Why is the composition of older adults' care network associated with psychological wellbeing: an application of the self-determination theory.

OBJECTIVES: Older care recipients have different types of care networks, varying from spouse-only to large mixed care networks, that add to different levels of wellbeing. Applying Self-Determination Theory (SDT) to the care context, we argue that the care network composition may foster or hamper the three basic needs for wellbeing: relatedness, autonomy and competence. METHOD: Data are from ten observations between 1992 and 2022 of the Longitudinal Aging Study Amsterdam (N = 18,434 observations from 4,837 older Dutch adults). Five care network types are used: no care, partner, informal, formal or privately paid care. Mixed-hybrid-multilevel regression analysis of depressive symptoms as measure of wellbeing is applied on care network type and loneliness, mastery and care sufficiency as indicators of the three basic needs for wellbeing. RESULTS: Receiving care from a partner care network is, compared to the formal care network, the most negatively associated with depressive symptoms, followed by informal care and privately paid care. Differences in care network types existed in loneliness and care sufficiency, but not in mastery, and in part explained the association between care network types and depressive symptoms. Results of between and within effects are comparable. CONCLUSION: Using a rich data set and advanced methodology support the hypotheses that formal care networks hamper wellbeing due to insufficient care and increased loneliness, in particular compared to partner and informal care. The role of mastery was less important, possibly because it does not measure care related level of control.

Mutational analysis of antistasin, an inhibitor of blood coagulation factor Xa derived from the Mexican leech Haementeria officinalis.

Antistasin is a Factor Xa inhibitor that is present in the salivary glands of the Mexican leech Haementeria officinalis. The antistasin protein consists of 119 amino acids, of which residues 1-55 (domain I) are 56% similar to residues 56-110 (domain II). Of the nine C-terminal amino acids (residues 111-119; domain III), four are positively charged. The reactive site for Factor Xa is located in domain I. In this study we assessed the role of separate domains and of individual amino acids in the reactive site for the inhibition of Factor Xa. A series of mutants was constructed and expressed in Chinese hamster ovary (CHO) cells. In vitro chromogenic assays for Factor Xa show that domain I is sufficient for inhibition of Factor Xa. Domains II and III neither contain any intrinsic Factor Xa inhibitory activity, nor contribute to the activity of domain I. Furthermore, domain II does not become a Factor Xa inhibitor by partially adaptating its sequence towards that of the reactive site in domain I. Mutation of the cysteine at position 33 is not crucial for Factor Xa inhibition, suggesting a relatively rigid reactive site loop structure.

Dissociation of heparin-dependent thrombin and factor Xa inhibitory activities of antithrombin-III by mutations in the reactive site.

Antithrombin-III (AT-III) is a heparin-dependent inhibitor of thrombin and Factor Xa, two serine proteases that are crucial for blood coagulation. In order to assess whether it would be possible to target AT-III only towards Factor Xa, we replaced parts of the reactive site, or P region, of AT-III by sequences present in prothrombin, a substrate of Factor Xa in the coagulation cascade. We show that replacement of the P3 to P3' region generates the hypothesized phenotype. In fact, point mutation of the P1' site from Ser (present in AT-III) to Ile (present in prothrombin) is sufficient to dissociate heparin-dependent thrombin and Factor Xa inhibitory activities. Interestingly, a combined mutation at P3 and P3' brings about the same dissociation. We show that besides Ile, other amino acids at P1' can lead to the dissociation in inhibitory activity. Amino acids with small side chains (Gly, Ser, Ala, and Thr) have only a marginal effect on the inhibitory activity against either protease. However, larger residues at the P1' position abolish the heparin-dependent anti-thrombin activity, whereas the heparin-dependent anti-Factor Xa activity is not at all or only moderately affected. These results can be rationalized by a comparison of the x-ray structure and a three-dimensional model of the S1' binding pockets of thrombin and Factor Xa, respectively. It appears that the S1' pocket of Factor Xa leaves much more space for the P1' residue of AT-III than the S1' pocket of thrombin.