Is anyone listening? Ireland, David C; Cormick, Craig; Kapeleris, John
Journal of commercial biotechnology,
02/2007, Letnik:
13, Številka:
2
Journal Article
Recenzirano
Emerging industries such as the life sciences, animal health, agricultural biotechnology and environmental products offer both a potential for economic growth and improvements in quality of life, ...crop and stock yield, the environment, and industrial productivity. The growth and success of these industries depends on a combination of good science and good business. Biotechnology, for instance, is one emerging industry that has promised much, yet the delivery still seems to be some way off. Difficulties convincing well-informed investors of the virtues of biotechnology may be indicative of a wider communication failure. Despite numerous initiatives to popularize and sell science, it seems the attitudes and understanding of society towards science and scientists and the importance scientists place on communicating with society remains depressingly low. One-way late-stage communication models have proven ineffective and have only further alienated the very audiences they meant to attract. Solving these problems requires the involvement of both the scientific community and wider society, where appropriate information is presented in a non-guarded and accessible language, and is received by open and willing ears, setting the scene for interactive, educated debates that can progress rather than hinder the science. This paper explores the various science-society interactions and identifies a need for early-stage two-way communication models. PUBLICATION ABSTRACT
Small cell lung cancer (SCLC) is a neuroendocrine tumor treated clinically as a single disease with poor outcomes. Distinct SCLC molecular subtypes have been defined based on expression of ASCL1, ...NEUROD1, POU2F3, or YAP1. Here, we use mouse and human models with a time-series single-cell transcriptome analysis to reveal that MYC drives dynamic evolution of SCLC subtypes. In neuroendocrine cells, MYC activates Notch to dedifferentiate tumor cells, promoting a temporal shift in SCLC from ASCL1+ to NEUROD1+ to YAP1+ states. MYC alternatively promotes POU2F3+ tumors from a distinct cell type. Human SCLC exhibits intratumoral subtype heterogeneity, suggesting that this dynamic evolution occurs in patient tumors. These findings suggest that genetics, cell of origin, and tumor cell plasticity determine SCLC subtype.
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•Multiple SCLC molecular subtypes arise from a neuroendocrine cell of origin•MYC drives the NEUROD1+ and YAP1+ subtypes of SCLC in a temporal evolution•MYC directly activates NOTCH signaling to reprogram neuroendocrine fate•Multiple SCLC molecular subtypes are present within individual human tumors
Ireland et al. show that MYC activates Notch signaling to dedifferentiate neuroendocrine small cell lung cancer (SCLC) in a conserved trajectory from ASCL1+ to NEUROD1+ to YAP1+ non-neuroendocrine subtypes, suggesting that these are not distinct subtypes but different stages of progressive evolution of SCLC.
Severe prenatal undernutrition is usually associated with low birth weights in offspring and disorders including hypertension, obesity, and diabetes. Whether alterations in maternal nutrition ...insufficient to impair birth weight or prenatal growth impact the cardiovascular, stress, or metabolic systems is unknown. In addition, little is known about the effects of maternal dietary restriction on development of the reproductive system in mammals. Here, we use the bovine model, which has a gestational length and birth rate similar to humans, to show that offspring from nutritionally restricted dams (during the first trimester) were born with identical birth weights and had similar postnatal growth rates (to 95 wk of age), puberty, glucose metabolism, and responses to stress compared to offspring from control mothers. However, an increase in maternal testosterone concentrations was detected during dietary restriction, and these dams had offspring with a diminished ovarian reserve (as assessed by a reduction in antral follicle count, reduced concentrations of anti-Müllerian hormone, and increased follicle-stimulating hormone concentrations), enlarged aorta, and increased arterial blood pressure compared with controls. Our study links transient maternal undernutrition and enhanced maternal androgen production with a diminished ovarian reserve as well as potential suboptimal fertility, enlarged aortic trunk size, and enhanced blood pressure independent of alterations in birth weight, postnatal growth, or stress response and glucose tolerance. The implications are that relatively mild transient reductions in maternal nutrition during the first trimester of pregnancy (even those that do not affect gross development) should be avoided to ensure healthy development of reproductive and cardiovascular systems in offspring.
A collaborative study was conducted involving 8 laboratories (including the authors' laboratories) to validate the streamlined enzymatic method for determination of beta-D-glucan in barley and oats. ...In the method, the flour sample is cooked to hydrate and gelatinize beta-glucan, which is subsequently hydrolyzed to soluble fragments with the lichenase enzyme. After volume and pH adjustments and filtration, the solution is treated with beta-glucosidase, which hydrolyzes beta-gluco-oligosaccharides to D-glucose. D-Glucose is measured with glucose oxidase-peroxidase reagent. Other portions of lichenase hydrolysate are treated directly with glucose oxidase-peroxidase reagent to measure free glucose in test sample. If levels of free glucose are high, the sample is extracted first with 80% ethanol. For all samples analyzed, the repeatability relative standard deviation (RSD(r)) values ranged from 3.1 to 12.3% and the reproducibility relative standard deviation (RSD(R)) values ranged from 6.6 to 12.3%. The streamlined enzymatic method for determination of beta-D-glucan in barley and oats has been adopted first action by AOAC INTERNATIONAL
Objective
COVID‐19 is a novel infectious disease with a broad spectrum of clinical severity. Patients with systemic vasculitis have an increased risk of serious infections and may be at risk of ...severe outcomes following COVID‐19. We undertook this study to establish the risk factors for severe COVID‐19 outcomes in these patients, including the impact of immunosuppressive therapies.
Methods
A multicenter cohort was developed through the participation of centers affiliated with national UK and Ireland vasculitis registries. Clinical characteristics and outcomes are described. Logistic regression was used to evaluate associations between potential risk factors and a severe COVID‐19 outcome, defined as a requirement for advanced oxygen therapy, a requirement for invasive ventilation, or death.
Results
The cohort included 65 patients with systemic vasculitis who developed COVID‐19 (median age 70 years, 49% women), of whom 25 patients (38%) experienced a severe outcome. Most patients (55 of 65 85%) had antineutrophil cytoplasmic antibody–associated vasculitis (AAV). Almost all patients required hospitalization (59 of 65 91%), 7 patients (11%) were admitted to intensive care, and 18 patients (28%) died. Background glucocorticoid therapy was associated with severe outcomes (adjusted odds ratio OR 3.7 95% confidence interval 1.1–14.9; P = 0.047), as was comorbid respiratory disease (adjusted OR 7.5 95% confidence interval 1.9–38.2; P = 0.006). Vasculitis disease activity and nonglucocorticoid immunosuppressive therapy were not associated with severe outcomes.
Conclusion
In patients with systemic vasculitis, glucocorticoid use at presentation and comorbid respiratory disease were associated with severe outcomes in COVID‐19. These data can inform clinical decision‐making relating to the risk of severe COVID‐19 in this vulnerable patient group.
ABSTRACT We confirm and characterize a close-in ( = 5.425 days), super-Neptune sized ( ) planet transiting K2-33 (2MASS J16101473-1919095), a late-type (M3) pre-main-sequence (11 Myr old) star in the ...Upper Scorpius subgroup of the Scorpius-Centaurus OB association. The host star has the kinematics of a member of the Upper Scorpius OB association, and its spectrum contains lithium absorption, an unambiguous sign of youth ( Myr) in late-type dwarfs. We combine photometry from K2 and the ground-based MEarth project to refine the planet's properties and constrain the host star's density. We determine K2-33's bolometric flux and effective temperature from moderate-resolution spectra. By utilizing isochrones that include the effects of magnetic fields, we derive a precise radius (6%-7%) and mass (16%) for the host star, and a stellar age consistent with the established value for Upper Scorpius. Follow-up high-resolution imaging and Doppler spectroscopy confirm that the transiting object is not a stellar companion or a background eclipsing binary blended with the target. The shape of the transit, the constancy of the transit depth and periodicity over 1.5 yr, and the independence with wavelength rule out stellar variability or a dust cloud or debris disk partially occulting the star as the source of the signal; we conclude that it must instead be planetary in origin. The existence of K2-33b suggests that close-in planets can form in situ or migrate within ∼10 Myr, e.g., via interactions with a disk, and that long-timescale dynamical migration such as by Lidov-Kozai or planet-planet scattering is not responsible for all short-period planets.
IFN-alpha/beta plays a critical role in limiting viral spread, restricting viral tropism and protecting mice from neurotropic coronavirus infection. However, the IFN-alpha/beta dependent mechanisms ...underlying innate anti-viral functions within the CNS are poorly understood. The role of RNase L in viral encephalomyelitis was explored based on its functions in inhibiting translation, inducing apoptosis, and propagating the IFN-alpha/beta pathway through RNA degradation intermediates. Infection of RNase L deficient (RL(-/-)) mice with a sub-lethal, demyelinating mouse hepatitis virus variant revealed that the majority of mice succumbed to infection by day 12 p.i. However, RNase L deficiency did not affect overall control of infectious virus, or diminish IFN-alpha/beta expression in the CNS. Furthermore, increased morbidity and mortality could not be attributed to altered proinflammatory signals or composition of cells infiltrating the CNS. The unique phenotype of infected RL(-/-) mice was rather manifested in earlier onset and increased severity of demyelination and axonal damage in brain stem and spinal cord without evidence for enhanced neuronal infection. Increased tissue damage coincided with sustained brain stem infection, foci of microglia infection in grey matter, and increased apoptotic cells. These data demonstrate a novel protective role for RNase L in viral induced CNS encephalomyelitis, which is not reflected in overall viral control or propagation of IFN-alpha/beta mediated signals. Protective function is rather associated with cell type specific and regional restriction of viral replication in grey matter and ameliorated neurodegeneration and demyelination.
Crowdfunding is a rapidly growing phenomenon wherein entrepreneurs seek funding for their entrepreneurial activities from a potentially large audience of interested individuals. Crowdfunding has ...exploded in popularity over the last decade and now accounts for tens of billions of dollars annually. But despite the importance and growth of crowdfunding, little scholarly knowledge exists about the topic. To address this gap, this special issue includes five articles that each advance knowledge about crowdfunding in important ways. We briefly review past work on crowdfunding in leading entrepreneurship and management journals. We then highlight the diverse contributions offered in the special issue articles.
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