An easy-to-implement noise estimation method for tuning state estimators is proposed. It outperforms benchmark methods in terms of accuracy or computational cost both in theory and in a case study. We assume parametric uncertainty in the process model, which we transform into noise statistics using the generalized unscented transformation (GenUT). While most other methods estimate only the noise covariance, we also estimate the mean. Our tuning method is suitable for input-output models, demonstrated through a case study involving process simulators and industrial data. We present a theoretical analysis of our method, which is based on splitting one large GenUT to two smaller GenUTs. This results in two theorems: i) mean approximations for the two systems are equal and ii) covariance approximations are similar under certain mild conditions. These theorems confirm the validity of our method, and we discuss their potential to realize a numerically stable GenUT for high-dimensional systems.
Organisms from all kingdoms of life release membrane vesicles, which are tiny and spherical structures made of a lipid bilayer. Membrane vesicles carry out a number of functions, such as forming new cell membranes, removing waste products from the cell, and transporting lipids and other substances from parent to recipient cells. The payloads often contained in the vesicles are sorted via the endosomal sorting complex required for transport (ESCRT) pathway in a stepwise manner. Alterations to this endomembrane system reduces formation of vesicles and aberrant endosomal compartments. Furthermore, in pathogenic fungi, the deletion of ESCRT genes negatively effects virulence and growth, suggesting the ESCRT pathway has links to disease. However, only a few fungal species have to date been evaluated for the ESCRT pathway. In this review, we evaluate recent developments in the ESCRT pathway of fungi that infect plant hosts and its role in pathogenesis. This will provide an overview of EV-mediated cell-cell communication during host-pathogen interactions.
A crucial challenge in ecology is understanding and predicting population responses to climate change. A key component of population responses to climate change are asymmetries in which focal intra- or interspecific rates (e.g. population growth rates) change in response to climate change due to non-compensatory changes in underlying components (e.g. birth and death rates) determining the focal rates. Asymmetric climate change responses have been documented in a variety of systems and arise at multiple levels of organization within and across species. Yet, how these asymmetries combine to influence the demographics of populations is often unclear, as varied asymmetries are typically not mapped back to the fundamental demographic asymmetry – the differential changes in a species’ birth and death rates -- that underlies population and community change. We provide a flexible framework incorporating asymmetric changes in rates within and among species and mapping their consequences for additional rates across scales to their eventual effects on population growth rates. Throughout we provide specific applications of the framework. We hope this framework helps to unify research on asymmetric climate change responses, provides researchers with a common language to discuss asymmetric responses, and enhances our ability to understand how populations are responding to climate change.
The relationship between biodiversity and ecosystem function (BEF) captivates ecologists, but the factors responsible for the direction of this relationship remain unclear. While higher ecosystem functioning at higher biodiversity levels (‘positive BEF’) is not universal in nature, negative BEF relationships seem puzzlingly rare. Here, we develop a dynamical consumer-resource model inspired by microbial decomposer communities in pitcher plant leaves to investigate BEF. We manipulate microbial diversity via controlled colonization and measure their function as total ammonia production. We test how niche partitioning among bacteria and other ecological processes influence BEF in the leaves. We find that a negative BEF can emerge from reciprocal interspecific inhibition in ammonia production causing a negative complementarity effect, or from competitive hierarchies causing a negative selection effect. Absent these factors, a positive BEF was the typical outcome. Our findings provide a potential explanation for the rarity of negative BEF in empirical data.
In the Arctic tundra, recurrent periods of food scarcity force predators to rely on a wide variety of resources. In particular most predators use ungulate carcasses as an alternative food supply, especially in winters when live preys are scarce. As important and localized resource patches, carrion promotes co-occurrence of different individuals, and its use by predators is likely to be affected by interspecific competition. Here, we studied how interspecific competition and resource availability impact winter use of carrion by Arctic and red foxes in low Arctic Fennoscandia. We predicted that presence of red foxes limits Arctic foxes' use of carrion, and that the outcome of competition for carrion depends on the availability of alternative food resources, such as rodents. We monitored Arctic and red fox presence at experimentally supplied carrion using camera traps, between 2006 and 2021 in late winter. Using a multi-species dynamic occupancy model at a week-to-week scale, we evaluated use of carrion by foxes, while accounting for the presence of competitors, rodent availability and supplemental feeding provided to Arctic foxes. Competition primarily affected carrion use by increasing both species' probability to leave occupied carcasses to a similar extent, suggesting a symmetrical avoidance. Rodent abundance was associated with an increase in the probability of colonizing carrion for both species. For Arctic foxes, however, this increase was only observed in carcasses unoccupied by red foxes, showing greater avoidance when alternative preys are available. Contrary to expectations, we did not find strong signs of asymmetric competition for carrion in winter. Our results suggest that interactions for resources at a short time scale are not necessarily aligned with interactions at the scale of the population. In addition, we found that competition for carcasses depends on the availability of other resources, suggesting that interactions between predators depend on the ecological context.
Background and Purpose: The classical theory of receptor action has been used for decades as a powerful tool to estimate molecular determinants of ligand-induced receptor activation (i.e. affinity and efficacy) from experimentally observable biological responses. However, it is also a well-recognized fact that the receptor-binding and activation mechanisms, and the parameters thereof, described in the classical theory contradict with the modern view of receptor activation based on allosteric principles. Experimental Approach: We used mathematical analysis, along with some numerical simulations, to answer the key question as to what extent the classical theory is compatible -if at all- with the modern understanding of receptor activation. Key Results: Here, we showed conclusively that 1) receptor activation equations based on allosteric principles contain the logic of the classical theory in disguise, and therefore, 2) estimates of “intrinsic efficacy” () obtained by means of classical techniques (i.e. null methods or fitting the operational model to concentration-response data) are equivalent to the allosteric coupling factors that represent the molecular efficacy of ligands. Conclusion and Implications: Thus, we conclude that despite the right criticisms it has received so far, the classical theory may continue to be useful in estimating ligand efficacy from experimental data, if used properly. Here, we also provide rigorous criteria for the proper use of the theory. These findings not only have implications on ligand classification, but also resolve some long lasting discussions in the field of bias agonism in GPCR, which requires reasonable estimates of relative ligand efficacies at different signalling pathways.
Textures in Molybdenum-Rhenium alloys are inevitable during thermal fabrication.  and  are common orientations in Molybdenum-Rhenium alloys and effect mechanical responses. However, orientation dependence of mechanical responses in Molybdenum-Rhenium alloys is not quite clear yet. To clarity this problem, micro-pillar compression tests are conducted in grains with orientation  and  separately. Orientation-dependent compressive properties are found in Mo-14Re and Mo-42Re, but are not found in Mo and Mo-5Re, which may be attributed to activated muiti-slip planes as increased Re. Solid solution effect of Re not only rely on orientations, but also on Re content. Softening effect occurs in both  and  Mo-5Re. while, strong strengthening effect happens in  Mo-14Re and Mo-42Re. Our research clarifies that Mo-Re alloys with  orientation / texture could be preferred to obtain good strengthening effect.
Resilience assessment is a widely-used tool to evaluate the ability of an object (e.g., an individual structure, or a system consisting of multiple interacting structures) to withstand, recover from, and adapt to disruptive events. This paper proposes a novel concept of “nonresilience curve”, which measures the nonresilience (complement of resilience) of an object of interest conditional on a specific hazard intensity. It is by nature an extension of the well-established fragility curves, integrating the multiple damage states of a post-hazard object. The applicability of the proposed nonresilience curve to individual structures and systems (including series systems, parallel systems, and more general & complicated systems) has been demonstrated in this paper. It is also preliminarily shown that the shape of the cumulative distribution function of a lognormal distribution is suitable to approximate the nonresilience curve, if only limited data points associated with the target nonresilience curve are available. Since the nonresilience curve is a function of the hazard intensity measure, one can estimate the nonresilience of an object in a fully probabilistic manner by additionally taking into account the uncertainty associated with the intensity measure. The proposed nonresilience curve can be further extended to formulate nonresilience surface, which is a joint function of both the intensity measure and the available resource that supports the post-hazard recovery process. The nonresilience curve is promising to be adopted in engineering practice for resilience assessment and resilience-based design of civil structures and infrastructures.
Adaptive radiation as a result of ecological opportunity can have profound effects on the evolutionary outcome of species. On coral reefs, parrotfishes have been considered as one of the most dramatic examples of adaptive radiation unique in their extreme dietary specialisation. Using abrasion-resistant biomineralized teeth, parrotfishes are able to mechanically extract protein-rich micro-photoautotrophs growing in and amongst reef carbonate material. This unique ability to exploit a previously untapped trophic resource is thought to have led to the early diversification of the parrotfishes. In order to better understand the key evolutionary innovations leading to the success of these dietary specialists, we sequenced and analysed the genome of the spotted parrotfish (Cetoscarus ocellatus). Our findings reveal significant expansion, selection, and duplication within several gene families responsible for detoxification, including the cytochrome p450 gene family and non-cyp450 carboxylesterases. We find preliminary evidence that the structural mechanism responsible for the extreme hardness and biomineralization of parrotfish teeth may be a result of poly-glutamine expansion in the enamel protein ameloblastin. We also detect expansion and selection for several genes related to pigmentation and sequential hermaphroditism. Together, these results highlight a potentially complex interplay of adaptive radiation and sexual selection operating on coral reef ecosystems.
Species interactions and abiotic factors are important determinants of abundance and distribution, but accounting for biotic interactions is complicated by the fact that interactions occur at the individual-level at unknown spatial scales. Ignoring individual-level interactions can yield incorrect conclusions about biotic interactions when analyzing aggregated count data or presence-absence data. We present a hierarchical species distribution model that includes a Markov point process in which an individual’s location is dependent upon both abiotic variables and the locations of individuals of another species. The model can be regarded as a thinned point process in which encounter probability is a function of the distance between individual activity centers and survey locations. We applied the model to spatial capture-recapture data on two ecologically similar songbird species – hooded warbler (Setophaga citrina) and black-throated blue warbler (Setophaga caerulescens) – that segregate over a climate gradient in the southern Appalachian Mountains, USA. In spite of coarse spatial segregation and many ecological similarities between the two species, we found minimal evidence of spatial competition. There were strong, and opposing effects of climate on spatial variation in population densities, but spatial competition did not influence their distributions. A small simulation study indicated that the model can identify the distinct effects of environmental variation and biotic interactions on co-occurring species distributions. Unlike previous statistical models that attempt to infer competition from species-level co-occurrence data, the framework proposed here can be used to investigate how population-level patterns emerge from individual-level processes, while also allowing for inference on the spatial scale of biotic interactions. Our finding of minimal spatial competition between black-throated blue warbler and hooded warbler adds to the growing body of literature suggesting that, contrary to early theory from biogeography, abiotic factors may be more important than competition at low-latitude range margins.
Background and Purpose: Abnormal activation of the NLRP3 inflammasome in macrophages is closely associated with Ulcerative colitis (UC), and targeting the NLRP3 inflammasome has been proposed as a potential therapeutic approach, but the underlying mechanism by which it regulates intestinal inflammation remains unclear. Anemoside B4 (AB4) has anti-inflammatory activity, but whether it alleviates UC by inhibiting the activation of NLRP3 inflammasome remains unclear. More importantly, the molecular targets of AB4 remain unknown. Experimental Approach: We explored the role of AB4 in the development of dextran sodium sulfate (DSS)-induced colitis in wild-type (WT) mice and its effect on NLRP3 inflammasome. We isolated intestinal macrophages and epithelial cells, and validated them in DSS-induced NLRP3-deficient (NLRP3-/-) mice. The target and molecular mechanism of AB4 were identified in LPS-induced macrophages in vitro and DSS-induced macrophage-specific CD1d depletion (CD1d-/-) mice in vivo. Key Results: This study showed that AB4 had a strong anti-inflammatory effect DSS-induced colitis in WT mice, whereas the protective effects were lost in NLRP3-/- mice. AB4 inhibited the activation of NLRP3 inflammasome in colonic macrophages without affecting intestinal epithelial cells. Mechanistically, AB4 might target CD1d thus reducing the AKT-STAT1-PRDX1-NF-κB signaling pathway, eventually inhibiting the activation of NLRP3 inflammasome. Macrophage-specific CD1d depletion had been shown to reverse the protective effect of AB4. Conclusions and Implications: Our data showed that AB4 attenuated DSS-induced colitis by inhibiting CD1d-dependent NLRP3 inflammasome activation in macrophages. Therefore, as a natural product with high safety index, AB4 might be considered a promising candidate drug for the treatment of colitis.
Exercise induced eosinophil responses: normal cell counts with a marked decrease in responsivenessTo the Editor,Type II inflammation is characterized by elevated blood eosinophils which makes these cells an important diagnostic and treatment target in, for instance, severe asthma. Therefore, blood eosinophil numbers are a main inclusion criterion for many clinical studies that investigated the treatment of eosinophilic asthma with anti-IL5(Rα). However, there is no consensus on cut-off values for blood eosinophils during inclusion, as evidenced by a high variability between studies, ranging from 150 to 400 cells/µL. Moreover, the range of blood eosinophils in a healthy population, without confounding factors for increased blood eosinophils, is 30 – 330 cells/µL in males and 30 – 310 cells/µL in females. This implies that the cut-off values used for clinical studies greatly overlap with blood eosinophil counts that are found in the healthy population. This inherently poses a problem as eosinophil blood counts seem to be inadequate to use for diagnosing eosinophilic disease.This overlap in eosinophil counts between patients and the healthy population limits the application of eosinophil numbers for discriminating between health and several inflammatory diseases. A more promising approach in diagnosing eosinophilic disease is to combine eosinophil numbers with their activation status. Unfortunately, there is surprisingly little evidence that blood eosinophil counts correlate with their activation status and/or responsiveness in vivo in disease. This lack of correlation can be caused by ex vivo activation and/or their homing to the lung leaving behind non-activated cells in the blood.To circumvent ex vivo activation, we analyzed blood eosinophils activation status directly after venipuncture with a fast, automated, point-of-care, mobile flow cytometer (AQUIOS CL, Beckman Coulter). As exercise can be used as a model to modulate eosinophil numbers in a healthy setting, we studied whether eosinophil blood counts correlate with their activation status and their responsiveness to formyl peptides in a cohort of long-distance runners participating in a mass-participation trail run (22, 29 or 43 km). The study was approved by medical research ethics committee Oost-Nederland (NL79864.091.22). After written informed was obtained, venous blood samples were collected from 35 athletes before, directly after and 24 hours after exercise. The eosinophil activation status was assessed by combining automated flow cytometry with a 5-dimensional algorithm-based gating.An acute leukocytosis with eosinopenia was present directly post-exercise, which is in agreement with previous research. These numbers normalized 24 hours after exercise (figure 1A, 1C ). Compared to before exercise, eosinophils showed a more activated phenotype (increased CD11b and decreased CD62L) directly after exercise which also normalized within 24 hours. In marked contrast to acute inflammation, such as caused by SARS-CoV2 infection, this eosinopenia directly after exercise did not lead to refractoriness to fNLF-stimulation. However, after the normalization of eosinophil counts 24 hours after exercise, the eosinophils were refractory for activation by fNLF (figure 1B, 1C ). This clearly showed a complete dissociation between blood eosinophil numbers and their relative activation status.Our results illustrate that the eosinophil blood compartment is not adequately characterized by solely counting cell numbers (‘quantity’) as normalized numbers do not necessarily reflect normalization of their activation status (‘quality’). This finding is not limited to measuring the state of type II immunity in eosinophilic disease, but probably also applies to other infectious/inflammatory conditions and to non-pathological settings. Our data call for a re-evaluation of using blood eosinophil counts as an adequate representation of the eosinophil compartment’s state. Until recently, determining the activation status of the eosinophil compartment was complicated by ex vivo artifacts already starting at the moment of venipuncture. Now with the availability of fast, automated, point-of-care flow cytometry, it is feasible to measure both the quantity and quality of eosinophils in a wide scope of health and disease settings.
INTRODUCTION:Tuberculosis (TB) is still one of the most prevalent infections, especially in the developing world. The World Health Organisation (WHO) estimates that there are 8 million new cases annually [1,2]. Cough, sputum with or without haemoptysis, fever, and constitutional symptoms are the hallmark manifestations of an active tuberculosis infection. In patients with pulmonary TB, an increase in haemoglobin levels is regarded as an indicator of a positive response to treatment. Furthermore, Omar et al. found that a fall in platelet count, white blood cell (WBC) count, and erythrocyte sedimentation rate (ESR) were strong indications of clinical response . Despite the possibility of an increase in white blood cells (WBC), which results in lymphocyte predominance, in clinical practice, eosinophilia is a usual finding that is self-limiting in moderate cases, but it is exceedingly infrequent in TB [4,5].Many allergic, viral, and neoplastic conditions may produce peripheral blood eosinophilia, necessitating a variety of examinations and subsequent therapy. Common causes of eosinophilia in children include infections with helminthic parasites, allergic diseases, malignancies, and adverse drug reactions [1,6]. One of the primary goals of the early evaluation is to identify an underlying cause that needs specific therapy. Even though difficulties linked with eosinophilia are more prevalent in individuals with higher eosinophil counts (>1500 eosinophils/uL), the peripheral blood eosinophil count does not accurately assess the risk of organ damage in each patient. A patient with modest peripheral blood eosinophilia may also have significant eosinophil organ involvement. Normal eosinophil counts in the human blood range between 0-350/mm3. This quantity accounts for between 1 and 3% of the differential leukocyte count . Most reports of eosinophilia in tuberculosis describe local eosinophilia as opposed to peripheral eosinophilia . To the best of our knowledge, reported cases are very rare. As a consequence, we describe one case of TB with considerable peripheral eosinophilia and the treatment outcome.
Urbanization reflects a major form of environmental change impacting wild birds globally. Whereas urban habitats may provide increased availability of water, some food items, and reduced predation levels compared to rural, they can also present novel stressors including increased light at night, ambient noise, and reduced nutrient availability. Urbanization can also alter levels of brood parasitism, with some host species experiencing elevated levels of brood parasitism in urban areas compared to rural areas. Though the demographic and behavioral consequences of urbanization and brood parasitism have received considerable attention, their consequences for cellular-level processes are less understood. Telomeres provide an opportunity to understand the cellular consequences of different environments as they are a well-established metric of biological state that can be associated with residual lifespan, disease risk, and behaviour, and are known to be sensitive to environmental conditions. Here we examine the relationships between urbanization, brood parasitism, and blood telomere lengths in adult and nestling song sparrows (Melospiza melodia). Song sparrows are a North American songbird found in both urban and rural habitats that experience high rates of brood parasitism by brown-headed cowbirds (Molothrus ater) in the urban, but not the rural, sites in our study system. Among adults and nestlings from non-parasitized nests, we found no differences in relative telomere lengths between urban and rural habitats. However, among urban nestlings, the presence of a brood parasite in the nest was associated with significantly shorter relative telomere lengths compared to when a brood parasite was absent. Our results suggest a novel, indirect, impact of urbanization on nestling songbirds through the physiological impacts of brood parasitism.
RATIONALE: Helium (He) is used in cutting-edge research in industry and science as a carrier and/or ionization gas. The global He shortages have dramatically increased its prices and reduced its availability, to what comes together the current energy crisis. A strategy is proposed to save He and energy in elemental analysis/isotope ratio mass spectrometry (EA/IRMS). METHODS: A method for analysis of carbon and nitrogen isotope composition (δ13C and δ15N values) is proposed using two or three sequential combustion reactions in a single EA/IRMS acquisition. The methods (hereafter called 2×EA/IRMS and 3×EA/IRMS) use the time needed for the peak center and reference gas (CO2 or N2) pulses to measure δ13C or δ15N in two or three capsules with samples or standards. The combustion cycles can be replicate analyses of the same or different material. RESULTS: The methods were validated with replicate analysis of C and N in RMs and laboratory standards of a broad range of biological and geological matrices, δ13C and δ15N values, and C/N molar ratios. The accuracy and precision of the 2×EA/IRMS and 3×EA/IRMS values were15 essentially the same, with good agreement between the mean ± 1 SD values from RMs and standard analyses and the recommended or accepted values and their uncertainties. CONCLUSIONS: The proposed methods save He, save energy, save reference gases (CO2, N2), and O2, while reducing the analysis and instrumental times by ca. 50 %.