12 research outputs found
Resistance to cisplatin does not affect sensitivity of human ovarian cancer cell lines to mifepristone cytotoxicity
<p>Abstract</p> <p>Background</p> <p>The prototypical antiprogestin mifepristone exhibits potent growth inhibition activity towards ovarian cancer cells <it>in vitro </it>and <it>in vivo</it>. The aim of this research was to establish whether mifepristone is capable of inhibiting cell proliferation and inducing apoptotic cell death regardless of the degree of sensitivity ovarian cancer cells exhibit to cisplatin.</p> <p>Methods</p> <p>OV2008, OV2008/C13, A2780, A2780/CP70, Caov-3, and SK-OV-3 cell lines exhibiting a range of sensitivities to cisplatin were used. Growth inhibition, cell viability, and sub-diploid DNA content in response to treatment with escalating doses of either mifepristone or cisplatin were assessed by microcapillary cytometry. Apoptotic cell death was evaluated by measuring genomic DNA fragmentation and cleavage of caspase-3 and poly (ADP ribose) polymerase (PARP).</p> <p>Results</p> <p>The sensitivities to cisplatin manifested by the cell lines were OV2008 > A2780 > Caov-3 > SK-OV-3 > OV2008/C13 > A2780/CP70. Mifepristone inhibited the growth of all six cell lines in a dose-related manner with IC<sub>50s </sub>ranging from ~6â12 ÎŒM and without significant correlation with the relative sensitivities the cells displayed for cisplatin. Moreover, at the highest concentration studied, mifepristone triggered apoptotic death in all six cell lines as evidenced by the increase in sub-diploid fragmented DNA content and cleavage of caspase-3 and of its downstream substrate PARP.</p> <p>Conclusion</p> <p>Mifepristone is cytotoxic towards ovarian cancer cells independent of the sensitivity exhibited by the cells to cisplatin, displaying cytostatic effects at lower concentrations and lethal effects at higher concentrations. Mifepristone monotherapy emerges as a valuable therapeutic alternative for platinum-resistant ovarian cancers.</p
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Broadening Participation in Biology Education Research: Engaging Community College Students and Faculty
Nearly half of all undergraduates are enrolled at community colleges (CCs), including the majority of U.S. students who represent groups underserved in the sciences. Yet only a small minority of studies published in discipline-based education research journals address CC biology students, faculty, courses, or authors. This marked underrepresentation of CC biology education research (BER) limits the availability of evidence that could be used to increase CC student success in biology programs. To address this issue, a diverse group of stakeholders convened at the Building Capacity for Biology Education Research at Community Colleges meeting to discuss how to increase the prevalence of CC BER and foster participation of CC faculty as BER collaborators and authors. The group identified characteristics of CCs that make them excellent environments for studying biology teaching and learning, including student diversity and institutional cultures that prioritize teaching, learning, and assessment. The group also identified constraints likely to impede BER at CCs: limited time, resources, support, and incentives, as well as misalignment between doing research and CC faculty identities as teachers. The meeting culminated with proposing strategies for faculty, administrators, journal editors, scientific societies, and funding agencies to better support CC BER
Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19
IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.
Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.
DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 nonâcritically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022).
INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (nâ=â257), ARB (nâ=â248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; nâ=â10), or no RAS inhibitor (control; nâ=â264) for up to 10 days.
MAIN OUTCOMES AND MEASURES The primary outcome was organ supportâfree days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes.
RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ supportâfree days among critically ill patients was 10 (â1 to 16) in the ACE inhibitor group (nâ=â231), 8 (â1 to 17) in the ARB group (nâ=â217), and 12 (0 to 17) in the control group (nâ=â231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ supportâfree days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively).
CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570
Mass-length Relationships for 3 Bee Species in Northwest Ohio
The ability to accurately estimate bee mass through measurements of intertegular distance (ITD) is an important tool for field biologists. ITD is the distance between the bases of the 2 wing tegulae on the beeâs thorax. However, the relationship between ITD and bee mass can vary based on species and sampling region. A collection of 92 beesârepresenting 3 speciesâwas examined to assess the accuracy of ITD in estimating dry mass for bees in northwest Ohio. The focus was on 3 species: silky striped sweat bees (Agapostemon sericeus), honey bees (Apis mellifera), and common eastern bumble bees (Bombus impatiens). Overall, there was a positive correlation between ITD and dry mass across all individuals sampled (R2 = 0.77), but within species the degree of correlation varied significantly. The results suggest that ITD accurately estimates dry mass in silky striped sweat bees (R2 = 0.93), but the correlation weakens in common eastern bumble bees (R2 = 0.54) and is non-existent in honey bees (R2 = 0.39). Field biologists interested in using ITD to estimate bee mass should take preliminary measurements when investigating bumble bees, and should avoid ITD estimates in honey bees
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The principles of tomorrow's university
In the 21st Century, research is increasingly data- and computation-driven. Researchers, funders, and the larger community today emphasize the traits of openness and reproducibility. In March 2017, 13 mostly early-career research leaders who are building their careers around these traits came together with ten university leaders (presidents, vice presidents, and vice provosts), representatives from four funding agencies, and eleven organizers and other stakeholders in an NIH- and NSF-funded one-day, invitation-only workshop titled "Imagining Tomorrow's University." Workshop attendees were charged with launching a new dialog around open research â the current status, opportunities for advancement, and challenges that limit sharing.The workshop examined how the internet-enabled research world has changed, and how universities need to change to adapt commensurately, aiming to understand how universities can and should make themselves competitive and attract the best students, staff, and faculty in this new world. During the workshop, the participants re-imagined scholarship, education, and institutions for an open, networked era, to uncover new opportunities for universities to create value and serve society. They expressed the results of these deliberations as a set of 22 principles of tomorrow's university across six areas: credit and attribution, communities, outreach and engagement, education, preservation and reproducibility, and technologies.Activities that follow on from workshop results take one of three forms. First, since the workshop, a number of workshop authors have further developed and published their white papers to make their reflections and recommendations more concrete. These authors are also conducting efforts to implement these ideas, and to make changes in the university system. Second, we plan to organise a follow-up workshop that focuses on how these principles could be implemented. Third, we believe that the outcomes of this workshop support and are connected with recent theoretical work on the position and future of open knowledge institutions
TESS Reveals a Short-period Sub-Neptune Sibling (HD 86226c) to a Known Long-period Giant Planet
The Transiting Exoplanet Survey Satellite mission was designed to find
transiting planets around bright, nearby stars. Here we present the detection
and mass measurement of a small, short-period (\,days) transiting
planet around the bright (), solar-type star HD 86226 (TOI-652, TIC
22221375), previously known to host a long-period (1600 days) giant
planet. HD 86226c (TOI-652.01) has a radius of and a
mass of 7.25 based on archival and new radial
velocity data. We also update the parameters of the longer-period,
not-known-to-transit planet, and find it to be less eccentric and less massive
than previously reported. The density of the transiting planet is g
cm, which is low enough to suggest that the planet has at least a small
volatile envelope, but the mass fractions of rock, iron, and water are not
well-constrained. Given the host star brightness, planet period, and location
of the planet near both the ``radius gap'' and the ``hot Neptune desert'', HD
86226c is an interesting candidate for transmission spectroscopy to further
refine its composition.Comment: Accepted in AJ on 22 June 202
TOI-824 b: A New Planet on the Lower Edge of the Hot Neptune Desert
We report the detection of a transiting hot Neptune exoplanet orbiting TOI-824 (SCR J1448-5735), a nearby (d = 64 pc) K4V star, using data from the Transiting Exoplanet Survey Satellite. The newly discovered planet has a radius R p = 2.93 ± 0.20 Râ and an orbital period of 1.393 days. Radial velocity measurements using the Planet Finder Spectrograph and the High Accuracy Radial velocity Planet Searcher spectrograph confirm the existence of the planet, and we estimate its mass to be 18.47 ± 1.84 Mâ. The planet's mean density is Ïp = 4.03-0.78+0.98 g cm-3, making it more than twice as dense as Neptune. TOI-824 b's high equilibrium temperature makes the planet likely to have a cloud-free atmosphere, and thus it is an excellent candidate for follow-up atmospheric studies. The detectability of TOI-824 b's atmosphere from both ground and space is promising and could lead to the detailed characterization of the most irradiated small planet at the edge of the hot Neptune desert that has retained its atmosphere to date