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To infer the parameters of mechanistic models with intractable likelihoods, techniques such as approximate Bayesian computation (ABC) are increasingly being adopted. One of the main disadvantages of ABC in practical situations, however, is that parameter inference must generally rely on summary statistics of the data. This is particularly the case for problems involving high-dimensional data, such as biological imaging experiments. However, some summary statistics contain more information about parameters of interest than others, and it is not always clear how to weight their contributions within the ABC framework. We address this problem by developing an automatic, adaptive algorithm that chooses weights for each summary statistic. Our algorithm aims to maximize the distance between the prior and the approximate posterior by automatically adapting the weights within the ABC distance function. Computationally, we use a nearest neighbour estimator of the distance between distributions. We justify the algorithm theoretically based on properties of the nearest neighbour distance estimator. To demonstrate the effectiveness of our algorithm, we apply it to a variety of test problems, including several stochastic models of biochemical reaction networks, and a spatial model of diffusion, and compare our results with existing algorithms.

Research seems to show that captions and subtitles are generally beneficial to learners of English as an Additional Language (EAL), but some research does contradict this. Research on slideware and slide design seems to focus more on attractiveness of slides and less on educational effectiveness. However, research on slide design and specific approaches to slide design continue to become more detailed. This study compared comprehension of explicit feedback received through either slideshow (text+audio) video or captioned video on an EAL writing task in an on-demand university setting. Results (n=163) indicated that approximately 50% of learners clicked the feedback video to advance to the quiz without viewing it completely. Of the learners with at least one full viewing (n=86), slideshow video seems to have engaged students for a longer duration than captioned video. The quiz items were easier for the slideshow video groups, and the quiz items performed better for these groups. The slideshow video groups had slightly higher means, but a significant difference between the effectiveness of slideshow video and captioned video to transmit feedback to students was not found.

Imaging data has become an essential tool to explore key biological questions at various scales, for example the motile behaviour of bacteria or the transport of mRNA, and it has the potential to transform our understanding of important transport mechanisms. Often these imaging studies require us to compare biological species or mutants, and to do this we need to quantitatively characterise their behaviour. Mathematical models offer a quantitative description of a system that enables us to perform this comparison, but to relate mechanistic mathematical models to imaging data, we need to estimate their parameters. In this work we study how collecting data at different temporal resolutions impacts our ability to infer parameters of biological transport models by performing exact inference for simple velocity jump process models in a Bayesian framework. The question of how best to choose the frequency with which data is collected is prominent in a host of studies because the majority of imaging technologies place constraints on the frequency with which images can be taken, and the discrete nature of observations can introduce errors into parameter estimates. In this work, we mitigate such errors by formulating the velocity jump process model within a hidden states framework. This allows us to obtain estimates of the reorientation rate and noise amplitude for noisy observations of a simple velocity jump process. We demonstrate the sensitivity of these estimates to temporal variations in the sampling resolution and extent of measurement noise. We use our methodology to provide experimental guidelines for researchers aiming to characterise motile behaviour that can be described by a velocity jump process. In particular, we consider how experimental constraints resulting in a trade-off between temporal sampling resolution and observation noise may affect parameter estimates. Finally, we demonstrate the robustness of our methodology to model misspecification, and then apply our inference framework to a dataset that was generated with the aim of understanding the localization of RNA-protein complexes.

Membrane budding entails forces to transform flat membrane into vesicles essential for cell survival. Accumulated studies have identified coat-proteins (e.g., clathrin) as potential budding factors. However, forces mediating many non-coated membrane buddings remain unclear. By visualizing proteins in mediating endocytic budding in live neuroendocrine cells, performing in vitro protein reconstitution and physical modeling, we discovered how non-coated-membrane budding is mediated: actin filaments and dynamin generate a pulling force transforming flat membrane into Λ-shape; subsequently, dynamin helices surround and constrict Λ-profile’s base, transforming Λ- to Ω-profile, and then constrict Ω-profile’s pore, converting Ω-profiles to vesicles. These mechanisms control budding speed, vesicle size and number, generating diverse endocytic modes differing in these parameters. Their impact is widespread beyond secretory cells, as the unexpectedly powerful functions of dynamin and actin, previously thought to mediate fission and overcome tension, respectively, may contribute to many dynamin/actin-dependent non-coated-membrane buddings, coated-membrane buddings, and other membrane remodeling processes. Shin et al. report the molecular mechanics of membrane budding: actin and dynamin pull membrane inward to form a Λ-shape profile; dynamin helices convert Λ- to Ω-shape by constricting Λ’s base, and then constrict Ω-profile’s pore to form a vesicle.

Current models infer that the microtubule-based mitotic spindle is built from GDP-tubulin with small GTP caps at microtubule plus-ends, including those that attach to kinetochores, forming the kinetochore-fibres. Here we reveal that kinetochore-fibres additionally contain a dynamic mixed-nucleotide zone that reaches several microns in length. This zone becomes visible in cells expressing fluorescently labelled end-binding proteins, a known marker for GTP-tubulin, and endogenously-labelled HURP - a protein which we show to preferentially bind the GDP microtubule lattice in vitro and in vivo. We find that in mitotic cells HURP accumulates on the kinetochore-proximal region of depolymerising kinetochore-fibres, whilst avoiding recruitment to nascent polymerising K-fibres, giving rise to a growing “HURP-gap”. The absence of end-binding proteins in the HURP-gaps leads us to postulate that they reflect a mixed-nucleotide zone. We generate a minimal quantitative model based on the preferential binding of HURP to GDP-tubulin to show that such a mixed-nucleotide zone is sufficient to recapitulate the observed in vivo dynamics of HURP-gaps. Microtubules are built from GDP-tubulin lattices with small GTP caps at their plus-ends. Here, the authors reveal that microtubules that attach to kinetochores in mitosis contain, in addition to the GTP-cap and the GDP-lattices, a dynamic micron-sized mixed-nucleotide zone.

Kinanthropometry is the study of body dimensions and composition measurements, which are influenced by factors such as age and nutritional status, establishing a relationship between static measurements and dynamic performance. This study aimed to evaluate the kinanthropometric differences among 403 individuals (aged 18–42), categorized by biological sex and the recreational sport they practiced. The main objective of this study was to clarify whether or not there were statistically significant differences between these groups. All of the measurements and indices were obtained following the International Society for the Advancement of Kinanthropometry (ISAK) protocol. Significant differences were found in most variables among the different sports. In general, the men showed higher values in terms of weight, height, body circumference, body mass index (BMI), relative index of the lower limbs (RILLs), percentage of muscle mass (%M), and percentage of residual mass (%R). The women exhibited higher values in terms of skinfold thicknesses, Cormic index (CI), body density index (BDI), percentage of fat mass (%F), and percentage of bone mass (%B). These findings can guide individuals in selecting sports based on their morphotype, optimizing their physical performance in recreational activities and improving their health and quality of life.

European canker, caused by Neonectria ditissima , is a major disease of apple ( Malus × domestica ) with limited control options, making host resistance a key management strategy. Although quantitative disease resistance (QDR) has been identified, the underlying molecular basis remains poorly understood. We investigated candidate genes associated with resistance using transcriptomic profiling of a bi-parental population segregating for six QTLs linked to canker resistance. RNA sequencing combined with machine learning enabled the identification of key biomarkers predictive of disease resistance. Integration of expression and QTL data highlighted genes involved in phenylpropanoid biosynthesis, immune receptors (NLRs, RLKs, WAKs), and epigenetic regulators, implicating their roles in host defense. Expression patterns were further resolved into cis- and trans-regulatory effects, providing insight into allele-dependent regulation. Independent validation in a separate dataset confirmed the robustness of key expression patterns. These findings advance understanding of the genetic architecture underlying QDR in apple and provide a basis for marker development to support breeding of cultivars with durable resistance to European canker.

Primary central nervous system (CNS) marginal zone B‐cell lymphoma (MZBCL) arising from the dural meninges is a rare but indolent disease. This malignancy can present in various ways, hence making it difficult to diagnose. Biopsy results dictate an appropriate treatment plan, which commonly consists of a combination of surgical resection, whole brain radiotherapy and systemic therapy. Primary central nervous system (CNS) marginal zone B‐cell lymphoma (MZBCL) arising from the dural meninges is a rare but indolent disease. This malignancy can present in various ways, hence making it difficult to diagnose. Biopsy results dictate an appropriate treatment plan, which commonly consists of a combination of surgical resection, whole brain radiotherapy and systemic therapy.

Although immunization against amyloid-β (Aβ) holds promise as a disease-modifying therapy for Alzheimer disease (AD), it is associated with an undesirable accumulation of amyloid in the cerebrovasculature [i.e., cerebral amyloid angiopathy (CAA)] and a heightened risk of micro-hemorrhages. The central and peripheral mechanisms postulated to modulate amyloid with anti-Aβ immunotherapy remain largely elusive. Here, we compared the effects of prolonged intracerebroventricular (icv) versus systemic delivery of anti-Aβ antibodies on the behavioral and pathological changes in an aged Tg2576 mouse model of AD. Prolonged icv infusions of anti-Aβ antibodies dose-dependently reduced the parenchymal plaque burden, astrogliosis, and dystrophic neurites at doses 10- to 50-fold lower than used with systemic delivery of the same antibody. Both icv and systemic anti-Aβ antibodies reversed the behavioral impairment in contextual fear conditioning. More importantly, unlike systemically delivered anti-Aβ antibodies that aggravated vascular pathology, icv-infused antibodies globally reduced CAA and associated micro-hemorrhages. We present data suggesting that the divergent effects of icv-delivered anti-Aβ antibodies result from gradually engaging the local (i.e., central) mechanisms for amyloid clearance, distinct from the mechanisms engaged by high doses of anti-Aβ antibodies that circulate in the vasculature following systemic delivery. With robust efficacy in reversing AD-related pathology and an unexpected benefit in reducing CAA and associated micro-hemorrhages, icv-targeted passive immunotherapy offers a promising therapeutic approach for the long-term management of AD.

Background Phosphate is an essential plant macronutrient required to achieve maximum crop yield. Roots are able to uptake soil phosphate from the immediate root area, thus creating a nutrient depletion zone. Many plants are able to exploit phosphate from beyond this root nutrient depletion zone through symbiotic association with Arbuscular Mycorrhizal Fungi (AMF). Here we characterise the relationship between root architecture, AMF association and low phosphate tolerance in strawberries. The contrasting root architecture in the parental strawberry cultivars ‘Redgauntlet’ and ‘Hapil’ was studied through a mapping population of 168 progeny. Low phosphate tolerance and AMF association was quantified for each genotype to allow assessment of the phenotypic and genotypic relationships between traits. Results A “phosphate scavenging” root phenotype where individuals exhibit a high proportion of surface lateral roots was associated with a reduction in root system size across genotypes. A genetic correlation between “root system size” traits was observed with a network of pleiotropic QTL found to represent five “root system size” traits. By contrast, average root diameter and the distribution of roots appeared to be under two discrete methods of genetic control. A total of 18 QTL were associated with plant traits, 4 of which were associated with solidity that explained 46% of the observed variation. Investigations into the relationship between AMF association and root architecture found that a higher root density was associated with greater AMF colonisation across genotypes. However, no phenotypic correlation or genotypic association was found between low phosphate tolerance and the propensity for AMF association, nor root architectural traits when plants are grown under optimal nutrient conditions. Conclusions Understanding the genetic relationships underpinning phosphate capture can inform the breeding of strawberry varieties with better nutrient use efficiency. Solid root systems were associated with greater AMF colonisation. However, low P-tolerance was not phenotypically or genotypically associated with root architecture traits in strawberry plants. Furthermore, a trade-off was observed between root system size and root architecture type, highlighting the energetic costs associated with a “phosphate scavenging” root architecture.