NMF) and is more robust than reference-dependent methods (e.g. MuSiC). We further demonstrate the practical utility of THUNDER to estimate cell type proportions and identify cell-type-specific interactions in Hi-C data from adult human cortex tissue samples. THUNDER will be a useful tool in adjusting for varying cell type composition in population samples, facilitating valid and more powerful downstream analysis such as differential chromatin organization studies. Additionally, THUNDER estimated contact profiles provide a useful exploratory framework to investigate cell-type-specificity of the chromatin interactome while experimental data is still rare.
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