140 research outputs found
On the existence of highly organized communities in networks of locally interacting agents
In this paper we investigate phenomena of spontaneous emergence or purposeful
formation of highly organized structures in networks of related agents. We show
that the formation of large organized structures requires exponentially large,
in the size of the structures, networks. Our approach is based on Kolmogorov,
or descriptional, complexity of networks viewed as finite size strings. We
apply this approach to the study of the emergence or formation of simple
organized, hierarchical, structures based on Sierpinski Graphs and we prove a
Ramsey type theorem that bounds the number of vertices in Kolmogorov random
graphs that contain Sierpinski Graphs as subgraphs. Moreover, we show that
Sierpinski Graphs encompass close-knit relationships among their vertices that
facilitate fast spread and learning of information when agents in their
vertices are engaged in pairwise interactions modelled as two person games.
Finally, we generalize our findings for any organized structure with succinct
representations. Our work can be deployed, in particular, to study problems
related to the security of networks by identifying conditions which enable or
forbid the formation of sufficiently large insider subnetworks with malicious
common goal to overtake the network or cause disruption of its operation
Developing the Critical Verbatim Theater Artist during the Pandemic: A Transatlantic Collaboration
Following recent social upheavals and an unprecedented pandemic, the development of theater students to work with stories from the community has become more urgent. Because verbatim theater brings to focus real voices and often involves sensitive topics, artists/educators consider key ethical questions before their engagement with educational or community contexts. Artists/educators are developed within the fieldwork of applied theater, during their study at university, through supervision to engage communities. The pandemic made such fieldwork difficult due to online learning and teaching, so university educators tested alternative ways of simulating the experience of working with participants. This article analyzes the rationale, application and evaluation of an educational verbatim theater case study that involved British theater students and American nursing students, from the University of Chichester and Kent State University respectively. It identifies how international collaborations might offer an alternative environment to fieldwork by inviting students to consider key ethical questions before their engagement with communities. The narrative of practice reveals how it was rooted in Paulo Freire’s pedagogy. The artist/educator’s reflection highlights how such collaborations invite students to explore dialectics and the ethics of representation in verbatim theater, and to develop accountability and empathy when working with participants, which hopefully, they bring to their future fieldwork
Chromosome Clustering in mitosis by the nuclear protein Ki-67
© 2021 The Author(s). Ki-67 is highly expressed in proliferating cells, a characteristic that made the protein a very important proliferation marker widely used in the clinic. However, the molecular functions and properties of Ki-67 remained quite obscure for a long time. Only recently important discoveries have shed some light on its function and shown that Ki-67 has a major role in the formation of mitotic chromosome periphery compartment, it is associated with protein phosphatase one (PP1) and regulates chromatin function in interphase and mitosis. In this review, we discuss the role of Ki-67 during cell division. Specifically, we focus on the importance of Ki-67 in chromosome individualisation at mitotic entry (prometaphase) and its contribution to chromosome clustering and nuclear remodelling during mitotic exit.Wellcome Trust. Investigator award 210742/Z/18/Z (Chromatin Re-Organisation at the Transition from Mitosis to G1: How Phospho-Switches Regulate the Process in Space and Time); Brunel University London (CHMLS scholarship)
Case Report: Vasculitis Triggered by SIRT in a Patient With Previously Untreated Cholangiocarcinoma.
Arising from the biliary tract, cholangiocarcinoma is a rare and aggressive epithelial cancer. According to the primary site, it can be further classified into intrahepatic, perihilar and distal types. Due to the lack of symptoms early in the disease course, most patients are diagnosed at advanced stages. Being not candidates for curative surgical management, these patients are treated with palliative systemic chemotherapy, and their prognosis remains poor. Using radioisotopes like yttrium-90 -labeled microspheres ( <sup>90</sup> Y), radioembolization represents a local approach to treat primary and secondary liver tumors. In the case of intrahepatic cholangiocarcinoma, radioembolization can be used as a primary treatment, as an adjunct to chemotherapy or after failing chemotherapy. An 88-year-old man underwent radioembolization for a previously untreated stage II intrahepatic cholangiocarcinoma. One week later, he presented to our clinic with a non-pruritic maculopapular rash of the lower extremities and abdomen, worsening fatigue and low-grade fever. Laboratory exams, including hepatitis screening, were within normal limits. Showing positive immunofluorescence staining for immunoglobulin M (IgM) and complement 3 (C3) in vessel walls without IgA involvement, the skin biopsy results were compatible with leukocytoclastic vasculitis. Apart from the anticancer intervention, there have been no recent medication changes which could explain this complication. Notably, we did not observe any side effects during or after the perfusion scan with technetium-99m macroaggregated albumin (MAA) performed prior to radioembolization. The symptoms resolved quickly after a short course of colchicine and did not reappear at cholangiocarcinoma progression. In the absence of other evident causes, we conclude that the onset of leukocytoclastic vasculitis in our patient was directly linked to the administration of yttrium-90 -labeled microspheres. Our report therefore demonstrates that this condition can be a rare but manageable complication of <sup>90</sup> Y liver radioembolization
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Ki-67 is necessary during DNA replication for fork protection and genome stability
Availability of data and materials:
The datasets generated and/or analysed during the current study are available at Arrayepress (accession E-MTAB-12279) for RNA sequencing data [74] and PRIDE PXD037513 for the proteomic data [75] respectively. Accession numbers are listed in the Additional file 2: Table S2.
Images and blots data are available from the lead contact upon request and will be shared via Figshare (https://ndownloader.figstatic.com/files/45799353).Supplementary Information is available online at: https://genomebiology.biomedcentral.com/articles/10.1186/s13059-024-03243-5#Sec38 .A preprint version of this article is available at BioRxiv, https://www.biorxiv.org/content/10.1101/2023.04.18.537310v1.abstract . It has not been certified by peer review. The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.Background:
The proliferation antigen Ki-67 has been widely used in clinical settings for cancer staging for many years, but investigations on its biological functions have lagged. Recently, Ki-67 has been shown to regulate both the composition of the chromosome periphery and chromosome behaviour in mitosis as well as to play a role in heterochromatin organisation and gene transcription. However, how the different roles for Ki-67 across the cell cycle are regulated and coordinated remain poorly understood. The progress towards understanding Ki-67 function have been limited by the tools available to deplete the protein, coupled to its abundance and fluctuation during the cell cycle.
Results:
Here, we use a doxycycline-inducible E3 ligase together with an auxin-inducible degron tag to achieve a rapid, acute and homogeneous degradation of Ki-67 in HCT116 cells. This system, coupled with APEX2 proteomics and phospho-proteomics approaches, allows us to show that Ki-67 plays a role during DNA replication. In its absence, DNA replication is severely delayed, the replication machinery is unloaded, causing DNA damage that is not sensed by the canonical pathways and dependent on HUWE1 ligase. This leads to defects in replication and sister chromatids cohesion, but it also triggers an interferon response mediated by the cGAS/STING pathway in all the cell lines tested.
Conclusions:
We unveil a new function of Ki-67 in DNA replication and genome maintenance that is independent of its previously known role in mitosis and gene regulation.The Vagnarelli lab is supported by the Wellcome Trust Investigator award 210742/Z/18/Z to Paola Vagnarelli. KS was supported by a CHMLS PhD scholarship (Brunel University London)
Validity of predictive equations for total energy expenditure against doubly labeled water
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