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The cullin–RING ubiquitin E3 ligase (CRL) family comprises over 200 members in humans. The COP9 signalosome complex (CSN) regulates CRLs by removing their ubiquitin-like activator NEDD8. The CUL4A–RBX1–DDB1–DDB2 complex (CRL4A DDB2 ) monitors the genome for ultraviolet-light-induced DNA damage. CRL4A DBB2 is inactive in the absence of damaged DNA and requires CSN to regulate the repair process. The structural basis of CSN binding to CRL4A DDB2 and the principles of CSN activation are poorly understood. Here we present cryo-electron microscopy structures for CSN in complex with neddylated CRL4A ligases to 6.4 Å resolution. The CSN conformers defined by cryo-electron microscopy and a novel apo-CSN crystal structure indicate an induced-fit mechanism that drives CSN activation by neddylated CRLs. We find that CSN and a substrate cannot bind simultaneously to CRL4A, favouring a deneddylated, inactive state for substrate-free CRL4 complexes. These architectural and regulatory principles appear conserved across CRL families, allowing global regulation by CSN. Much of the intracellular protein degradation in eukaryotes is controlled by cullin–RING ubiquitin ligases (CRLs), a vast class of enzymes which are regulated by the COP9 signalosome (CSN); structural characterization of CSN–N8CRL4A complexes by cryo-electron microscopy reveals an induced-fit mechanism of CSN activation triggered only by catalytically activated CRLs without bound substrate, explaining how CSN acts as a global regulator of CRLs. Control of intracellular protein degradation Much of the intracellular protein degradation in eukaryotes is controlled by cullin–RING ubiquitin ligases (CRLs). The structure of these enzymes and their substrates vary greatly, yet all are regulated by a single complex — the COP9 signalosome (CSN). What enables CSN to be a master regulator of diverse CRLs? Nicolas Thomä and colleagues present biochemical data and cryo-electron microscopy of CSN–CRL4 complexes revealing an induced-fit mechanism that activates CSN only in the presence of a catalytically activated CRL not bound to a substrate. The authors identify both unique and less-specific CSN–CRL contacts.

In this Article, in Fig. 1a, the 5' and 3' labels were reversed in the DNA sequence, and Fig. 4 was missing panel labels a-e. These errors have been corrected online.In this Article, in Fig. 1a, the 5' and 3' labels were reversed in the DNA sequence, and Fig. 4 was missing panel labels a-e. These errors have been corrected online.

Access to DNA packaged in nucleosomes is critical for gene regulation, DNA replication and DNA repair. In humans, the UV-damaged DNA-binding protein (UV-DDB) complex detects UV-light-induced pyrimidine dimers throughout the genome; however, it remains unknown how these lesions are recognized in chromatin, in which nucleosomes restrict access to DNA. Here we report cryo-electron microscopy structures of UV-DDB bound to nucleosomes bearing a 6–4 pyrimidine–pyrimidone dimer or a DNA-damage mimic in various positions. We find that UV-DDB binds UV-damaged nucleosomes at lesions located in the solvent-facing minor groove without affecting the overall nucleosome architecture. In the case of buried lesions that face the histone core, UV-DDB changes the predominant translational register of the nucleosome and selectively binds the lesion in an accessible, exposed position. Our findings explain how UV-DDB detects occluded lesions in strongly positioned nucleosomes, and identify slide-assisted site exposure as a mechanism by which high-affinity DNA-binding proteins can access otherwise occluded sites in nucleosomal DNA. Cryo-electron microscopy structures reveal that the DNA-repair factor UV-DDB exposes inaccessible nucleosome lesions for binding by inducing a translational shift in the nucleosome position.

The cullin-RING ubiquitin E3 ligase (CRL) family comprises over 200 members in humans. The COP9 signalosome complex (CSN) regulates CRLs by removing their ubiquitin-like activator NEDD8. The CUL4A-RBX1-DDB1-DDB2 complex (CRL4A.sup.DDB2) monitors the genome for ultraviolet-light-induced DNA damage. CRL4A.sup.DBB2 is inactive in the absence of damaged DNA and requires CSN to regulate the repair process. The structural basis of CSN binding to CRL4A.sup.DDB2 and the principles of CSN activation are poorly understood. Here we present cryo-electron microscopy structures for CSN in complex with neddylated CRL4A ligases to 6.4 Å resolution. The CSN conformers defined by cryo-electron microscopy and a novel apo-CSN crystal structure indicate an induced-fit mechanism that drives CSN activation by neddylated CRLs. We find that CSN and a substrate cannot bind simultaneously to CRL4A, favouring a deneddylated, inactive state for substrate-free CRL4 complexes. These architectural and regulatory principles appear conserved across CRL families, allowing global regulation by CSN.

Autonomous navigation in ice-covered waters poses significant challenges due to the frequent lack of viable collision-free trajectories. When complete obstacle avoidance is infeasible, it becomes imperative for the navigation strategy to minimize collisions. Additionally, the dynamic nature of ice, which moves in response to ship maneuvers, complicates the path planning process. To address these challenges, we propose a novel deep learning model to estimate the coarse dynamics of ice movements triggered by ship actions through occupancy estimation. To ensure real-time applicability, we propose a novel approach that caches intermediate prediction results and seamlessly integrates the predictive model into a graph search planner. We evaluate the proposed planner both in simulation and in a physical testbed against existing approaches and show that our planner significantly reduces collisions with ice when compared to the state-of-the-art. Codes and demos of this work are available at https://github.com/IvanIZ/predictive-asv-planner.

The-growing influence of urbanisation on green areas can greatly benefit from passive acoustic monitoring (PAM) across spatiotemporal continua to provide biodiversity estimation and useful information for conservation planning and development decisions. The capability of eco-acoustic indices to capture different sound features has been harnessed to identify areas within the Parco Nord of Milan, Italy, characterised by different degrees of anthropic disturbance and biophonic activity. For this purpose, we used a network of very low-cost sensors distributed over an area of approximately 20 hectares to highlight areas with different acoustic properties. The audio files analysed in this study were recorded at 16 sites on four sessions during the period 25–29 May (2015), from 06:30 a.m. to 10:00 a.m. Seven eco-acoustic indices, namely Acoustic Complexity Index (ACI), Acoustic Diversity Index (ADI), Acoustic Evenness Index (AEI), Bio-Acoustic Index (BI), Acoustic Entropy Index (H), Normalized Difference Soundscape Index (NSDI), and Dynamic Spectral Centroid (DSC) were computed at 1 s integration time and the resulting time series were described by seven statistical descriptors. A dimensionality reduction of the indices carrying similar sound information was obtained by performing principal component analysis (PCA). Over the retained dimensions, describing a large (∼80%) variance of the original variables, a cluster analysis allowed discriminating among sites characterized by different combination of eco-acoustic indices (dimensions). The results show that the obtained groups are well correlated with the results of an aural survey aimed at determining the sound components at the sixteen sites (biophonies, technophonies, and geophonies). This outcome highlights the capability of this analysis of discriminating sites with different environmental sounds, thus allowing to create a map of the acoustic environment over an extended area.

The authors of this study found that single-nucleotide polymorphisms in long pentraxin 3 (PTX3) were associated with the development of invasive aspergillosis after hematopoietic stem-cell transplantation. Long pentraxin 3 (PTX3) is a soluble pattern-recognition receptor produced by phagocytes and nonimmune cells at sites of inflammation or injury. In addition to its major role in female fertility and vascular biology, 1 PTX3 has a nonredundant role in modulating various effector pathways involved in immune resistance to Aspergillus fumigatus, including activating innate immune cells 2 and driving protective adaptive immunity. 3 PTX3 forms complexes on the conidial surface of the fungus and acts as an opsonin, enhancing recognition and phagocytosis of conidia through mechanisms that depend on Fcγ receptor, CD11b, and complement. 4 The interaction of PTX3 with the yeast phase of . . .

Eco-acoustic indices allow us to rapidly evaluate habitats and ecosystems and derive information about anthropophonic impacts. However, it is proven that indices’ values and trends are not comparable between studies. These incongruences may be caused by the availability on the market of recorders with different characteristics and costs. Thus, there is a need to reduce these biases and incongruences to ensure an accurate analysis and comparison between soundscape ecology studies and habitat assessments. In this study, we propose and validate an audio recording equalization protocol to reduce eco-acoustic indices’ biases, by testing three soundscape recorder models: Song Meter Micro, Soundscape Explorer Terrestrial and Audiomoth. The equalization process aligns the signal amplitude and frequency response of the soundscape recorders to those of a type 1 level meter. The adjustment was made in MATLAB R2023a using a filter curve generated comparing a reference signal (white noise); the measurements were performed in an anechoic chamber using 11 audio sensors and a type 1 sound level meter (able to produce a .WAV file). The statistical validation of the procedure was performed on recordings obtained in an urban and Regional Park (Italy) assessing a significant reduction in indices’ biases on the Song Meter Micro and Audiomoth.

Aim Species–area relationships (SARs) are fundamental scaling laws in ecology although their shape is still disputed. At larger areas, power laws best represent SARs. Yet, it remains unclear whether SARs follow other shapes at finer spatial grains in continuous vegetation. We asked which function describes SARs best at small grains and explored how sampling methodology or the environment influence SAR shape. Location Palaearctic grasslands and other non‐forested habitats. Taxa Vascular plants, bryophytes and lichens. Methods We used the GrassPlot database, containing standardized vegetation‐plot data from vascular plants, bryophytes and lichens spanning a wide range of grassland types throughout the Palaearctic and including 2,057 nested‐plot series with at least seven grain sizes ranging from 1 cm2 to 1,024 m2. Using nonlinear regression, we assessed the appropriateness of different SAR functions (power, power quadratic, power breakpoint, logarithmic, Michaelis–Menten). Based on AICc, we tested whether the ranking of functions differed among taxonomic groups, methodological settings, biomes or vegetation types. Results The power function was the most suitable function across the studied taxonomic groups. The superiority of this function increased from lichens to bryophytes to vascular plants to all three taxonomic groups together. The sampling method was highly influential as rooted presence sampling decreased the performance of the power function. By contrast, biome and vegetation type had practically no influence on the superiority of the power law. Main conclusions We conclude that SARs of sessile organisms at smaller spatial grains are best approximated by a power function. This coincides with several other comprehensive studies of SARs at different grain sizes and for different taxa, thus supporting the general appropriateness of the power function for modelling species diversity over a wide range of grain sizes. The poor performance of the Michaelis–Menten function demonstrates that richness within plant communities generally does not approach any saturation, thus calling into question the concept of minimal area.

Parkinson disease (PD) is a progressive neurodegenerative disorder characterized by motor symptoms. Recently, dance has started to be considered an effective intervention for people with PD. Several findings in the literature emphasize the necessity for deeper exploration into the synergistic impacts of dance therapy and exergaming for PD management. Moreover, socially engaging robotic platforms equipped with advanced interaction and perception features offer potential for monitoring patients' posture and enhancing workout routines with tailored cues. This paper presents the results of the Social Robotics for Active and Healthy Ageing (SI-Robotics) project, aimed at designing an innovative rehabilitation program targeted at seniors affected by (early-stage) PD. This study therefore aims to assess the usefulness of a dance-based rehabilitation program enriched by artificial intelligence-based exergames and contextual robotic assistance in improving motor function, balance, gait, and quality of life in patients with PD. The acceptability of the system is also investigated. The study is designed as a technical feasibility pilot to test the SI-Robotics system. For this study, 20 patients with PD were recruited. A total of 16 Irish dance-based rehabilitation sessions of 50 minutes were conducted (2 sessions per week, for 8 wks), involving 2 patients at a time. The designed rehabilitation session involves three main actors: (1) a therapist, (2) a patient, and (3) a socially interacting robot. To stimulate engagement, sessions were organized in the shape of exergames where an avatar shows patients the movements they should perform to correctly carry out a dance-based rehabilitation exercise. Statistical analysis reveals a significant difference on the Performance-Oriented Mobility Assessment scale, both on balance and gait aspects, together with improvements in Short Physical Performance Battery, Unified Parkinson Disease Rating Scale-III, and Timed Up and Go test, underlying the usefulness of the rehabilitation intervention on the motor symptoms of PD. The analysis of the Unified Theory of Acceptance and Use of Technology subscales provided valuable insights into users' perceptions and interactions with the system. This research underscores the promise of merging dance therapy with interactive exergaming on a robotic platform as an innovative strategy to enhance motor function, balance, gait, and overall quality of life for patients grappling with PD.