Evidence based or person centered? An ontological debate

Evidence based medicine (EBM) is under critical debate, and person centered healthcare (PCH) has been proposed as an improvement. But is PCH offered as a supplement or as a replacement of EBM? Prima facie PCH only concerns the practice of medicine, while the contended features of EBM also include methods and medical model. I here argue that there are good philosophical reasons to see PCH as a radical alternative to the existing medical paradigm of EBM, since the two seem committed to conflicting ontologies. This paper aims to make explicit some of the most fundamental assumptions that motivate EBM and PCH, respectively, in order to show that the choice between them ultimately comes down to ontological preference. While EBM has a solid foundation in positivism, or what I here call Humeanism, PCH is more consistent with causal dispositionalism. I conclude that if there is a paradigmatic revolution on the way in medicine, it is first of all one of ontology

Why do leaf-tying caterpillars abandon their leaf ties?

Leaf-tying caterpillars act as ecosystem engineers by building shelters between overlapping leaves, which are inhabited by other arthropods. Leaf-tiers have been observed to leave their ties and create new shelters (and thus additional microhabitats), but the ecological factors affecting shelter fidelity are poorly known. For this study, we explored the effects of resource limitation and occupant density on shelter fidelity and assessed the consequences of shelter abandonment. We first quantified the area of leaf material required for a caterpillar to fully develop for two of the most common leaf-tiers that feed on white oak, Quercus alba. On average, Psilocorsis spp. caterpillars consumed 21.65 ± 0.67 cm2 leaf material to complete development. We also measured the area of natural leaf ties found in a Maryland forest, to determine the distribution of resources available to caterpillars in situ. Of 158 natural leaf ties examined, 47% were too small to sustain an average Psilocorsis spp. caterpillar for the entirety of its development. We also manipulated caterpillar densities within experimental ties on potted trees to determine the effects of cohabitants on the likelihood of a caterpillar to leave its tie. We placed 1, 2, or 4 caterpillars in ties of a standard size and monitored the caterpillars twice daily to track their movement. In ties with more than one occupant, caterpillars showed a significantly greater propensity to leave their tie, and left sooner and at a faster rate than those in ties as single occupants. To understand the consequences of leaf tie abandonment, we observed caterpillars searching a tree for a site to build a shelter in the field. This is a risky behavior, as 17% of the caterpillars observed died while searching for a shelter site. Caterpillars that successfully built a shelter traveled 110 ± 20 cm and took 28 ± 7 min to find a suitable site to build a shelter. In conclusion, leaf-tying caterpillars must frequently abandon their leaf tie due to food limitation and interactions with other caterpillars, but this is a costly behavior

Translocation and insertion of precursor proteins into isolated outer membranes of mitochondria

Nuclear-encoded proteins destined for mitochondria must cross the outer or both outer and inner membranes to reach their final sub- mitochondrial locations. While the inner membrane can translocate preproteins by itself, it is not known whether the outer membrane also contains an endogenous protein translocation activity which can function independently of the inner membrane. To selectively study the protein transport into and across the outer membrane of Neurospora crassa mitochondria, outer membrane vesicles were isolated which were sealed, in a right-side-out orientation, and virtually free of inner membranes. The vesicles were functional in the insertion and assembly of various outer membrane proteins such as porin, MOM19, and MOM22. Like with intact mitochondria, import into isolated outer membranes was dependent on protease-sensitive surface receptors and led to correct folding and membrane integration. The vesicles were also capable of importing a peripheral component of the inner membrane, cytochrome c heme lyase (CCHL), in a receptor-dependent fashion. Thus, the protein translocation machinery of the outer mitochondrial membrane can function as an independent entity which recognizes, inserts, and translocates mitochondrial preproteins of the outer membrane and the intermembrane space. In contrast, proteins which have to be translocated into or across the inner membrane were only specifically bound to the vesicles, but not imported. This suggests that transport of such proteins involves the participation of components of the intermembrane space and/or the inner membrane, and that in these cases the outer membrane translocation machinery has to act in concert with that of the inner membrane

Temporal variation in bird assemblages: how representative is a one-year snapshot?

Bird assemblages generally are no longer regarded as stable entities, but rather as fluctuating in response to many factors. Australia’s highly variable climate is likely to result in a high degree of dynamism in its bird assemblages, yet few studies have investigated variation on an inter-annual temporal scale. We compared two year-long samples of the bird assemblages of a series of highly fragmented buloke Allocasuarina luehmannii (Casuarinaceae)woodland remnants in south-eastern Australia, the first sample taken in 1994–1995 and the second in 2001–2002. Bird densities were almost three times higher in the second period than in the first. Mean species richness also was significantly higher. Species richness of each individual site was unrelated between the two years. Minimum species turnover was 63% and was higher, on average, for migratory and nomadic than for sedentary species. Therefore, site-level bird assemblage composition was markedly different between the two survey periods and, on average, the assemblage composition of each site bore greater resemblance to those of other sites in the same year than to that of the same site in the other survey period. Most species changed substantially in their distribution among remnants between the two periods. The change in distribution of most species did not differ significantly from that expected if the species had redistributed at random among the sites. This suggests that although the remnant vegetation of the area is highly fragmented with minimal interpatch connectivity, bird movements among remnants must be relatively frequent. Interannual variability in Australian bird assemblages may be higher than is commonly recognized. In such dynamic systems, we must be cautious when extrapolating from the findings of short-term studies to longer temporal scales, especially in relation to conservation management. A greater understanding of the processes driving distributional patterns is likely to enable better predictions of species’ responses to habitat change

Functional independence of the protein translocation machineries in mitochondrial outer and inner membranes

The protein translocation machineries of the outer and inner mitochondrial membranes usually act in concert during translocation of matrix and inner membrane proteins. We considered whether the two machineries can function independently of each other in a sequential reaction. Fusion proteins (pF-CCHL) were constructed which contained dual targeting information, one for the intermembrane space present in cytochrome c heme lyase (CCHL) and the other for the matrix space contained in the signal sequence of the precursor of F1-ATPase beta-subunit (pF1 beta). In the absence of a membrane potential, delta psi, the fusion proteins moved into the intermembrane space using the CCHL pathway. In contrast, in the presence of delta psi they followed the pF1 beta pathway and eventually were translocated into the matrix. The fusion protein pF51-CCHL containing 51 amino acids of pF1 beta, once transported into the intermembrane space in the absence of a membrane potential, could be further chased into the matrix upon re-establishing delta psi. The sequential and independent movement of the fusion protein across the two membranes demonstrates that the translocation machineries act as distinct entities. Our results support a model in which the two translocation machineries can function independently of each other, but generally interact in a dynamic fashion to achieve simultaneous translocation across both membranes. In addition, the results provide information about the targeting sequences within CCHL. The protein does not contain a signal for retention in the intermembrane space; rather, it lacks matrix targeting information, and therefore is unable to undergo delta psi-dependent interaction with the protein translocation apparatus in the inner membrane

Regionaalhaigla X-korpus – samm uude sajandisse

Põhja-Eesti Regionaalhaigla avas eelmise aasta 11. detsembril Mustamäe meditsiinilinnakus haigla uue korpuse. See on innovaati line diagnostikaja aktiivravikompleks, kus hakkab toimuma kõige tehnoloogiamahukam osa ravitööst. Eesti Arst 2010; 89(1):67−6

A Novel Peptide-Based SILAC Method to Identify the Posttranslational Modifications Provides Evidence for Unconventional Ubiquitination in the ER-Associated Degradation Pathway.

The endoplasmic reticulum-associated degradation (ERAD) pathway is responsible for disposing misfolded proteins from the endoplasmic reticulum by inducing their ubiquitination and degradation. Ubiquitination is conventionally observed on lysine residues and has been demonstrated on cysteine residues and protein N-termini. Ubiquitination is fundamental to the ERAD process; however, a mutant T-cell receptor α (TCRα) lacking lysine residues is targeted for the degradation by the ERAD pathway. We have shown that ubiquitination of lysine-less TCRα occurs on internal, non-lysine residues and that the same E3 ligase conjugates ubiquitin to TCRα in the presence or absence of lysine residues. Mass-spectrometry indicates that WT-TCRα is ubiquitinated on multiple lysine residues. Recent publications have provided indirect evidence that serine and threonine residues may be modified by ubiquitin. Using a novel peptide-based stable isotope labeling in cell culture (SILAC) approach, we show that specific lysine-less TCRα peptides become modified. In this study, we demonstrate that it is possible to detect both ester and thioester based ubiquitination events, although the exact linkage on lysine-less TCRα remains elusive. These findings demonstrate that SILAC can be used as a tool to identify modified peptides, even those with novel modifications that may not be detected using conventional proteomic work flows or informatics algorithms