47011 research outputs found
Sort by
Integrating microclimate to understand vector development and disease patterns: challenges and lessons from plague in Madagascar’s Central Highlands
Get PDFPlague, the zoonotic vector-borne disease caused by the bacterium Yersinia pestis, shows seasonal infection patterns across the Central Highlands of Madagascar. The disease persists within a complex ecological network involving host and vector species, all influenced by climate. Due to this complexity, links between climate, Y. pestis ecology and human infection remain incomplete. This study developed microclimate-based models to assess climatic impacts on growth cycles of plague vectors Xenopsylla cheopis and Synopsyllus fonquerniei. Using microclimatic modelling, the vector development index (VDI) was calculated to estimate annual developmental phases for each flea species. The uncorrected VDI suggested that development rates were highly variable for X. cheopis compared to S. fonquerniei, which shows greater temporal consistency. Elevated VDI slopes, representing an increased rate of vector development, correlated with plague cases across 61.8–14.7% of areas, implying possible climatic influence on vector-driven disease cycles. However, these associations were not maintained after adjusting modelled temperatures using limited field validation. These findings highlight the complex interactions between climate, vector dynamics and Y. pestis transmission, and emphasize the need for further investigation into burrow microclimates and their seasonal epidemiological roles
Mammalian Target of Rapamycin in Chronic Liver Disease and the Potential for Therapeutic Manipulation
Get PDFChronic Liver Disease (CLD) represents a growing epidemic in the Western world, yet treatment options that effectively slow its progression remain limited. Mammalian target of rapamycin (mTOR) inhibitors, such as sirolimus (also known as rapamycin), have been proposed as potential antifibrotic agents over the past decade; however, their role in chronic liver disease remains underexplored. mTOR is a protein kinase integral to a key cellular pathway, which is essential for normal liver physiology but is also implicated in the pathogenesis of CLD and hepatocellular carcinoma (HCC).This narrative review summarises the role of mTOR in the healthy liver, its dysregulation across common aetiologies of CLD, and its role in HCC. An electronic literature search of Ovid MEDLINE was conducted from database inception to 2025 to identify studies evaluating the role of MTOR in CLD. The review underscores a clear unmet need for well-designed human clinical trials to specifically assess mTOR inhibitors as potential anti-fibrotic therapies
‘The Song of the Innuit’: Circulating Arctic ethnographic knowledge through verse
Get PDFThis article seeks to advance recent literatures exploring the important role of poetry in the production and circulation of geographical knowledge. It does this by critically analysing a poem that was written by the traveller and scholar Wiliam Healey Dall during the 1899 Harriman Alaska Expedition. This leisurely excursion travelled along the coastlines of Alaska and the Siberian peninsula, and involved a series of encounters with the indigenous Yupik/Yup’ik communities inhabiting this region. It was these encounters that provided the basis for Dall’s problematic poem. As the analysis presented demonstrates, this pseudo-ethnographic poem contained a range of ‘temperate normative’ descriptions of these indigenous Arctic peoples. This in turn perpetuated erroneous depictions of these peoples within the geographical imaginations of non-indigenous peoples across Europe and North America. The article therefore argues that geographers and other scholars must take poetry and other forms of verse seriously as a crucial means by which geographical knowledges pertaining to indigenous peoples were circulated during the long 19th century. This will in turn reveal their vital role in supporting and justifying troubling colonial interventions into the lives of indigenous peoples across the Arctic and beyond
Mechanisms underlying the accuracy of stimulus representations: Within-event learning and outcome mediation.
Get PDFValid predictors of an outcome attract more attention than stimuli that are nonpredictive. Furthermore, stimuli that have a probabilistic association with an outcome attract more attention than stimuli that have a deterministic association with an outcome. Two experiments investigated whether predictive validity and outcome uncertainty resulted in the establishment of a more accurate stimulus representation, in which accuracy was measured as the strength of associations between different elements of a compound stimulus. In Experiment 1, pairs of stimuli were established as outcome predictive (always followed by the same outcome) and presented in conjunction with nonpredictive pairs of stimuli (equally likely to be followed by two different outcomes). Outcome uncertainty was also manipulated, between groups, by establishing either a deterministic (100%) or probabilistic (80%) contingency between the predictive pairs and their outcomes. The test trials revealed more accurate recognition for which predictive stimuli were paired together relative to nonpredictive stimuli; however, there was no effect of outcome uncertainty. Experiment 2 reproduced the effect observed in the deterministic group from Experiment 1 and also demonstrated that the superior performance to the predictive stimuli over the nonpredictive stimuli was only evident when, at test, the choice stimuli had predicted different outcomes during training. These results were interpreted as the consequence of two pathways to accurate stimulus representation: direct (within-compound associations) and indirect (mediated through the activation of the outcome) and are discussed in the context of attentional theories of associative learning
Energy consumption and carbon emissions of residential buildings with phase-change panels and geopolymer envelopes in China’s cold region
Get PDFApproximately 40 % of worldwide energy usage and 30 % of CO2 emissions are attributed to building sector. Utilizing geopolymer mortar derived from fly ash as an alternative to conventional cement mortar, along with integrating phase-change panels in building envelopes, presents a substantial chance to markedly descend energy usage and CO2 emissions. The energy consumption and CO2 emissions of buildings in China’s cold region with phase-change geopolymer and cement mortars were investigated through life cycle assessment. The results indicate that when installed 20 mm thick phase-change panels on interior walls, surpass both sandwich and exterior wall configurations in terms of energy-saving efficiency, resulting in a 3.26 % drop in energy required to cooling. Additionally, the interior wall oriented eastward and equipped with phase-change panels demonstrated superior energy-saving capabilities compared to walls oriented in other directions. This configuration resulted in a decrease of energy consumption by 3.05 × 103 kWh and a decrease in summer cooling energy consumption by 3.88 %. In comparison to cement mortar, geopolymer mortar of equivalent volume significantly reduces CO2 emissions during production by 2.96 × 104 kgCO2e, achieving a carbon reduction of 90.63 %. For buildings incorporating phase-change panels on east-facing interior walls, the CO2 equivalents in the life span amount to 2.12 × 103 kgCO2e/m2, representing a decrease of 61.70 kgCO2e/m2 relative to traditional cement mortar envelope systems, thereby yielding an average annual reduction of 2.83 %. The energy-saving and carbon-reduction benefits of installing PCM panels in buildings are comparable in Beijing and Xi’an to those observed in Xuzhou. The findings are pivotal for formulating strategies aimed at minimizing energy consumption and CO2 emissions in residential buildings
A simplified low-cost and reliable plant genomic DNA extraction method for PCR-based genotyping and screening
No full textBackground: Extraction of plant genomic DNA is a critical step for PCR-based genotyping, mapping, and breeding applications. Conventional CTAB protocols and commercial kits provide reliable DNA but are labour-intensive, costly, and generate substantial plastic waste. Simplified crude-extract methods are available, yet their performance is often compromised by PCR inhibition from salts and cellular debris. A rapid, low-cost, and high-throughput method is therefore needed for routine molecular applications. Results: We developed a single-tube DNA extraction protocol that eliminates supernatant transfers, thereby reducing handling errors, plastic consumption, and processing time. The method consistently produces DNA of sufficient yield and purity for PCR-based assays. Validation in wheat and wheat–wild relative introgression lines demonstrated robust amplification in KASP assays. Cross-species testing in maize, Arabidopsis, and tomato using two Tris-salt extraction buffers confirmed broad applicability, supported by NanoDrop and Qubit measurements. Freeze-dried and frozen tissue produced higher yields than fresh samples, confirming their suitability for high-throughput and large-scale studies. Conclusions: This streamlined protocol provides a cost-effective, reliable, and scalable approach for extracting plant genomic DNA suitable for PCR-based genotyping, marker development, and diversity analysis. Its simplicity and throughput make it particularly valuable for breeding programmes, although it is not intended for applications requiring highly pure DNA, such as whole-genome resequencing
Evaluating quality of novel alternative protein sources (microbial and insect proteins) using the INFOGEST in vitro digestion model
Get PDFSustainable alternative protein sources are needed for humans and animals, but their quality, including digestibility and Indispensable Amino Acid (IAA) contents, need to be determined. We evaluated the protein quality of novel microbial (MPX) and insect (BSFL) proteins, in comparison with more conventional, Fishmeal (FM) and Pea Protein (PP), using the INFOGEST model. MPX was highly digestible (92.6 %) and similar to PP (99.3 %), but higher than both FM (82.4 %) and BSFL (72.9 %, p < 0.001). The use of 6.25 as conversion factor for N, overestimated the protein content of MPX and BSFL, due to their high non-protein N contents, impacting the measure of quality. Digestible IAA Ratios for MPX and BSFL were underestimated when crude protein was used, but use of total AA resulted in similar Digestible IAA Scores for MPX (0.96) and FM (0.95), with PP (0.72) and BSFL (0.51) being lower (P < 0.001). MPX is the better quality novel protein source
Bioconvergence of sound-guided and supramolecular assembly strategies to create peptide-protein composite hydrogels with predictable shape-to-function features
Get PDFPurely protein-based hydrogels are widely used in tissue engineering for their biomimicry and biocompatibility, yet remain challenging to tailor with precision and predictability at biological and mechanical levels. To overcome this, synthetic self-assembling peptide amphiphiles (PAs) offer opportunities for supramolecular customization, both as single-phase materials and co-assembled with proteins to create hybrid nanocomposites with emerging functionalities. Similarly, contactless, sound-guided bioassembly techniques using liquid-phase hydrogel precursors are emerging as strategic tools for obtaining structured and functional hydrogels. Leveraging these advances, here a fast, contactless, ‘one-pot’ bioassembly strategy merging supramolecular PA self-assembly with sound-guided patterning to fabricate hybrid peptide-protein hydrogels with predictable, shape-dependent functionality is presented. Using fibrin as proof-of-concept, material performance is biologically enhanced by incorporating growth factor-binding PAs, while inorganic microparticles are embedded and spatially organized via acoustic fields to tune mechanical properties. This strategy allows predictable tuning of composite stiffness and architecture by adjusting sound wave frequency, with acoustic fields guiding material organization from nano-to-macroscale. Composite hydrogels result highly permissive to cell infiltration in vitro and versatile platforms to tune immune cell-material interactions. This modular biofabrication platform integrating supramolecular and sound-guided processes can be generalized to other building blocks, opening unique opportunities for scalable, tunable, and hierarchically-organized biomaterials
Temporally-aware diffusion model for brain progression modelling with bidirectional temporal regularisation
Get PDFGenerating realistic MRIs to accurately predict future changes in the structure of brain is an invaluable tool for clinicians in assessing clinical outcomes and analysing the disease progression at the patient level. However, current existing methods present some limitations: (i) some approaches fail to explicitly capture the relationship between structural changes and time intervals, especially when trained on age-imbalanced datasets; (ii) others rely only on scan interpolation, which lack clinical utility, as they generate intermediate images between timepoints rather than future pathological progression; and (iii) most approaches rely on 2D slice-based architectures, thereby disregarding full 3D anatomical context, which is essential for accurate longitudinal predictions. We propose a 3D Temporally-Aware Diffusion Model (TADM-3D), which accurately predicts brain progression on MRI volumes. To better model the relationship between time interval and brain changes, TADM-3D uses a pre-trained Brain-Age Estimator (BAE) that guides the diffusion model in the generation of MRIs that accurately reflect the expected age difference between baseline and generated follow-up scans. Additionally, to further improve the temporal awareness of TADM-3D, we propose the Back-In-Time Regularisation (BITR), by training TADM-3D to predict bidirectionally from the baseline to follow-up (forward), as well as from the follow-up to baseline (backward). Although predicting past scans has limited clinical applications, this regularisation helps the model generate temporally more accurate scans. We train and evaluate TADM-3D on the OASIS-3 dataset, and we validate the generalisation performance on an external test set from the NACC dataset. The code is available at https://github.com/MattiaLitrico/TADM-3D
Clinical isolates from chronic wounds reveal strain-specific, alkyl-quinolone-independent competition in Pseudomonas aeruginosa-Staphylococcus aureus biofilms
No full textIntroduction. Chronic wounds are notoriously difficult to treat and are associated with decreased limb function, reduced quality of life and significant morbidity. Their recurrent nature, despite aggressive antibiotic therapy, is due in part to the presence of polymicrobial biofilms. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most frequently co-isolated pathogens in these infections and are known to form complex biofilms that hinder treatment.Hypothesis. We hypothesized that co-existence and competitive dynamics between P. aeruginosa and S. aureus in chronic wound infections are influenced by strain-specific interactions and may not rely solely on well-characterized inhibitory mechanisms such as 2-alkyl-4-quinolone (AQ) production by P. aeruginosa impacting on S. aureus fitness.Aim. To establish a polymicrobial chronic wound infection model and assess the contribution of AQ signalling and strain-specific interactions on co-existence.Methodology. We used a modified chronic wound biofilm model to co-culture matched and mismatched clinical isolate pairs of P. aeruginosa and S. aureus, collected from two different chronic wound patients. Viable bacterial counts (c.f.u.) were quantified over an 8-day period. AQ production by each P. aeruginosa strain was quantified using liquid chromatography-MS.Results. A stable culture of P. aeruginosa strains was achieved, but distinct behaviours between each S. aureus strain were seen. One matched clinical isolate pair maintained stable c.f.u. levels of both species throughout the 8-day model, indicating a compatible co-existence. In contrast, mismatched pairs showed early loss of S. aureus viability and the emergence of small colony variants after 4 days, not seen in matched pair growth. Interestingly, the most competitive P. aeruginosa strain exhibited undetectable levels of all AQs tested, indicating that its dominance was not due to AQ-mediated antagonism, as has previously been described.Conclusion. Our findings demonstrate that stable dual-species biofilm formation in chronic wounds is strain-dependent and that P. aeruginosa can impact on S. aureus fitness through AQ-independent mechanisms. These results highlight the importance of using clinical isolates in biofilm research and caution against generalizing findings from laboratory strains to complex clinical infections
Access Repository Dashboard
Do you manage Open Research Online? Become a CORE Member to access insider analytics, issue reports and manage access to outputs from your repository in the CORE Repository Dashboard! 👇