| 1. |
|
|
| 2. |
|
|
| 3. |
- Kogan, PS, et al.
(author)
-
Uncovering the molecular identity of cardiosphere-derived cells (CDCs) by single-cell RNA sequencing
- 2022
-
In: Basic research in cardiology. - : Springer Science and Business Media LLC. - 1435-1803 .- 0300-8428. ; 117:1, s. 11-
-
Journal article (peer-reviewed)abstract
- Cardiosphere-derived cells (CDCs) generated from human cardiac biopsies have been shown to have disease-modifying bioactivity in clinical trials. Paradoxically, CDCs’ cellular origin in the heart remains elusive. We studied the molecular identity of CDCs using single-cell RNA sequencing (sc-RNAseq) in comparison to cardiac non-myocyte and non-hematopoietic cells (cardiac fibroblasts/CFs, smooth muscle cells/SMCs and endothelial cells/ECs). We identified CDCs as a distinct and mitochondria-rich cell type that shared biological similarities with non-myocyte cells but not with cardiac progenitor cells derived from human-induced pluripotent stem cells. CXCL6 emerged as a new specific marker for CDCs. By analysis of sc-RNAseq data from human right atrial biopsies in comparison with CDCs we uncovered transcriptomic similarities between CDCs and CFs. By direct comparison of infant and adult CDC sc-RNAseq data, infant CDCs revealed GO-terms associated with cardiac development. To analyze the beneficial effects of CDCs (pro-angiogenic, anti-fibrotic, anti-apoptotic), we performed functional in vitro assays with CDC-derived extracellular vesicles (EVs). CDC EVs augmented in vitro angiogenesis and did not stimulate scarring. They also reduced the expression of pro-apoptotic Bax in NRCMs. In conclusion, CDCs were disclosed as mitochondria-rich cells with unique properties but also with similarities to right atrial CFs. CDCs displayed highly proliferative, secretory and immunomodulatory properties, characteristics that can also be found in activated or inflammatory cell types. By special culture conditions, CDCs earn some bioactivities, including angiogenic potential, which might modify disease in certain disorders.
|
|
| 4. |
- Mukundan, Arvind, et al.
(author)
-
Kalam Rover
- 2021
-
In: AIAA SCITECH 2022 Forum, January 3-7 2022, San Diego, CA & Virtual. - Reston, Virginia : American Institute of Aeronautics and Astronautics Inc, AIAA.
-
Conference paper (peer-reviewed)abstract
- Our knowledge about the formation and feasibility for the near-future manned mission of the lunar farside highlands is still restricted since relatively few missions and research studies have been conducted. However, there are many interesting particulars on the far side, and finding sufficient evidence for practically accessible water ice near those land sites can potentially increase the prospect for future human colonization. Therefore, this paper proposes a novel rover design that would provide a base foundation for future human missions and lunar outposts. A small, lightweight, and low-power consuming rover have been developed, designed, and analyzed to perform in-situ research and excavation on the lunar far side. This paper put forward the scientific objectives, the payloads on the rover, the design of the rover with integrated excavation drill mechanism, the telemetry & telecommand, the technology, and the power and mass budget of building such a lunar rover.
|
|
| 5. |
- Tomar, AS, et al.
(author)
-
Retinoblastoma seeds: impact on American Joint Committee on Cancer clinical staging
- 2023
-
In: The British journal of ophthalmology. - : BMJ. - 1468-2079 .- 0007-1161. ; 107:1, s. 127-132
-
Journal article (peer-reviewed)abstract
- To investigate whether the American Joint Committee on Cancer (AJCC) clinical category cT2b needs to be subclassified by the type and distribution of retinoblastoma (RB) seeding.MethodsMulticentre, international registry-based data were collected from RB centres enrolled between January 2001 and December 2013. 1054 RB eyes with vitreous or subretinal seeds from 18 ophthalmic oncology centres, in 13 countries within six continents were analysed. Local treatment failure was defined as the use of secondary enucleation or external beam radiation therapy (EBRT) and was estimated with the Kaplan-Meier method.ResultsClinical category cT2b included 1054 eyes. Median age at presentation was 16.0 months. Of these, 428 (40.6%) eyes were salvaged, and 430 (40.8%) were treated with primary and 196 (18.6%) with secondary enucleation. Of the 592 eyes that had complete data for globe salvage analysis, the distribution of seeds was focal in 143 (24.2%) and diffuse in 449 (75.8%). The 5-year Kaplan-Meier cumulative globe-salvage (without EBRT) was 78% and 49% for eyes with focal and diffuse RB seeding, respectively. Cox proportional hazards regression analysis confirmed a higher local treatment failure risk with diffuse seeds as compared with focal seeds (hazard rate: 2.8; p<0.001). There was insufficient evidence to prove or disprove an association between vitreous seed type and local treatment failure risk(p=0.06).ConclusionThis international, multicentre, registry-based analysis of RB eyes affirmed that eyes with diffuse intraocular distribution of RB seeds at diagnosis had a higher risk of local treatment failure when compared with focal seeds. Subclassification of AJCC RB category cT2b into focal vs diffuse seeds will improve prognostication for eye salvage.
|
|
| 6. |
- Zulkifli, M, et al.
(author)
-
Yeast homologs of human MCUR1 regulate mitochondrial proline metabolism
- 2020
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 4866-
-
Journal article (peer-reviewed)abstract
- Mitochondria house evolutionarily conserved pathways of carbon and nitrogen metabolism that drive cellular energy production. Mitochondrial bioenergetics is regulated by calcium uptake through the mitochondrial calcium uniporter (MCU), a multi-protein complex whose assembly in the inner mitochondrial membrane is facilitated by the scaffold factor MCUR1. Intriguingly, many fungi that lack MCU contain MCUR1 homologs, suggesting alternate functions. Herein, we characterize Saccharomyces cerevisiae homologs Put6 and Put7 of MCUR1 as regulators of mitochondrial proline metabolism. Put6 and Put7 are tethered to the inner mitochondrial membrane in a large hetero-oligomeric complex, whose abundance is regulated by proline. Loss of this complex perturbs mitochondrial proline homeostasis and cellular redox balance. Yeast cells lacking either Put6 or Put7 exhibit a pronounced defect in proline utilization, which can be corrected by the heterologous expression of human MCUR1. Our work uncovers an unexpected role of MCUR1 homologs in mitochondrial proline metabolism.
|
|
