The intracellular region of Notch ligands: does the tail make the difference?

The cytoplasmic tail of Notch ligands drives endocytosis, mediates association with proteins implicated in the organization of cell-cell junctions and, through regulated intra-membrane proteolysis, is released from the membrane as a signaling fragment. We survey these findings and discuss the role of Notch ligands intracellular region in bidirectional signaling and possibly in signal modulation in mammals

Российская интеллигенция: блеск и нищета духа

Hairy and enhancer of split 1, one of the main downstream effectors in Notch signaling, is a transcriptional repressor of the basic helix-loop-helix (bHLH) family. Using nuclear magnetic resonance methods, we have determined the structure and dynamics of a recombinant protein, H1H, which includes an N-terminal segment, b1, containing functionally important phosphorylation sites, the basic region b2, required for binding to DNA, and the HLH domain. We show that a proline residue in the sequence divides the protein in two parts, a flexible and disordered N-terminal region including b1 and a structured, mainly helical region comprising b2 and the HLH domain. Binding of H1H to a double strand DNA oligonucleotide was monitored through the chemical shift perturbation of backbone amide resonances, and showed that the interaction surface involves not only the b2 segment but also several residues in the b1 and HLH regions

Lateral hypothalamic activity indicates hunger and satiety states in humans

Lateral hypothalamic area (LHA) local field potentials (LFPs) were recorded in a Prader–Willi patient undergoing deep brain stimulation (DBS) for obesity. During hunger, exposure to food-related cues induced an increase in beta/ low-gamma activity. In contrast, recordings during satiety were marked by prominent alpha rhythms. Based on these findings, we have delivered alphafrequency DBS prior to and during food intake. Despite reporting an early sensation of fullness, the patient continued to crave food. This suggests that the pattern of activity in LHA may indicate hunger/satiety states in humans but attest to the complexity of conducting neuromodulation studies in obesity

Current Wildland Fire Patterns and Challenges in Europe : A Synthesis of National Perspectives

Changes in climate, land use, and land management impact the occurrence and severity of wildland fires in many parts of the world. This is particularly evident in Europe, where ongoing changes in land use have strongly modified fire patterns over the last decades. Although satellite data by the European Forest Fire Information System provide large-scale wildland fire statistics across European countries, there is still a crucial need to collect and summarize in-depth local analysis and understanding of the wildland fire condition and associated challenges across Europe. This article aims to provide a general overview of the current wildland fire patterns and challenges as perceived by national representatives, supplemented by national fire statistics (2009-2018) across Europe. For each of the 31 countries included, we present a perspective authored by scientists or practitioners from each respective country, representing a wide range of disciplines and cultural backgrounds. The authors were selected from members of the COST Action "Fire and the Earth System: Science & Society" funded by the European Commission with the aim to share knowledge and improve communication about wildland fire. Where relevant, a brief overview of key studies, particular wildland fire challenges a country is facing, and an overview of notable recent fire events are also presented. Key perceived challenges included (1) the lack of consistent and detailed records for wildland fire events, within and across countries, (2) an increase in wildland fires that pose a risk to properties and human life due to high population densities and sprawl into forested regions, and (3) the view that, irrespective of changes in management, climate change is likely to increase the frequency and impact of wildland fires in the coming decades. Addressing challenge (1) will not only be valuable in advancing national and pan-European wildland fire management strategies, but also in evaluating perceptions (2) and (3) against more robust quantitative evidence.Peer reviewe

Chemical shift assignment of the alternative scaffold protein IscA

The IscA protein (11.5\ua0kDa) is an essential component of the iron sulphur cluster biogenesis machine. In bacteria, the machine components are clustered in operons, amongst which the most important is the isc operon. Bacterial IscA has direct homologues also in eukaryotes. Like the protein IscU, IscA is thought to assist cluster formation as an alternative scaffold protein which receives the cluster before transferring it further to the final acceptors. Several crystal structures have been published. They all report an IscA dimeric form, although the packing of the protomers in the dimers differs amongst structures. No solution studies have currently been reported. Here we report the 1H, 13C and 15N backbone and side-chain chemical shift assignments of the cluster-free E. coli IscA as a starting point for further studies of the structure and functions of this still poorly characterized protein. We show that IscA exists in solution as an equilibrium between different species. Spectrum assignment was thus challenging given the heterogeneous nature of the sample but doable through judicious choice of selective labelling and concentration dependent studies

Electrical stimulation of the forearm:a method for transmitting sensory signals from the artificial hand to the brain

This research is in line with an important comment from the first amputee who tried the prosthetic hand with tactile feedback developed within the Smarthand project [1]. While trying the system with tactile feedback the patient said: "It's a feeling I have not had in a long time. When I grab something tightly I can feel it in the fingertips. It's strange since I don't have them anymore! It's amazing." We describe here the instrumentation and methods for testing the abilities of humans to discriminate sensations generated by electrical stimulation applied to the skin on the forearm. The instruments allowed testing of electrical stimulation with various properties (pulse duration, intensity, and rate). We tested the perception and pain thresholds, with the emphasis that comfortable sensations are a must. During the tests subjects were asked to locate the point on the skin that was stimulated and describe their perception of the elicited sensation. Results of first tests with small concentric electrodes suggest that non-amputees can distinguish up to seven perceptual qualities (the most common one was vibration, followed by tingling and tickling). Certain sensations had a higher occurrence rate along one axial line of the forearm than another of the forearm. In terms of spatial acuity, the subjects had more difficulties in distinguishing between the positions in the axial direction of the forearm compared with the circumferential direction. These results guided the design of the new array electrode with multiple cathodes and anodes positioned circumferential to the forearm. The results of the tests conducted with this electrode design showed high location discernment accuracy, and demonstrated the ability to memorize and later accurately recall six different electrical ?messages? created by delivering electrical stimulation onto three different electrode pads with two different stimulation parameters.</jats:p