A methylated lysine is a switch point for conformational communication in the chaperone Hsp90

Methylation of a conserved lysine in C-terminal domain of the molecular chaperone Hsp90 was shown previously to affect its in vivo function. However, the underlying mechanism remained elusive. Through a combined experimental and computational approach, this study shows that this site is very sensitive to sidechain modifications and crucial for Hsp90 activity in vitro and in vivo. Our results demonstrate that this particular lysine serves as a switch point for the regulation of Hsp90 functions by influencing its conformational cycle, ATPase activity, co-chaperone regulation, and client activation of yeast and human Hsp90. Incorporation of the methylated lysine via genetic code expansion specifically shows that upon modification, the conformational cycle of Hsp90 is altered. Molecular dynamics simulations including the methylated lysine suggest specific conformational changes that are propagated through Hsp90. Thus, methylation of the C-terminal lysine allows a precise allosteric tuning of Hsp90 activity via long distances. Methylation of a lysine residue in Hsp90 is a recently discovered post-translational modification but the mechanistic effects of this modification have remained unknown so far. Here the authors combine biochemical and biophysical approaches, molecular dynamics (MD) simulations and functional experiments with yeast and show that this lysine is a switch point, which specifically modulates conserved Hsp90 functions including co-chaperone regulation and client activation

Author Correction: A methylated lysine is a switch point for conformational communication in the chaperone Hsp90

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Ultra-high-resolution marine 2D-3D seismic investigation of the Liman Tepe/Karantina Island archaeological site (Urla/Turkey)

2D and 3D high-resolution seismic investigations were performed on submerged coastal archaeological sites at Iskele and near to Karantina Island in the Bay of Izmir in western Turkey. Tectonic subsidence of the coastline has submerged a number of archaeological features associated with an important Early Bronze Archaic settlement (Liman Tepe) and the classical Ionian city of Clazomenae. Seismic surveys were focused on imaging of an Archaic harbour structure and other submerged Hellenistic and Roman architectural features. Seismic data were acquired with the SEAMAP-3D ultra-high-resolution 3D marine seismic acquisition system developed for detailed archaeological site investigation. A 2D reconnaissance survey was performed over a 2 km2 area around Karantina Island to evaluate the seismic penetrability and to locate sites for further 3D investigation. This survey predominantly revealed marine sediment layers covering the local bedrock, which is characterized by scattering of seismic energy showing its rocky nature. Two ultra-high-resolution 3D seismic surveys were performed. The first covered a 350 m × 30 m area in the modern harbour targeting a prominent Archaic harbour structure. The second was acquired across a 120 m × 40 m area on the southeast shore of the Karantina Island close to a Roman architectural feature. The 3D surveys were acquired with nominal line spacings of 1 m, using a 8 × 4 pseudo-rigid hydrophone array and a Boomer source firing at 3 Hz shot frequency. Automated processing of the seismic data using a portable Linux cluster provided stacked 3D seismic volumes with 25 cm × 25 cm bin size on-site. The 3D seismic survey of the harbour clearly imaged the submerged Archaic structure and the underlying sediment sequence. The seismic time slices reveal two seismic anomalies (2-3 m in diameter) in the harbour basin sediments. The 3D surveys southeast of Karantina identified a thicker marine sediment sequence overlying steeply dipping bedrock reflectors. The sediment sequence records the rapid accumulation and progradation of the coastline following the construction the Alexander causeway linking the mainland with the island in 334 B.C. © 2008 Elsevier B.V. All rights reserved

Effects of Working Memory Load on Oscillatory Power in Human Intracranial EEG

Studies of working memory load effects on human EEG power have indicated divergent effects in different frequency bands. Although gamma power typically increases with load, the load dependency of the lower frequency theta and alpha bands is uncertain. We obtained intracranial electroencephalography measurements from 1453 electrode sites in 14 epilepsy patients performing a Sternberg task, in order to characterize the anatomical distribution of load-related changes across the frequency spectrum. Gamma power increases occurred throughout the brain, but were most common in the occipital lobe. In the theta and alpha bands, both increases and decreases were observed, but with different anatomical distributions. Increases in theta and alpha power were most prevalent in frontal midline cortex. Decreases were most commonly observed in occipital cortex, colocalized with increases in the gamma range, but were also detected in lateral frontal and parietal regions. Spatial overlap with group functional magnetic resonance imaging results was minimal except in the precentral gyrus. These findings suggest that power in any given frequency band is not a unitary phenomenon; rather, reactivity in the same frequency band varies in different brain regions, and may relate to the engagement or inhibition of a given area in a cognitive task

Visual search performance is predicted by both prestimulus and poststimulus electrical brain activity

© The Author(s) 2016. An individual's performance on cognitive and perceptual tasks varies considerably across time and circumstances. We investigated neural mechanisms underlying such performance variability using regression-based analyses to examine trial-by-trial relationships between response times (RTs) and different facets of electrical brain activity. Thirteen participants trained five days on a color-popout visual-search task, with EEG recorded on days one and five. The task was to find a color-popout target ellipse in a briefly presented array of ellipses and discriminate its orientation. Later within a session, better preparatory attention (reflected by less prestimulus Alpha-band oscillatory activity) and better poststimulus early visual responses (reflected by larger sensory N1 waves) correlated with faster RTs. However, N1 amplitudes decreased by half throughout each session, suggesting adoption of a more efficient search strategy within a session. Additionally, fast RTs were preceded by earlier and larger lateralized N2pc waves, reflecting faster and stronger attentional orienting to the targets. Finally, SPCN waves associated with target-orientation discrimination were smaller for fast RTs in the first but not the fifth session, suggesting optimization with practice. Collectively, these results delineate variations in visual search processes that change over an experimental session, while also pointing to cortical mechanisms underlying performance in visual search

Differential orientation effect in the neural response to interacting biological motion of two agents

<p>Abstract</p> <p>Background</p> <p>A recent behavioral study demonstrated that the meaningful interaction of two agents enhances the detection sensitivity of biological motion (BM), however, it remains unclear when and how the 'interaction' information of two agents is represented in our neural system. To clarify this point, we used magnetoencephalography and introduced a novel experimental technique to extract a neuromagnetic response relating to two-agent BM perception. We then investigated how this response was modulated by the interaction of two agents. In the present experiment, we presented two kinds of visual stimuli (interacting and non-interacting BM) with two orientations (upright and inverted).</p> <p>Results</p> <p>We found a neuromagnetic response in the bilateral occipitotemporal region, on average 300 – 400 ms after the onset of a two-agent BM stimulus. This result showed that interhemispheric differences were apparent for the peak amplitudes. For the left hemisphere, the orientation effect was manifest when the two agents were made to interact, and the interaction effect was manifest when the stimulus was inverted. In the right hemisphere, the main effects of both orientation and interaction were significant, suggesting that the peak amplitude was attenuated when the visual stimulus was inverted or made to interact.</p> <p>Conclusion</p> <p>These results demonstrate that the 'interaction' information of two agents can affect the neural activities in the bilateral occipitotemporal region, on average 300 – 400 ms after the onset of a two-agent BM stimulus, however, the modulation was different between hemispheres: the left hemisphere is more concerned with dynamics, whereas the right hemisphere is more concerned with form information.</p

Transient reduction of tinnitus intensity is marked by concomitant reductions of delta band power

<p>Abstract</p> <p>Background</p> <p>Tinnitus is an auditory phantom phenomenon characterized by the sensation of sounds without objectively identifiable sound sources. To date, its causes are not well understood. Previous research found altered patterns of spontaneous brain activity in chronic tinnitus sufferers compared to healthy controls, yet it is unknown whether these abnormal oscillatory patterns are causally related to the tinnitus sensation. Partial support for this notion comes from a neurofeedback approach developed by our group, in which significant reductions in tinnitus loudness could be achieved in patients who successfully normalized their patterns of spontaneous brain activity. The current work attempts to complement these studies by scrutinizing how modulations of tinnitus intensity alter ongoing oscillatory activity.</p> <p>Results</p> <p>In the present study the relation between tinnitus sensation and spontaneous brain activity was investigated using residual inhibition (RI) to reduce tinnitus intensity and source-space projected magnetencephalographic (MEG) data to index brain activity. RI is the sustained reduction (criteria: 50% for at least 30 s) in tinnitus loudness after cessation of a tonal tinnitus masker. A pilot study (n = 38) identified 10 patients who showed RI. A significant reduction of power in the delta (1.3–4.0 Hz) frequency band was observed in temporal regions during RI (p ≤ 0.001).</p> <p>Conclusion</p> <p>The current results suggest that changes of tinnitus intensity induced by RI are mediated by alterations in the pathological patterns of spontaneous brain activity, specifically a reduction of delta activity. Delta activity is a characteristic oscillatory activity generated by deafferented/deprived neuronal networks. This implies that RI effects might reflect the transient reestablishment of balance between excitatory and inhibitory neuronal assemblies, via reafferentation, that have been perturbed (in most tinnitus individuals) by hearing damage. As enhancements have been reported in the delta frequency band for tinnitus at rest, this result conforms to our assumption that a normalization of oscillatory properties of cortical networks is a prerequisite for attenuating the tinnitus sensation. For RI to have therapeutic significance however, this normalization would have to be stabilized.</p

The effects of migrant remittances on population–environment dynamics in migrant origin areas: international migration, fertility, and consumption in highland Guatemala

International migration impacts origin regions in many ways. As examples, remittances from distant migrants may alter consumption patterns within sending communities, while exposure to different cultural norms may alter other behaviors. This paper combines these insights to offer a unique lens on migration’s environmental impact. From an environmental perspective, we ask the following question: is the likely rise in consumption brought about by remittances counterbalanced by a reduction in fertility in migrant households following exposure to lower fertility cultures? Based on ethnographic case studies in two western highland Guatemalan communities, we argue that the near-term rise in consumption due to remittances is not counterbalanced by rapid decline in migrant household fertility. However, over time, the environmental cost of consumption may be mitigated at the community level through diffusion of contraception and family planning norms yielding lower family size

Pre-Stimulus Activity Predicts the Winner of Top-Down vs. Bottom-Up Attentional Selection

Our ability to process visual information is fundamentally limited. This leads to competition between sensory information that is relevant for top-down goals and sensory information that is perceptually salient, but task-irrelevant. The aim of the present study was to identify, from EEG recordings, pre-stimulus and pre-saccadic neural activity that could predict whether top-down or bottom-up processes would win the competition for attention on a trial-by-trial basis. We employed a visual search paradigm in which a lateralized low contrast target appeared alone, or with a low (i.e., non-salient) or high contrast (i.e., salient) distractor. Trials with a salient distractor were of primary interest due to the strong competition between top-down knowledge and bottom-up attentional capture. Our results demonstrated that 1) in the 1-sec pre-stimulus interval, frontal alpha (8–12 Hz) activity was higher on trials where the salient distractor captured attention and the first saccade (bottom-up win); and 2) there was a transient pre-saccadic increase in posterior-parietal alpha (7–8 Hz) activity on trials where the first saccade went to the target (top-down win). We propose that the high frontal alpha reflects a disengagement of attentional control whereas the transient posterior alpha time-locked to the saccade indicates sensory inhibition of the salient distractor and suppression of bottom-up oculomotor capture