Time processing in visual cortices: How the visual brain encodes and keeps track of time

Time is embedded in any sensory experience: the movements of a dance, the rhythm of a piece of music, the words of a speaker are all examples of temporally structured sensory events. In humans, if and how visual cortices perform temporal processing remains unclear. Here we show that both primary visual cortex (V1) and extrastriate area V5/MT are causally involved in encoding and keeping time in memory and that this involvement is independent from low-level visual processing. Most importantly we demonstrate that V1 and V5/MT are functionally linked and temporally synchronized during time encoding whereas they are functionally independent and operate serially (V1 followed by V5/MT) while maintaining temporal information in working memory. These data challenge the traditional view of V1 and V5/MT as visuo-spatial features detectors and highlight the functional contribution and the temporal dynamics of these brain regions in the processing of time in millisecond range. The present project resulted in the paper entitled: 'How the visual brain encodes and keeps track of time' by Paolo Salvioni, Lysiann Kalmbach, Micah Murray and Domenica Bueti that is now submitted for publication to the Journal of Neuroscience.

Impact of tamoxifen dose on tamoxifen and its active metabolites exposure in breast cancer patients: preliminary results from a prospective, open-label trial

Background: CYP2D6 is the key enzyme responsible for tamoxifen bioactivation mainly into endoxifen. This gene is highly polymorphic and breast cancer patients classified as CYP2D6 poor metabolizers (PM) or intermediate metabolizers (IM) appear to show low concentrations of endoxifen and to achieve less benefit from tamoxifen treatment. Purpose: This prospective, open-label trial aimed to assess how the increase of tamoxifen dose influences the level of endoxifen in the different genotype groups (poor-, intermediate-, and extensive-metabolizers (EM)). We examined the impact of doubling tamoxifen dose to 20mg twice daily on endoxifen plasma concentrations across these genotype groups. Patients and methods: Patients were assayed for CYP2D6 genotype and phenotype using dextromethorphan test. Tamoxifen, N-desmethyltamoxifen, 4-hydroxytamoxifen and endoxifen plasma levels were determined on 2 occasions at baseline (20mg/day of tamoxifen) and at day 30, 90 and 120 after dose increase (20 mg twice daily) using liquid chromatography-tandem-mass spectrometry. Endoxifen plasma levels were measured 6 to 24 hours after last drug intake to evaluate its accumulation before and after doubling tamoxifen dosage. ANOVA was used to evaluate endoxifen levels increase and difference between genotype groups. Results: 63 patients are available for analysis to date. Tamoxifen, N-desmethyltamoxifen, 4-hydroxytamoxifen and endoxifen plasma reached steady state at 30 day after tamoxifen dose escalation, with a significant increase compared to baseline by 1.6 to 1.8 fold : geometric mean plasma concentrations (CV %) were 140 ng/mL (45%) at baseline vs 255 (47%) at day 30 for tamoxifen (P < 0.0001); 256 (49%) vs 408 (64%) for N-desmethyltamoxifen (P < 0.0001); 2.4 (46%) vs 3.9 (51%) for 4-OH-tamoxifen (P < 0.0001); and 20 (91%) vs 33 (91%) for endoxifen (P < 0.02). On baseline, endoxifen levels tended to be lower in PM: 7 ng/mL (36%), than IM: 16 ng/mL (70%), P=0.08, and EM: 24 ng/mL (71%), P<0.001. After doubling tamoxifen dosage, endoxifen concentrations rose similarly in PM, IM and EM with respectively, 1.5 (18%), 1.5 (28%) and 1.7 (30%) fold increase from baseline, P=0.18. Conclusion: Endoxifen exposure varies widely under standard tamoxifen dosage, with CYP2D6 genotype explaining only a minor part of this variability. It increases consistently on doubling tamoxifen dose, similarly across genotypes. This would enable exposure optimization based on concentration monitoring.

Engaging students in an e-learning experience : how to manage information resources through wikis and web blogs

The purpose of this paper is to describe the collaboration between librarians and scholars, from a virtual university, in order to facilitate collaborative learning on how to manage information resources. The personal information behaviour of e-learning students when managing information resources for academic, professional and daily life purposes was studied from 24 semi-structured face-to-face interviews. The results of the content analysis of the interview' transcriptions, highlighted that in the workplace and daily life contexts, competent information behaviour is always linked to a proactive attitude, that is to say, that participants seek for information without some extrinsic reward or avoiding punishment. In the academic context, it was observed a low level of information literacy and it seems to be related with a prevalent uninvolved attitude.

How robust are global conservation priorities to climate change?

International conservation organisations have identified priority areas for biodiversity conservation. These global-scale prioritisations affect the distribution of funds for conservation interventions. As each organisation has a different focus, each prioritisation scheme is determined by different decision criteria and the resultant priority areas vary considerably. However, little is known about how the priority areas will respond to the impacts of climate change. In this paper, we examined the robustness of eight global-scale prioritisations to climate change under various climate predictions from seven global circulation models. We developed a novel metric of the climate stability for 803 ecoregions based on a recently introduced method to estimate the overlap of climate envelopes. The relationships between the decision criteria and the robustness of the global prioritisation schemes were statistically examined. We found that decision criteria related to level of endemism and landscape fragmentation were strongly correlated with areas predicted to be robust to a changing climate. Hence, policies that prioritise intact areas due to the likely cost efficiency, and assumptions related to the potential to mitigate the impacts of climate change, require further examination. Our findings will help determine where additional management is required to enable biodiversity to adapt to the impacts of climate change

Eeny meeny miny moe, catch a transcript by the toe, or how to enumerate eukaryotic transcripts.

In this issue of Genes & Development, Revyakin and colleagues (pp. 1691-1702) measure the relation between individual RNA polymerase II transcription events and transcription factor assembly by counting RNA transcripts retained on the template DNA using single-molecule fluorescence.

How effective are policies to reduce gasoline consumption? evaluating a quasi-natural experiment in Spain

Using a panel of 48 provinces for four years we empirically analyze a series of temporary policies aimed at curbing fuel consumption implemented in Spain between March and June 2011. The first policy was a reduction in the speed limit in highways. The second policy was an increase in the biofuel content of fuels used in the transport sector. The third measure was a reduction of 5% in commuting and regional train fares that resulted in two major metropolitan areas reducing their overall fare for public transit. The results indicate that the speed limit reduction in highways reduced gasoline consumption by between 2% and 3%, while an increase in the biofuel content of gasoline increased this consumption. This last result is consistent with experimental evidence that indicates that mileage per liter falls with an increase in the biofuel content in gasolines. As for the reduction in transit fares, we do not find a significant effect for this policy. However, in specifications including the urban transit fare for the major cities in each province the estimated cross-price elasticity of the demand for gasoline -used as a proxy for car use- with respect to the price of transit is within the range reported in the literature. This is important since one of the main eficiency justification for subsidizing public transit rests on the positive value of this parameter and most of the estimates reported in the literature are quite dated.

Cancers du sein : comment associer l'hormonothérapie et la radiothérapie en situation adjuvante [How to combine hormonotherapy and radiation treatment in adjuvant breast cancer?]

Combined radiation and hormone therapies have become common clinical practice in recent years for locally-advanced prostate cancers. The use of such concomitant therapy in the treatment of breast disease has been infrequently reported in the literature, but seems justified given the common hormonal dependence of breast cancer and the potential synergistic effect of these two treatment modalities. As adjuvant therapy, two strategies are used in daily clinical practice: upfront aromatase inhibitors or sequentially after a variable delay of tamoxifen. These molecules may, thus, interact with radiotherapy. Retrospectives studies recently published did not show any differences in terms of locoregional recurrences between concurrent or sequential radiohormonotherapy. Lung and skin fibroses due to concurrent treatment are still under debate. Nevertheless, late side effects appeared to be increased by such a treatment, particularly in hypersensitive patients identified at risk by the lymphocyte predictive test. Concurrent radiohormonotherapy should, thus, be delivered cautiously at least for these patients. This article details the potent advantages and risks of concurrent use of adjuvant hormonotherapy and radiotherapy in localized breast cancers.