183 research outputs found
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)
The Impact of Diabetes Type 2 in the Pathogenesis of Benign Prostatic Hyperplasia: A Review
Introduction. Clinical observation of larger prostate glands in men with diabetes mellitus type 2 led some investigators to hypothesize that an association between these two conditions exists. In fact, both diseases are very common in men as they age and seem to be sharing similar epidemiologic features. Several studies examining the above hypothesis were yielded. Aim. The purpose of this paper is to summarize the existing literature focusing on the coexistence of BPH and diabetes mellitus type 2 and to elucidate whether or not an association among these conditions exists. Methods. We identified studies published from 1990 onwards by searching the MEDLINE database of the National Library of Medicine. Initial search terms were benign prostatic hyperplasia, epidemiology, and risk factor, combined with diet hyperinsulinemia, and diabetes mellitus type 2. Results. Diabetes mellitus type 2 and hyperinsulinemia are quite common conditions and often coexist with BPH. There are several studies (observational, epidemiological, and experimental) examining the association between them in literature. Conclusion. Evidence suggests that an association between BPH and diabetes through a common pathogenic mechanism is possible. The specific pathway interfering in the development of both conditions is still poorly investigated; thus, the exact relationship of BPH to diabetes remains unclear
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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)
Resistance of uropathogens to antibacterial agents: Emerging threats, trends and treatments
Urinary tract infections are among the most common infectious diseases in humans. Today, resistance to nearly all antimicrobial classes is dramatically growing, and extremely drug-resistant or even pan-drug resistant pathogens are increasingly isolated around the world. It is foreseen that in the next decades the world will be facing a major medical emergency generated by the rapid spread of pathogens carrying resistance determinants of unprecedented power. Carbapenemase-producing Enterobacteriaceae, multidrug-resistant Enterococci and fluoroquinolone resistance determinants in both Gram-negative and Gram-positive uropathogens are among the greatest emergencies. In this article, the major emerging threats of particular interest to urologists are reviewed, worldwide resistance trends are illustrated, and novel and older-but still active-recommended drugs are summarized
Insights from the first global population estimate of Weddell seals in Antarctica
The Weddell seal is one of the best-studied marine mammals in the world, owing to a multidecadal demographic effort in the southernmost part of its range. Despite their occurrence around the Antarctic coastline, we know little about larger scale patterns in distribution, population size, or structure. We combined high-resolution satellite imagery from 2011, crowd-sourcing, and habitat modeling to report the first global population estimate for the species and environmental factors that influence its distribution. We estimated ~202,000 (95% confidence interval: 85,345 to 523,140) sub-adult and adult female seals, with proximate ocean depth and fast-ice variables as factors explaining spatial prevalence. Distances to penguin colonies were associated with seal presence, but only emperor penguin population size had a strong negative relationship. The small, estimated population size relative to previous estimates and the seals' nexus with trophic competitors indicates that a community ecology approach is required in efforts to monitor the Southern Ocean ecosystem
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