54 research outputs found

    p27 Deficiency Cooperates with Bcl-2 but Not Bax to Promote T-Cell Lymphoma

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    The effect of Bcl-2 on oncogenesis is complex and expression may either delay or accelerate oncogenesis. The pro-oncogenic activity is attributed to its well characterized anti-apoptotic function while the anti-oncogenic function has been attributed to its inhibition of cellular proliferation. Recent studies demonstrate that p27 may mediate the effects of Bcl-2 on cellular proliferation. We hypothesized that p27 may suppress tumor formation by Bcl-2 family members. To test this hypothesis, cell cycle inhibition and lymphoma development were examined in Lck-Bcl-2 and Lck-Bax38/1 transgenic mice deficient in p27. Strikingly, p27 deficiency synergistically cooperates with Bcl-2 to increase T cell hyperplasia and development of spontaneous T cell lymphomas. Within 1 year, >90% of these mice had developed thymic T cell lymphomas. This high penetrance contrasts with a one year incidence of <5% of thymic lymphoma in Lck-Bcl-2 or p27 −/− mice alone. In contrast, p27 deficiency had no effect on tumor formation in Lck-Bax38/1 transgenic mice, another model of T cell lymphoma. Histologically the lymphomas in p27 −/− Lck-Bcl-2 mice are lymphoblastic and frequently involve multiple organs suggesting an aggressive phenotype. Interestingly, in mature splenic T cells, Bcl-2 largely retains its anti-proliferative function even in the absence of p27. T cells from p27 −/− Lck-Bcl-2 mice show delayed kinetics of CDK2 Thr-160 phosphorylation. This delay is associated with a delay in the up regulation of both Cyclin D2 and D3. These data demonstrate a complex relationship between the Bcl-2 family, cellular proliferation, and oncogenesis and demonstrate that p27 up-regulation is not singularly important in the proliferative delay observed in T cells expressing Bcl-2 family members. Nonetheless, the results indicate that p27 is a critical tumor suppressor in the context of Bcl-2 expression

    Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

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    PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

    Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

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    PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

    Conventional distance sampling versus strip transects and abundance indices for estimating abundance of greater gliders (Petauroides volans) and eastern ringtail possums (Pseudocheirus peregrinus)

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    Context: Accurate estimates of abundance are extremely useful for wildlife management and conservation. Estimates generated from distance sampling are typically considered superior to strip transects and abundance indices, as the latter do not account for probability of detection, thereby risking significant error. Aims: To compare density estimates generated from conventional distance sampling (CDS) of arboreal marsupials with strip transect density estimates and abundance indices. Methods: Off-track CDS and strip transects were used to estimate densities of P. volans and P. peregrinus across ∼ 2.6 km2 of remnant eucalypt forest at Mt Duval in north-eastern New South Wales. Key Results: CDS density estimates for P. volans (1.36 ha−1, 95% confidence interval (CI) of 1.07-1.72 ha−1) and P. peregrinus (0.28 ha−1, 95% CI 0.22-0.35 ha−1) were consistent with densities reported in other studies conducted in open eucalypt forests. A strip transect width of 40m for P. volans resulted in a collective set of values for density (1.35 ha−1), error (s.e. ∓ 0.14), precision (cv 0.10) and 95% CI (1.07–1.62 ha−1) closest to those associated with the CDS-generated density estimate (1.36 ha−1, s.e. ∓ 0.15, cv 0.10, 95% CI 1.07–1.72 ha−1). Strip widths of 10 to 40m resulted in density estimates for P. peregrinus closest to those generated through CDS, but much less precise. Conclusions: Although a 40-m wide strip transect provided a robust density estimate for P. volans at Mt Duval, this is unlikely to be consistent across different study areas. Strip transects provided less precise density estimates, or underestimated P. peregrinus density at Mt Duval, when compared with CDS density estimates. CDS should be favoured over strip transects or abundance indices for estimating P. volans and P. peregrinus abundance, because it is capable of providing more meaningful and robust abundance estimates by accounting for the probability of detection from the transect line across different habitats. Implications: Researchers, conservation managers and decision makers should be aware that common methods for assessing arboreal marsupial abundance have serious potential weaknesses. Thus, it would be prudent to invest in studies that address imperfect detection to improve the quality of monitoring data

    Data from: Dragons in our midst: phyloforensics of illegally traded Southeast Asian monitor lizards

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    We provide a phylogenetic and population genetic evaluation of the illegal pet and bush meat trade of monitor lizards in the Philippines. We use a molecular dataset assembled from vouchered samples with known localities throughout the country, as a reference for statistical phylogenetic, population genetic, and DNA barcoding analyses of genetic material obtained during a three year survey of the Manila pet trade. Our results provide the first genetic evaluation of a major Southeast Asian city’s illegal trade in monitors and allow us to establish several important conclusions regarding actual, versus reported, origins of Manila’s black market Varanus. Monitor lizards are clearly transported throughout the archipelago for trade; we identified genotypes from areas surrounding Manila, the distinct Bicol faunal subregion of Luzon, Mindanao Island, the Visayan islands, islands of the Romblon Province, the Babuyan islands, and Mindoro Island. Numerous species are involved, including multiple endemic Philippine taxa, the threatened Gray’s monitor (Varanus olivaceus), and the presumably non-Philippine rough-neck monitor (Varanus rudicollis). Our results suggest that traders frequently and deliberately misrepresent the provenance of traded animals, in an apparent effort to increase their perceived market value

    Varanus_Combined

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    Nexus file with character block. Alignment used in phylogenetic analyses for the study

    A unified model of species abundance, genetic diversity, and functional diversity reveals the mechanisms structuring ecological communities

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    International audienceBiodiversity accumulates hierarchically by means of ecological and evolutionary processes and feedbacks. Within ecological communities drift, dispersal, speciation, and selection operate simultaneously to shape patterns of biodiversity. Reconciling the relative importance of these is hindered by current models and inference methods, which tend to focus on a subset of processes and their resulting predictions. Here we introduce Massive Eco-evolutionary Synthesis Simulations (MESS), a unified mechanistic model of community assembly, rooted in classic island biogeography theory, which makes temporally explicit joint predictions across three biodiversity data axes: i) species richness and abundances; ii) population genetic diversities; and iii) trait variation in a phylogenetic context. Using simulations we demonstrate that each data axis captures information at different timescales, and that integrating these axes enables discriminating among previously unidentifiable community assembly models. MESS is unique in generating predictions of community-scale genetic diversity, and in characterizing joint patterns of genetic diversity, abundance, and trait values. MESS unlocks the full potential for investigation of biodiversity processes using multi-dimensional community data including a genetic component, such as might be produced by contemporary eDNA or metabarcoding studies. We combine MESS with supervised machine learning to fit the parameters of the model to real data and infer processes underlying how biodiversity accumulates, using communities of tropical trees, arthropods, and gastropods as case studies that span a range of data availability scenarios, and spatial and taxonomic scales

    The VISTA IR camera

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    The VISTA IR Camera has now completed its detailed design phase and is on schedule for delivery to ESO's Cerro Paranal Observatory in 2006. The camera consists of 16 Raytheon VIRGO 2048×2048 HgCdTe arrays in a sparse focal plane sampling a 1.65 degree field of view. A 1.4m diameter filter wheel provides slots for 7 distinct science filters, each comprising 16 individual filter panes. The camera also provides autoguiding and curvature sensing information for the VISTA telescope, and relies on tight tolerancing to meet the demanding requirements of the f/1 telescope design. The VISTA IR camera is unusual in that it contains no cold pupil-stop, but rather relies on a series of nested cold baffles to constrain the light reaching the focal plane to the science beam. In this paper we present a complete overview of the status of the final IR Camera design, its interaction with the VISTA telescope, and a summary of the predicted performance of the system
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