Understanding how proteins and their complex interaction networks convert the genomic information into a dynamic living organism is a fundamental challenge in biological sciences. As an important ...step towards understanding the systems biology of a complex eukaryote, we cataloged 63% of the predicted Drosophila melanogaster proteome by detecting 9,124 proteins from 498,000 redundant and 72,281 distinct peptide identifications. This unprecedented high proteome coverage for a complex eukaryote was achieved by combining sample diversity, multidimensional biochemical fractionation and analysis-driven experimentation feedback loops, whereby data collection is guided by statistical analysis of prior data. We show that high-quality proteomics data provide crucial information to amend genome annotation and to confirm many predicted gene models. We also present experimentally identified proteotypic peptides matching approximately 50% of D. melanogaster gene models. This library of proteotypic peptides should enable fast, targeted and quantitative proteomic studies to elucidate the systems biology of this model organism.
Poly(3,4-ethylenedioxythiophene) (PEDOT) is an intrinsically conductive polymer that is used in a wide range of applications such as antistatics, capacitors, touch panels, organic light emitting ...diodes, organic solar cells and printed electronics. This paper describes the characteristic parameters of 31 different commercially available PEDOT dispersions. It shows how the PEDOT dispersions have been tailored to each of those applications and thereby the opportunities and limitations of this material.
Growth and metastasis of colorectal cancer is closely connected to the biosynthetic capacity of tumor cells, and colorectal cancer stem cells that reside at the top of the intratumoral hierarchy are ...especially dependent on this feature. By performing disease modeling on patient-derived tumor organoids, we found that elevated expression of the ribosome biogenesis factor NLE1 occurs upon SMAD4 loss in TGFβ1-exposed colorectal cancer organoids. TGFβ signaling-mediated downregulation of NLE1 was prevented by ectopic expression of c-MYC, which occupied an E-box-containing region within the NLE1 promoter. Elevated levels of NLE1 were found in colorectal cancer cohorts compared with normal tissues and in colorectal cancer subtypes characterized by Wnt/MYC and intestinal stem cell gene expression. In colorectal cancer cells and organoids, NLE1 was limiting for de novo protein biosynthesis. Upon NLE1 ablation, colorectal cancer cell lines activated p38/MAPK signaling, accumulated p62- and LC3-positive structures indicative of impaired autophagy, and displayed more reactive oxygen species. Phenotypically, knockout of NLE1 inhibit.ed proliferation, migration and invasion, clonogenicity, and anchorage-independent growth. NLE1 loss also increased the fraction of apoptotic tumor cells, and deletion of TP53 further sensitized NLE1-deficient colorectal cancer cells to apoptosis. In an endoscopy-guided orthotopic mouse transplantation model, ablation of NLE1 impaired tumor growth in the colon and reduced primary tumor-derived liver metastasis. In patients with colorectal cancer, NLE1 mRNA levels predicted overall and relapse-free survival. Taken together, these data reveal a critical role of NLE1 in colorectal cancer growth and progression and suggest that NLE1 represents a potential therapeutic target in colorectal cancer patients.
NLE1 limits de novo protein biosynthesis and the tumorigenic potential of advanced colorectal cancer cells, suggesting NLE1 could be targeted to improve the treatment of metastatic colorectal cancer.
The completion of the sequencing of the human genome and the concurrent, rapid development of high-throughput proteomic methods have resulted in an increasing need for automated approaches to archive ...proteomic data in a repository that enables the exchange of data among researchers and also accurate integration with genomic data. PeptideAtlas (http://www.peptideatlas.org/) addresses these needs by identifying peptides by tandem mass spectrometry (MS/MS), statistically validating those identifications and then mapping identified sequences to the genomes of eukaryotic organisms. A meaningful comparison of data across different experiments generated by different groups using different types of instruments is enabled by the implementation of a uniform analytic process. This uniform statistical validation ensures a consistent and high-quality set of peptide and protein identifications. The raw data from many diverse proteomic experiments are made available in the associated PeptideAtlas repository in several formats. Here we present a summary of our process and details about the Human, Drosophila and Yeast PeptideAtlas builds.
Peripheral blocks are increasingly used for analgesia after video-assisted thoracic surgery (VATS). We hypothesised that addition of sufentanil and adrenaline to levobupivacaine would improve the ...analgesic effect of a continuous extrapleural block.
We randomised 60 patients undergoing VATS to a 5-mL h
extrapleural infusion of levobupivacaine at 2.7 mg mL
(LB group) or levobupivacaine at 1.25 mg mL
, sufentanil at 0.5 μg mL
, and adrenaline at 2 μg mL
(LBSA group). The primary outcome was the cumulative morphine dose administered as patient-controlled analgesia (PCA-morphine) at 48 and 72 h. The secondary outcomes were pain according to numerical rating scale (NRS) at rest and after two deep breaths twice daily, peak expiratory flow (PEF) daily, quality of recovery (QoR)-15 score at 1 day and 3 weeks postoperatively, serum levobupivacaine concentrations at 1 h after the start and at the end of the intervention, and adverse events.
At 48 h, the median cumulative PCA-morphine dose for the LB group was 6 mg (IQR, 2-10 mg) and for the LBSA group 7 mg (IQR, 3-13.5 mg; p = .378). At 72 h, morphine doses were 10 mg (IQR, 3-22 mg) and 12.5 mg (IQR, 4-21 mg; p = .738), respectively. Median NRS score at rest and after two deep breaths was 3 or lower at all time points for both treatment groups. PEF did not differ between groups. Three weeks postoperatively, only the LB group returned to baseline QoR-15 score. The LB group had higher, but well below toxic, levobupivacaine concentrations at 48 and 72 h. The incidence of nausea, dizziness, pruritus and headache was equally low overall.
For a continuous extrapleural block, and compared to plain levobupivacaine at 13.5 mg h
, levobupivacaine at 6.25 mg h
with addition of sufentanil and adrenaline did not decrease postoperative morphine consumption. The levobupivacaine serum concentrations after 48 and 72 h of infusion were well below toxic levels, therefore our findings support the use of the maximally recommended dose of levobupivacaine for a 2- to 3-day continuous extrapleural block.
Concentrated solar power (CSP)—photovoltaic (PV) hybrid power plants allow for the generation of cheap electrical energy with a high capacity factor (CF). A deep integration of both technologies ...offers synergies, using parts of the PV generated electricity for heating the thermal storage tank of the CSP unit. Such configurations have been previously studied for systems coupled by an electric resistance heater (ERH). In this work, the coupling of a CSP and a PV plant using a heat pump (HP) was analyzed due to the higher efficiency of heat pumps. The heat pump is used as a booster to lift the salt temperature in the storage system from 383 to 565 °C in order to reach higher turbine efficiency. A techno-economic analysis of the system was performed using the levelized cost of electricity (LCOE), the capacity factor and nighttime electricity fraction as variables for the representation. The CSP–PV hybrid with a booster heat pump was compared with other technologies such as a CSP–PV hybrid plant coupled by an electric heater, a standalone parabolic trough plant (PT), a photovoltaic system with battery storage (PV–BESS), and a PV thermal power plant (PVTP) consisting of a PV plant with an electric heater, thermal energy storage (TES) and a power block (PB).
This audience segmentation of visitors at coastal parks in Hawaii and North Carolina addresses an emergent natural resource management concern and risk to aquatic ecosystems: sunscreen chemical ...pollution. Four audiences were identified that correspond to different behavioral profiles: sunscreen protection tourists, multimodal sun protection tourists, in‐state frequent park visitors, and frequent beachgoers who skip sunscreen. The second‐largest audience, sunscreen protection tourists, represents 29% of visitors at Cape Lookout National Seashore and 25% at Kaloko‐Honokōhau National Historical Park. This group ranks of most concern for chemical pollution because they use sunscreen, but not typically mineral formulations or other methods such as protective clothing, and they have lower levels of sunscreen chemical issue awareness. The identification of similar audience segments across regions with differing cultural characteristics and sunscreen regulation status suggests the robustness of the model and its indicator variables, with implications for both environmental protection and public health. Further, coastal visitors’ interest in enacting pro‐environmental sun protection behaviors during their next park or beach visit indicates the potential for natural resource managers to holistically address risks in both domains through targeted interventions with audiences of most concern.
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