39 research outputs found
Issue #6 - February 6, 2007
No full textFeb. 6, 2007 16 pgs
Debate growing in Europe as to which drinks should be labeled as "vodka"; "Jane Doe" speaks at York University about rape for the women's studies department; Positive Space works to create a safe campus environment for queer youth at Glendon; preparing for a federal election.
Contributers: Gavin Atkins, Genevieve Bowens, Lidia Giosa, Marley Highman, Peter Kent, Josiane Messier, Cynthia Morinville, Mark Nichols, Cindy Ouellet, Sepehr Radjpoust, Kayla Whyte
Editor-In-Chief: Tia Brazda
Assistant Editor: Ashley Jestin
News: Clara Wille
Politics: Ashley Jestin
Campus Life: Kaitlyn Chambers
Talk Back: Laura Scrivener
Creative Writing: Hannah Renglich
Metropolis: Tia Brazda
Entertainment: Jacinto Wong
Arts and Culture: Sarah Maharajah
Reviews: Juan Llamas Rodriguez
Photographer: Irena Kramer
Design/layout: Jennifer Rong, Jacinto Wong
French: Gabriel Rompre
Article titles:
Get involved with Pro-Tem
Letter to the editor
We asked you
Vodka shmodka, just give it to me
York University fails to take strong stand against rape
L'homme, un cocktail a requin
Vous etes pas tannes de payer
Songe d'une nuit d'hiver
Snow, skis, and shindigs at Stoneham
Where is Positive Space
Radio Glendon: who's listening
Watt an idea
Flocons de saveur dans l'hiver gris
An upcoming election?
Same Shins, different album
Get a crush
Le journal de Knud Rasmussen
Like father, like daughter
Drague par un dragshow
The beauty and the horro
Extensive patient-to-patient single nucleus transcriptome heterogeneity in pheochromocytomas and paragangliomas
No full textPheochromocytoma, neuroendocrine tumor, single cell RNA-sequencing, transcriptome, heterogeneity, SDHB, RET, paraganglinoma; Pheochromocytomas (PC) and paragangliomas (PG) are rare neuroendocrine tumors with varied genetic makeup and are associated with high cardiovascular morbidity and a variable risk of malignancy. The source of the transcriptional heterogeneity of the disease and the underlying biological processes that determine the outcome of PCPG remain largely unclear. We focused on PCPG tumors with germline SDHB and RET mutations, which represent distinct prognostic groups with worse or better prognoses, respectively. We applied single-nuclei RNA sequencing (snRNA-seq) to tissue samples from 11 patients and found high patient-to-patient transcriptome heterogeneity in neuroendocrine tumor cells. The tumor microenvironment also showed heterogeneous profiles, mainly contributed by macrophages of the immune cell clusters and Schwann cells of the stroma. By performing non-negative matrix factorization, we identified common transcriptional programs active in RET and SDHB, as well as distinct modules, including neuronal development, hormone synthesis and secretion, and DNA replication. Similarities between the transcriptomes of the tumor cells and those of the chromaffin- and precursor cell types suggests different developmental stages at which PC and PG tumors appear to be arrested
Dual-targeting of cancer-metabolome and stress antigens impacts transcriptomic heterogeneity and efficacy of engineered T-cells
No full text<p>Few cancers can be efficiently targeted with engineered T-cell strategies. Here, we explored whether γδTCR-mediated cancer-metabolome targeting can be combined with the attack of cancer-associated stress antigens, like NKG2D-ligands or CD277, through the addition of chimeric co-receptors. This strategy overcame suboptimal γ9δ2TCR-engagement of TEGs (αβT-cell engineered to express a defined γδTCR) and improved serial killing, proliferation and persistence of TEGs. <em>In vivo</em>, the NKG2D-CD28<sub>WT</sub>-chimera enhanced only liquid tumor control, NKG2D-4-1BB<sub>CD28TM</sub>-chimera prolonged persistence of TEGs and improved tumor control of liquid and solid tumors. The CD277-targeting chimera (103-4-1BB-chimera) was the most optimal co-stimulation format, mediating eradication of both liquid and solid tumors. Single-cell transcriptomic analysis revealed that NKG2D-4-1BB<sub>CD28TM </sub>and 103-4-1BB chimeras reprogrammed TEGs through NF-κB. Due to the competition with naturally expressed NKG2D in CD8+ TEGs, NKG2D-4-1BB<sub>CD28TM </sub>chimera mainly skewed CD4+ TEGs towards adhesion, proliferation, cytotoxicity and less-exhausted signatures, while the 103-4-1BB-chimera additionally shaped the CD8+ subset towards a proliferative state.</p>
Transcriptional Heterogeneity and Clonal Evolution between Diagnosis and Relapse in Pediatric Acute Myeloid Leukemia
No full textLongitudinal single-cell transcriptomics reveals distinct patterns of recurrence in acute myeloid leukemia
No full textBACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous and aggressive blood cancer that results from diverse genetic aberrations in the hematopoietic stem or progenitor cells (HSPCs) leading to the expansion of blasts in the hematopoietic system. The heterogeneity and evolution of cancer blasts can render therapeutic interventions ineffective in a yet poorly understood patient-specific manner. In this study, we investigated the clonal heterogeneity of diagnosis (Dx) and relapse (Re) pairs at genetic and transcriptional levels, and unveiled the underlying pathways and genes contributing to recurrence. METHODS: Whole-exome sequencing was used to detect somatic mutations and large copy number variations (CNVs). Single cell RNA-seq was performed to investigate the clonal heterogeneity between Dx-Re pairs and amongst patients. RESULTS: scRNA-seq analysis revealed extensive expression differences between patients and Dx-Re pairs, even for those with the same -presumed- initiating events. Transcriptional differences between and within patients are associated with clonal composition and evolution, with the most striking differences in patients that gained large-scale copy number variations at relapse. These differences appear to have significant molecular implications, exemplified by a DNMT3A/FLT3-ITD patient where the leukemia switched from an AP-1 regulated clone at Dx to a mTOR signaling driven clone at Re. The two distinct AML1-ETO pairs share genes related to hematopoietic stem cell maintenance and cell migration suggesting that the Re leukemic stem cell-like (LSC-like) cells evolved from the Dx cells. CONCLUSIONS: In summary, the single cell RNA data underpinned the tumor heterogeneity not only amongst patient blasts with similar initiating mutations but also between each Dx-Re pair. Our results suggest alternatively and currently unappreciated and unexplored mechanisms leading to therapeutic resistance and AML recurrence. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12943-022-01635-4
Single‐cell multi‐omics characterize colorectal tumors, adjacent healthy tissue and matched (tumor) organoids identifying CRC‐unique features
No full text: Colorectal cancer (CRC) arises in the colorectal tissue driven by genetic disorder or the accumulation of somatic mutations, leading to abnormal epithelial cell growth. In this study, we employed single-nucleus multi-omics analysis, including single-nucleus RNA-seq and single-nucleus ATAC-seq, on over 100,000 high-quality nuclei to investigate the molecular landscape of both primary tissue and patient-derived organoids (PDOs). Our analysis showed that normal PDOs (N-PDOs) derived from tissue adjacent to tumors replicate the cellular composition and differentiation trajectory of colorectal crypts. In contrast, tumor PDOs (T-PDOs) showed patient-specific transcriptomic and epigenomic heterogeneity yet consistently maintained a stem cell-like state. T-PDOs retained the somatic mutation profile of the primary tumor while also exhibiting de novo mutations not detected in either the primary tumor or N-PDOs. Notably, inferred cell-cell interaction analysis highlighted the activin signaling pathway as a potential unique feature of fibroblast-epithelial interactions within the tumor microenvironment. This study provides a comprehensive view of the transition from normal to malignant colorectal epithelium and underscores the utility of PDOs as a faithful model for capturing both conserved and patient-specific features of colorectal cancer
Co-operative Development and Corporate Governance Structures in German Co-operatives: Problems and Perspectives
No full textIn Germany exist a large number of co-operatives that are engaged in a broad variety of business activities. Their organisational structure is determined by co-operative law and to a lesser degree by statutes or by-laws. As has been shown for German rural co-operatives by applying property rights theory the corporate governance structure as determined by law is formally still in existence, while it actually has been shifted in favour of the executive board. This has created an imbalance where on the one hand no longer any corporate governance is actually taking place while on the other hand members' interests may easily be neglected, because it is the executive board that determines the members' interests and also whether they have benefited from the cooperatives activities. In theory, suitable instruments to improve the corporate governance structure within such co-operative are the promotion plan and the promotion report as developed by Boettcher. However, for transaction cost reasons and due to the current attenuation of property rights, it is unlikely that these instruments will be implemented without outside pressure, e. g. through a change in cooperative law. A superior alternative to promotion plan and promotion report may be a combination of promotion task controlling and member oriented quality management. While such instruments would indeed improve members' ability to execute co-operative governance, managers' willingness to submit themselves to stronger governance may well be assumed to be very low. Taking into account the current distribution of property rights in big German co-operatives, managers will accept stronger governance structures only if some other incentives exist. An ongoing research project indicates that such incentives might exist in the realm of improved business opportunities due to better information about members' aims and needs. --
