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Inter-areal synchronization of neuronal oscillations at frequencies below ~100 Hz is a pervasive feature of neuronal activity and is thought to regulate communication in neuronal circuits. In contrast, faster activities and oscillations have been considered to be largely local-circuit-level phenomena without large-scale synchronization between brain regions. We show, using human intracerebral recordings, that 100–400 Hz high-frequency oscillations (HFOs) may be synchronized between widely distributed brain regions. HFO synchronization expresses individual frequency peaks and exhibits reliable connectivity patterns that show stable community structuring. HFO synchronization is also characterized by a laminar profile opposite to that of lower frequencies. Importantly, HFO synchronization is both transiently enhanced and suppressed in separate frequency bands during a response-inhibition task. These findings show that HFO synchronization constitutes a functionally significant form of neuronal spike-timing relationships in brain activity and thus a mesoscopic indication of neuronal communication per se. High-frequency oscillations (HFOs) are common in mammalian brains and have been assumed to be strictly local. Using human intracerebral recordings, the authors find that HFOs can be phase synchronized across long distances between active cortical sites during resting and task states, which may reflect neuronal communication.

Studies have shown that chronic obstructive pulmonary disease (COPD) exacerbation events are related to future events; however, previous literature typically reports frequent vs infrequent exacerbations per patient-year and no studies have investigated increasing number of severe exacerbations in relation to COPD outcomes. To investigate the association between baseline frequency and severity of exacerbations and subsequent mortality and exacerbation risk in a COPD cohort. Clinical Practice Research Datalink (CPRD) Aurum and Hospital Episode Statistics data were used to identify patients registered at general practices in the UK, who had a diagnosis of COPD, were over the age of 40 years, were smokers or ex-smokers and had data recorded from 2004 onwards. Frequency and severity of exacerbations in the baseline year were identified as moderate exacerbations (general practice events) and severe exacerbations (hospitalised events). Patients were categorised as having: none, 1 moderate only, 2 moderate only, 3+ moderate only, 1 severe (and any moderate), 2 severe (and any moderate), and 3+ severe (and any moderate exacerbations). Poisson regression was used to investigate the association between baseline exacerbation frequency/severity and exacerbation events and mortality over follow-up. Overall, 340,515 COPD patients were included. Patients had higher rates of future exacerbations with increasing frequency and severity of baseline exacerbations compared to no baseline exacerbations. Adjusted incidence rate ratios (IRR) for patients with 1, 2, and 3+ moderate exacerbations compared to 0 exacerbations were 1.70 (95% CI 1.66-1.74), 2.31 (95% CI 2.24-2.37), and 3.52 (95% CI 3.43-3.62), respectively. Patients with increased frequency of baseline exacerbations were more likely to die from all-cause, COPD-related, and cardiovascular-related mortality in a graduated fashion. Increasing number and severity of exacerbations were associated with increasing risk of subsequent exacerbations, all-cause mortality and COPD-related mortality. Even a single moderate event increases the risk of future events, illustrating that every exacerbation counts.

•Focal lesions can lead to network effects whose neuronal mechanisms are elusive.•We contrast intracranial EEG recorded before and after surgical lesions in humans.•Full-fledged, sleep-like slow waves appear in the perilesional area.•Slow waves also percolate through long-range existing patterns of connectivity.•The intrusion of sleep-like activity may underlie the network effect of focal lesions. Focal cortical lesions are known to result in large-scale functional alterations involving distant areas; however, little is known about the electrophysiological mechanisms underlying these network effects. Here, we addressed this issue by analysing the short and long distance intracranial effects of controlled structural lesions in humans. The changes in Stereo-Electroencephalographic (SEEG) activity after Radiofrequency-Thermocoagulation (RFTC) recorded in 21 epileptic subjects were assessed with respect to baseline resting wakefulness and sleep activity. In addition, Cortico-Cortical Evoked Potentials (CCEPs) recorded before the lesion were employed to interpret these changes with respect to individual long-range connectivity patterns. We found that small structural ablations lead to the generation and large-scale propagation of sleep-like slow waves within the awake brain. These slow waves match those recorded in the same subjects during sleep, are prevalent in perilesional areas, but can percolate up to distances of 60 mm through specific long-range connections, as predicted by CCEPs. Given the known impact of slow waves on information processing and cortical plasticity, demonstrating their intrusion and percolation within the awake brain add key elements to our understanding of network dysfunction after cortical injuries.

The city of Venice and the surrounding lagoonal ecosystem are highly vulnerable to variations in relative sea level. In the past ∼150 years, this was characterized by an average rate of relative sea-level rise of about 2.5 mm/year resulting from the combined contributions of vertical land movement and sea-level rise. This literature review reassesses and synthesizes the progress achieved in quantification, understanding and prediction of the individual contributions to local relative sea level, with a focus on the most recent studies. Subsidence contributed to about half of the historical relative sea-level rise in Venice. The current best estimate of the average rate of sea-level rise during the observational period from 1872 to 2019 based on tide-gauge data after removal of subsidence effects is 1.23 ± 0.13 mm/year. A higher – but more uncertain – rate of sea-level rise is observed for more recent years. Between 1993 and 2019, an average change of about +2.76 ± 1.75 mm/year is estimated from tide-gauge data after removal of subsidence. Unfortunately, satellite altimetry does not provide reliable sea-level data within the Venice Lagoon. Local sea-level changes in Venice closely depend on sea-level variations in the Adriatic Sea, which in turn are linked to sea-level variations in the Mediterranean Sea. Water mass exchange through the Strait of Gibraltar and its drivers currently constitute a source of substantial uncertainty for estimating future deviations of the Mediterranean mean sea-level trend from the global-mean value. Regional atmospheric and oceanic processes will likely contribute significant interannual and interdecadal future variability in Venetian sea level with a magnitude comparable to that observed in the past. On the basis of regional projections of sea-level rise and an understanding of the local and regional processes affecting relative sea-level trends in Venice, the likely range of atmospherically corrected relative sea-level rise in Venice by 2100 ranges between 32 and 62 cm for the RCP2.6 scenario and between 58 and 110 cm for the RCP8.5 scenario, respectively. A plausible but unlikely high-end scenario linked to strong ice-sheet melting yields about 180 cm of relative sea-level rise in Venice by 2100. Projections of human-induced vertical land motions are currently not available, but historical evidence demonstrates that they have the potential to produce a significant contribution to the relative sea-level rise in Venice, exacerbating the hazard posed by climatically induced sea-level changes.

Decadal and bi-decadal climate responses to tropical strong volcanic eruptions (SVEs) are inspected in an ensemble simulation covering the last millennium based on the Max Planck Institute—Earth system model. An unprecedentedly large collection of pre-industrial SVEs (up to 45) producing a peak annual-average top-of-atmosphere radiative perturbation larger than −1.5 Wm −2 is investigated by composite analysis. Post-eruption oceanic and atmospheric anomalies coherently describe a fluctuation in the coupled ocean–atmosphere system with an average length of 20–25 years. The study provides a new physically consistent theoretical framework to interpret decadal Northern Hemisphere (NH) regional winter climates variability during the last millennium. The fluctuation particularly involves interactions between the Atlantic meridional overturning circulation and the North Atlantic gyre circulation closely linked to the state of the winter North Atlantic Oscillation. It is characterized by major distinctive details. Among them, the most prominent are: (a) a strong signal amplification in the Arctic region which allows for a sustained strengthened teleconnection between the North Pacific and the North Atlantic during the first post-eruption decade and which entails important implications from oceanic heat transport and from post-eruption sea ice dynamics, and (b) an anomalous surface winter warming emerging over the Scandinavian/Western Russian region around 10–12 years after a major eruption. The simulated long-term climate response to SVEs depends, to some extent, on background conditions. Consequently, ensemble simulations spanning different phases of background multidecadal and longer climate variability are necessary to constrain the range of possible post-eruption decadal evolution of NH regional winter climates.

The biosynthetic pathway of the peptidoglycan cell wall is one of the most favorable targets for antibiotic development. Lipid II, the lipid-linked PG precursor, is made in the inner leaflet of the cytoplasmic membrane and then transported by the MurJ flippase so that it can be used to build the peptidoglycan cell wall. Most bacteria have a peptidoglycan cell wall that determines their cell shape and helps them resist osmotic lysis. Peptidoglycan synthesis depends on the translocation of the lipid-linked precursor lipid II across the cytoplasmic membrane by the MurJ flippase. Structure-function analyses of MurJ from Thermosipho africanus (MurJ Ta ) and Escherichia coli (MurJ Ec ) have revealed that MurJ adopts multiple conformations and utilizes an alternating-access mechanism to flip lipid II. MurJ Ec activity relies on membrane potential, but the specific counterion has not been identified. Crystal structures of MurJ Ta revealed a chloride ion bound to the N-lobe of the flippase and a sodium ion in its C-lobe, but the role of these ions in transport is unknown. Here, we investigated the effect of various ions on the function of MurJ Ta and MurJ Ec in vivo . We found that chloride, and not sodium, ions are necessary for MurJ Ta function, but neither ion is required for MurJ Ec function. We also showed that murJ Ta alleles encoding changes at the crystallographically identified sodium-binding site still complement the loss of native murJ Ec , although they decreased protein stability and/or function. Based on our data and previous work, we propose that chloride ions are necessary for the conformational change that resets MurJ Ta after lipid II translocation and suggest that MurJ orthologs may function similarly but differ in their requirements for counterions. IMPORTANCE The biosynthetic pathway of the peptidoglycan cell wall is one of the most favorable targets for antibiotic development. Lipid II, the lipid-linked PG precursor, is made in the inner leaflet of the cytoplasmic membrane and then transported by the MurJ flippase so that it can be used to build the peptidoglycan cell wall. MurJ functions using an alternating-access mechanism thought to depend on a yet-to-be-identified counterion. This study fills a gap in our understanding of MurJ's energy-coupling mechanism by showing that chloride ions are required for MurJ in some, but not all, organisms. Based on our data and prior studies, we propose that, while the general transport mechanism of MurJ may be conserved, its specific mechanistic details may differ across bacteria, as is common in transporters. These findings are important to understand MurJ function and its development as an antibiotic target.

Tidal measurements from the Italian city of Venice, available since 1872 and constituting the longest sea-level record in the Mediterranean area, indicate that local flooding statistics have dramatically worsened during the last decades. Individual flooding episodes are associated with adverse meteorological conditions, and their increased frequency is mainly attributed to the rise of the average local Relative Sea Level (RSL). However, the role of interannual-to-multidecadal modes of average RSL variability in shaping the evolution of Venice flooding is highly significant and can cause sharp increases in the flood frequency episodes. Here, we use local tidal measurements in Venice covering 1872–2020 to deeply inspect the contribution and predictability of the different components characterizing the observed average RSL variability, including a long-term trend and four quasi-periodic modes. Our results demonstrate that the observed increase in flooding frequency is not only due to the average RSL rise but also due to a progressive widening of tidal anomalies around the average RSL, revealed by opposite trends in mean tidal maxima and minima. Moreover, interannual and decadal periodicities are not negligible in modulating the timing of annual mean RSL and flood frequency extremes. This study demonstrates that the last decades experienced an unprecedented sharp increase in sea level, which significantly affected the decadal predictability of RSL with statistical methods. Our work contributes to a deeper understanding of the sources of uncertainty in decadal sea-level variability and predictability in the Venice lagoon.

The dwarf cuttlefish, Ascarosepion bandense (formerly Sepia bandensis), is a coleoid cephalopod like octopus and squid, and an emerging model organism for scientific research. Dwarf cuttlefish can change the color, pattern, and texture of their skin in milliseconds to camouflage with their surroundings and communicate with conspecifics. Their skin displays are directly controlled by the brain. Thus, observing the skin provides a window into neural processes in the brain. Despite the popularity of dwarf cuttlefish in public aquariums and laboratory research, little is known about their natural habitat and behaviors in the wild. We conducted a field study in the Batangas region of the Philippines using underwater photography, videography, and environmental measurements. We generated an image bank of the natural features in the environment, characterized the change in color profile at different depths, and surveyed the population of dwarf cuttlefish in coral reefs and silty barren environments (muck), at a range of depths, during both the day and night. All dwarf cuttlefish sightings occurred after sunset, at depths of 6–12 m, and on coral reefs. The animals exhibited multiple camouflage strategies, including complex skin patterning and adhesion of sand to their skin, as well as social skin displays in the presence of fish. Notably, despite apparent colorblindness, dwarf cuttlefish produced skin patterns with vibrant colors not recorded in laboratory settings, with some instances of apparent color matching to their surroundings. These findings challenge our understanding of cephalopod visual perception and camouflage and highlight the importance of studying animal behavior in its natural context. Our image bank and behavioral data are freely available on the interactive web tool, Cuttlebase (www.cuttlebase.org). Gibbons et al. performed a field study to characterize the dwarf cuttlefish—a popular aquarium and research cephalopod—in its natural habitat. They observed dynamic camouflage, social behaviors, and use of an expanded color palette in wild animals compared to laboratory animals. All of the wild data is hosted on a web tool, cuttlebase.org

We assess the responses of North Atlantic, North Pacific, and tropical Indian Ocean Sea Surface Temperatures (SSTs) to natural forcing and their linkage to simulated global surface temperature (GST) variability in the MPI-Earth System Model simulation ensemble for the last millennium. In the simulations, North Atlantic and tropical Indian Ocean SSTs show a strong sensitivity to external forcing and a strong connection to GST. The leading mode of extra-tropical North Pacific SSTs is, on the other hand, rather resilient to natural external perturbations. Strong tropical volcanic eruptions and, to a lesser extent, variability in solar activity emerge as potentially relevant sources for multidecadal SST modes’ phase modulations, possibly through induced changes in the atmospheric teleconnection between North Atlantic and North Pacific that can persist over decadal and multidecadal timescales. Linkages among low-frequency regional modes of SST variability, and among them and GST, can remarkably vary over the integration time. No coherent or constant phasing is found between North Pacific and North Atlantic SST modes over time and among the ensemble members. Based on our assessments of how multidecadal transitions in simulated North Atlantic SSTs compare to reconstructions and of how they contribute characterizing simulated multidecadal regional climate anomalies, past regional climate multidecadal fluctuations seem to be reproducible as simulated ensemble-mean responses only for temporal intervals dominated by major external forcings.

Sea‐level rise is one of the most critical consequences of global warming, with potentially vast impacts on coastal environments and societies. Sea‐level changes are spatially and temporally heterogeneous on multiannual‐to‐multidecadal timescales. Here, we demonstrate that the observed rate of winter sea‐level rise in the Italian city of Venice contains significant multidecadal fluctuations, including interdecadal periods of near‐zero trend. Previous literature established a connection between the local sea‐level trend in Venice and over the broad subpolar and eastern North Atlantic. We demonstrate that for multidecadal variations in sea‐level trend such connection holds only since the mid‐20th Century. Such multidecadal sea‐level fluctuations relate to North Atlantic sea‐surface temperature changes described by the Atlantic multidecadal variability, or AMV. The link is explained by combined effect of AMV‐linked steric variations in the North Atlantic propagating in the Mediterranean Sea, and large‐scale atmospheric circulation anomalies over the North Atlantic with a local effect on sea level in Venice. We discuss the implications of such variability for near‐term predictability of winter sea‐level changes in Venice. Combining available sea‐level projections for Venice with a scenario of imminent AMV cooling yields a slowdown in the rate of sea‐level rise in Venice, with the possibility of mean values remaining even roughly constant in the next two decades as AMV effects contrast the expected long‐term sea‐level rise. Acknowledging, understanding, and communicating this multidecadal variability in local sea‐level rise is crucial for management and protection of this world‐class historical site. Plain Language Summary Environmental and socioeconomic impacts of sea‐level rise are one of the major concerns of global warming. Here, we consider the case of the Italian city of Venice, one of the iconic locations for the potentially dramatic effects of sea‐level rise. We show that the sea‐level evolution in Venice during the past ∼150 years contains strong multidecadal fluctuations, so that periods of more than two decades when there is little or no trend occurred even in the recent past. We link these fluctuations with sea‐level and climatic variations in the North Atlantic. In particular, we focus on the phenomenon known as Atlantic multidecadal variability, or AMV, which describes the alternation over multidecadal periods of warm and cold phases of the North Atlantic surface. Our results indicate that warm AMV phases are linked to faster sea‐level rise in Venice and vice versa. Accordingly, we build sea‐level rise scenarios for Venice until 2035 by considering an imminent AMV cooling as suggested by recent studies. The scenarios yield a temporary slowdown of sea‐level rise as the AMV contrasts the effects of global warming. This sea‐level variability can strongly impact on the management of protective measures against flooding currently operative in Venice. Key Points The historical rate of sea‐level rise in Venice contains large multidecadal fluctuations and interdecadal periods of near‐zero trend Multidecadal sea‐level trend variations in Venice follow those in the subpolar North Atlantic since the mid‐20th Century Atlantic multidecadal variability paves the way for the exploration of decadal predictability of sea‐level rise in Venice