Individual differences in decision making: Drive and reward responsiveness affect strategic bargaining in economic games

BACKGROUND: In the growing body of literature on economic decision making, the main focus has typically been on explaining aggregate behavior, with little interest in individual differences despite considerable between-subject variability in decision responses. In this study, we were interested in asking to what degree individual differences in fundamental psychological processes can mediate economic decision-making behavior. METHODS: Specifically, we studied a personality dimension that may influence economic decision-making, the Behavioral Activation System, (BAS) which is composed of three components: Reward Responsiveness, Drive, and Fun Seeking. In order to assess economic decision making, we utilized two commonly-used tasks, the Ultimatum Game and Dictator Game. Individual differences in BAS were measured by completion of the BIS/BAS Scales, and correlations between the BAS scales and monetary offers made in the two tasks were computed. RESULTS: We found that higher scores on BAS Drive and on BAS Reward Responsiveness were associated with a pattern of higher offers on the Ultimatum Game, lower offers on the Dictator Game, and a correspondingly larger discrepancy between Ultimatum Game and Dictator Game offers. CONCLUSION: These findings are consistent with an interpretation that high scores on Drive and Reward Responsiveness are associated with a strategy that first seeks to maximize the likelihood of reward, and then to maximize the amount of reward. More generally, these results suggest that there are additional factors other than empathy, fairness and selfishness that contribute to strategic decision-making

Novel tau filament fold in chronic traumatic encephalopathy encloses hydrophobic molecules

Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy that is associated with repetitive head impacts or exposure to blast waves. First described as punch-drunk syndrome and dementia pugilistica in retired boxers1-3, CTE has since been identified in former participants of other contact sports, ex-military personnel and after physical abuse4-7. No disease-modifying therapies currently exist, and diagnosis requires an autopsy. CTE is defined by an abundance of hyperphosphorylated tau protein in neurons, astrocytes and cell processes around blood vessels8,9. This, together with the accumulation of tau inclusions in cortical layers II and III, distinguishes CTE from Alzheimer's disease and other tauopathies10,11. However, the morphologies of tau filaments in CTE and the mechanisms by which brain trauma can lead to their formation are unknown. Here we determine the structures of tau filaments from the brains of three individuals with CTE at resolutions down to 2.3 Å, using cryo-electron microscopy. We show that filament structures are identical in the three cases but are distinct from those of Alzheimer's and Pick's diseases, and from those formed in vitro12-15. Similar to Alzheimer's disease12,14,16-18, all six brain tau isoforms assemble into filaments in CTE, and residues K274-R379 of three-repeat tau and S305-R379 of four-repeat tau form the ordered core of two identical C-shaped protofilaments. However, a different conformation of the β-helix region creates a hydrophobic cavity that is absent in tau filaments from the brains of patients with Alzheimer's disease. This cavity encloses an additional density that is not connected to tau, which suggests that the incorporation of cofactors may have a role in tau aggregation in CTE. Moreover, filaments in CTE have distinct protofilament interfaces to those of Alzheimer's disease. Our structures provide a unifying neuropathological criterion for CTE, and support the hypothesis that the formation and propagation of distinct conformers of assembled tau underlie different neurodegenerative diseases

When unfamiliarity matters: changing environmental context between study and test affects recognition memory for unfamiliar stimuli.

Item does not contain fulltextPerformance in recognition memory has been shown to be relatively insensitive to the effect of environmental context changes between study and test. Recent evidence (P. Dalton, 1993) showed that environmental context changes between study and test affected recognition memory discrimination for unfamiliar stimuli (faces). The present study presented 2 experiments that replicated this finding, refined the experimental methodology, and extended the findings to unfamiliar verbal material (nonwords). Finally, a 3rd experiment showed that contextual changes did not affect recognition memory discrimination for familiar verbal material (words). Overall, the present study provides evidence in favor of context-dependent recognition when the material to be remembered is unfamiliar12 p

Progress of the ALIFE2 study : a dynamic road towards more evidence

Investigator-initiated studies are invaluable, especially in fields that are not particularly of interest for the pharmaceutical industry because they are either less profitable or concern special patient groups such as pregnant women. However, designing, conducting, and completing an investigator-initiated randomised controlled trial is challenging. Patients and physicians' preferences, ethics requirements, (international) legislation and funding are all areas where such challenges are encountered. The Anticoagulants for LIving FEtuses (ALIFE)2 study (NTR3361) is an example of an investigator initiated international multicenter trial that progresses slowly, at least initially, as many challenges had to be overcome. Here, we discuss the challenges we faced during the course of the ALIFE2 study up till now and we explain how some of these challenges can be tackled or even avoided

Tau filaments from multiple cases of sporadic and inherited Alzheimer's disease adopt a common fold.

The ordered assembly of tau protein into abnormal filaments is a defining characteristic of Alzheimer's disease (AD) and other neurodegenerative disorders. It is not known if the structures of tau filaments vary within, or between, the brains of individuals with AD. We used a combination of electron cryo-microscopy (cryo-EM) and immuno-gold negative-stain electron microscopy (immuno-EM) to determine the structures of paired helical filaments (PHFs) and straight filaments (SFs) from the frontal cortex of 17 cases of AD (15 sporadic and 2 inherited) and 2 cases of atypical AD (posterior cortical atrophy). The high-resolution structures of PHFs and SFs from the frontal cortex of 3 cases of AD, 2 sporadic and 1 inherited, were determined by cryo-EM. We also used immuno-EM to study the PHFs and SFs from a number of cortical and subcortical brain regions. PHFs outnumbered SFs in all AD cases. By cryo-EM, PHFs and SFs were made of two C-shaped protofilaments with a combined cross-β/β-helix structure, as described previously for one case of AD. The higher resolution structures obtained here showed two additional amino acids at each end of the protofilament. The immuno-EM findings, which indicated the presence of repeats 3 and 4, but not of the N-terminal regions of repeats 1 and 2, of tau in the filament cores of all AD cases, were consistent with the cryo-EM results. These findings show that there is no significant variation in tau filament structures between individuals with AD. This knowledge will be crucial for understanding the mechanisms that underlie tau filament formation and for developing novel diagnostics and therapies

Comparison of optimal performance at 300keV of three direct electron detectors for use in low dose electron microscopy

Low dose electron imaging applications such as electron cryo-microscopy are now benefitting from the improved performance and flexibility of recently introduced electron imaging detectors in which electrons are directly incident on backthinned CMOS sensors. There are currently three commercially available detectors of this type: the Direct Electron DE-20, the FEI Falcon II and the Gatan K2 Summit. These have different characteristics and so it is important to compare their imaging properties carefully with a view to optimise how each is used. Results at 300 keV for both the modulation transfer function (MTF) and the detective quantum efficiency (DQE) are presented. Of these, the DQE is the most important in the study of radiation sensitive samples where detector performance is crucial. We find that all three detectors have a better DQE than film. The K2 Summit has the best DQE at low spatial frequencies but with increasing spatial frequency its DQE falls below that of the Falcon II

Structures of filaments from Pick's disease reveal a novel tau protein fold

The ordered assembly of tau protein into abnormal filamentous inclusions underlies many human neurodegenerative diseases1. Tau assemblies seem to spread through specific neural networks in each disease2, with short filaments having the greatest seeding activity3. The abundance of tau inclusions strongly correlates with disease symptoms4. Six tau isoforms are expressed in the normal adult human brain-three isoforms with four microtubule-binding repeats each (4R tau) and three isoforms that lack the second repeat (3R tau)1. In various diseases, tau filaments can be composed of either 3R or 4R tau, or of both. Tau filaments have distinct cellular and neuroanatomical distributions5, with morphological and biochemical differences suggesting that they may be able to adopt disease-specific molecular conformations6,7. Such conformers may give rise to different neuropathological phenotypes8,9, reminiscent of prion strains10. However, the underlying structures are not known. Using electron cryo-microscopy, we recently reported the structures of tau filaments from patients with Alzheimer's disease, which contain both 3R and 4R tau11. Here we determine the structures of tau filaments from patients with Pick's disease, a neurodegenerative disorder characterized by frontotemporal dementia. The filaments consist of residues Lys254-Phe378 of 3R tau, which are folded differently from the tau filaments in Alzheimer's disease, establishing the existence of conformers of assembled tau. The observed tau fold in the filaments of patients with Pick's disease explains the selective incorporation of 3R tau in Pick bodies, and the differences in phosphorylation relative to the tau filaments of Alzheimer's disease. Our findings show how tau can adopt distinct folds in the human brain in different diseases, an essential step for understanding the formation and propagation of molecular conformers

A PHABULOSA/cytokinin feedback loop controls root growth in arabidopsis

The hormone cytokinin (CK) controls root length in Arabidopsis thaliana by defining where dividing cells, derived from stem cells of the root meristem, start to differentiate [ [1], [2], [3], [4], [5] and [6]]. However, the regulatory inputs directing CK to promote differentiation remain poorly understood. Here, we show that the HD-ZIPIII transcription factor PHABULOSA (PHB) directly activates the CK biosynthesis gene ISOPENTENYL TRANSFERASE 7 (IPT7), thus promoting cell differentiation and regulating root length. We further demonstrate that CK feeds back to repress both PHB and microRNA165, a negative regulator of PHB. These interactions comprise an incoherent regulatory loop in which CK represses both its activator and a repressor of its activator. We propose that this regulatory circuit determines the balance of cell division and differentiation during root development and may provide robustness against CK fluctuations

Cryo-EM structures of tau filaments from Alzheimer's disease

Alzheimer's disease is the most common neurodegenerative disease, and there are no mechanism-based therapies. The disease is defined by the presence of abundant neurofibrillary lesions and neuritic plaques in the cerebral cortex. Neurofibrillary lesions comprise paired helical and straight tau filaments, whereas tau filaments with different morphologies characterize other neurodegenerative diseases. No high-resolution structures of tau filaments are available. Here we present cryo-electron microscopy (cryo-EM) maps at 3.4-3.5 Å resolution and corresponding atomic models of paired helical and straight filaments from the brain of an individual with Alzheimer's disease. Filament cores are made of two identical protofilaments comprising residues 306-378 of tau protein, which adopt a combined cross-β/β-helix structure and define the seed for tau aggregation. Paired helical and straight filaments differ in their inter-protofilament packing, showing that they are ultrastructural polymorphs. These findings demonstrate that cryo-EM allows atomic characterization of amyloid filaments from patient-derived material, and pave the way for investigation of a range of neurodegenerative diseases

Architecture of Pol II(G) and molecular mechanism of transcription regulation by Gdown1.

Tight binding of Gdown1 represses RNA polymerase II (Pol II) function in a manner that is reversed by Mediator, but the structural basis of these processes is unclear. Although Gdown1 is intrinsically disordered, its Pol II interacting domains were localized and shown to occlude transcription factor IIF (TFIIF) and transcription factor IIB (TFIIB) binding by perfect positioning on their Pol II interaction sites. Robust binding of Gdown1 to Pol II is established by cooperative interactions of a strong Pol II binding region and two weaker binding modulatory regions, thus providing a mechanism both for tight Pol II binding and transcription inhibition and for its reversal. In support of a physiological function for Gdown1 in transcription repression, Gdown1 co-localizes with Pol II in transcriptionally silent nuclei of early Drosophila embryos but re-localizes to the cytoplasm during zygotic genome activation. Our study reveals a self-inactivation through Gdown1 binding as a unique mode of repression in Pol II function