Browse Articles

Trust in the sea-bed mining authority is fragile — here’s how to change that

Evidence that freshwater mussels attempt temporal partitioning of their host fishes

An analysis of light that reaches the eye surface in an outdoor environment

Make cities more walkable, in the real world and in virtual reality

RAIM: three-stage stackelberg game for hierarchical federated learning with reputation-aware incentive mechanism

Abstract Hierarchical Federated Learning (HFL) significantly enhances communication efficiency and device participation, while improving personalized learning outcomes. In this framework, incentive mechanisms are crucial as they ensure that devices actively participate and make genuine contributions. However, existing incentive mechanisms struggle to effectively address the issue of unreliable devices, which may negatively impact model training due to malicious behavior or faults, leading to low-quality updates or even failure of the global model. Additionally, participants’ strategic behaviors and device heterogeneity can further diminish the effectiveness of these mechanisms. To tackle these challenges, this paper proposes a Reputation-Aware Incentive Mechanism (RAIM) aimed at optimizing node cooperation within HFL and enhancing overall system performance. Specifically, we first evaluate the reputation value of end devices based on their training quality and historical records, which can identify and defend against malicious data attacks. Participants’ reputations are maintained through a consortium blockchain, thereby ensuring transparency and fairness. Next, we model the interaction of HFL as a three-stage Stackelberg game to address hierarchical decision-making processes, and also prove that there is a unique Stackelberg equilibrium, derived through cautiously proposed algorithms. Since the existing equilibrium may not be optimal, we further design optimal server selection algorithm to motivate high-reputation and low-cost devices to participate in training, while maximizing both system performance and social utility. Finally, extensive experiments using both synthetic and real datasets show that our RAIM outperforms state-of-the-art baseline methods.

Technology leaders should ‘pay back’ society to support the common good

Positive perceptions of brown bears linked to long-term cohabitation in the Iberian Peninsula

Abstract The brown bear (Ursus arctos) populations are expanding in the Iberian Peninsula, particularly in the Cantabrian Mountains. This ongoing expansion and the species’ return to Portugal could be jeopardized by a lack of sustainable coexistence strategies. To shed light on how experiences with bears have shaped human perceptions and attitudes toward this species, we distributed online questionnaires (n = 441) across Portugal and Spain. In addition, we evaluated differences in attitudes and perceptions among regions with varying levels of exposure to bears: those with (BAS) or without (NBAS) bear presence in Spain and those with (BAP) or without (NBAP) the potential to sustain bears in Portugal. Despite observing overall positive attitudes toward bears, Spanish respondents showed stronger attachment and receptiveness toward the species. Respondents from BAS, having more interactions with wild bears, were also more favourable toward sharing territory with them. Conversely, Portuguese respondents showed more neutral attitudes toward bear presence, as well as higher perception of risk and lower perception of benefit than previously reported. Our findings highlight the importance of understanding the social landscape in bears’ expansion range. As human-bear interactions increase, this knowledge is key to adopt proactive and targeted socio-ecological measures to address local community’s concerns.

Molecular mechanism of ultrafast transport by plasma membrane Ca2+-ATPases

Abstract Tight control of intracellular Ca2+ levels is fundamental as they are used to control numerous signal transduction pathways1. Plasma membrane Ca2+-ATPases (PMCAs) have a crucial role in this process by extruding Ca2+ against a steep concentration gradient from the cytosol to the extracellular space2. Although new details of PMCA biology are constantly being uncovered, the structural basis of the most distinguishing features of these pumps, namely, transport rates in the kilohertz range and regulation of activity by the plasma membrane phospholipid PtdIns(4,5)P2, has so far remained elusive. Here we present the structures of mouse PMCA2 in the presence and absence of its accessory subunit neuroplastin in eight different stages of its transport cycle. Combined with whole-cell recordings that accurately track PMCA-mediated Ca2+ extrusion in intact cells, these structures enable us to establish the first comprehensive transport model for a PMCA, reveal the role of disease-causing mutations and uncover the structural underpinnings of regulatory PMCA–phospholipid interaction. The transport cycle-dependent dynamics of PtdIns(4,5)P2 are fundamental for its role as a ‘latch’ promoting the fast release of Ca2+ and opening a passageway for counter-ions. These actions are required for maintaining the ultra-fast transport cycle. Moreover, we identify the PtdIns(4,5)P2-binding site as an unanticipated target for drug-mediated manipulation of intracellular Ca2+ levels. Our work provides detailed structural insights into the uniquely fast operation of native PMCA-type Ca2+ pumps and its control by membrane lipids and drugs.

Accurate prediction of substitution rates at protein sites with a mutation-selection model

Abstract The pattern of substitutions at sites in proteins provides invaluable information about their biophysical and functional importance and what selection pressures are acting at individual sites. Amino acid site rates are typically estimated using phenomenological models where sequence variability is described by rate factors that scale the overall substitution rate in a protein to sites. In this study, we demonstrate that site rates can be calculated accurately from amino acid sequences from a multiple sequence alignment using a mutation-selection model in combination with a simple nucleotide substitution model. The method performs better than the standard phylogenetic approach on sequences generated by structure-based evolutionary dynamics simulations, robustly estimates rates for shallow multiple sequence alignments, and can be rapidly calculated also on larger sequence alignments. On natural sequences, site rates from the mutation-selection model are strongly correlated with rates calculated with the empirical Bayes methods. The model complements other work in providing a link between amino acid substitution rates and equilibrium frequency distributions at sites in proteins. We show how an ensemble of equilibrium frequency vectors can be used to represent the rate variation encoded in empirical amino acid substitution matrices. This study demonstrates that a rapid and simple method can be developed from the mutation-selection model to predict substitution rates from amino acid data, complementing the standard phylogenetic approach.

Curcumin’s dual effect on pyroptosis and autophagy in metabolic- associated fatty liver disease: a potential therapeutic strategy

How money, politics and technology are redefining the PhD experience in 2025

Numerical investigation to improve thermal performance of a water-cooling PVT collector with novel cooling subchannels

Power and profit drive what we eat: here’s why the food system needs a revolution

A novel bacterial protein family that catalyses nitrous oxide reduction

A missing enzyme-rescue metabolite as cause of a rare skeletal dysplasia

Abstract Living cells depend on an intricate network of chemical reactions catalysed by enzymes, which sometimes make mistakes that lead to their inactivation. Here we report a metabolite-based mechanism for preserving enzyme function in an unfavourable environment. We found that the enzyme TGDS produces UDP-4-keto-6-deoxyglucose, a mimic of the reaction intermediate of the enzyme UXS1, which regenerates the essential cofactor NAD+ within the catalytic pocket of UXS1 by completing its catalytic cycle. Thus, the production of an ‘enzyme-rescue metabolite’ by TGDS represents a mechanism for maintaining the activity of an enzyme in a subcellular compartment where NAD+ is scarce. Using a combination of in vitro and in vivo studies, we demonstrate that the inability to produce sufficient amounts of this enzyme-rescue metabolite leads to the inactivation of UXS1, impairing the synthesis of specific glycans that are crucial for skeletal development. This provides an explanation for the development of the hereditary skeletal disorder Catel–Manzke syndrome in individuals with TGDS deficiency. Defects in similar protective layers might contribute to metabolic changes in other diseases that cannot be explained with common concepts in metabolic biochemistry.

Public trust in science has declined since COVID — virologists need to unite around safety standards

Little urchins, mischievous molluscs: my life as a sea champion

Common air pollutant has a secret weapon: bacterial toxins

Remodelling of corticostriatal axonal boutons during motor learning

Abstract Motor skill learning induces long-lasting synaptic plasticity at dendritic spines1–4 and at the outputs of motor cortical neurons to the striatum5,6. However, little is known about corticostriatal axon activity and structural plasticity during learning in the adult brain. Here, using longitudinal in vivo two-photon imaging, we tracked thousands of corticostriatal axonal boutons in the dorsolateral striatum of awake mice. We found that learning a new motor skill dynamically regulated these boutons. The activities of motor corticostriatal axonal boutons exhibited selectivity for rewarded movements (RM) and unrewarded movements (UM). Notably, boutons on the same axonal branches showed diverse responses during behaviour. Motor learning significantly increased the proportion of RM boutons and reduced the heterogeneity of bouton activities. Moreover, motor learning induced profound structural dynamism in boutons. By combining structural and functional imaging, we saw that newly formed axonal boutons were more likely to exhibit selectivity for RM and were stabilized during motor learning, whereas UM boutons were selectively eliminated. These findings reveal a novel form of plasticity in corticostriatal axons and show that motor learning drives dynamic bouton reorganization to support motor skill acquisition and execution.

Huntington’s disease treated for first time using gene therapy