Taking the Pulse of PyroCumulus Clouds

Forest fires can burn large areas, but can also inject smoke into the upper troposphere/lower stratosphere (UT/LS), where stakes are even higher for climate, because emissions tend to have a longer lifetime, and can produce significant regional and even global climate effects, as is the case with some volcanoes. Large forest fires are now believed to be more common in summer, especially in the boreal regions, where pyrocumulus (pyroCu), and occasionally pyrocumuionimbus (pyroCb) clouds are formed, which can transport emissions into the UT/LS. A major difficulty in developing realistic fire plume models is the lack of observational data within fire plumes that resolves structure at a few 100 m scales, which can be used to validate these models. Here, we report detailed airborne radiation measurements within strong pyroCu taken over boreal forest fires in Saskatchewan, Canada during the Arctic Research of the Composition of the Troposphere from Aircraft and Satellites (ARCTAS) summer field campaign in 2008. We find that the angular distribution of radiance within the pyroCu is closely related to the diffusion domain in water clouds and can be described by very similar simple cosine functions. We demonstrate with Monte Carlo simulations that radiation transport in pyroCu is inherently a 3D phenomenon and must account for particle absorption. However, the simple cosine function promises to offer an easy solution for climate models. The presence of a prominent smoke core, defined by strong extinction in the UV, VIS and NIR, suggests that the core might be an important pathway for emission transport to the upper troposphere and lower stratosphere. We speculate that this plume injection core is generated and sustained by complex processes not yet well understood, but not necessarily related directly to the intense fires that originally initiated the plume rise

Pharmacogenomic biomarkers in docetaxel treatment of prostate cancer: from discovery to implementation

Prostate cancer is the fifth leading cause of male cancer death worldwide. Although docetaxel chemotherapy has been used for more than fifteen years to treat metastatic castration resistant prostate cancer, the high inter-individual variability of treatment efficacy and toxicity is still not well understood. Since prostate cancer has a high heritability, inherited biomarkers of the genomic signature may be appropriate tools to guide treatment. In this review, we provide an extensive overview and discuss the current state of the art of pharmacogenomic biomarkers modulating docetaxel treatment of prostate cancer. This includes (1) research studies with a focus on germline genomic biomarkers, (2) clinical trials including a range of genetic signatures, and (3) their implementation in treatment guidelines. Based on this work, we suggest that one of the most promising approaches to improve clinical predictive capacity of pharmacogenomic biomarkers in docetaxel treatment of prostate cancer is the use of compound, multigene pharmacogenomic panels defined by specific clinical outcome measures. In conclusion, we discuss the challenges of integrating prostate cancer pharmacogenomic biomarkers into the clinic and the strategies that can be employed to allow a more comprehensive, evidence-based approach to facilitate their clinical integration. Expanding the integration of pharmacogenetic markers in prostate cancer treatment procedures will enhance precision medicine and ultimately improve patient outcomes

Cloud Droplet Size and Liquid Water Path Retrievals From Zenith Radiance Measurements: Examples From the Atmospheric Radiation Measurement Program and the Aerosol Robotic Network

The ground-based Atmospheric Radiation Measurement Program (ARM) and NASA Aerosol Robotic Network (AERONET) routinely monitor clouds using zenith radiances at visible and near-infrared wavelengths. Using the transmittance calculated from such measurements, we have developed a new retrieval method for cloud effective droplet size and conducted extensive tests for non-precipitating liquid water clouds. The underlying principle is to combine a water-absorbing wavelength (i.e. 1640 nm) with a nonwater-absorbing wavelength for acquiring information on cloud droplet size and optical depth. For simulated stratocumulus clouds with liquid water path less than 300 g/sq m and horizontal resolution of 201m, the retrieval method underestimates the mean effective radius by 0.8 m, with a root-mean-squared error of 1.7 m and a relative deviation of 13 %. For actual observations with a liquid water path less than 450 gm.2 at the ARM Oklahoma site during 2007-2008, our 1.5 min-averaged retrievals are generally larger by around 1 m than those from combined ground-based cloud radar and microwave radiometer at a 5min temporal resolution. We also compared our retrievals to those from combined shortwave flux and microwave observations for relatively homogeneous clouds, showing that the bias between these two retrieval sets is negligible, but the error of 2.6 m and the relative deviation of 22% are larger than those found in our simulation case. Finally, the transmittance-based cloud effective droplet radii agree to better than 11% with satellite observations and have a negative bias of 1 m. Overall, the retrieval method provides reasonable cloud effective radius estimates, which can enhance the cloud products of both ARM and AERONET

PIP5KIβ Selectively Modulates Apical Endocytosis in Polarized Renal Epithelial Cells

Localized synthesis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] at clathrin coated pits (CCPs) is crucial for the recruitment of adaptors and other components of the internalization machinery, as well as for regulating actin dynamics during endocytosis. PtdIns(4,5)P2 is synthesized from phosphatidylinositol 4-phosphate by any of three phosphatidylinositol 5-kinase type I (PIP5KI) isoforms (α, β or γ). PIP5KIβ localizes almost exclusively to the apical surface in polarized mouse cortical collecting duct cells, whereas the other isoforms have a less polarized membrane distribution. We therefore investigated the role of PIP5KI isoforms in endocytosis at the apical and basolateral domains. Endocytosis at the apical surface is known to occur more slowly than at the basolateral surface. Apical endocytosis was selectively stimulated by overexpression of PIP5KIβ whereas the other isoforms had no effect on either apical or basolateral internalization. We found no difference in the affinity for PtdIns(4,5)P2-containing liposomes of the PtdIns(4,5)P2 binding domains of epsin and Dab2, consistent with a generic effect of elevated PtdIns(4,5)P2 on apical endocytosis. Additionally, using apical total internal reflection fluorescence imaging and electron microscopy we found that cells overexpressing PIP5KIβ have fewer apical CCPs but more internalized coated structures than control cells, consistent with enhanced maturation of apical CCPs. Together, our results suggest that synthesis of PtdIns(4,5)P2 mediated by PIP5KIβ is rate limiting for apical but not basolateral endocytosis in polarized kidney cells. PtdIns(4,5)P2 may be required to overcome specific structural constraints that limit the efficiency of apical endocytosis. © 2013 Szalinski et al

Lime pretreatment of sugar beet pulp and evaluation of synergy between ArfA, ManA and XynA from Clostridium cellulovorans on the pretreated substrate

Sugar beet pulp (SBP) is a waste product from the sugar beet industry and could be used as a potential biomass feedstock for second generation biofuel technology. Pretreatment of SBP with ‘slake lime’ (calcium hydroxide) was investigated using a 23 factorial design and the factors examined included lime loading, temperature and time. The pretreatment was evaluated for its ability to enhance enzymatic degradation using a combination of three hemicellulases, namely ArfA (an arabinofuranosidase), ManA (an endo-mannanase) and XynA (an endo-xylanase) from C. cellulovorans to determine the conditions under which optimal activity was facilitated. Optimal pretreatment conditions were found to be 0.4 g lime/g SBP, with 36 h digestion at 40 °C. The synergistic interactions between ArfA, ManA and XynA from C. cellulovorans were subsequently investigated on the pretreated SBP. The highest degree of synergy was observed at a protein ratio of 75% ArfA to 25% ManA, with a specific activity of 2.9 U/g protein. However, the highest activity was observed at 4.2 U/g protein at 100% ArfA. This study demonstrated that lime treatment enhanced enzymatic hydrolysis of SBP. The ArfA was the most effective hemicellulase for release of sugars from pretreated SBP, but the synergy with the ManA indicated that low levels of mannan in SBP were probably masking the access of the ArfA to its substrate. XynA displayed no synergy with the other two hemicellulases, indicating that the xylan in the SBP was not hampering the access of ArfA or ManA to their substrates and was not closely associated with the mannan and arabinan in the SBP

Public involvement in the governance of population-level biomedical research: unresolved questions and future directions

Population-level biomedical research offers new opportunities to improve population health, but also raises new challenges to traditional systems of research governance and ethical oversight. Partly in response to these challenges, various models of public involvement in research are being introduced. Yet, the ways in which public involvement should meet governance challenges are not well understood. We conducted a qualitative study with 36 experts and stakeholders using the World Café method to identify key governance challenges and explore how public involvement can meet these challenges. This brief report discusses four cross-cutting themes from the study: the need to move beyond individual consent; issues in benefit and data sharing; the challenge of delineating and understanding publics; and the goal of clarifying justifications for public involvement. The report aims to provide a starting point for making sense of the relationship between public involvement and the governance of population-level biomedical research, showing connections, potential solutions and issues arising at their intersection. We suggest that, in population-level biomedical research, there is a pressing need for a shift away from conventional governance frameworks focused on the individual and towards a focus on collectives, as well as to foreground ethical issues around social justice and develop ways to address cultural diversity, value pluralism and competing stakeholder interests. There are many unresolved questions around how this shift could be realised, but these unresolved questions should form the basis for developing justificatory accounts and frameworks for suitable collective models of public involvement in population-level biomedical research governance. [Abstract copyright: © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.

Synergy between EngE, XynA and ManA from Clostridium cellulovorans on corn stalk, grass and pineapple pulp substrates

The synergistic interaction between various hemi/cellulolytic enzymes has become more important in order to achieve effective and optimal degradation of complex lignocellulose substrates for biofuel production. This study investigated the synergistic effect of three enzymes endoglucanase (EngE), mannanase (ManA) and xylanase (XynA) on the degradation of corn stalk, grass, and pineapple fruit pulp and determined the optimal degree of synergy between combinations of these enzymes. It was established that EngE was essential for degradation of all of the substrates, while the hemicellulases were able to contribute in a synergistic fashion to increase the activity on these substrates. Maximum specific activity and degree of synergy on the corn stalk and grass was found with EngE:XynA in a ratio of 75:25%, with a specific activity of 41.1 U/mg protein and a degree of synergy of 6.3 for corn stalk, and 44.1 U/mg protein and 3.4 for grass, respectively. The pineapple fruit pulp was optimally digested using a ManA:EngE combination in a 50:50% ratio; the specific activity and degree of synergy achieved were 52.4 U/mg protein and 2.7, respectively. This study highlights the importance of hemicellulases for the synergistic degradation of complex lignocellulose. The inclusion of a mannanase in an enzyme consortium for biomass degradation should be examined further as this study suggests that it may play an important, although mostly overlooked, role in the synergistic saccharification of lignocellulose

Understanding the Sequence-Dependence of DNA Groove Dimensions: Implications for DNA Interactions

BACKGROUND: The B-DNA major and minor groove dimensions are crucial for DNA-protein interactions. It has long been thought that the groove dimensions depend on the DNA sequence, however this relationship has remained elusive. Here, our aim is to elucidate how the DNA sequence intrinsically shapes the grooves. METHODOLOGY/PRINCIPAL FINDINGS: The present study is based on the analysis of datasets of free and protein-bound DNA crystal structures, and from a compilation of NMR (31)P chemical shifts measured on free DNA in solution on a broad range of representative sequences. The (31)P chemical shifts can be interpreted in terms of the BI↔BII backbone conformations and dynamics. The grooves width and depth of free and protein-bound DNA are found to be clearly related to the BI/BII backbone conformational states. The DNA propensity to undergo BI↔BII backbone transitions is highly sequence-dependent and can be quantified at the dinucleotide level. This dual relationship, between DNA sequence and backbone behavior on one hand, and backbone behavior and groove dimensions on the other hand, allows to decipher the link between DNA sequence and groove dimensions. It also firmly establishes that proteins take advantage of the intrinsic DNA groove properties. CONCLUSIONS/SIGNIFICANCE: The study provides a general framework explaining how the DNA sequence shapes the groove dimensions in free and protein-bound DNA, with far-reaching implications for DNA-protein indirect readout in both specific and non specific interactions

Integrated annotation and analysis of genomic features reveal new types of functional elements and large-scale epigenetic phenomena in the developing zebrafish

Zebrafish, a popular model for embryonic development and for modelling human diseases, has so far lacked a systematic functional annotation programme akin to those in other animal models. To address this, we formed the international DANIO-CODE consortium and created the first central repository to store and process zebrafish developmental functional genomic data. Our Data Coordination Center (https://danio-code.zfin.org) combines a total of 1,802 sets of unpublished and reanalysed published genomics data, which we used to improve existing annotations and show its utility in experimental design. We identified over 140,000 cis-regulatory elements in development, including novel classes with distinct features dependent on their activity in time and space. We delineated the distinction between regulatory elements active during zygotic genome activation and those active during organogenesis, identifying new aspects of how they relate to each other. Finally, we matched regulatory elements and epigenomic landscapes between zebrafish and mouse and predict functional relationships between them beyond sequence similarity, extending the utility of zebrafish developmental genomics to mammals