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Multigene analysis reveals that Pseudopalaemon Sollaud, 1911 is a junior synonym of the widespread genus Macrobrachium Spence Bate, 1868 (Decapoda: Caridea: Palaemonidae)
No full textPseudopalaemon Sollaud, 1911 is a species-poor genus of freshwater palaemonid shrimps endemic to South America, especially the Amazon Basin. Morphologically, the differentiation between Pseudopalaemon and Macrobrachium Spence Bate, 1868 is based solely on the presence or absence of a mandibular palp. Previous phylogenetic studies, based on inclusion of a single species, have nevertheless questioned the reliability of this character as the sole taxonomic criterion for differentiating these two genera. Herein we provide genetic data for three out of a total of seven species, currently included in the genus, including its type species. The results clearly demonstrate that Pseudopalaemon is fully nested within Macrobrachium and furthermore does not constitute a monophyletic group. Therefore, Pseudopalaemon is herein considered to be a junior synonym of Macrobrachium
Libertas: privacy-preserving collaborative computation for decentralised personal data stores
Get PDFData and their processing have become an indispensable aspect for our society. Insights drawn from collective data make invaluable contribution to scientific, societal and communal research and business. However, there are increasing worries about privacy issues and data misuse, prompting the emergence of decentralised personal data stores (PDS) like Solid. However, existing PDS frameworks face challenges in ensuring data privacy when performing collective computation to combine data from multiple users. At a glance, Secure Multi-Party Computation (MPC) offers input secrecy protection while performing collective computation without relying on any single party. However, issues emerge when directly applying MPC in the context of PDS, particularly due to key factors like autonomy and decentralisation. In this work, we discuss the essence of this issue, identify the potential solution, and introduce a modular system architecture, Libertas, to integrate MPC with PDS like Solid, without requiring protocol-level changes. We introduce the paradigm shift from an ‘omniscient’ view to individual-based, user-centric view of trust and security, and discuss the threat model of Libertas. Two realistic use cases for collaborative data processing are used for evaluation, both for technical feasibility and empirical benchmark, highlighting its effectiveness in empowering gig workers and generating differentially private synthetic data. The results of our experiments underscore Libertas’ linear scalability and provide valuable insights into compute optimisations, thereby advancing the state-of-the-art in privacy-preserving data processing practices. By offering practical solutions for maintaining both individual autonomy and privacy in collaborative data processing environments, Libertas contributes significantly to the ongoing discourse on privacy protection in data-driven decision-making contexts
Defocus correction and noise reduction using a hybrid ptychography and Centre‐of‐Mass algorithm
Get PDFIntegrated Centre‐of‐Mass (iCOM) is a widely used phase‐contrast imaging method based on Centre‐of‐Mass (COM), which makes use of a 4D Scanning Transmission Electron Microscopy (STEM) dataset using an in‐focus probe. In this paper, we introduce a novel approach that combines Single‐Side Band (SSB) ptychography with COM and iCOM, termed Side Band masked Centre‐of‐Mass (SBm‐COM) and integrated Centre‐of‐Mass (SBm‐iCOM) which is applicable to weak‐phase objects. This method compensates for residual aberrations in 4DSTEM datasets while also reducing the noise contribution up to the 2 α resolution limit. The aberration compensation and noise filtering features make the SBm‐(i)COM suitable for samples that are difficult to focus or those that require minimal electron fluence. SBm‐iCOM transfers the same information as SSB ptychography but results in an intrinsic transfer function that enhances low‐frequency information
Fragment‐Based Drug Discovery of Novel High‐affinity, Selective, and Anti‐inflammatory Inhibitors of the Keap1‐Nrf2 Protein‐Protein Interaction
Get PDFActivating the cytoprotective response of nuclear factor erythroid 2‐related factor 2 (Nrf2) can reduce oxidative stress and inflammation. A promising strategy is to inhibit the protein‐protein interaction between Kelch‐like ECH‐associated protein 1 (Keap1) and Nrf2 using noncovalent compounds that target the Keap1 Kelch domain. These compounds may be more specific than covalent Keap1‐reacting Nrf2 activators. However, the development of drug‐like noncovalent Keap1‐Nrf2 inhibitors faces challenges due to the size and polarity of the Kelch binding pocket. Here, we present a new series of noncovalent Keap1‐Nrf2 inhibitors developed from a weak fragment hit identified by crystallographic screening. A two‐step growing strategy and optimization guided by several X‐ray cocrystal structures led to compounds with low nanomolar affinities and complete selectivity for Keap1 in a panel of homologous Kelch domains. In cells, compounds 24 and 28 potently activated the expression of Nrf2‐controlled genes and showed anti‐inflammatory effects by downregulating NLRP3 inflammasome and STING signalling activation. RNA sequencing revealed activation of cytoprotective pathways and a different profile from typical covalent Nrf2 activators. This work highlights the potential of fragment‐based drug discovery for challenging targets like Keap1 and introduces novel Keap1‐Nrf2 inhibitors as chemical probes and drug leads
Echocardiographic risk stratification in light chain and transthyretin amyloidosis: a meta-analysis
Get PDFAims: The role of echocardiography in amyloidosis prognostication remains undefined in international guidelines. This meta-analysis aims to evaluate associations between echocardiography-derived measurements and clinical outcomes in light chain (AL) and transthyretin (ATTR) amyloidosis. Methods and results: MEDLINE, Embase, Cochrane Library, and Google Scholar were systematically searched through July 2024 for studies reporting associations between echocardiographic variables [left ventricular global longitudinal strain (LV-GLS), LV ejection fraction (LVEF), tricuspid annular plane systolic excursion (TAPSE), interventricular septum diameter (IVSd), LV mass index (LVMi) and E/e′ ratios] and adverse events in AL or ATTR amyloidosis. Prespecified demographic items and clinical outcomes were extracted by two blinded, independent reviewers. The prespecified primary outcome was all-cause mortality. Random-effect models were applied to pool hazard ratios (HR). 94 studies comprising 16158 patients (n = 4788 AL, n = 8241 ATTR, n = 3129 mixed aetiologies) were included. Median follow-up was 22.3 (IQR, 16.9–31.4) months. Higher all-cause mortality risk (HR, 1.10: 95%CI, 1.08–1.12; P < 0.001) was observed per 1% LV-GLS decrement, consistent across AL and ATTR subgroups. Lower all-cause mortality risk was seen with increasing LVEF (per 1%) and TAPSE (per 1 mm) in the overall population (HRLVEF, 0.98; 95%CI, 0.98–0.98; P < 0.001; and HRTAPSE, 0.94; 95%CI, 0.93–0.95; P < 0.001) and in AL and ATTR subgroups. Higher E/e′ ratios (per 1 unit) were associated with all-cause mortality (HR, 1.02; 95%CI, 1.02–1.03; P < 0.001), consistent across AL and ATTR subtypes. No reliable associations between structural parameters (IVSd, LVMi) and clinical outcomes were found. Conclusion: Echocardiographic measures of biventricular deformation, systolic and diastolic function, were consistently associated with mortality in amyloidosis, while structural parameters were not. Echocardiography may have an important role in the initial risk stratification of cardiac amyloidosis
A Photo‐Patternable Solid‐State Electrolyte for High‐Performance, Miniaturized, and Implantable Organic Electrochemical Transistor‐Based Circuits
Get PDFOrganic electrochemical transistors (OECTs) are crucial for next‐generation (bio‐)electronic devices but are often constrained by the use of aqueous electrolytes, which introduce crosstalk, hinder miniaturization, and limit circuit integration. Here, a photo‐patternable solid‐state electrolyte based on ‐carrageenan (‐CGN) and poly(ethylene glycol) diacrylate (PEGDA) is presented, enabling high‐performance OECTs and complementary circuits. The ‐CGN electrolyte exhibits high ionic conductivity (>10 mS cm−1), comparable to a 0.1 m NaCl aqueous electrolyte, while supporting precise patterning down to 15 µm, fast transient response times, minimal hysteresis, and excellent stability in both p‐ and n‐type OECTs. Compact solid‐state NAND/NOR gates (500 × 800 µm2), 4‐input NAND gates (1600 × 800 µm2, 8 OECTs), and half‐adders (2 × 1 mm2, 18 OECTs) are demonstrated, all exhibiting correct logic functions and low‐voltage operation. To highlight its potential for implantable bioelectronics, solid‐state spiking circuits, monolithically integrated with flexible cuff electrodes, are developed for vagus nerve stimulation in mice. These findings establish ‐CGN‐based solid‐state electrolytes as a promising platform for scalable, implantable circuits, paving the way for next‐generation bioelectronic devices
Yuri’s Story: Memory, Relational Healing, and the Reflexive Logics of Art Therapy in Japanese Clinical Psychology
Get PDFMental health care is a vibrant part of child protective services in Japan, and the adoption and utilization of psychotherapeutic techniques from abroad mark a complex site of cross-cultural exchanges. This paper explores how art therapy has been brought into Japan’s protection system and its implications for professional practice. Focusing on clinical psychologist Yuri and her narratives on learning art therapy, this paper utilizes an interpretive and phenomenological framework to illustrate the importance of embodied experience in delivering care and how practitioners may reform their perspectives on care by reframing their own traumatic memories. Yuri’s art therapy offers a culturally contextualized view of the self as social, care purpose, and resilience
Predicting short-term risk of colorectal cancer using primary care records, genetics and lifestyle factors
Get PDFThe evolving global landscape of nuclear security
No full textThis roundtable examines sources of change in the rapidly evolving global nuclear order. Quantitative expansion combines with qualitative doctrinal changes to challenge traditional deterrence frameworks. Emerging security arrangements such as AUKUS, the Washington Declaration, and expanded NATO–Indo-Pacific ties illustrate evolving alliance strategies, while adversarial cooperation among Russia, China, and North Korea heightens risks of coordinated nuclear coercion. Across democratic and authoritarian systems alike, domestic politics increasingly influence nuclear decision-making, shaping perceptions of credibility, creating proliferation pressures, and dampening arms control prospects. Essays in this collection analyze six regional loci—Europe, Latin America, the Middle East, South Asia, China, and the Korean Peninsula—highlighting two themes: the centrality of domestic political drivers and the cascading effects of nuclear dynamics across interconnected states and regions. Together, this analysis offers a two-level framework for understanding and addressing the complex challenges confronting today’s nuclear order
Hypotheses in light detection by vertebrate ancient opsin in the bird brain
Get PDFExtra‐retinal photoreception is common across fish and avian species. In birds, the hypothalamus contains non‐visual photoreceptors that detect light and regulate multiple endocrine systems. To date, light‐dependent control of seasonal reproduction is one of the most well‐studied systems that require deep brain photoreception. However, the precise photoreceptor(s) that detect light and the neuroendocrine connection between opsin‐expressing cells and the gonadotropin‐releasing hormone‐1 (GnRH1) system remain poorly defined. In the past couple of decades, two opsin molecules have been proposed to link light detection with seasonal reproduction in birds: neuropsin (Opn5) and vertebrate ancient opsin (VA opsin). Only VA opsin is expressed in GnRH1 cells and has an absorption spectrum that matches the action spectrum of the avian photoperiodic reproductive response. This perspective describes how the annual change in daylength, referred to as photoperiod, regulates the neuroendocrine control of seasonal reproduction. The opsin genes are then outlined, and the cellular phototransduction cascade is described, highlighting the common feature of hyperpolarization in response to light stimulation. We then discuss the latest evidence using short‐hairpin RNA to temporarily knock down VA opsin and Opn5 on transcripts involved in the neuroendocrine regulation of reproduction. Based on emerging data, we outline three theoretical scenarios in which VA opsin might regulate GnRH1 synthesis and release in birds. The models proposed provide a series of testable hypotheses that can be used to improve our understanding of avian light detection by VA opsin or other opsin‐expressing cells in the brain