Comparison of mitotic cell death by chromosome fragmentation to premature chromosome condensation

Mitotic cell death is an important form of cell death, particularly in cancer. Chromosome fragmentation is a major form of mitotic cell death which is identifiable during common cytogenetic analysis by its unique phenotype of progressively degraded chromosomes. This morphology however, can appear similar to the morphology of premature chromosome condensation (PCC) and thus, PCC has been at times confused with chromosome fragmentation. In this analysis the phenomena of chromosome fragmentation and PCC are reviewed and their similarities and differences are discussed in order to facilitate differentiation of the similar morphologies. Furthermore, chromosome pulverization, which has been used almost synonymously with PCC, is re-examined. Interestingly, many past reports of chromosome pulverization are identified here as chromosome fragmentation and not PCC. These reports describe broad ranging mechanisms of pulverization induction and agree with recent evidence showing chromosome fragmentation is a cellular response to stress. Finally, biological aspects of chromosome fragmentation are discussed, including its application as one form of non-clonal chromosome aberration (NCCA), the driving force of cancer evolution

Understanding aneuploidy in cancer through the lens of system inheritance, fuzzy inheritance and emergence of new genome systems

Abstract Background In the past 15 years, impressive progress has been made to understand the molecular mechanism behind aneuploidy, largely due to the effort of using various -omics approaches to study model systems (e.g. yeast and mouse models) and patient samples, as well as the new realization that chromosome alteration-mediated genome instability plays the key role in cancer. As the molecular characterization of the causes and effects of aneuploidy progresses, the search for the general mechanism of how aneuploidy contributes to cancer becomes increasingly challenging: since aneuploidy can be linked to diverse molecular pathways (in regards to both cause and effect), the chances of it being cancerous is highly context-dependent, making it more difficult to study than individual molecular mechanisms. When so many genomic and environmental factors can be linked to aneuploidy, and most of them not commonly shared among patients, the practical value of characterizing additional genetic/epigenetic factors contributing to aneuploidy decreases. Results Based on the fact that cancer typically represents a complex adaptive system, where there is no linear relationship between lower-level agents (such as each individual gene mutation) and emergent properties (such as cancer phenotypes), we call for a new strategy based on the evolutionary mechanism of aneuploidy in cancer, rather than continuous analysis of various individual molecular mechanisms. To illustrate our viewpoint, we have briefly reviewed both the progress and challenges in this field, suggesting the incorporation of an evolutionary-based mechanism to unify diverse molecular mechanisms. To further clarify this rationale, we will discuss some key concepts of the genome theory of cancer evolution, including system inheritance, fuzzy inheritance, and cancer as a newly emergent cellular system. Conclusion Illustrating how aneuploidy impacts system inheritance, fuzzy inheritance and the emergence of new systems is of great importance. Such synthesis encourages efforts to apply the principles/approaches of complex adaptive systems to ultimately understand aneuploidy in cancer.https://deepblue.lib.umich.edu/bitstream/2027.42/143540/1/13039_2018_Article_376.pd

The building up of the disk galaxy M33 and the evolution of the metallicity gradient

The evolution of radial gradients of metallicity in disk galaxies and its relation with the disk formation are not well understood. Theoretical models of galactic chemical evolution make contrasting predictions about the time evolution of metallicity gradients. To test chemical evolution models and trace the star formation and accretion history of low luminosity disk galaxies we focus on the Local Group galaxy M33. We analyze O/H and S/H abundances in planetary nebulae, H{\sc ii} regions, and young stars, together with known [Fe/H] abundances in the old stellar population of M33. With a theoretical model, we follow the time evolution of gas (diffuse and condensed in clouds), stars, and chemical abundances in the disk of M33, assuming that the galaxy is accreting gas from an external reservoir. Our model is able to reproduce the available observational constraints on the distribution of gas and stars in M33 and to predict the time evolution of several chemical abundances. In particular, we find that a model characterized by a continuous infall of gas on the disk, at a rate of $\dot M_{\rm inf}\approx 1$ $M_\odot$ yr$^{-1}$, almost constant with time, can also account for the relatively high rate of star formation and for the shallow chemical gradients. Supported by a large sample of high resolution observations for this nearby galaxy, we conclude that the metallicity in the disk of M33 has increased with time at all radii, with a continuous flattening of the gradient over the last $\sim 8$ Gyr.Comment: 16 pages, 11 figures, A&A accepte

Relationships between CYP2D6 phenotype, breast cancer and hot flushes in women at high risk of breast cancer receiving prophylactic tamoxifen: results from the IBIS-I trial

Licensed under a Creative Commons Attribution Non-Commercial Share Alike Licens

Uncovering the Origins of Spiral Structure by Measuring Radial Variation in Pattern Speeds

Current theories of spiral and bar structure predict a variety of pattern speed behaviors, calling for detailed, direct measurement of the radial variation of pattern speeds. Our recently developed Radial Tremaine-Weinberg (TWR) method allows this goal to be achieved for the first time. Here we present TWR spiral pattern speed estimates for M101, IC 342, NGC 3938 and NGC 3344 in order to investigate whether spiral structure is steady or winding, whether spirals are described by multiple pattern speeds, and the relation between bar and spiral speeds. Where possible, we interpret our pattern speeds estimates according to the resonance radii associated with each (established with the disk angular rotation), and compare these to previous determinations. By analyzing the high-quality HI and CO data cubes available for these galaxies, we show that it is possible to determine directly multiple pattern speeds within these systems, and hence identify the characteristic signatures of the processes that drive the spiral structure. Even this small sample of galaxies reveals a surprisingly complex taxonomy, with the first direct evidence for the presence of resonant coupling of multiple patterns found in some systems, and the measurement of a simple single pattern speed in others. Overall, this study demonstrates that we are now in a position to uncover more of the apparently complex physics that lies behind spiral structure.Comment: 15 pages in emulateapj format, 12 figures, accepted for publication in Ap

Genotyping concordance in DNA extracted from formalin‐fixed paraffin embedded (FFPE) breast tumor and whole blood for pharmacogenetic analyses

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135708/1/mol22015991868.pd

Engineered liposomes sequester bacterial exotoxins and protect from severe invasive infections in mice

Gram-positive bacterial pathogens that secrete cytotoxic pore-forming toxins, such as Staphylococcus aureus and Streptococcus pneumoniae, cause a substantial burden of disease. Inspired by the principles that govern natural toxin-host interactions, we have engineered artificial liposomes that are tailored to effectively compete with host cells for toxin binding. Liposome-bound toxins are unable to lyse mammalian cells in vitro. We use these artificial liposomes as decoy targets to sequester bacterial toxins that are produced during active infection in vivo. Administration of artificial liposomes within 10 h after infection rescues mice from septicemia caused by S. aureus and S. pneumoniae, whereas untreated mice die within 24-33 h. Furthermore, liposomes protect mice against invasive pneumococcal pneumonia. Composed exclusively of naturally occurring lipids, tailored liposomes are not bactericidal and could be used therapeutically either alone or in conjunction with antibiotics to combat bacterial infections and to minimize toxin-induced tissue damage that occurs during bacterial clearance

Misconceptions on COVID-19 Risk Among Ugandan Men: Results From a Rapid Exploratory Survey, April 2020

© Copyright © 2020 Kasozi, MacLeod, Ssempijja, Mahero, Matama, Musoke, Bardosh, Ssebuufu, Wakoko-Studstil, Echoru, Ayikobua, Mujinya, Nambuya, Onohuean, Zirintunda, Ekou and Welburn. Background: Transmission of COVID-19 in developing countries is expected to surpass that in developed countries; however, information on community perceptions of this new disease is scarce. The aim of the study was to identify possible misconceptions among males and females toward COVID-19 in Uganda using a rapid online survey distributed via social media. Methods: A cross-sectional survey carried out in early April 2020 was conducted with 161 Ugandans, who purposively participated in the online questionnaire that assessed understandings of COVID-19 risk and infection. Sixty-four percent of respondents were male and 36% were female. Results: We found significant divergences of opinion on gendered susceptibility to COVID-19. Most female respondents considered infection risk, symptoms, severe signs, and death to be equally distributed between genders. In contrast, male respondents believed they were more at risk of infection, severe symptoms, severe signs, and death (52.7 vs. 30.6%, RR = 1.79, 95% CI: 1.14–2.8). Most women did not share this perception and disagreed that males were at higher risk of infection (by a factor of three), symptoms (79% disagree), severe signs (71%, disagree), and death (70.2% disagree). Overall, most respondents considered children less vulnerable (OR = 1.12, 95% CI: 0.55–2.2) to COVID-19 than adults, that children present with less symptoms (OR = 1.57, 95% CI: 0.77–3.19), and that there would be less mortality in children (OR = 0.92, 95% CI: 0.41–1.88). Of female respondents, 76.4% considered mortality from COVID-19 to be different between the young and the elderly (RR = 1.7, 95% CI: 1.01–2.92) and 92.7% believed young adults would show fewer signs than the elderly, and 71.4% agreed that elderly COVID-19 patients would show more severe signs than the young (OR = 2.2, 95% CI: 1.4, 4.8). While respondents considered that all races were susceptible to the signs and symptoms of infection as well as death from COVID-19, they considered mortality would be highest among white people from Europe and the USA. Some respondents (mostly male 33/102, 32.4%) considered COVID-19 to be a “disease of whites” (30.2%). Conclusion: The WHO has identified women and children in rural communities as vulnerable persons who should be given more attention in the COVID-19 national response programs across Africa; however, our study has found that men in Uganda perceive themselves to be at greater risk and that these contradictory perceptions (including the association of COVID-19 with “the white” race) suggest an important discrepancy in the communication of who is most vulnerable and why. Further research is urgently needed to validate and expand the results of this small exploratory study

Can local application of Tranexamic acid reduce post-coronary bypass surgery blood loss? A randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Diffuse microvascular bleeding remains a common problem after cardiac procedures.</p> <p>Systemic use of antifibrinolytic reduces the postoperative blood loss.</p> <p>The purpose of this study was to examine the effectiveness of local application of tranexamic acid to reduce blood loss after coronary artery bypass grafting (CABG).</p> <p>Methods</p> <p>Thirty eight patients scheduled for primary isolated coronary artery bypass grafting were included in this double blind, prospective, randomized, placebo controlled study.</p> <p>Tranexamic acid (TA) group (19 patients) received 1 gram of TA diluted in 100 ml normal saline. Placebo group (19 patients) received 100 ml of normal saline only. The solution was purred in the pericardial and mediastinal cavities.</p> <p>Results</p> <p>Both groups were comparable in their baseline demographic and surgical characteristics. During the first 24 hours post-operatively, cumulative blood loss was significantly less in TA group (median of 626 ml) compared to Placebo group (median of 1040 ml) (P = 0.04). There was no significant difference in the post-op Packed RBCs transfusion between both groups (median of one unit in each) (P = 0.82). Significant less platelets transfusion required in TA group (median zero unit) than in placebo group (median 2 units) (P = 0.03). Apart from re-exploration for excessive surgical bleeding in one patient in TA group, no difference was found in morbidity or mortality between both groups.</p> <p>Conclusion</p> <p>Topical application of tranexamic acid in patients undergoing primary coronary artery bypass grafting led to a significant reduction in postoperative blood loss without adding extra risk to the patient.</p