4,083 research outputs found
High chance that current atmospheric greenhouse concentrations commit to warmings greater than 1.5 °C over land
This is the final version of the article. Available from Springer Nature via the DOI in this record.The recent Paris UNFCCC climate meeting discussed the possibility of limiting global warming to 2 °C since pre-industrial times, or possibly even 1.5 °C, which would require major future emissions reductions. However, even if climate is stabilised at current atmospheric greenhouse gas (GHG) concentrations, those warming targets would almost certainly be surpassed in the context of mean temperature increases over land only. The reason for this is two-fold. First, current transient warming lags significantly below equilibrium or "committed" warming. Second, almost all climate models indicate warming rates over land are much higher than those for the oceans. We demonstrate this potential for high eventual temperatures over land, even for contemporary GHG levels, using a large set of climate models and for which climate sensitivities are known. Such additional land warming has implications for impacts on terrestrial ecosystems and human well-being. This suggests that even if massive and near-immediate emissions reductions occur such that atmospheric GHGs increase further by only small amounts, careful planning is needed by society to prepare for higher land temperatures in an eventual equilibrium climatic state.CH Acknowledges the NERC CEH National Capability fund
Interactomics and targeted protein degradation for kinase substrate discovery
Reversible phosphorylation is one of the most important post translational modifications that has allowed us as a species to quickly adapt to changing molecular environments due to external stimulation. This process is only capable through the activity of kinases to carry out the targeting of specific substrates defined by their recognition motif allowing for selective phosphorylation and activation and inactivation of distinct pathways as well as other changes that permit cell survival. By being so important for the maintenance of the cells disruption often leads to worsening of the cells, leading to various diseases like cancer, immunological and neurodegenerative disorders. This is why the comprehension of kinases, and their substrates is so important for making progress in the medical care of the patients.
For this exact purpose we chose Polo like kinase 2 (Plk2) as the target of study. Even though a great deal of knowledge exists about it, like the fact that it plays roles during the cell cycle, cell differentiation, ontogenesis, stress response, tumorigenesis, neurodegenerative diseases, and inflammation. The mechanisms at play i.e the specific interactions that permits its function in all these systems is not entirely known. As such, we employed the use CRISPR/Cas9 as the method of genetic modification for the endogenous tagging of Plk2 with the auxin inducible degron (AID) for the selective degradation of our target. After having observed through LC/MS the limitations of being a low abundant protein, we combined proximity labeling through Turbo-ID and targeted degradation as a method of accomplishing this task. We were successful in the identification of novel substrates of Plk2 in the cell cycle, and capable of study the interactome of Plk2 in asynchronous and G1/S arrested cells. Providing a sundry of new insight into Plk2 biology and the diversification of its interactions.
AID technology in combination with proximity labeling provides the next steps in the ability of study for any type of protein. Capable of gathering information about the context of the protein in regard to its environment, the interactions, and what the absence of that protein would have for specific pathways, while minimizing off-target effects
Constructions of the soluble potentials for the non-relativistic quantum system by means of the Heun functions
The Schr\"{o}dinger equation where
is rewritten as a more popular form of a second order
differential equation through taking a similarity transformation
with . The Schr\"{o}dinger invariant
can be calculated directly by the Schwarzian derivative and the
invariant of the differential equation . We
find an important relation for moving particle as and thus
explain the reason why the Schr\"{o}dinger invariant keeps constant.
As an illustration, we take the typical Heun differential equation as an object
to construct a class of soluble potentials and generalize the previous results
through choosing different as before. We get a more general
solution through integrating
directly and it includes all
possibilities for those parameters. Some particular cases are discussed in
detail.Comment: 11 page
Evidence that fish death after Vibrio vulnificus infection is due to an acute inflammatory response triggered by a toxin of the MARTX family.
Vibrio vulnificus is an emerging zoonotic pathogen associated with fish farms that is capable of causing a hemorrhagic septicemia known as warm-water vibriosis. According to a recent transcriptomic and functional study, the death of fish due to vibriosis is more related to the inflammatory response of the host than to the tissue lesions caused by the pathogen. In this work, we hypothesize that the RtxA1 toxin (a V. vulnificus toxin of the MARTX (Multifunctional Autoprocessing Repeats in Toxin) family) is the key virulence factor that would directly or indirectly trigger this fatal inflammatory response. Our hypothesis was based on previous studies that showed that rtxA1-deficient mutants maintained their ability to colonize and invade, but were unable to kill fish. To demonstrate this hypothesis, we infected eels (model of fish vibriosis) by immersion with a mutant deficient in RtxA1 production and analyzed their transcriptome in blood, red blood cells and white blood cells during early vibriosis (0, 3 and 12 h post-infection). The transcriptomic results were compared with those obtained in the previous study in which eels were infected with the V. vulnificus parental strain, and were functionally validated. Overall, our results confirm that fish death after V. vulnificus infection is due to an acute, early and atypical inflammatory response triggered by RtxA1 in which red blood cells seem to play a central role. These results could be relevant to other vibriosis as the toxins of this family are widespread in the Vibrio genus
Technical note: A simple theoretical model framework to describe plant stomatal "sluggishness" in response to elevated ozone concentrations
This is the final version. Available from European Geosciences Union (EGU) via the DOI in this record.Elevated levels of tropospheric ozone, O3, cause damage to terrestrial vegetation, affecting leaf stomatal functioning and reducing photosynthesis. Climatic impacts under future raised atmospheric greenhouse gas (GHG) concentrations will also impact on the net primary productivity (NPP) of vegetation, which might for instance alter viability of some crops. Together, ozone damage and climate change may adjust the current ability of terrestrial vegetation to offset a significant fraction of carbon dioxide (CO2) emissions. Climate impacts on the land surface are well studied, but arguably large-scale modelling of raised surface level O3effects is less advanced. To date most models representing ozone damage use either O3concentration or, more recently, flux-uptake-related reduction of stomatal opening, estimating suppressed land-atmosphere water and CO2fluxes. However there is evidence that, for some species, O3damage can also cause an inertial sluggishness of stomatal response to changing surface meteorological conditions. In some circumstances (e.g. droughts), this loss of stomata control can cause them to be more open than without ozone interference. To both aid model development and provide empiricists with a system on to which measurements can be mapped, we present a parameter-sparse framework specifically designed to capture sluggishness. This contains a single time-delay parameter τO3, characterizing the timescale for stomata to catch up with the level of opening they would have without damage. The larger the value of this parameter, the more sluggish the modelled stomatal response. Through variation of τO3, we find it is possible to have qualitatively similar responses to factorial experiments with and without raised O3, when comparing to reported measurement time series presented in the literature. This low-parameter approach lends itself to the inclusion of ozone-induced inertial effects being incorporated in the terrestrial vegetation component of Earth system models (ESMs).NERC-CEH National Capability FundNatural Environment Research Counci
Usage and Attitudes of Physicians in Japan Concerning Traditional Japanese Medicine (Kampo Medicine): A Descriptive Evaluation of a Representative Questionnaire-Based Survey
Kampo medicine has been the primary medical model in Japan until the mid 1800s, regained a prominent role in today's Japanese medical system. Today, 148 herbal Kampo formulas can be prescribed under the national health insurance system, allowing physicians to integrate Kampo in their daily practice. This article aims to provide information about the extent to which Kampo is now used in clinics throughout Japan and about physician's current attitudes toward Kampo. We used the results of a 2008 survey that was administered to physicians throughout Japan (n = 684). The data showed that 83.5% of physicians currently use Kampo in the clinic, although the distribution of physicians who use Kampo differ widely depending on the specialty and provided a breakdown of Kampo usage by specialty. It will be interesting to see how each specialty incorporates Kampo into its respective field as Kampo continues to play a pertinent role in Japanese medical system
Evaluating the Effectiveness of Marketing Mix Used By Transport Network Vehicle Services
This research assessed the level of effectiveness of the 4Ps or the marketing mix employed by Grab Car using the Four Ps of Marketing—Price, Place, Promotion, and to identify if Grab Car really is living up to the expectations of the riding public in the NCR. Findings may have shown that passengers are satisfied with the services provided by Grab Car, focusing on the concerns of the commuters can still be used by Grab and other Transport Network Vehicle Services in improving their marketing strategies.
Keywords: Grab Car, Marketing Mix, Marketing Strategies, Transport Network Vehicle Service
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The intracellular fate of an amphipathic pH-responsive polymer: Key characteristics towards drug delivery.
Biopolymers have become important drug delivery systems for therapeutic molecules by enhancing their accessibility and efficacy intracellularly. However, the transport of these drugs across the cell membrane and their release into the cytosol remain a challenge. The trafficking of poly (l-lysine iso-phthalamide) grafted with phenylalanine (PP-50) was investigated using an osteosarcoma cell line (SAOS-2). Colocalisation of this amphipathic biopolymer with endocytosis tracers, such as transferrin and lactosylceramide, suggested that PP-50 is partially internalised by both clathrin and caveolin-mediated endocytosis. Macropinocytosis was also investigated, but a smaller correlation was found between this mechanism and PP-50 transport. A significant decrease in polymer-mediated calcein uptake was found when cells were pre-incubated with endocytosis inhibitors, suggesting also the use of a combination of mechanisms for cell internalisation. In addition, PP-50 colocalisation with endosome and lysosome pathway markers showed that the polymer was able to escape the endolysosomal compartment before maturation. This is a critical characteristic of a biopolymer towards use as drug delivery systems and biomedical applications.Agency for Science and Technology Research, CONICYT (Chile) (Studentship)This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.msec.2016.08.00
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