Malaria parasites utilize a short N-terminal amino acid motif termed the Plasmodium export element (PEXEL) to export an array of proteins to the host erythrocyte during blood stage infection. Using immunoaffinity chromatography and mass spectrometry, insight into this signalmediated trafficking mechanism was gained by discovering that the PEXEL motif is cleaved and N-acetylated. PfHRPII and PfEMP2 are two soluble proteins exported by Plasmodium falciparum that were demonstrated to undergo PEXEL cleavage and N-acetylation, thus indicating that this Nterminal processing may be general to many exported soluble proteins. It was established that PEXEL processing occurs upstream of the brefeldin A-sensitive trafficking step in the P. falciparum secretory pathway, therefore cleavage and N-acetylation of the PEXEL motif occurs in the endoplasmic reticulum (ER) of the parasite. Furthermore, it was shown that the recognition of the processed N-terminus of exported proteins within the parasitophorous vacuole may be crucial for protein transport to the host erythrocyte. It appears that the PEXEL may be defined as a novel ER peptidase cleavage site and a classical N-acetyltransferase substrate sequence.
It is known that when bilayers of some saturated phosphatidylcholines are stored for 3 or more days at approximately 0 degrees C, a lamellar subgel (Lc) phase is detected at temperatures below the pretransition by differential scanning calorimetry (DSC). However, the subgel (Lc) phase and the corresponding subtransition (Lc--> Lbeta') for dimyristoylphosphatidylcholine (DMPC) has not been clearly characterized. In this study, using the temperature jump protocol first developed by Tristram-Nagle et al. for the dipalmitoylphosphatidylcholine (DPPC) system, new and accurate data characterizing the subgel formation and subtransition of DMPC were obtained through DSC and fluorescence spectroscopy with 1,6-diphenyl-1,3,5-hexatriene (DPH). It was discovered that the formation of the DMPC subgel phase requires incubation at temperatures of -5 degrees C or lower for 2 h or more. Kinetics of the subgel formation indicate that it is a very complex process and demonstrates that the planar gel phase is merely metastable below the subtransition, and not the thermodynamically stable phase. The subgel growth of DMPC is proven to be the dehydration of the headgroup region, and the subtransition is a process in which poorly hydrated DMPC becomes hydrated.
Patient-centric healthcare and evidence-based medicine with the emphasis on prevention and wellness promise to deliver better and more affordable healthcare. At minimal, they require health related information to be shared among a community including patients, providers, payers, and regulators. It is important for IT systems to facilitate information sharing within such communities. Furthermore, we argue that it is highly valuable to develop IT technologies that can foster sustainable healthcare ecosystems for collaborative, coordinated healthcare delivery.The emerging cloud computing appears well-suited to meet the demand of a broad set of health service scenarios. In particular, the concept of shared infrastructure and services provides the foundation for supporting healthcare service ecosystems. This paper proposes an ecosystem approach to identify high-level requirements for cloud computing technologies to provide hosting environments for sustainable healthcare ecosystems. We draw the lessons and principles from the sustainable ecological ecosystems, review some of the existing IT-enabled healthcare ecosystems, and provide our view on the imperatives for cloud computing research to support future healthcare IT needs.
The self-association of the tranquilizer chlorpromazine hydrochloride in aqueous solution was studied. Using isothermal titration calorimetry, the critical micelle concentration and solvent-micelle interactions were evaluated as a function of temperature, ionic strength, and pH. The enthalpy of demicellization, ∆Hdemic, was directly measured from the experimental enthalpy values, which showed that the spontaneous demicellization of chlorpromazine hydrochloride is a highly endothermic process under all experimental conditions studied. The thermodynamic parameters were subsequently calculated from the temperature dependent thermograms. At 25 °C, the critical micelle concentration was determined to be 3.2 mM at pH 6.5 with a ∆Hdemic of 12.5 kJ/mol, a ∆Gdemic of 24.3 kJ/mol, and a T∆Sdemic of -10.1 kJ/mol. Our results suggest that the enthalpy-entropy compensation theory may be applied to these micelles. In addition, using differential scanning calorimetry, a broad endothermic demicellization peak was observed in postmicelle solutions during heating scans at approximately 45 °C. Cooling scans revealed a very broad peak centered around 40 °C that corresponds to the heat of micellization.
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