Efficient synthesis of novel benzo[b][1,8]naphthyridin-4(1H)-ones and pyrido[2,3-b]quinoxalin-4(1H)-ones from alkynones and primary amines

An efficient palladium-catalyzed cyclization of o-chlorohetaryl ynones with aliphatic and aromatic primary amines represents a simple access to a wide range of benzo[b][1,8]naphthyridin-4(1H)-one and pyrido[2,3-b]quinoxalin-4(1H)- one derivatives in good to excellent yields. © 2013 Elsevier Ltd. All rights reserved

DBT-enhanced cognitive-behavioral treatment for trichotillomania: A randomized controlled trial

Background and aims: Limited treatment options are available for trichotillomania (TTM) and most have modest outcomes. Suboptimal treatment results may be due to the failure of existing approaches to address all TTM styles. Methods: Thirty-eight DSM-IV TTM participants were randomly assigned across two study sites to Dialectical Behavior Therapy (DBT) -enhanced cognitive-behavioral treatment (consisting of an 11-week acute treatment and 3-month maintenance treatment) or a minimal attention control (MAC) condition. MAC participants had active treatment after the 11-week control condition. Follow-up study assessments were conducted three and six months after the maintenance period. Results: Open trial treatment resulted in significant improvement in TTM severity, emotion regulation (ER) capacity, experiential avoidance, anxiety and depression with changes generally maintained over time. In the randomized controlled trial, those with active treatment had greater improvement than those in the MAC condition for both TTM severity and ER capacity. Correlations between changes in TTM severity and ER capacity were not reported at post-treatment but did occur in maintenance and follow-up indicating reduced TTM severity with improved ER capacity. Conclusions: DBT-enhanced cognitive-behavioral treatment is a promising treatment for TTM. Future studies should compare this approach to other credible treatment interventions and investigate the efficacy of this approach in more naturalistic samples with greater comorbidity

Remote in vivo stress assessment of aquatic animals with microencapsulated biomarkers for environmental monitoring

Remote in vivo scanning of physiological parameters is a major trend in the development of new tools for the fields of medicine and animal physiology. For this purpose, a variety of implantable optical micro- and nanosensors have been designed for potential medical applications. At the same time, the important area of environmental sciences has been neglected in the development of techniques for remote physiological measurements. In the field of environmental monitoring and related research, there is a constant demand for new effective and quick techniques for the stress assessment of aquatic animals, and the development of proper methods for remote physiological measurements in vivo may significantly increase the precision and throughput of analyses in this field. In the present study, we apply pH-sensitive microencapsulated biomarkers to remotely monitor the pH of haemolymph in vivo in endemic amphipods from Lake Baikal, and we compare the suitability of this technique for stress assessment with that of common biochemical methods. For the first time, we demonstrate the possibility of remotely detecting a change in a physiological parameter in an aquatic organism under ecologically relevant stressful conditions and show the applicability of techniques using microencapsulated biomarkers for remote physiological measurements in environmental monitoring

Additive Pressures of Elevated Sea Surface Temperatures and Herbicides on Symbiont-Bearing Foraminifera

Elevated ocean temperatures and agrochemical pollution individually threaten inshore coral reefs, but these pressures are likely to occur simultaneously. Experiments were conducted to evaluate the combined effects of elevated temperature and the photosystem II (PSII) inhibiting herbicide diuron on several types of symbiotic algae (diatom, dinoflagellate or rhodophyte) of benthic foraminifera in hospite. Diuron was shown to evoke a direct effect on photosynthetic efficiency (reduced effective PSII quantum yield ΔF/F′m), while elevated temperatures (>30°C, only 2°C above current average summer temperatures) were observed to impact photosynthesis more indirectly by causing reductions in maximum PSII quantum yield (Fv/Fm), interpreted as photodamage. Additionally, elevated temperatures were shown to cause bleaching through loss of chlorophyll a in foraminifera hosting either diatoms or dinoflagellates. A significant linear correlation was found between reduced Fv/Fm and loss of chlorophyll a. In most cases, symbionts within foraminifera proved more sensitive to thermal stress in the presence of diuron (≥1 µg L−1). The mixture toxicity model of Independent Action (IA) described the combined effects of temperature and diuron on the photosystem of species hosting diatoms or dinoflagellates convincingly and in agreement with probabilistic statistics, so a response additive joint action can be assumed. We thus demonstrate that improving water quality can improve resilience of symbiotic phototrophs to projected increases in ocean temperatures. As IA described the observed combined effects from elevated temperature and diuron stress it may therefore be employed for prediction of untested mixtures and for assessing the efficacy of management measures

Environmental Risk Assessment of Fluctuating Diazinon Concentrations in an Urban and Agricultural Catchment Using Toxicokinetic–Toxicodynamic Modeling

Temporally resolved environmental risk assessment of fluctuating concentrations of micropollutants is presented. We separated the prediction of toxicity over time from the extrapolation from one to many species and from acute to sublethal effects. A toxicokinetic–toxicodynamic (TKTD) model predicted toxicity caused by fluctuating concentrations of diazinon, measured by time-resolved sampling over 108 days from three locations in a stream network, representing urban, agricultural and mixed land use. We calculated extrapolation factors to quantify variation in toxicity among species and effect types based on available toxicity data, while correcting for different test durations with the TKTD model. Sampling from the distribution of extrapolation factors and prediction of time-resolved toxicity with the TKTD model facilitated subsequent calculation of the risk of undesired toxic events. Approximately one-fifth of aquatic organisms were at risk and fluctuating concentrations were more toxic than their averages. Contribution of urban and agricultural sources of diazinon to the overall risk varied. Thus using fixed concentrations as water quality criteria appears overly simplistic because it ignores the temporal dimension of toxicity. However, the improved prediction of toxicity for fluctuating concentrations may be small compared to uncertainty due to limited diversity of toxicity data to base the extrapolation factors on

Extreme disorder in an ultrahigh-affinity protein complex

Molecular communication in biology is mediated by protein interactions. According to the current paradigm, the specificity and affinity required for these interactions are encoded in the precise complementarity of binding interfaces. Even proteins that are disordered under physiological conditions or that contain large unstructured regions commonly interact with well-structured binding sites on other biomolecules. Here we demonstrate the existence of an unexpected interaction mechanism: the two intrinsically disordered human proteins histone H1 and its nuclear chaperone prothymosin-α associate in a complex with picomolar affinity, but fully retain their structural disorder, long-range flexibility and highly dynamic character. On the basis of closely integrated experiments and molecular simulations, we show that the interaction can be explained by the large opposite net charge of the two proteins, without requiring defined binding sites or interactions between specific individual residues. Proteome-wide sequence analysis suggests that this interaction mechanism may be abundant in eukaryotes