381 research outputs found

    Analysis of technology pathway of China's liquid fuel production with consideration of energy supply security and carbon price

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    Efforts to provide alternative resources and technologies for producing liquid fuel have recently been intensified. Different levels of dependence on oil imports and carbon prices have a significant impact on the composition of the cost-minimizing portfolio of technologies. Considering such factors, how should China plan its future liquid fuel industry? The model for supporting the technology portfolio and capacity configuration that minimizes the total system cost until 2045 is described in this study. The results obtained for different carbon prices and levels of dependence on oil import indicate that the oil-to-liquid fuel (OTL) will remain dominant in China's liquid fuel industry over the next three decades. If the carbon price is low, the coal-to-liquid fuel (CTL) process is competitive. For a high carbon price, the biomass-to-liquid fuel (BTL) technology expands more rapidly. The results also reveal that developing the BTL and CTL can effectively reduce the oil-import dependency; moreover, a high carbon price can lead to the CTL being replaced with the low-carbon technology (e.g., BTL). Improvement in energy raw material conversion and application of CO2 removal technologies are also effective methods to control carbon emissions for achieving the carbon emission goals and ultimately emission reduction targets

    A common intronic variant of PARP1 confers melanoma risk and mediates melanocyte growth via regulation of MITF

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    Previous genome-wide association studies have identified a melanoma-associated locus at 1q42.1 that encompasses a ~100-kb region spanning the PARP1 gene. Expression quantitative trait locus (eQTL) analysis in multiple cell types of the melanocytic lineage consistently demonstrated that the 1q42.1 melanoma risk allele (rs3219090[G]) is correlated with higher PARP1 levels. In silico fine-mapping and functional validation identified a common intronic indel, rs144361550 (βˆ’/GGGCCC; r2 = 0.947 with rs3219090), as displaying allele-specific transcriptional activity. A proteomic screen identified RECQL as binding to rs144361550 in an allele-preferential manner. In human primary melanocytes, PARP1 promoted cell proliferation and rescued BRAFV600E-induced senescence phenotypes in a PARylation-independent manner. PARP1 also transformed TERT-immortalized melanocytes expressing BRAFV600E. PARP1-mediated senescence rescue was accompanied by transcriptional activation of the melanocyte-lineage survival oncogene MITF, highlighting a new role for PARP1 in melanomagenesis

    Massively parallel reporter assays of melanoma risk variants identify MX2 as a gene promoting melanoma

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    Genome-wide association studies (GWAS) have identified ~20 melanoma susceptibility loci, most of which are not functionally characterized. Here we report an approach integrating massively-parallel reporter assays (MPRA) with cell-type-specific epigenome and expression quantitative trait loci (eQTL) to identify susceptibility genes/variants from multiple GWAS loci. From 832 high-LD variants, we identify 39 candidate functional variants from 14 loci displaying allelic transcriptional activity, a subset of which corroborates four colocalizing melanocyte cis-eQTL genes. Among these, we further characterize the locus encompassing the HIV-1 restriction gene, MX2 (Chr21q22.3), and validate a functional intronic variant, rs398206. rs398206 mediates the binding of the transcription factor, YY1, to increase MX2 levels, consistent with the cis-eQTL of MX2 in primary human melanocytes. Melanocyte-specific expression of human MX2 in a zebrafish model demonstrates accelerated melanoma formation in a BRAFV600E background. Our integrative approach streamlines GWAS follow-up studies and highlights a pleiotropic function of MX2 in melanoma susceptibility

    First-pass perfusion CMR two days after infarction predicts severity of functional impairment six weeks later in the rat heart

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    <p>Abstract</p> <p>Background</p> <p>In humans, dynamic contrast CMR of the first pass of a bolus infusion of Gadolinium-based contrast agent has become a standard technique to identify under-perfused regions of the heart and can accurately demonstrate the severity of myocardial infarction. Despite the clinical importance of this method, it has rarely been applied in small animal models of cardiac disease. In order to identify perfusion delays in the infarcted rat heart, here we present a method in which a T<sub>1 </sub>weighted MR image has been acquired during each cardiac cycle.</p> <p>Methods and results</p> <p>In isolated perfused rat hearts, contrast agent infusion gave uniform signal enhancement throughout the myocardium. Occlusion of the left anterior descending coronary artery significantly reduced the rate of signal enhancement in anterior regions of the heart, demonstrating that the first-pass method was sensitive to perfusion deficits. <it>In vivo </it>measurements of myocardial morphology, function, perfusion and viability were made at 2 and 8 days after infarction. Morphology and function were further assessed using cine-MRI at 42 days. The perfusion delay was larger in rat hearts that went on to develop greater functional impairment, demonstrating that first-pass CMR can be used as an early indicator of infarct severity. First-pass CMR at 2 and 8 days following infarction better predicted outcome than cardiac ejection fraction, end diastolic volume or end systolic volume.</p> <p>Conclusion</p> <p>First-pass CMR provides a predictive measure of the severity of myocardial impairment caused by infarction in a rodent model of heart failure.</p

    Viruses: incredible nanomachines. New advances with filamentous phages

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    During recent decades, bacteriophages have been at the cutting edge of new developments in molecular biology, biophysics, and, more recently, bionanotechnology. In particular filamentous viruses, for example bacteriophage M13, have a virion architecture that enables precision building of ordered and defect-free two and three-dimensional structures on a nanometre scale. This could not have been possible without detailed knowledge of coat protein structure and dynamics during the virus reproduction cycle. The results of the spectroscopic studies conducted in our group compellingly demonstrate a critical role of membrane embedment of the protein both during infectious entry of the virus into the host cell and during assembly of the new virion in the host membrane. The protein is effectively embedded in the membrane by a strong C-terminal interfacial anchor, which together with a simple tilt mechanism and a subtle structural adjustment of the extreme end of its N terminus provides favourable thermodynamical association of the protein in the lipid bilayer. This basic physicochemical rule cannot be violated and any new bionanotechnology that will emerge from bacteriophage M13 should take this into account

    Low potency toxins reveal dense interaction networks in metabolism

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    Background The chemicals of metabolism are constructed of a small set of atoms and bonds. This may be because chemical structures outside the chemical space in which life operates are incompatible with biochemistry, or because mechanisms to make or utilize such excluded structures has not evolved. In this paper I address the extent to which biochemistry is restricted to a small fraction of the chemical space of possible chemicals, a restricted subset that I call Biochemical Space. I explore evidence that this restriction is at least in part due to selection again specific structures, and suggest a mechanism by which this occurs. Results Chemicals that contain structures that our outside Biochemical Space (UnBiological groups) are more likely to be toxic to a wide range of organisms, even though they have no specifically toxic groups and no obvious mechanism of toxicity. This correlation of UnBiological with toxicity is stronger for low potency (millimolar) toxins. I relate this to the observation that most chemicals interact with many biological structures at low millimolar toxicity. I hypothesise that life has to select its components not only to have a specific set of functions but also to avoid interactions with all the other components of life that might degrade their function. Conclusions The chemistry of life has to form a dense, self-consistent network of chemical structures, and cannot easily be arbitrarily extended. The toxicity of arbitrary chemicals is a reflection of the disruption to that network occasioned by trying to insert a chemical into it without also selecting all the other components to tolerate that chemical. This suggests new ways to test for the toxicity of chemicals, and that engineering organisms to make high concentrations of materials such as chemical precursors or fuels may require more substantial engineering than just of the synthetic pathways involved

    Interrogating and Predicting Tolerated Sequence Diversity in Protein Folds: Application to E. elaterium Trypsin Inhibitor-II Cystine-Knot Miniprotein

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    Cystine-knot miniproteins (knottins) are promising molecular scaffolds for protein engineering applications. Members of the knottin family have multiple loops capable of displaying conformationally constrained polypeptides for molecular recognition. While previous studies have illustrated the potential of engineering knottins with modified loop sequences, a thorough exploration into the tolerated loop lengths and sequence space of a knottin scaffold has not been performed. In this work, we used the Ecballium elaterium trypsin inhibitor II (EETI) as a model member of the knottin family and constructed libraries of EETI loop-substituted variants with diversity in both amino acid sequence and loop length. Using yeast surface display, we isolated properly folded EETI loop-substituted clones and applied sequence analysis tools to assess the tolerated diversity of both amino acid sequence and loop length. In addition, we used covariance analysis to study the relationships between individual positions in the substituted loops, based on the expectation that correlated amino acid substitutions will occur between interacting residue pairs. We then used the results of our sequence and covariance analyses to successfully predict loop sequences that facilitated proper folding of the knottin when substituted into EETI loop 3. The sequence trends we observed in properly folded EETI loop-substituted clones will be useful for guiding future protein engineering efforts with this knottin scaffold. Furthermore, our findings demonstrate that the combination of directed evolution with sequence and covariance analyses can be a powerful tool for rational protein engineering

    Measuring Energy Expenditure in Sub-Adult and Hatchling Sea Turtles via Accelerometry

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    Measuring the metabolic of sea turtles is fundamental to understanding their ecology yet the presently available methods are limited. Accelerometry is a relatively new technique for estimating metabolic rate that has shown promise with a number of species but its utility with air-breathing divers is not yet established. The present study undertakes laboratory experiments to investigate whether rate of oxygen uptake (o2) at the surface in active sub-adult green turtles Chelonia mydas and hatchling loggerhead turtles Caretta caretta correlates with overall dynamic body acceleration (ODBA), a derivative of acceleration used as a proxy for metabolic rate. Six green turtles (25–44 kg) and two loggerhead turtles (20 g) were instrumented with tri-axial acceleration logging devices and placed singly into a respirometry chamber. The green turtles were able to submerge freely within a 1.5 m deep tank and the loggerhead turtles were tethered in water 16 cm deep so that they swam at the surface. A significant prediction equation for mean o2 over an hour in a green turtle from measures of ODBA and mean flipper length (R2β€Š=β€Š0.56) returned a mean estimate error across turtles of 8.0%. The range of temperatures used in the green turtle experiments (22–30Β°C) had only a small effect on o2. A o2-ODBA equation for the loggerhead hatchling data was also significant (R2β€Š=β€Š0.67). Together these data indicate the potential of the accelerometry technique for estimating energy expenditure in sea turtles, which may have important applications in sea turtle diving ecology, and also in conservation such as assessing turtle survival times when trapped underwater in fishing nets
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