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Biomimetic total synthesis of ten Securinega alkaloids
Get PDFThe Securinega alkaloids are a diverse family of polycyclic alkaloids with broad biological importance. In this study, a formal [4 + 2] cycloaddition strategy has been used to complete the biomimetic total synthesis of six Securinega alkaloids, notably using biosynthetically plausible scaffold-forming steps and aqueous reaction conditions. A further four alkaloids were also generated via subsequent rearrangement reactions. Altogether, the total syntheses of ten Securinega alkaloids are described, in one or two linear steps from proposed biosynthetic precursor menisdaurilide. These results support the hypothesis that the same or similar pathways may operate in planta
Impact of bile salts, biopolymer coatings, and food matrix on bilosome-mediated delivery of trans-resveratrol
Get PDFThis study compared liposomes, bilosomes, and biopolymer-coated bilosomes for trans-resveratrol (t-res) delivery, evaluating the effects of bile salts, biopolymer coatings, and oat milk (OM) on digestion behaviour, bioaccessibility, and intestinal absorption. The bioaccessibility of t-res increased by 1.82-fold with liposomes and by 2.14–2.32-fold with bilosomes. Ex vivo absorption studies using murine intestinal tissue confirmed enhanced uptake and tissue accumulation with bilosomes, reaching 16.801 μM compared to 0.400 μM for liposomes. Coating bilosomes with chitosan (CH) and polygalacturonic acid (PGA) improved stability and surface properties but reduced bioaccessibility to 8–40%, depending on biopolymer concentration. The OM influenced both initial and digestion-related properties, enhancing bioaccessibility in uncoated systems while reducing intestinal tissue accumulation of t-res. Overall, these findings indicate that bilosomes outperform liposomes for hydrophobic compound delivery; however, their performance is highly formulation-dependent and strongly influenced by food matrix interactions, underscoring the importance of consumption context in functional food design
Recruitment of the multiple sclerosis cohort within the European Mobilise-D clinical validation study—lessons learnt, baseline demographics and clinical characteristics
Get PDFBackground
Multiple sclerosis (MS) is a common cause of disability in working age adults. Current clinical assessments are inadequate at disability assessment or predicting clinically relevant outcomes. Loss of mobility is an important functional disability to people with MS. Mobilise-D aims to develop, validate, and implement a digital mobility solution which measures unsupervised mobility performance across several chronic conditions, including MS, using a single wearable device.
Methods
Six hundred two adults with MS, an Expanded Disability Status Scale (EDSS) score of 3.0–6.5, documented disability worsening over the previous 2 years and a 30-day freedom from relapses, were recruited across four European centres.
Results
Of 1416 invited, 602 participants (42%) were recruited. Primary recruitment sources were clinicians (42%) and local registries (42%). Among 616 who declined screening, the main reasons were a lack of interest (44%), the time commitment (25%) or the travel involved (13%). Participants had a mean age of 52 years; 64% were female, with a median EDSS score of 5.0. Of those, 56% had relapsing-remitting MS, 33% secondary progressive MS and 10% primary progressive MS. Falls occurred in 58% of participants in the 12 months prior to recruitment. Of those recruited, 556 (93%) participants had valid mobility data recorded.
Conclusions
The longitudinal collection of clinical and unsupervised mobility assessments will provide a comprehensive dataset, allowing for the determination of digital mobility assessments’ construct validity, predictive capacity, responsiveness, and clinical meaningfulness. Novel insights into real-world mobility that describe both walking activity and gait outcomes will be gained.
Trial registration
The study was registered at the ISRCTN registry on 12/10/2020, titled “Clinical validation of a mobility monitor to measure and predict health outcomes” (ISRCTN Number: 12051706)
Victim-survivor experiences of police responses to coercive control: finding a place for ‘lived experience’
No full textCoercive and controlling behaviour (CCB) was criminalised in England and Wales in 2015. This article, drawing on data from two victim-survivor centred research projects conducted over an eight-year period since the criminalisation of CCB, documents the continuities and discontinuities in their experiences of policing responses to CCB. It points to victim-survivor changing expectations of policing and considers the import of these changes for not only listening to their experiences but also hearing them. The challenges that evolving and dynamic lived experiences pose for policing policy and practice in relation to CCB are explored
Molecular-Scale Tuning of Low-Molecular-Weight Gelators Controls Supramolecular Assembly and Directs Human Mesenchymal Stem Cell Growth
Get PDFWe report the synthesis and characterisation of a simple alcohol-functionalized low-molecular-weight gelator (LMWG) based on 1,3:2,4-dibenzylidenesorbitol scaffold (DBS-CH2OH) and explore its self-assembly in comparison to acylhydrazide-functionalized DBS-CONHNH2. DBS-CH2OH forms a stiffer, highly organized, less-soluble self-assembled hydrogel, with a different assembly mode and much higher entropy/enthalpy of dissociation. On mixing, the LMWGs co-assemble into gel nanofibers with similar thermodynamics to DBS-CONHNH2. DBS-CH2OH is an excellent scaffold for the growth of human mesenchymal stem cells (hMSCs), which exhibit extended spread-shaped morphologies on the gel surface. In contrast, for DBS-CONHNH2, hMSCs have a rounded morphology and penetrate into the softer gel. A simple functional group change on the LMWG therefore leads to a remarkable change in cell growth outcomes. When hMSCs are grown on the co-assembled gel, they have the rounded morphology characteristic of DBS-CONHNH2 but remain on the gel surface, like DBS-CH2OH. The multi-component gel thus shares characteristics of the individual LMWGs, with hMSC growth being controlled by factors like structure, stiffness and dynamics. This work demonstrates how chemical manipulation of gels based on deceptively simple LMWGs can have profound impacts in biomaterials engineering
Cryptosporidium spp. infection drives distinct alterations in the faecal extracellular vesicles metaproteome of calves
Get PDFBackground
The gut is primarily responsible for digestion and nutrient absorption, plays essential roles in immune regulation and metabolic balance, and is supported by a diverse microbiome essential for digestion, absorption, and defence from pathogens. Understanding gut physiology and pathophysiology in pre-weaned calves is essential, as infections like cryptosporidiosis can lead to gut dysbiosis, impair growth, and negatively affect long-term productivity. Faeces are considered easily accessible biological specimens that can be used to monitor gastrointestinal disorders. The methods employed in this study aimed to investigate the potential use of faecal extracellular vesicles (fEVs) as a non-invasive tool for assessing gut health and infections in calves. Particularly, considering Cryptosporidiosis as a model for gut infectious disease.
Results
The analysis using a hybrid reference-based metaproteomic approach revealed that the proteomic profiles of fEVs significantly differed from that of faecal crude (FC) suspensions. Both sample types contained microbial and host proteins, which are important for maintaining gut defence and microbial homeostasis. However, Cryptosporidium spp. infection significantly shifted the fEV proteome, reducing both host and microbial proteins involved in gut defence. It also reduced proteins from microbes that are important for maintaining microbial homeostasis, while increasing stress-related proteins. Further, lyophilisation of fEVs significantly altered the protein profiles.
Conclusion
These findings underscore that fEVs contain host and microbial proteins that are a valuable resource for studying gut physiology, pathophysiology, host-microbe-pathogen interactions, and microbiome dynamics. Changes in the proteomic profile of fEVs during Cryptosporidium spp. infection demonstrates the pathogen’s ability to manipulate host immune defences and microbiome composition for its survival and replication. Overall, these findings support the utility of fEV proteomics as a non-invasive platform for biomarker discovery and advancing research in gastrointestinal health and disease in livestock
Unraveling the intersection of aging and Parkinson’s disease: a collaborative roadmap for advancing research models
Get PDFAging is the most significant risk factor for Parkinson’s disease (PD), yet its role remains underexplored. The International Network for Parkinson’s Disease Modelling and Aging (PD-AGE), funded by the Michael J. Fox Foundation, was established to address these challenges. Through collaborative efforts, the PD-AGE mouse-model working group developed a roadmap to prioritize mouse models, reach consensus on experimental approaches, and standardize protocols to investigate the intersection of aging and PD
A survey on automatic credibility assessment using textual credibility signals in the era of large language models
Get PDFIn the age of social media and generative AI, the ability to automatically assess the credibility of online content has become increasingly critical, complementing traditional approaches to false information detection. Credibility assessment relies on aggregating diverse credibility signals—small units of information, such as content subjectivity, bias or a presence of persuasion techniques—into a final credibility label/score. However, current research in automatic credibility assessment and credibility signals detection remains highly fragmented, with many signals studied in isolation and lacking integration. Notably, there is a scarcity of approaches that detect and aggregate multiple credibility signals simultaneously. These challenges are further exacerbated by the absence of a comprehensive and up-to-date overview of research works that connects these research efforts under a common framework and identifies shared trends, challenges and open problems. In this survey, we address this gap by presenting a systematic and comprehensive literature review of 175 research papers, focusing on textual credibility signals within the field of Natural Language Processing (NLP), which undergoes a rapid transformation due to advancements in Large Language Models (LLMs). While positioning the NLP research into the broader multidisciplinary landscape, we examine both automatic credibility assessment methods as well as the detection of nine categories of credibility signals. We provide an in-depth analysis of three key categories: (1) factuality, subjectivity and bias, (2) persuasion techniques and logical fallacies and (3) check-worthy and fact-checked claims. In addition to summarising existing methods, datasets and tools, we outline future research direction and emerging opportunities, with particular attention to evolving challenges posed by generative AI
Mismatched partners in human-robot interaction: biomimetic insights on aligning internal states with external expressions
Get PDFHuman-robot interaction (HRI) is fundamentally constrained by the fact that humans and social robots are mismatched conversational partners. While social robots often exhibit human-like expressive features, they lack the underlying mechanisms that support human social reasoning, resulting in mismatches that disrupt users’ perception, interpretation, and adaptation, increasing the cognitive effort required to interact effectively. This paper explores how biomimetic insights from social behaviours in nature can help address these mismatches. To analyse these mismatches, this paper introduces a conceptual framework, the ‘Theory of Lenses’ (ToL), which identifies misalignment types in signal transmission and interpretation across interpersonal and intrapersonal dimensions. Drawing from communication strategies in nature, we argue that one promising direction lies in the design of honest signals that reliably reflect a robot’s internal states and limitations. Future work will focus on empirical validation and operationalising this principle by developing a framework to design and evaluate honest signals in diverse HRI scenarios. Ultimately, our goal is to build social robots that are not only expressive but also socially intelligible and interactionally sustainable
Emotional Self-Dissonance
Get PDFThis paper identifies and characterizes a commonplace but philosophically neglected aspect of human emotional experience, which I call emotional self-dissonance. I start from the position that emotional experiences generally involve taking things to matter in ways that reflect what we already care about. Building on this, I suggest that our various projects, pastimes, commitments, relationships, and habits together comprise an evaluative orientation through which we experience things emotionally. Although this orientation is for the most part cohesively organized, tensions within it are inevitable. I suggest that emotions of familiar kinds often incorporate a sense of these tensions. In addition, emotional self-dissonance can amount to a form of emotional experience in its own right, one that encompasses considerable variety
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