Regulated Formation of an Amyloid-like Translational Repressor Governs Gametogenesis

Message-specific translational control is required for gametogenesis. In yeast, the RNA-binding protein Rim4 mediates translational repression of numerous mRNAs, including the B-type cyclin CLB3, which is essential for establishing the meiotic chromosome segregation pattern. Here, we show that Rim4 forms amyloid-like aggregates and that it is the amyloid-like form of Rim4 that is the active, translationally repressive form of the protein. Our data further show that Rim4 aggregation is a developmentally regulated process. Starvation induces the conversion of monomeric Rim4 into amyloid-like aggregates, thereby activating the protein to bring about repression of translation. At the onset of meiosis II, Rim4 aggregates are abruptly degraded allowing translation to commence. Although amyloids are best known for their role in the etiology of diseases such as Alzheimer’s, Parkinson’s, and diabetes by forming toxic protein aggregates, our findings show that cells can utilize amyloid-like protein aggregates to function as central regulators of gametogenesis.Charles A. King Trust (Postdoctoral Fellowship)American Cancer Society (Fellowship)National Institutes of Health (U.S.) (Grants GM62207, GM77537, and GM094303

Personality predictors of the time course for lung cancer onset

Numerous findings suggest that personality is linked to the incidence and experience of negative health outcomes. More specifically, trait negative affect is negatively related to a number of health outcomes. The current study expands our understanding of the link between personality and disease by examining the time course for lung cancer onset. In a sample of patients who had recently undergone surgical resection for lung cancer, a variety of negative affect-related personality variables were assessed to determine their relationship with age at surgery. After controlling for smoking behavior, it was found that trait negative affect was associated with time course for lung cancer onset, such that those with higher (vs. lower) levels of trait negative affect manifested lung cancer earlier in their lives. Thus, trait negative affect represents an independent risk factor among those prone to lung cancer (i.e. smokers)

The resting human brain and motor learning.

Functionally related brain networks are engaged even in the absence of an overt behavior. The role of this resting state activity, evident as low-frequency fluctuations of BOLD (see [1] for review, [2-4]) or electrical [5, 6] signals, is unclear. Two major proposals are that resting state activity supports introspective thought or supports responses to future events [7]. An alternative perspective is that the resting brain actively and selectively processes previous experiences [8]. Here we show that motor learning can modulate subsequent activity within resting networks. BOLD signal was recorded during rest periods before and after an 11 min visuomotor training session. Motor learning but not motor performance modulated a fronto-parietal resting state network (RSN). Along with the fronto-parietal network, a cerebellar network not previously reported as an RSN was also specifically altered by learning. Both of these networks are engaged during learning of similar visuomotor tasks [9-22]. Thus, we provide the first description of the modulation of specific RSNs by prior learning--but not by prior performance--revealing a novel connection between the neuroplastic mechanisms of learning and resting state activity. Our approach may provide a powerful tool for exploration of the systems involved in memory consolidation

The Design of a Best Execution Market

The notion of best execution on securities markets is manifold. Best execution has different meanings to different market participants, therefore, it is difficult to find a unique market structure that meets this requirements for all the participants. Traditional market structures are either static or flexible, meaning that an individual market participant has no influence regarding the concrete market structure’s characteristics, like e. g. the price discovery mechanism, trading frequency or the market transparency. Traditional market structures are either static or flexible, meaning that an individual market participant has no influence regarding the Focussing on customer orientation, we propose a new type of market structure: the dynamic market model, where participants individually choose the characteristics of the market structure for each transaction they perform. Furthermore, this paper offers an approach to design dynamic market models from scratch. We briefly sketch the necessary steps towards a dynamic market model. Traditional market structures are either static or flexible, meaning that an individual market participant has no influence regarding the Finally, we present AMTRAS; the prototype of an electronic trading system that was conceived and implemented following the aforementioned approach. AMTRAS is an software-agent based bond trading system designed for the need of institutional investors. It implements a dynamic market model, a sophisticated product- and partner matching scheme as well as an innovative price discovery approach

Depression Symptoms and Antidepressant Medicine Use in Diabetes Prevention Program Participants

OBJECTIVE: To assess depression markers (symptoms and antidepressant medicine use) in Diabetes Prevention Program (DPP) participants and to determine whether changes in depression markers during the course of the study were associated with treatment arm, weight change, physical activity level, or participant demographic characteristics. RESEARCH DESIGN AND METHODS: DPP participants (n = 3,187) in three treatment arms (intensive lifestyle, metformin, and placebo) completed the Beck Depression Inventory (BDI) and reported on use of antidepressant medicines at randomization and subsequently at each annual visit (average duration in study 3.2 years). RESULTS: On study entry, 10.3% of participants had BDI scores > or =11, which was used as a threshold for mild depression, 5.7% took antidepressant medicines, and 0.9% had both depression markers. During the DPP, the proportion of participants with elevated BDI scores declined (from 10.3% at baseline to 8.4% at year 3), while the proportion taking antidepressant medicines increased (from 5.7% at baseline to 8.7% at year 3), leaving the proportion with either marker unchanged. These time trends were not significantly associated with the DPP treatment arm. Depression markers throughout the study were associated with some participant demographic factors, adjusted for other factors. Men were less likely to have elevated depression scores and less likely to use antidepressant medicine at baseline (9.0% of men and 17.9% of women had at least one marker of depression) and throughout the study (P or =11 (P = 0.03), but white participants were more likely to be taking antidepressant medicine than any other racial/ethnic group (P <0.0001). CONCLUSIONS: DPP participation was not associated with changes in levels of depression. Countervailing trends in the proportion of DPP participants with elevated depression symptoms and the proportion taking antidepressant medicine resulted in no significant change in the proportion with either marker. The finding that those taking antidepressant medicine often do not have elevated depression symptoms indicates the value of assessing both markers when estimating overall depression rates

Heparan sulfate and heparin interactions with proteins.

Heparan sulfate (HS) polysaccharides are ubiquitous components of the cell surface and extracellular matrix of all multicellular animals, whereas heparin is present within mast cells and can be viewed as a more sulfated, tissuespecific, HS variant. HS and heparin regulate biological processes through interactions with a large repertoire of proteins. Owing to these interactions and diverse effects observed during in vitro, ex vivo and in vivo experiments, manifold biological/pharmacological activities have been attributed to them. The properties that have been thought to bestow protein binding and biological activity upon HS and heparin vary from high levels of sequence specificity to a dependence on charge. In contrast to these opposing opinions, we will argue that the evidence supports both a level of redundancy and a degree of selectivity in the structure–activity relationship. The relationship between this apparent redundancy, the multi-dentate nature of heparin and HS polysaccharide chains, their involvement in protein networks and the multiple binding sites on proteins, each possessing different properties, will also be considered. Finally, the role of cations in modulating HS/heparin activity will be reviewed and some of the implications for structure–activity relationships and regulation will be discussed

Training of Instrumentalists and Development of New Technologies on SOFIA

This white paper is submitted to the Astronomy and Astrophysics 2010 Decadal Survey (Astro2010)1 Committee on the State of the Profession to emphasize the potential of the Stratospheric Observatory for Infrared Astronomy (SOFIA) to contribute to the training of instrumentalists and observers, and to related technology developments. This potential goes beyond the primary mission of SOFIA, which is to carry out unique, high priority astronomical research. SOFIA is a Boeing 747SP aircraft with a 2.5 meter telescope. It will enable astronomical observations anywhere, any time, and at most wavelengths between 0.3 microns and 1.6 mm not accessible from ground-based observatories. These attributes, accruing from the mobility and flight altitude of SOFIA, guarantee a wealth of scientific return. Its instrument teams (nine in the first generation) and guest investigators will do suborbital astronomy in a shirt-sleeve environment. The project will invest $10M per year in science instrument development over a lifetime of 20 years. This, frequent flight opportunities, and operation that enables rapid changes of science instruments and hands-on in-flight access to the instruments, assure a unique and extensive potential - both for training young instrumentalists and for encouraging and deploying nascent technologies. Novel instruments covering optical, infrared, and submillimeter bands can be developed for and tested on SOFIA by their developers (including apprentices) for their own observations and for those of guest observers, to validate technologies and maximize observational effectiveness.Comment: 10 pages, no figures, White Paper for Astro 2010 Survey Committee on State of the Professio

Reduced Susceptibility to Interference in the Consolidation of Motor Memory before Adolescence

Are children superior to adults in consolidating procedural memory? This notion has been tied to “critical,” early life periods of increased brain plasticity. Here, using a motor sequence learning task, we show, in experiment 1, that a) the rate of learning during a training session, b) the gains accrued, without additional practice, within a 24 hours post-training interval (delayed consolidation gains), and c) the long-term retention of these gains, were as effective in 9, 12 and 17-year-olds and comparable to those reported for adults. However, a follow-up experiment showed that the establishment of a memory trace for the trained sequence of movements was significantly more susceptible to interference by a subsequent motor learning experience (practicing a reversed movement sequence) in the 17-year-olds compared to the 9 and 12-year-olds. Unlike the 17-year-olds, the younger age-groups showed significant delayed gains even after interference training. Altogether, our results indicate the existence of an effective consolidation phase in motor learning both before and after adolescence, with no childhood advantage in the learning or retention of a motor skill. However, the ability to co-consolidate different, successive motor experiences, demonstrated in both the 9 and 12-year-olds, diminishes after puberty, suggesting that a more selective memory consolidation process takes over from the childhood one. Only the adult consolidation process is gated by a recency effect, and in situations of multiple, clashing, experiences occurring within a short time-interval, adults may less effectively establish in memory experiences superseded by newer ones