Modification of Seurat v4 for the Development of a Phase Assignment Tool Able to Distinguish between G2 and Mitotic Cells.

Single-cell RNA sequencing (scRNAseq) is a rapidly advancing field enabling the characterisation of heterogeneous gene expression profiles within a population. The cell cycle phase is a major contributor to gene expression variance between cells and computational analysis tools have been developed to assign cell cycle phases to cells within scRNAseq datasets. Whilst these tools can be extremely useful, all have the drawback that they classify cells as only G1, S or G2/M. Existing discrete cell phase assignment tools are unable to differentiate between G2 and M and continuous-phase-assignment tools are unable to identify a region corresponding specifically to mitosis in a pseudo-timeline for continuous assignment along the cell cycle. In this study, bulk RNA sequencing was used to identify differentially expressed genes between mitotic and interphase cells isolated based on phospho-histone H3 expression using fluorescence-activated cell sorting. These gene lists were used to develop a methodology which can distinguish G2 and M phase cells in scRNAseq datasets. The phase assignment tools present in Seurat were modified to allow for cell cycle phase assignment of all stages of the cell cycle to identify a mitotic-specific cell population.

CD9 co-operation with syndecan-1 is required for a major staphylococcal adhesion pathway.

Epithelial colonization is a critical first step in bacterial pathogenesis. Staphylococcus aureus can utilize several host factors to associate with cells, including α5ß1 integrin and heparan sulfate proteoglycans, such as the syndecans. Here, we demonstrate that a partner protein of both integrins and syndecans, the host membrane adapter protein tetraspanin CD9, is essential for syndecan-mediated staphylococcal adhesion. Fibronectin is also essential in this process, while integrins are only critical for post-adhesion entry into human epithelial cells. Treatment of epithelial cells with CD9-derived peptide or heparin caused significant reductions in staphylococcal adherence, dependent on both CD9 and syndecan-1. Exogenous fibronectin caused a CD9-dependent increase in staphylococcal adhesion, whereas blockade of ß1 integrins did not affect adhesion but did reduce the subsequent internalization of adhered bacteria. CD9 disruption or deletion increased ß1 integrin-mediated internalization, suggesting that CD9 coordinates sequential staphylococcal adhesion and internalization. CD9 controls staphylococcal adhesion through syndecan-1, using a mechanism that likely requires CD9-mediated syndecan organization to correctly display fibronectin at the host cell surface. We propose that CD9-derived peptides or heparin analogs could be developed as anti-adhesion treatments to inhibit the initial stages of staphylococcal pathogenesis. IMPORTANCE Staphylococcus aureus infection is a significant cause of disease and morbidity. Staphylococci utilize multiple adhesion pathways to associate with epithelial cells, including interactions with proteoglycans or ß1 integrins through a fibronectin bridge. Interference with another host protein, tetraspanin CD9, halves staphylococcal adherence to epithelial cells, although CD9 does not interact directly with bacteria. Here, we define the role of CD9 in staphylococcal adherence and uptake, observing that CD9 coordinates syndecan-1, fibronectin, and ß1 integrins to allow efficient staphylococcal infection. Two treatments that disrupt this action are effective and may provide an alternative to antibiotics. We provide insights into the mechanisms that underlie staphylococcal infection of host cells, linking two known adhesion pathways together through CD9 for the first time.

Availability and use of web-based interventions for patients with head and neck cancer: a scoping review.

PURPOSE: To identify and review the nature, scope and use of web-based interventions for patients with head and neck cancer (HNC). METHOD: A scoping review guided by the methodological framework described by the Joanna Briggs Institute was performed to review empirical studies and websites. Seven electronic databases (CINAHL, Medline, Scopus, Embase, Cochrane, PubMed and PsycInfo) were searched from 2010 to 2020, data extracted and synthesised using thematic analysis. The Google search engine was employed, identifying the first 100 websites, using the search term head and neck cancer. Websites meeting eligibility criteria were assessed using the QUEST analysis tool, and descriptively summarised. RESULTS: Thirteen empirical studies and 32 websites were included. As identified by empirical studies, web-based interventions were developed to provide (1) patient information on HNC and related treatments, (2) advice and support during treatment and (3) management strategies promoting adjustment to life with and beyond HNC. The reviewed websites provided minimal information to aid shared decision-making and facilitate preparedness for treatment, with few utilising patient narratives. Web-based interventions for HNC patients were mainly text based and focused on survivorship. CONCLUSIONS: There is a paucity of theory-based, co-designed web-based interventions using patient narratives. IMPLICATIONS FOR CANCER SURVIVORS: As patients increasingly look to the internet for advice and support, healthcare professionals are in a position to provide high-quality web-based interventions. There is an opportunity to rigorously develop a web-based intervention, containing narratives of peoples' lives before and after HNC treatment, aiding decision-making, preparedness for treatment and self-management.

Human Melioidosis Caused by Novel Transmission of Burkholderia pseudomallei from Freshwater Home Aquarium, United States1.

Nearly all cases of melioidosis in the continental United States are related to international travel to areas to which Burkholderia pseudomallei, the bacterium that causes melioidosis, is endemic. We report the diagnosis and clinical course of melioidosis in a patient from the United States who had no international travel history and the public health investigation to determine the source of exposure. We tested environmental samples collected from the patient's home for B. pseudomallei by PCR and culture. Whole-genome sequencing was conducted on PCR-positive environmental samples, and results were compared with sequences from the patient's clinical specimen. Three PCR-positive environmental samples, all collected from a freshwater home aquarium that had contained imported tropical fish, were a genetic match to the clinical isolate from the patient. This finding suggests a novel route of exposure and a potential for importation of B. pseudomallei, a select agent, into the United States from disease-endemic areas.

FANCI functions as a repair/apoptosis switch in response to DNA crosslinks.

Cells counter DNA damage through repair or apoptosis, yet a direct mechanism for this choice has remained elusive. When facing interstrand crosslinks (ICLs), the ICL-repair protein FANCI heterodimerizes with FANCD2 to initiate ICL excision. We found that FANCI alternatively interacts with a pro-apoptotic factor, PIDD1, to enable PIDDosome (PIDD1-RAIDD-caspase-2) formation and apoptotic death. FANCI switches from FANCD2/repair to PIDD1/apoptosis signaling in the event of ICL-repair failure. Specifically, removing key endonucleases downstream of FANCI/FANCD2, increasing ICL levels, or allowing damaged cells into mitosis (when repair is suppressed) all suffice for switching. Reciprocally, apoptosis-committed FANCI reverts from PIDD1 to FANCD2 after a failed attempt to assemble the PIDDosome. Monoubiquitination and deubiquitination at FANCI K523 impact interactor selection. These data unveil a repair-or-apoptosis switch in eukaryotes. Beyond ensuring the removal of unrepaired genomes, the switch's bidirectionality reveals that damaged cells can offset apoptotic defects via de novo attempts at lesion repair.

Ethics and governance for internet-based conservation science research.

Internet-based research is increasingly important for conservation science and has wide-ranging applications and contexts, including culturomics, illegal wildlife trade, and citizen science. However, online research methods pose a range of ethical and legal challenges. Online data may be protected by copyright, database rights, or contract law. Privacy rights may also restrict the use and access of data, as well as ethical requirements from institutions. Online data have real-world meaning, and the ethical treatment of individuals and communities must not be marginalized when conducting internet-based research. As ethics frameworks originally developed for biomedical applications are inadequate for these methods, we propose that research activities involving the analysis of preexisting online data be treated analogous to offline social science methods, in particular, nondeceptive covert observation. By treating internet users and their data with respect and due consideration, conservationists can uphold the public trust needed to effectively address real-world issues.

Ética y Gestión para la Investigación Científica de la Conservación Basada en Internet Resumen La investigación basada en internet es cada vez más importante para las ciencias de la conservación, además de tener contextos y aplicaciones de gran alcance como el análisis de textos, el mercado ilegal de fauna y la ciencia ciudadana. Sin embargo, los métodos de investigación en línea representan una gama de retos éticos y legales pues los datos virtuales pueden estar protegidos por derechos de autor, derechos de base de datos o leyes contractuales. Además, los derechos de privacidad pueden restringir el uso y el acceso a los datos, así como también los requerimientos éticos impuestos por las instituciones. Los datos virtuales tienen valor en el mundo real y el tratamiento ético de los individuos y de las comunidades no se debe marginalizar cuando se realiza una investigación por internet. Ya que los marcos éticos desarrollados originalmente para aplicarse en temas biomédicos son inadecuados para estos métodos, proponemos que las actividades de investigación que involucran el análisis de los datos virtuales preexistentes sean tratadas como análogas a los métodos no virtuales de las ciencias sociales, especialmente la observación encubierta no engañosa. Si se trata a los usuarios del internet y a sus datos con respeto y la consideración debida, los conservacionistas pueden mantener la confianza pública necesaria para tratar efectivamente los asuntos del mundo real.

Impact of proximal and distal cuff inflation on brachial artery endothelial function in healthy individuals.

PURPOSE: In this study, we examined whether the decrease in endothelial function associated with short-term exposure to elevated retrograde shear rate (SR), could be prevented when combined with a concurrent drop in transmural pressure in humans. METHODS: Twenty-five healthy individuals reported to our laboratory on three occasions to complete 30-min experimental conditions, preceded and followed by assessment of endothelial function using flow-mediated dilation (FMD). We used cuff inflation for 30-min to manipulate retrograde SR and transmural pressure in the brachial artery. Subjects underwent, in randomised order: (1) forearm cuff inflation to 60 mmHg (distal cuff; causing increase in retrograde SR), (2) upper arm cuff inflation to 60 mmHg (proximal cuff; causing increase in retrograde SR + decrease in transmural pressure), and (3) no cuff inflation (Control). RESULTS: The distal and proximal cuff conditions both increased brachial artery retrograde SR (p < 0.001) and oscillatory shear index (p < 0.001). The Control intervention did not alter SR patterns or FMD (p > 0.05). A significant interaction-effect was found for FMD (p < 0.05), with the decrease during distal cuff (from 6.9 ± 2.3% to 6.1 ± 2.5%), being reversed to an increase with proximal cuff (from 6.3 ± 2.0 to 6.9 ± 2.0%). The proximal cuff-related increase in FMD could not be explained by the decrease in antegrade or increase in retrograde shear. CONCLUSION: This study suggests that a decrease in transmural pressure may ameliorate the decline in endothelial function that occurs following exposure to elevated retrograde shear in healthy individuals.

Poly(ADP-Ribose) Glycohydrolase (PARG) vs. Poly(ADP-Ribose) Polymerase (PARP) - Function in Genome Maintenance and Relevance of Inhibitors for Anti-cancer Therapy.

Poly(ADP-ribose) polymerases (PARPs) are a family of enzymes that catalyze the addition of poly(ADP-ribose) (PAR) subunits onto themselves and other acceptor proteins. PARPs are known to function in a large range of cellular processes including DNA repair, DNA replication, transcription and modulation of chromatin structure. Inhibition of PARP holds great potential for therapy, especially in cancer. Several PARP1/2/3 inhibitors (PARPi) have had success in treating ovarian, breast and prostate tumors harboring defects in the homologous recombination (HR) DNA repair pathway, especially BRCA1/2 mutated tumors. However, treatment is limited to specific sub-groups of patients and resistance can occur, limiting the use of PARPi. Poly(ADP-ribose) glycohydrolase (PARG) reverses the action of PARP enzymes, hydrolysing the ribose-ribose bonds present in poly(ADP-ribose). Like PARPs, PARG is involved in DNA replication and repair and PARG depleted/inhibited cells show increased sensitivity to DNA damaging agents. They also display an accumulation of perturbed replication intermediates which can lead to synthetic lethality in certain contexts. In addition, PARG is thought to play an important role in preventing the accumulation of cytoplasmic PAR and therefore parthanatos, a caspase-independent PAR-mediated type of cell death. In contrast to PARP, the therapeutic potential of PARG has been largely ignored. However, several recent papers have demonstrated the exciting possibilities that inhibitors of this enzyme may have for cancer treatment, both as single agents and in combination with cytotoxic drugs and radiotherapy. This article discusses what is known about the functions of PARP and PARG and the potential future implications of pharmacological inhibition in anti-cancer therapy.

Aortic thrombosis in a dog with chronic lymphocytic leukemia / Trombose aórtica em cão com leucemia linfocítica crônica

ABSTRACT: The aim of this report was to describe a case of aortic thrombosis (AT) secondary to chronic lymphocytic leukemia (CLL). Although, different types of neoplasms are described as possible causes of aortic thrombosis, CLL was not yet considered. The dog showed signs of lameness that worsened with exercise. The diagnosis of AT was made by ultrasound examination. The diagnosis of CLL was made by necropsy, which showed the presence of small lymphocytes with the appearance of mature lymphocytes in the bone marrow, spleen, liver and kidneys. The importance of including CLL in the possible causes of AT in dogs, in addition to the suspicion of AT in cases of neuromuscular disease, was highlighted.

RESUMO: O objetivo do presente relato é descrever um caso de trombose aórtica (AT) secundária a leucemia linfocítica crônica (LLC). Embora diferentes tipos de neoplasmas sejam descritos como possíveis causas de trombose aórtica, a LLC ainda não foi considerada. O cão mostrou sinais de claudicação que pioravam com o exercício. O diagnóstico de AT foi realizado por exame ultrassonográfico. O diagnóstico de LLC foi feito por necropsia, que mostrou a presença de pequenos linfócitos com aparência de linfócitos maduros na medula óssea, baço, fígado e rins. Destaca-se a importância da inclusão da LLC nas possíveis causas de AT em cães, além da suspeita de AT em casos de doença neuromuscular.

How Cells Handle DNA Breaks during Mitosis: Detection, Signaling, Repair, and Fate Choice.

Mitosis is controlled by a complex series of signaling pathways but mitotic control following DNA damage remains poorly understood. Effective DNA damage sensing and repair is integral to survival but is largely thought to occur primarily in interphase and be repressed during mitosis due to the risk of telomere fusion. There is, however, increasing evidence to suggest tight control of mitotic progression in the incidence of DNA damage, whether induced in mitotic cells or having progressed from failed interphase checkpoints. Here we will discuss what is known to date about signaling pathways controlling mitotic progression and resulting cell fate in the incidence of mitotic DNA damage.

An Ex Vivo Evaluation of Tomographic 3-D Ultrasound, B-Mode Ultrasound, CT And MR Imaging to Measure Artery Diameter, Length and Wall Volume.

Precise measurement of luminal diameter in arteries is important when planning interventional vascular procedures in patients. Measuring wall volume may be important in detecting early artery disease and in the assessment of treatments to prevent atherosclerosis. An ex vivo phantom using porcine arteries was used to evaluate the accuracy with which (i) B-mode ultrasound, (ii) 3-D tomographic ultrasound (tUS), (iii) computed tomography (CT) and (iv) magnetic resonance imaging (MRI) measured length, diameters and volume. The mean error in inner-to-inner diameter measurements by B mode, tUS, CT and MRI were 0.08 ± 0.26, -0.73 ± 0.96 mm, 0.09 ± 0.55 and 0.60 ± 1.01 mm, respectively. The mean error in outer-to-outer diameter measurements by B mode, tUS, CT and MRI were -1.33 ± 0.61, -1.03 ± 0.35, 0.02 ± 1.00 and -0.47 ± 1.32 mm, respectively. The mean error in volume measurements by B mode, tUS, CT and MRI were -0.54 ± 0.62, -0.06 ± 0.09, 0.01 ± 0.18 and -0.20 ± 0.32 cm3, respectively. Errors in length and diameters remain within clinically acceptable thresholds where MRI was the least accurate. tUS was the most accurate method of volume measurement.

Clinical-epidemiological, anatomic-pathological, histochemical and immunohistochemical characterization of renal cystadenocarcinoma-nodular dermatofibrosis syndrome in 11 German Shepherd dogs / Caracterização clínico-epidemiológica, anátomo-patológica, histoquímica e imuno-histoquímica da síndrome cistadenocarcinoma-dermatofibrose nodular em 11 cães Pastor Alemão

Eleven cases of renal cystadenoma/cystadenocarcinoma-nodular dermatofibrosis syndrome (RCND) are described in German Shepherd dogs diagnosed from January 1994 to January 2018 at the Veterinary Pathology Laboratory of the "Universidade Federal de Santa Maria" (LPV-UFSM). The study sample was composed of eight male and three female dogs at a ratio of 2.67:1. Age ranged from six to 12 years (mean=8.7 years). The main clinical signs reported in descending order of frequency were multiple cutaneous nodules (nodular dermatofibrosis), dyspnea, anorexia, weight loss, recurrent hematuria, vomiting, and polydipsia. Results demonstrated that it is not always easy to clinically recognize this syndrome, but its peculiar anatomical-pathological characteristics allow safe diagnosis. Histologically, it was possible to detect all phases (cysts, papillary intratubular hyperplasia, and cystadenomas or cystadenocarcinomas) of a possible pathological continuum of the renal lesions. Uterine leiomyomas were observed in only one of the cases. Through histochemical techniques, it was possible to identify the presence of type I collagen in both cutaneous and renal lesions and consider its possible involvement in the pathogenesis of renal cystadenocarcinoma. Immunohistochemistry (IHC) showed partially satisfactory results in the staining of epithelial cells of renal cysts and neoplasms for pan-cytokeratin.(AU)

São descritos 11 casos da síndrome cistadenoma/cistadenocarcinoma-dermatofibrose nodular (CR-DN) em cães Pastor Alemão, diagnosticados entre janeiro de 1994 e janeiro de 2018 no Laboratório de Patologia Veterinária da Universidade Federal de Santa Maria (LPV-UFSM). Os cães afetados foram oito machos e três fêmeas, estabelecendo-se uma relação de 2,67:1. A idade variou de seis a 12 anos, sendo a média de idade de 8,7 anos. Os principais sinais clínicos relatados foram, em ordem decrescente de frequência, múltiplos nódulos cutâneos (dermatofibrose nodular), dispneia, anorexia, emagrecimento, hematúria recorrente, vômito e polidipsia. Este estudo permitiu estabelecer que o reconhecimento clínico da síndrome nem sempre é fácil, porém suas características anátomo-patológicas peculiares permitem um diagnóstico com segurança. Histologicamente, foi possível detectar todas as fases (cistos, hiperplasia intratubular papilífera, cistadenomas ou cistadenocarcinomas) de um possível continuum patológico das lesões renais. Leiomiomas uterinos foram observados somente em um caso. Através das técnicas histoquímicas foi possível estabelecer que o colágeno tipo I está presente em ambas as lesões, cutâneas e renais, e cogitar seu possível envolvimento na patogênese dos cistadenocarcinomas renais. A técnica de IHQ mostrou resultados parcialmente satisfatórios na imunomarcação das células epiteliais dos cistos e dos neoplasmas renais para pancitoceratina.(AU)

An IRAK1-PIN1 signalling axis drives intrinsic tumour resistance to radiation therapy.

Drug-based strategies to overcome tumour resistance to radiotherapy (R-RT) remain limited by the single-agent toxicity of traditional radiosensitizers (for example, platinums) and a lack of targeted alternatives. In a screen for compounds that restore radiosensitivity in p53 mutant zebrafish while tolerated in non-irradiated wild-type animals, we identified the benzimidazole anthelmintic oxfendazole. Surprisingly, oxfendazole acts via the inhibition of IRAK1, a kinase thus far implicated in interleukin-1 receptor (IL-1R) and Toll-like receptor (TLR) immune responses. IRAK1 drives R-RT in a pathway involving IRAK4 and TRAF6 but not the IL-1R/TLR-IRAK adaptor MyD88. Rather than stimulating nuclear factor-κB, radiation-activated IRAK1 prevented apoptosis mediated by the PIDDosome complex (comprising PIDD, RAIDD and caspase-2). Countering this pathway with IRAK1 inhibitors suppressed R-RT in tumour models derived from cancers in which TP53 mutations predict R-RT. Moreover, IRAK1 inhibitors synergized with inhibitors of PIN1, a prolyl isomerase essential for IRAK1 activation in response to pathogens and, as shown here, in response to ionizing radiation. These data identify an IRAK1 radiation-response pathway as a rational chemoradiation therapy target.

NPM1 directs PIDDosome-dependent caspase-2 activation in the nucleolus.

The PIDDosome (PIDD-RAIDD-caspase-2 complex) is considered to be the primary signaling platform for caspase-2 activation in response to genotoxic stress. Yet studies of PIDD-deficient mice show that caspase-2 activation can proceed in the absence of PIDD. Here we show that DNA damage induces the assembly of at least two distinct activation platforms for caspase-2: a cytoplasmic platform that is RAIDD dependent but PIDD independent, and a nucleolar platform that requires both PIDD and RAIDD. Furthermore, the nucleolar phosphoprotein nucleophosmin (NPM1) acts as a scaffold for PIDD and is essential for PIDDosome assembly in the nucleolus after DNA damage. Inhibition of NPM1 impairs caspase-2 processing, apoptosis, and caspase-2-dependent inhibition of cell growth, demonstrating that the NPM1-dependent nucleolar PIDDosome is a key initiator of the caspase-2 activation cascade. Thus we have identified the nucleolus as a novel site for caspase-2 activation and function.

A mitosis-sensing caspase activation platform? New insights into the PIDDosome.

In contrast to the apoptosome and death-inducing signaling complex, the PIDDosome remains an orphan caspase activation platform unassigned to a specific apoptotic pathway. We found that DNA damage-induced PIDDosome formation is blocked by the mitotic checkpoint factor BUBR1 (budding uninhibited by benzimidazole-related 1), via a direct interaction that disrupts the PIDDosome core scaffold. This inhibition occurs at the kinetochore, thus physically connecting the mitotic and apoptotic machineries.

Degenerate four-wave mixing in a silica hollow bottle-like microresonator.

A hollow, bottle-like microresonator (BLMR) was fabricated from a microcapillary with a nearly parabolic profile. From simulations at 1.55 µm the fundamental bottle mode is shown to be in the anomalous dispersion regime, while the conventional whispering gallery mode, confined to the center of the BLMR, is in the normal dispersion regime. Therefore, we have experimentally shown that, for a BLMR with a diameter of 102 um, degenerate four-wave mixing can only be observed by judicious selection of the tapered fiber coupling position. Dispersion tuning in such a system is also briefly discussed theoretically. BLMRs are promising devices for the implementation of sparsely distributed, widely spanned frequency combs at the telecommunications C-band.

A subset of cancer cell lines is acutely sensitive to the Chk1 inhibitor MK-8776 as monotherapy due to CDK2 activation in S phase.

DNA damage activates Checkpoint kinase 1 (Chk1) to halt cell cycle progression thereby preventing further DNA replication and mitosis until the damage has been repaired. Consequently, Chk1 inhibitors have emerged as promising anticancer therapeutics in combination with DNA damaging drugs, but their single agent activity also provides a novel approach that may be particularly effective in a subset of patients. From analysis of a large panel of cell lines, we demonstrate that 15% are very sensitive to the Chk1 inhibitor MK-8776. Upon inhibition of Chk1, sensitive cells rapidly accumulate DNA double-strand breaks in S phase in a CDK2- and cyclin A-dependent manner. In contrast, resistant cells can continue to grow for at least 7 days despite continued inhibition of Chk1. Resistance can be circumvented by inhibiting Wee1 kinase and thereby directly activating CDK2. Hence, sensitivity to Chk1 inhibition is regulated upstream of CDK2 and correlates with accumulation of CDC25A. We conclude that cells poorly tolerate CDK2 activity in S phase and that a major function of Chk1 is to ensure it remains inactive. Indeed, inhibitors of CDK1 and CDK2 arrest cells in G1 or G2, respectively, but do not prevent progression through S phase demonstrating that neither kinase is required for S phase progression. Inappropriate activation of CDK2 in S phase underlies the sensitivity of a subset of cell lines to Chk1 inhibitors, and this may provide a novel therapeutic opportunity for appropriately stratified patients.

An Inhibitor of PIDDosome Formation.

The PIDDosome-PIDD-RAIDD-caspase-2 complex-is a proapoptotic caspase-activation platform of elusive significance. DNA damage can initiate complex assembly via ATM phosphorylation of the PIDD death domain (DD), which enables RAIDD recruitment to PIDD. In contrast, the mechanisms limiting PIDDosome formation have remained unclear. We identify the mitotic checkpoint factor BubR1 as a direct PIDDosome inhibitor, acting in a noncanonical role independent of Mad2. Following its phosphorylation by ATM at DNA breaks, "primed" PIDD relocates to kinetochores via a direct interaction with BubR1. BubR1 binds the PIDD DD, competes with RAIDD recruitment, and negates PIDDosome-mediated apoptosis after ionizing radiation. The PIDDosome thus sequentially integrates DNA damage and mitotic checkpoint signals to decide cell fate in response to genotoxic stress. We further show that by sequestering PIDD at the kinetochore, BubR1 acts to delay PIDDosome formation until the next cycle, defining a new mechanism by which cells evade apoptosis during mitosis.