Post-training inactivation of the anterior thalamic nuclei impairs spatial performance on the radial arm maze

The limbic thalamus, specifically the anterior thalamic nuclei (ATN), contains brain signals including that of head direction cells, which fire as a function of an animal\u27s directional orientation in an environment. Recent work has suggested that this directional orientation information stemming from the ATN contributes to the generation of hippocampal and parahippocampal spatial representations, and may contribute to the establishment of unique spatial representations in radially oriented tasks such as the radial arm maze. While previous studies have shown that ATN lesions can impair spatial working memory performance in the radial maze, little work has been done to investigate spatial reference memory in a discrimination task variant. Further, while previous studies have shown that ATN lesions can impair performance in the radial maze, these studies produced the ATN lesions prior to training. It is therefore unclear whether the ATN lesions disrupted acquisition or retention of radial maze performance. Here, we tested the role of ATN signaling in a previously learned spatial discrimination task on a radial arm maze. Rats were first trained to asymptotic levels in a task in which two maze arms were consistently baited across training. After 24 h, animals received muscimol inactivation of the ATN before a 4 trial probe test. We report impairments in post-inactivation trials, suggesting that signals from the ATN modulate the use of a previously acquired spatial discrimination in the radial-arm maze. The results are discussed in relation to the thalamo-cortical limbic circuits involved in spatial information processing, with an emphasis on the head direction signal. © 2017 Harvey, Thompson, Sanchez, Yoder and Clark

Substrate Flexibility of a Mutated Acyltransferase Domain and Implications for Polyketide Biosynthesis

SummaryPolyketides are natural products frequently used for the treatment of various diseases, but their structural complexity hinders efficient derivatization. In this context, we recently introduced enzyme-directed mutasynthesis to incorporate non-native extender units into the biosynthesis of erythromycin. Modeling and mutagenesis studies led to the discovery of a variant of an acyltransferase domain in the erythromycin polyketide synthase capable of accepting a propargylated substrate. Here, we extend molecular rationalization of enzyme-substrate interactions through modeling, to investigate the incorporation of substrates with different degrees of saturation of the malonic acid side chain. This allowed the engineered biosynthesis of new erythromycin derivatives and the introduction of additional mutations into the AT domain for a further shift of the enzyme's substrate scope. Our approach yields non-native polyketide structures with functional groups that will simplify future derivatization approaches, and provides a blueprint for the engineering of AT domains to achieve efficient polyketide synthase diversification

Comparative efficacy between atorvastatin and rosuvastatin in the prevention of cardiovascular disease recurrence

Background: There is no randomized clinical trials with recurrence of atherosclerotic cardiovascular disease (ASCVD) as a major outcome with rosuvastatin. In order to analyze potential differences in the clinical response to atorvastatin and rosuvastatin in secondary ASCVD prevention, we have analyzed the clinical evolution of those subjects of the Dyslipemia Registry of the Spanish Society of Arteriosclerosis (SEA) who at the time of inclusion in the Registry had already suffered an ASCVD. Methods: This observational, retrospective, multicenter, national study was designed to determine potential differences between the use of atorvastatin and rosuvastatin in the ASCVD recurrence. Three different follow-up start-times were performed: time of inclusion in the registry; time of first event if this occurred after 2005, and time of first event without date restriction. Results: Baseline characteristics were similar between treatment groups. Among atorvastatin or rosuvastatin users, 89 recurrences of ASCVD were recorded (21.9%), of which 85.4% were coronary. At the inclusion of the subject in the registry, 345 participants had not suffered a recurrence yet. These 345 subjects accumulated 1050 person-years in a mean follow-up of 3 years. Event rates were 2.73 (95% CI: 1.63, 4.25) cases/100 person-years and 2.34 (95% CI: 1.17, 4.10) cases/100 person-years in the atorvastatin and rosuvastatin groups, respectively. There were no statistically significant differences between the two groups independently of the follow-up start-time. Conclusions: This study does not find differences between high doses of rosuvastatin and atorvastatin in the recurrence of ASCVD, and supports their use as clinically equivalent in secondary prevention of ASCVD

Predictors of weight gain in a Mediterranean cohort: the Seguimiento Universidad de Navarra Study 1

BACKGROUND: High consumption of sugar-sweetened drinks has been associated with weight gain and obesity in the United States. This trend may also be affecting populations with different eating patterns who increasingly are adopting typical US dietary patterns. OBJECTIVE: We assessed whether the consumption of sweetened drinks and other food items increased the likelihood of weight gain in a Mediterranean population. DESIGN: This was a prospective cohort analysis of 7194 men and women with a mean age of 41 y who were followed-up for a median of 28.5 mo with mailed questionnaires. Dietary exposure was assessed with a previously validated semiquantitative food-frequency questionnaire. RESULTS: During follow-up, we observed that 49.5% of the participants increased their weight (x weight gain: 0.64 kg; 95% CI: 0.55, 0.73 kg). In the participants who had gained > or =3 kg in the 5 y before baseline, the adjusted odds ratio of subsequent weight gain for the fifth quintile compared with the first quintile of sugar-sweetened soft drink consumption was 1.6 (95% CI: 1.2, 2.1; P for trend = 0.02). This association was absent in the participants who had not gained weight in the 5-y period before baseline. The consumption of hamburgers, pizza, and sausages (as a proxy for fast-food consumption) was also independently associated with weight gain (adjusted odds ratio for the fifth compared with the first quintile = 1.2; 95% CI: 1.0, 1.4; P for trend = 0.05). We also found a significant, but weaker, association between weight gain and both red meat and sweetened fruit juice consumption. CONCLUSION: In a Mediterranean cohort, particularly in the participants who had already gained weight, an increased consumption of sugar-sweetened soft drinks and of hamburgers, pizza, and sausages was associated with a higher risk of additional subsequent weight gain

Streamlined structure determination by cryo-electron tomography and subtomogram averaging using TomoBEAR

Structures of macromolecules in their native state provide unique unambiguous insights into their functions. Cryo-electron tomography combined with subtomogram averaging demonstrated the power to solve such structures in situ at resolutions in the range of 3 Angstrom for some macromolecules. In order to be applicable to the structural determination of the majority of macromolecules observable in cells in limited amounts, processing of tomographic data has to be performed in a high-throughput manner. Here we present TomoBEAR—a modular configurable workflow engine for streamlined processing of cryo-electron tomographic data for subtomogram averaging. TomoBEAR combines commonly used cryo-EM packages with reasonable presets to provide a transparent (“white box”) approach for data management and processing. We demonstrate applications of TomoBEAR to two data sets of purified macromolecular targets, to an ion channel RyR1 in a membrane, and the tomograms of plasma FIB-milled lamellae and demonstrate the ability to produce high-resolution structures. TomoBEAR speeds up data processing, minimizes human interventions, and will help accelerate the adoption of in situ structural biology by cryo-ET. The source code and the documentation are freely available

Reflection, radiation and interference for black holes

Black holes are capable of reflection: there is a finite probability for any particle that approaches the event horizon to bounce back. The albedo of the black hole depends on its temperature and the energy of the incoming particle. The reflection shares its physical origins with the Hawking process of radiation, both of them arise as consequences of the mixing of the incoming and outgoing waves that takes place on the event horizon.Comment: 10 pages, 1 figure, Revte

Star formation histories in mergers: the spatially resolved properties of the early-stage merger luminous infrared galaxies IC 1623 and NGC 6090

The role of major mergers in galaxy evolution is investigated through a detailed characterization of the stellar populations, ionized gas properties and star formation rates (SFR) in the early-stage merger luminous infrared galaxies (LIRGs) IC 1623 W and NGC 6090, by analysing optical integral field spectroscopy and high-resolution Hubble Space Telescope imaging. The spectra were processed with the starlight full spectral fitting code, and the emission lines measured in the residual spectra. The results are compared with non-interacting control spiral galaxies from the Calar Alto Legacy Integral Field Area survey. Merger-induced star formation is extended and recent, as revealed by the young ages (50–80 Myr) and high contributions to light of young stellar populations (50–90 per cent), in agreement with merger simulations in the literature. These early-stage mergers have positive central gradients of the stellar metallicity, with an average ∼0.6 Z⊙. Compared to non-interacting spirals, they have lower central nebular metallicity, and flatter profiles, in agreement with the gas inflow scenario. We find that they are dominated by star formation, although shock excitation cannot be discarded in some regions, where high velocity dispersion is found (170–200 km s−1). The average SFR in these early-stage mergers (∼23–32 M⊙ yr−1) is enhanced with respect to main-sequence Sbc galaxies by factors of 6–9, slightly above the predictions from classical merger simulations, but still possible in about 15 per cent of major galaxy mergers, where U/LIRGs belong

Neuroimaging paradigms for tonotopic mapping (II): the influence of acquisition protocol.

AbstractNumerous studies on the tonotopic organisation of auditory cortex in humans have employed a wide range of neuroimaging protocols to assess cortical frequency tuning. In the present functional magnetic resonance imaging (fMRI) study, we made a systematic comparison between acquisition protocols with variable levels of interference from acoustic scanner noise. Using sweep stimuli to evoke travelling waves of activation, we measured sound-evoked response signals using sparse, clustered, and continuous imaging protocols that were characterised by inter-scan intervals of 8.8, 2.2, or 0.0s, respectively. With regard to sensitivity to sound-evoked activation, the sparse and clustered protocols performed similarly, and both detected more activation than the continuous method. Qualitatively, tonotopic maps in activated areas proved highly similar, in the sense that the overall pattern of tonotopic gradients was reproducible across all three protocols. However, quantitatively, we observed substantial reductions in response amplitudes to moderately low stimulus frequencies that coincided with regions of strong energy in the scanner noise spectrum for the clustered and continuous protocols compared to the sparse protocol. At the same time, extreme frequencies became over-represented for these two protocols, and high best frequencies became relatively more abundant. Our results indicate that although all three scanning protocols are suitable to determine the layout of tonotopic fields, an exact quantitative assessment of the representation of various sound frequencies is substantially confounded by the presence of scanner noise. In addition, we noticed anomalous signal dynamics in response to our travelling wave paradigm that suggest that the assessment of frequency-dependent tuning is non-trivially influenced by time-dependent (hemo)dynamics when using sweep stimuli