The role of patient expectations in predicting outcome after total knee arthroplasty

Introduction  

Patient's expectations are variably reported to influence self-rated outcome and satisfaction after medical treatment; this prospective study examined which of the following was the most important unique determinant of global outcome/satisfaction after total knee arthroplasty (TKA): baseline expectations; fulfilment of expectations; or current symptoms and function.     

Human Pluripotent Stem Cells Have a Novel Mismatch Repair-dependent Damage Response

Human pluripotent stem cells (PSCs) are presumed to have robust DNA repair pathways to ensure genome stability. PSCs likely need to protect against mutations that would otherwise be propagated throughout all tissues of the developing embryo. How these cells respond to genotoxic stress has only recently begun to be investigated. Although PSCs appear to respond to certain forms of damage more efficiently than somatic cells, some DNA damage response pathways such as the replication stress response may be lacking. Not all DNA repair pathways, including the DNA mismatch repair (MMR) pathway, have been well characterized in PSCs to date. MMR maintains genomic stability by repairing DNA polymerase errors. MMR is also involved in the induction of cell cycle arrest and apoptosis in response to certain exogenous DNA-damaging agents. Here, we examined MMR function in PSCs. We have demonstrated that PSCs contain a robust MMR pathway and are highly sensitive to DNA alkylation damage in an MMR-dependent manner. Interestingly, the nature of this alkylation response differs from that previously reported in somatic cell types. In somatic cells, a permanent G₂/M cell cycle arrest is induced in the second cell cycle after DNA damage. The PSCs, however, directly undergo apoptosis in the first cell cycle. This response reveals that PSCs rely on apoptotic cell death as an important defense to avoid mutation accumulation. Our results also suggest an alternative molecular mechanism by which the MMR pathway can induce a response to DNA damage that may have implications for tumorigenesis.     

Silicium-Stoffwechsel bei Mikroorganismen

Zusammenfassung Untersuchungen zur Mobilität der aufgenommenen Kieselsäure in Bakterien zeigen, daß die Kieselsäure in Abwesenheit von Glucose rasch wieder gegen Phosphat ausgetauscht werden kann. Wenn jedoch die Aufnahme der Kieselsäure aus glucosehaltigen Si-Lösungen erfolgte, so ergibt sich, daß nur ein geringer Teil dieser Kieselsäure durch Inkubation in Phosphatlösungen wieder ausgetauscht werden kann. Dieser Si-Anteil wird jedoch bei Inkubation der Zellen in Carbonatlösung vollständig ausgeschieden. Die Möglichkeit, daß diese Kieselsäure in Form von C–Si-Bindungen in der Zelle vorliegt, wird diskutiert. Weitere Untersuchungen zu diesen Fragen sind im Gange.

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Summary Studies on the mobility of silicon in bacterial cells show, that Si is readily excanged against phosphate if the cells are incubated in absence of glucose. However if the bacteria are preincubated in silicate solutions in the presence of glucose, the silicon taken up is not mobile any more during incubation in phosphate solutions. The element is extruded completely by incubating the cells in carbonate solutions. Evidence has been made that silicon is deposited within the cells as organic compound in which C–Si-bonds are formed.

     

The natural history of Get3‐like chaperones

Get3 in yeast or TRC40 in mammals is an ATPase that, in eukaryotes, is a central element of the GET or TRC pathway involved in the targeting of tail‐anchored proteins. Get3 has also been shown to possess chaperone holdase activity. A bioinformatic assessment was performed across all domains of life on functionally important regions of Get3 including the TRC40‐insert and the hydrophobic groove essential for tail‐anchored protein binding. We find that such a hydrophobic groove is much more common in bacterial Get3 homologs than previously appreciated based on a directed comparison of bacterial ArsA and yeast Get3. Furthermore, our analysis shows that the region containing the TRC40‐insert varies in length and methionine content to an unexpected extent within eukaryotes and also between different phylogenetic groups. In fact, since the TRC40‐insert is present in all domains of life, we suggest that its presence does not automatically predict a tail‐anchored protein targeting function. This opens up a new perspective on the function of organellar Get3 homologs in plants which feature the TRC40‐insert but have not been demonstrated to function in tail‐anchored protein targeting. Our analysis also highlights a large diversity of the ways Get3 homologs dimerize. Thus, based on the structural features of Get3 homologs, these proteins may have an unexplored functional diversity in all domains of life.      

Identification of flavonoids as regulators of YbeY activity in Liberibacter asiaticus

Liberibacter asiaticus is the prevalent causative pathogen of Huanglongbing or citrus greening disease, which has resulted in a devastating crisis in the citrus industry. A thorough understanding of this pathogen's physiology and mechanisms to control cell survival is critical in the identification of therapeutic targets. YbeY is a highly conserved bacterial RNase that has been implicated in multiple roles. In this study, we evaluated the biochemical characteristics of the L. asiaticus YbeY (CLIBASIA_01560) and assessed its potential as a target for antimicrobials. YbeY_Las was characterized as an endoribonuclease with activity on 3′ and 5′ termini of 16S and 23S rRNAs, and the capacity to suppress the E. coli ΔybeY phenotype. We predicted the YbeY_Las protein:ligand interface and subsequently identified a flavone compound, luteolin, as a selective inhibitor. Site-directed mutagenesis was subsequently used to identify key residues involved in the catalytic activity of YbeY_Las. Further evaluation of naturally occurring flavonoids in citrus trees indicated that both flavones and flavonols had potent inhibitory effects on YbeY_Las. Luteolin was subsequently examined for efficacy against L. asiaticus in Huanglongbing-infected citrus trees, where a significant reduction in L. asiaticus gene expression was observed.