Secondary nucleating sequences affect kinetics and thermodynamics of tau aggregation

Tau protein was scanned for highly amyloidogenic sequences in amphiphilic motifs (X)nZ, Z(X)nZ (n≥2) or (XZ)n (n≥2), where X is a hydrophobic residue and Z is a charged or polar residue. N-acetyl peptides homologous to these sequences were used to study aggregation. Transmission electron microscopy (TEM) showed 7 peptides, in addition to well known primary nucleating sequences c275VQIINK (AcPHF6*) and Ac306VQIVYK (AcPHF6), formed fibers, tubes, ribbons or rolled sheets. Of the peptides shown by TEM to form amyloid, Ac10VME, AcPHF6*, Ac375KLTFR, and Ac393VYK were found to enhance the fraction of β-structure of AcPHF6 formed at equilibrium, and Ac375KLTFR was found to inhibit AcPHF6 and AcPHF6* aggregation kinetics in a dose-dependent manner, consistent with its participation in a hybrid steric zipper model. Single site mutants were generated which transformed predicted amyloidogenic sequences in tau into non-amyloidogenic ones. A M11K mutant had fewer filaments and showed a decrease in aggregation kinetics and an increased lag time compared to wild type tau, while a F378K mutant showed significantly more filaments. Our results infer that sequences throughout tau, in addition to PHF6 and PHF6*, can seed amyloid formation or affect aggregation kinetics or thermodynamics

Development of legal expertise

In a comprehensive empirical investigation (N = 71,405) we analyzed the development of legal expertise in a critical 1-year period of academic legal training in which advanced law students start practicing to solve complex cases. We were particularly interested in the functional form of the learning curve and inter-individual differences in learning. Performance increases monotonically with the number of practice exams following a slightly concave learning curve without any considerable kinks. Considering the performance development over time, however, the curve is not monotonic and shows intermediate drops in performance. We provide evidence which suggests that these drops are due to cyclic drops in motivation. There are about equally sized marginal effects of practicing law exams in general and practicing exams in the specific area of law. However, students with high (vs. low) initial performance profit more from practicing exams within a specific area of law whereas students with low initial performance profit more from practicing exams in general. The concave increase in performance with the number of practicing exams is mainly driven by individuals with low initial performance. Those with high initial performance mainly display a linear learning trend. We discuss the practical implications of these findings for academic legal training

Retrospective Descriptions of Relational Behaviors That Negatively Influenced Perinatal Perceptions During Traumatic Experiences Among Cesarean Birth Women

Currently, cesarean births account for 24% of all births in the United States. Cesarean deliveries are known to have numerous emotional, psychological, and physical impacts on women, some of which are traumatic. However, past research has indicated that: 1) not all women who have cesarean deliveries are traumatized, and 2) that the cesarean delivery experience may not be universal for all women. The purpose of this study was to identify relationally based behaviors that occurred throughout the perinatal period that contributed to the cesarean delivered women\u27s perception of trauma. Nineteen white, middle class, midcentral women were included in this study. Inclusion criteria was that the women must have had a cesarean delivery that: 1) left the woman feeling sad, depressed, angry, anxious, or otherwise psychologically or emotionally distressed, and 2) evoked recurring troublesome memories or repetitive negative thought patterns not exclusive to the outcome of the baby. Data was gathered utilizing naturalistic inquiry and was analyzed through matrix analysis. Sixteen negative relational (intrapersonal, interpersonal, and situational) behaviors were identified: 1) Lack of understanding, 2) Displaying indifference, 3) Violating, 4) Dehumanizing, 5) Unsupporting, 6) Conveying incompetence, 7) Abandoning, 8) Focusing on Tasks, 9) Restraining, 10) Coercing, 11) Withholding explanation, 12) Invalidating, 13) Minimizing, 14) Pacifying, 15) Stigmatizing, and 16) Blaming. These behaviors were labeled as betraying behaviors defined as actions/inactions that result in a perception that expectations built on trust were not met. The greatest number of betraying behaviors were displayed in the situational relationship context by the nursing staff (n=182), followed by physicians (n=107), spouse (interpersonal relationship, n=47), and self (intrapersonal relationship, n=34)

Symbolism and Incommensurability in Civil Sanctioning: Decision Makers as Goal Managers

Factfinders in civil cases must often make a constellation of decisions, such as assigning responsibility and blame, making compensation and (sometimes) giving out punishment. These decisions are likely to evoke numerous social and moral concerns and, therefore, inevitably implicate a variety of instrumental and symbolic goals. We argue that descriptions of legal decision making that fail to consider the psychological interplay among these different goals are likely to come up short in their efforts to explicate the ways in which jurors and other factfinders make decisions in civil cases. Instead, we suggest that decision making in civil cases can profitably be thought of as a process by which decision makers attempt to maximally satisfy a wide variety of goals in parallel. In contrast to many traditional legal and economic portrayals of legal decision making which posit that decision makers can pursue single motives as instructed, Part I argues that jurors and other finders of fact deciding civil cases ought to be thought of as pursuing many different goals simultaneously. This Part briefly describes many of the goals that may underlie decision making in civil cases and introduces a set of basic goal management principles that define how these goals interrelate. Part 11 describes social psychological research that suggests that legal decision makers may be motivated to pursue a variety of goals in addition to the traditional goals of determining fault, compensating plaintiffs, and deterring defendants. Different motives for distributing resources, value expressive goals and a need to restore the proper relative moral balance between the parties may all play a role in civil decision making. In Part 111, we propose that decision makers may attempt to simultaneously satisfy these multiple goals through a process of parallel constraint satisfaction