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WISIT vaccines based on IL-31-derived peptides as a novel therapeutic approach for chronic pruritic dermatoses
Vaccines are a promising therapy for the treatment of chronic conditions such as pruritus. IL-31 has been identified as an important mediator of itch. By targeting IL-31 signaling with immunotherapy, CP can be effectively alleviated. However, self-antigens such as IL-31 are highly tolerated, which has rendered conventional conjugate vaccines (CCVs) ineffective at generating sufficient antibody (Ab) responses to alleviate CP. Novel Win the Skin Immune System Trick (WISIT) vaccines however have been shown to induce substantially stronger Ab responses than CCVs in Parkinson’s Disease, and so may be capable of overcoming IL-31 tolerance to effectively treat CP. In this report, WISIT vaccines presenting ten different IL-31-specific peptides were compared to CCVs presenting the same peptides. Multiple response parameters were assessed, including Ab titers induced, avidity of these Abs, and IL-31 signaling inhibition. Results demonstrated that WISIT vaccines outperform CCVs across all investigated metrics, culminating in the identification of 3 promising candidate WISIT vaccines to be taken forward for further clinical development. This report thus provides evidence that the improved immunogenicity of WISIT vaccines is not disease-specific and that WISIT vaccines may also be translated to treat dermatological disorders. Further preclinical development will be necessary to prepare the identified IL-31 targeting WISIT vaccine candidates for clinical testing.
Assessing physical literacy and establishing normative reference curves for 8–12-year-old children from South Punjab, Pakistan: The PAK-IPPL cross-sectional study
Background Physical literacy (PL) encompasses an individual’s motivation, confidence, physical competence, and knowledge, all of which foster lifelong engagement in physical activities. In developing countries like Pakistan, there is a pressing need to assess PL status using culturally valid tools. This study aims to evaluate PL among children aged 8–12 in South Punjab, Pakistan while developing normative reference curves and exploring factors influencing PL. Methods A cross-sectional study was conducted with 1,360 students (mean age = 10.00, SD = 1.41 years) from 85 schools, using a culturally adapted and validated version of the CAPL-2 tool. The CAPL-2 scoring system was validated to align with the population and cultural context. Statistical analyses, including t-tests, Chi-squared tests, Pearson’s correlation, multivariate logistic regression, and Classification and regression tree methods, were performed to identify factors associated with PL classifications, with significance set at p < 0.05. The Generalized Additive Models for Location, Scale, and Shape were used to create age- and sex-specific PL normative reference curves. Result The study revealed significant influences of gender, socioeconomic status (SES), and locality on PL. Boys consistently scored higher in PL across all domains compared to girls, with significant differences (p < 0.001) in all but the knowledge and understanding domain (p = 0.160). Boys’ PL scores were 6% higher overall, with a 7% and 5% advantage in the daily behavior and physical competence domains, respectively. Children from low SES and rural settings exhibited significantly higher PL scores than their middle/high SES and urban counterparts (p < 0.001). Walking to school was positively correlated with higher PL scores, while children traveling by car had the lowest scores (p < 0.001). Anthropometric differences between genders were noted, further emphasizing the disparities in physical competence. Most participants (71.6%) fell into the "Beginning" or "Progressing" PL categories, with females predominantly in these lower stages. Conclusion This study reveals that gender, SES, and locality significantly impact PL among children in South Punjab, Pakistan. Boys, lower SES groups, and rural children showed higher PL scores, with everyday activities like walking to school positively contributing to PL development. These findings emphasize the need for targeted, demographically sensitive interventions to enhance PL in the region.
Prey depletion, interspecific competition, and the energetics of hunting in endangered African wild dogs, <i>Lycaon pictus</i>
Large herbivores are in decline in much of the world, including sub-Saharan Africa, and true apex carnivores like the lion ( Panthera leo ) decline in parallel with their prey. As a consequence, competitively subordinate carnivores like the African wild dog ( Lycaon pictus ) are simultaneously experiencing a costly reduction in resources and a beneficial reduction in dominant competitors. The net effect is not intuitively obvious, but wild dogs’ density, survival, and reproduction are all low in areas that are strongly affected by prey depletion. To assess whether these correlations are causal, we tested the hypothesized mechanism, using data from 13 wild dog packs in two ecosystems to relate the energetic costs and benefits of hunting to variation in prey density, while controlling for the effects of local lion density, pack size, the number of dependent pups, and the level of protection. All of these variables affected the energetic costs and benefits of hunting. In areas with low prey density, the magnitude of movements and vectorial dynamic body acceleration (a measure of energy expenditure) both increased, the mass of killed prey decreased, and the number of kills per day did not change detectably. Programs to reduce or reverse the decline of large herbivore populations should be an effective means of improving the status of endangered subordinate competitors like the wild dog, and should be a high priority. Our results demonstrate the utility of research that integrates data from biomonitoring with direct, long-term observation of endangered species, their competitors, and their resources.
‘Aqua tweezers’ manipulate particles with water waves
Scientists fight Norway’s language law, warning of talent exodus
Daily briefing: ‘Devastating’ cuts to NIH grants blocked by legal challenge
Precisely metal doped nanographenes via a carbaporphyrin approach
Muscle abnormalities in Long COVID
Dynamics of cooperation in concurrent games
Abstract People frequently encounter situations where individually optimal decisions conflict with group interests. To navigate such social dilemmas, they often employ simple heuristics based on direct reciprocity: cooperate when others do and cease cooperation when partners defect. However, prior research typically assumes that individuals only interact in one game at a time. In reality, people engage in multiple games concurrently, and the outcome of one interaction can influence behavior in another. Here, we introduce a theoretical framework to study the resulting cross-over and spill-over effects. Participants repeatedly engage in two independent stage games, either with the same or different partners, adapting their strategies over time through an evolutionary learning process. Our findings indicate that individuals often link their behavior across games, particularly under cognitive constraints like imperfect recall. A behavioral experiment with 316 UK-based students suggests that concurrent games negatively affect cooperation, highlighting how strategic motives and spillovers impact reciprocity.
The neurobench framework for benchmarking neuromorphic computing algorithms and systems
Abstract Neuromorphic computing shows promise for advancing computing efficiency and capabilities of AI applications using brain-inspired principles. However, the neuromorphic research field currently lacks standardized benchmarks, making it difficult to accurately measure technological advancements, compare performance with conventional methods, and identify promising future research directions. This article presents NeuroBench, a benchmark framework for neuromorphic algorithms and systems, which is collaboratively designed from an open community of researchers across industry and academia. NeuroBench introduces a common set of tools and systematic methodology for inclusive benchmark measurement, delivering an objective reference framework for quantifying neuromorphic approaches in both hardware-independent and hardware-dependent settings. For latest project updates, visit the project website (neurobench.ai).
Emissions leakage and economic losses may undermine deforestation-linked oil crop import restrictions
Ultrahigh piezoelectricity and temperature stability in piezoceramics by synergistic design
CerS6 links ceramide metabolism to innate immune responses in diabetic kidney disease
Author Correction: Brucella abortus impairs T lymphocyte responsiveness by mobilizing IL-1RA-secreting omental neutrophils
A pathogen effector HaRxL10 hijacks the circadian clock component CHE to perturb both plant development and immunity
Abstract The intertwining between the life cycle of plants and their pathogens made the plant circadian clock an integral constituent of the plant immune system. Reciprocally, pathogens were also found to perturb the expression pattern of certain clock genes. However, how pathogens influence clock components remains largely unknown. Here we show that an oomycete effector HaRxL10 directly targets Arabidopsis central clock component CCA1 HIKING EXPEDITION (CHE) to manipulate its function. HaRxL10 stabilises CHE by disrupting E3 ligase ZEITLUPE-mediated CHE protein degradation. Surprisingly, the accumulation of CHE does not enhance but rather suppresses CHE function, inhibiting its binding to the downstream gene promoter. HaRxL10 triggers reprogramming of the transcriptome including expression of genes related to circadian oscillations. Moreover, HaRxL10 hijacks CHE to repress plant immunity and manipulate physiological processes, including hypocotyl growth and flowering. Taken together, our study discovers the first plant pathogen effector that directly targets a plant circadian clock component and elucidates the underlying molecular mechanism.
Lack of harmonisation of greenhouse gases reporting standards and the methane emissions gap
Abstract Monitoring companies’ contributions to climate dynamics and their exposure to transition risks requires accurate measurements of their non-carbon dioxide greenhouse gas emissions (non-CO2 GHG). However, carbon accounting standards are not harmonised and allow for some discretion when converting emissions of different GHGs into CO2 equivalent units, the currency in which carbon footprints are expressed. Focusing on methane, we build counterfactual harmonised standards using the latest IPCC Global Warming Potential (GWP) values over 100 years and estimate a cumulative gap in reported methane emissions of 170MtCO2e ( ~6Tg) over a sample of 2864 companies. Changing the counterfactual from GWP100to GWP20, as recently codified in certain jurisdictions and initiatives, increases the cumulative gap to 3300MtCO2e ( ~40Tg). The gap only covers direct emissions and hence understates the extent of potential under-reporting across value chains. Overall, our study underscores the importance of global harmonisation of CO2-equivalence standards to coherently track corporate GHG emissions and their exposure to transition risks.
Accelerated epigenetic aging in Huntington’s disease involves polycomb repressive complex 1
Abstract Loss of epigenetic information during physiological aging compromises cellular identity, leading to de-repression of developmental genes. Here, we assessed the epigenomic landscape of vulnerable neurons in two reference mouse models of Huntington neurodegenerative disease (HD), using cell-type-specific multi-omics, including temporal analysis at three disease stages via FANS-CUT&Tag. We show accelerated de-repression of developmental genes in HD striatal neurons, involving histone re-acetylation and depletion of H2AK119 ubiquitination and H3K27 trimethylation marks, which are catalyzed by polycomb repressive complexes 1 and 2 (PRC1 and PRC2), respectively. We further identify a PRC1-dependent subcluster of bivalent developmental transcription factors that is re-activated in HD striatal neurons. This mechanism likely involves progressive paralog switching between PRC1-CBX genes, which promotes the upregulation of normally low-expressed PRC1-CBX2/4/8 isoforms in striatal neurons, alongside the down-regulation of predominant PRC1-CBX isoforms in these cells (e.g., CBX6/7). Collectively, our data provide evidence for PRC1-dependent accelerated epigenetic aging in HD vulnerable neurons.
Author Correction: Northern Scandinavian mountains supported by a low-grade eclogitic crustal keel
A comprehensive metabolomic study of three Egyptian Salsola species revealed their potential anti-inflammatory activity
Abstract Salsola plants are halophytic crops that are distributed worldwide, with more than 100 species figured out in Asia, the Mediterranean region and North Africa. Different Salsola species were reported to exert marked anti-inflammatory activities, whereas the potential anti-inflammatory activities of the three species, S. tetrandra, S. tetragona and S. vermiculata, have not been evaluated. This study provides a comprehensive metabolic study of the shoots and roots of those three species to identify potential anti-inflammatory candidates. An ultra-high performance liquid chromatography mass-mass spectrometry (UHPLC MS/MS) method in conjunction with multivariate analysis principles was utilized in an attempt to decipher their bio-active metabolites and their relevant anti-inflammatory activities. Eighty metabolites were identified in the tested extracts, where nitrogenous compounds and phenolics were highly detected in S. tetragona samples, meanwhile, saponins and phenolic acids were highly dominant in S. tetrendra sample and S. vermiculata samples have a similar chemical profile as S. tetrandra. Concerning the anti-inflammatory activity of the tested extracts, the safety margin of all the tested extracts was higher than that of the standard drug piroxicam. The shoots of the three species demonstrated more potent anti-inflammatory activities compared to the roots. The shoot extract of S. tetrandra was the most biologically active fraction. The obtained results revealed the shoots of the three Salosla species to be promising anti-inflammatory drug candidates of high safety and efficacy that could be used in the pharmaceutical industry.