Phosphatidylserine (PS) is a major component of membrane bilayers whose change in distribution between inner and outer leaflets is an important physiological signal. Normally, members of the type IV ...P-type ATPases spend metabolic energy to create an asymmetric distribution of phospholipids between the two leaflets, with PS confined to the cytoplasmic membrane leaflet. On occasion, membrane enzymes, known as scramblases, are activated to facilitate transbilayer migration of lipids, including PS. Recently, two proteins required for such randomization have been identified: TMEM16F, a scramblase regulated by elevated intracellular Ca(2+), and XKR8, a caspase-sensitive protein required for PS exposure in apoptotic cells. Once exposed at the cell surface, PS regulates biochemical reactions involved in blood coagulation, and bone mineralization, and also regulates a variety of cell-cell interactions. Exposed on the surface of apoptotic cells, PS controls their recognition and engulfment by other cells. This process is exploited by parasites to invade their host, and in specialized form is used to maintain photoreceptors in the eye and modify synaptic connections in the brain. This review discusses what is known about the mechanism of PS exposure at the surface of the plasma membrane of cells, how actors in the extracellular milieu sense surface exposed PS, and how this recognition is translated to downstream consequences of PS exposure.
Abstract
Objective
this systematic review aimed to identify immutable and modifiable prognostic factors of functional outcomes and their proposed mechanism after hip fracture surgery.
Design
...systematic search of MEDLINE, Embase, CINAHL, PEDRO, OpenGrey and ClinicalTrials.gov for observational studies of prognostic factors of functional outcome after hip fracture among surgically treated adults with mean age of 65 years and older. Study selection, quality assessment, and data extraction were completed independently by two reviewers. The Quality in Prognosis Studies Tool was used for quality assessment and assigning a level of evidence to factors. Proposed mechanisms for reported associations were extracted from discussion sections.
Results
from 33 studies of 9,552 patients, we identified 25 prognostic factors of functional outcome after hip fracture surgery. We organised factors into groups: demographics, injury and comorbidities, body composition, complications, and acute care. We assigned two factors a weak evidence level—anaemia and cognition. We assigned Parkinson’s disease an inconclusive evidence level. We could not assign an evidence level to the remaining 22 factors due to the high risk of bias across studies. Frailty was the proposed mechanism for the association between anaemia and functional outcome. Medication management, perceived potential, complications and time to mobility were proposed as mechanisms for the association between cognition and functional outcome.
Conclusion
we identified one modifiable and one immutable prognostic factor for functional outcomes after hip fracture surgery. Future research may target patients with anaemia or cognitive impairment by intervening on the prognostic factor or the underlying mechanisms.
Nuclear fuel operates in an environment that induces complex multiphysics phenomena, occurring over distances ranging from inter-atomic spacing to meters, and times scales ranging from microseconds ...to years. This multiphysics behavior is often tightly coupled and many important aspects are inherently multidimensional. Most current fuel modeling codes employ loose multiphysics coupling and are restricted to 2D axisymmetric or 1.5D approximations. This paper describes a new modeling tool able to simulate coupled multiphysics and multiscale fuel behavior, for either 2D axisymmetric or 3D geometries. Specific fuel analysis capabilities currently implemented in this tool are described, followed by a set of demonstration problems which include a 10-pellet light water reactor fuel rodlet, three-dimensional analysis of pellet clad mechanical interaction in the vicinity of a defective fuel pellet, coupled heat transfer and fission product diffusion in a TRISO-coated fuel particle, a demonstration of the ability to couple to lower-length scale models to account for material property variation with microstructural evolution, and a demonstration of the tool’s ability to efficiently solve very large and complex problems using massively-parallel computing. A final section describes an early validation exercise, comparing simulation results to a light water reactor fuel rod experiment.
Phospholipid scramblase: An update Bevers, Edouard M.; Williamson, Patrick L.
FEBS letters,
July 02, 2010, Letnik:
584, Številka:
13
Journal Article
Recenzirano
Odprti dostop
The best understood consequence of the collapse of lipid asymmetry is exposure of phosphatidylserine (PS) in the external leaflet of the plasma membrane bilayer, where it is known to serve at least ...two major functions: providing a platform for development of the blood coagulation cascade and presenting the signal that induces phagocytosis of apoptotic cells. Lipid asymmetry is collapsed by activation of phospholipid scramblase(s) that catalyze bidirectional transbilayer movement of the major classes of phospholipid. The protein corresponding to this activity is not yet known. Observations on cells from patients with Scott syndrome, a rare hereditary bleeding disorder resulting from impaired lipid scrambling, have shown that there are multiple activation pathways that converge on scramblase activity.
Synthetic and mechanistic aspects of the diarylborinic acid-catalyzed regioselective monofunctionalization of 1,2- and 1,3-diols are presented. Diarylborinic acid catalysis is shown to be an ...efficient and general method for monotosylation of pyranoside derivatives bearing three secondary hydroxyl groups (7 examples, 88% average yield). In addition, the scope of the selective acylation, sulfonylation, and alkylation is extended to 1,2- and 1,3-diols not derived from carbohydrates (28 examples); the efficiency, generality, and operational simplicity of this method are competitive with those of state-of-the-art protocols including the broadly applied organotin-catalyzed or -mediated reactions. Mechanistic details of the organoboron-catalyzed processes are explored using competition experiments, kinetics, and catalyst structure-activity relationships. These experiments are consistent with a mechanism in which a tetracoordinate borinate complex reacts with the electrophilic species in the turnover-limiting step of the catalytic cycle.
Higgs alignment from extended supersymmetry Benakli, Karim; Goodsell, Mark D.; Williamson, Sophie L.
The European physical journal. C, Particles and fields,
2018/8, Letnik:
78, Številka:
8
Journal Article
Recenzirano
Odprti dostop
We consider the effective type-II two-Higgs doublet model originating from Dirac gaugino models with extended supersymmetry in the gauge sector, which is automatically aligned in the simplest ...realisations. We show that raising the scale at which the extended supersymmetry is manifest and including quantum corrections actually improves the alignment. Using an effective field theory approach including new threshold corrections and two-loop RGEs, plus two-loop corrections to the Higgs mass in the low-energy theory, we study the implications from the Higgs mass and other experimental constraints on the scale of superpartners. We contrast the results of the minimal Dirac gaugino model, where alignment is automatic, with the hMSSM and the MRSSM, where it is not, also providing an hMSSM-inspired analysis for the new models.
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