Functional Response Research Articles

Iron Is Critical for Mucosal-Associated Invariant T Cell Metabolism and Effector Functions.

Mucosal-Associated Invariant T (MAIT) cells are a population of innate T cells that play a critical role in host protection against bacterial and viral pathogens. Upon activation, MAIT cells can rapidly respond via both TCR-dependent and -independent mechanisms, resulting in robust cytokine production. The metabolic and nutritional requirements for optimal MAIT cell effector responses are still emerging. Iron is an important micronutrient and is essential for cellular fitness, in particular cellular metabolism. Iron is also critical for many pathogenic microbes, including those that activate MAIT cells. However, iron has not been investigated with respect to MAIT cell metabolic or functional responses. In this study, we show that human MAIT cells require exogenous iron, transported via CD71 for optimal metabolic activity in MAIT cells, including their production of ATP. We demonstrate that restricting iron availability by either chelating environmental iron or blocking CD71 on MAIT cells results in impaired cytokine production and proliferation. These data collectively highlight the importance of a CD71-iron axis for human MAIT cell metabolism and functionality, an axis that may have implications in conditions where iron availability is limited.

Temporal sensitivity for achromatic and chromatic flicker across the visual cortex.

The retinal ganglion cells (RGCs) receive different combinations of L, M, and S cone inputs and give rise to one achromatic and two chromatic post-receptoral channels. Beyond the retina, RGC outputs are subject to filtering and normalization along the geniculo-striate pathway, ultimately producing the properties of human vision. The goal of the current study was to determine temporal sensitivity across the three post-receptoral channels in subcortical and cortical regions involved in vision. We measured functional magnetic resonance imaging (MRI) responses at 7 Tesla from three participants (two males, one female) viewing a high-contrast, flickering, spatially-uniform wide field (∼140°). Stimulus flicker frequency varied logarithmically between 2 and 64 Hz and targeted the L+M+S, L-M, and S-[L+M] cone combinations. These measurements were used to create temporal sensitivity functions of primary visual cortex (V1) across eccentricity, and spatially averaged responses from lateral geniculate nucleus (LGN), V2/V3, hV4, and V3A/B. Functional MRI responses reflected known properties of the visual system, including higher peak temporal sensitivity to achromatic vs. chromatic stimuli, and low-pass filtering between the LGN and V1. Peak temporal sensitivity increased across levels of the cortical visual hierarchy. Unexpectedly, peak temporal sensitivity varied little across eccentricity within area V1. Measures of adaptation and distributed pattern activity revealed a subtle influence of 64 Hz achromatic flicker in area V1, despite this stimulus evoking only a minimal overall response. Comparison of measured cortical responses to a model of integrated retinal output to our stimuli demonstrates that extensive filtering and amplification is applied to post-retinal signals.Significance Statement We report the temporal sensitivity of human visual cortex across the three canonical post-receptoral channels from central vision to the far periphery. Functional MRI measurements of responses from the LGN, V1, and higher visual cortical areas demonstrate modification of temporal sensitivity across the visual hierarchy. This includes amplification of chromatic signals between the LGN and V1, and an increase in peak temporal sensitivity in visual areas beyond V1. Within V1, we find a surprising stability of peak temporal sensitivity in the periphery for all three post-receptoral directions. Comparison of our results to a model of retinal output demonstrates the presence of substantial post-retinal filtering, yielding greater uniformity of responses across area V1 than would be predicted from unmodified retinal signals.

Improving species distribution forecasts by measuring and communicating uncertainty: An invasive species case study.

Forecasting invasion risk under future climate conditions is critical for the effective management of invasive species, and species distribution models (SDMs) are key tools for doing so. However, SDM-based forecasts are uncertain, especially when correlative statistical models extrapolate to nonanalog environmental domains, such as future climate conditions. Different assumptions about the functional form of the temperature-suitability relationship can impact predicted habitat suitability under novel conditions. Hence, methods to understand the sources of uncertainty are critical when applying SDMs. Here, we use high-resolution predictions of lake water temperatures to project changes in habitat suitability under future climate conditions for an invasive macrophyte (Myriophyllym spicatum). Future suitability was predicted using five global circulation models and three statistical models that assumed different species-temperature functional responses. The suitability of lakes for M. spicatum was overall predicted to increase under future climate conditions, but the magnitude and direction of change in suitability varied greatly among lakes. Variability was most pronounced for lakes under nonanalog temperature conditions, indicating that predictions for these lakes remained highly uncertain. Integrating predictions from SDMs that differ in their species-environment response function, while explicitly quantifying uncertainty across analog and nonanalog domains, can provide a more robust and useful approach to forecasting invasive species distribution under climate change.

Mechanical and Functional Responses in Astrocytes under Alternating Deformation Modes Using Magneto-Active Substrates.

This work introduces NeoMag, a system designed to enhance cell mechanics assays in substrate deformation studies. NeoMag uses multidomain magneto-active materials to mechanically actuate the substrate, transmitting reversible mechanical cues to cells. The system boasts full flexibility in alternating loading substrate deformation modes, seamlessly adapting to both upright and inverted microscopes. The multidomain substrates facilitate mechanobiology assays on 2D and 3D cultures. The integration of the system with nanoindenters allows for precise evaluation of cellular mechanical properties under varying substrate deformation modes. The system was used to study the impact of substrate deformation on astrocytes, simulating mechanical conditions akin to traumatic brain injury and ischemic stroke. The results reveal local heterogeneous changes in astrocyte stiffness, influenced by the orientation of subcellular regions relative to substrate strain. These stiffness variations, exceeding 50% in stiffening and softening, and local deformations significantly alter calcium dynamics. Furthermore, sustained deformations induce actin network reorganisation and activate Piezo1 channels, leading to an initial increase followed by a long-term inhibition of calcium events. Conversely, fast and dynamic deformations transiently activate Piezo1 channels and disrupt the actin network, causing long-term cell softening. These findings unveil mechanical and functional alterations in astrocytes during substrate deformation, illustrating the multiple opportunities this technology offers.

A Novel Interaction of Nesidiocoris tenuis (Hemiptera: Miridae) as a Biological Control Agent of Bactericera cockerelli (Hemiptera: Triozidae) in Potato

Nesidiocoris tenuis (Hemiptera: Miridae) is a generalist predator commonly used to control the whitefly Bemisia tabaci in Europe. This mirid has been found and established in South Texas, where it was initially observed feeding on nymphs of the psyllid Bactericera cockerelli (Hemiptera: Triozidae) in open tomato fields. B. cockerelli is the vector of the fastidious bacterium “Candidatus Liberibacter solanacearum” that causes diseases in several solanaceous crops, including zebra chip (ZC) disease in potatoes. There is a need to better understand how this predator impacts the control of important crop pests, such as potato psyllids. We assessed the interactions between N. tenuis and B. cockerelli in three different environmental settings. First, we estimated the numeric response of N. tenuis preying on B. cockerelli under laboratory and greenhouse conditions. Second, we evaluated the predator–prey interaction under controlled field cage conditions. Then, we exposed N. tenuis under controlled field release conditions to the natural occurrence of B. cockerelli. Finally, we assessed the compatibility between the use of N. tenuis as a biological control agent in a field study and its impact on ZC disease incidence, severity in potato tubers, and potato yield. Laboratory and greenhouse experiments resulted in diverse types of functional model responses, including exponential and linear mathematical models. Our findings revealed a significant predation effect exerted by N. tenuis, resulting in a reduction of more than fourfold in the number of B. cockerelli nymphs per cage. Specifically, the nymphal population decreased from 21 ± 3.2 in the absence of N. tenuis to 5 ± 1.6 when N. tenuis was present. Furthermore, the combination of N. tenuis with a reduced insecticide program increased potato yields, but only reduced ZC tuber incidence in one of two potato cultivars evaluated, and in one season. Findings from these studies indicate that N. tenuis could be effective as a biological control agent for B. cockerelli in potato production in South Texas. This is the first report of N. tenuis preying on immature stages of any psyllid species.

Deciphering S100B Allosteric Signaling: The Role of a Peptide Target, TRTK-12, as an Ensemble Modulator.

Allostery is an essential biological phenomenon in which perturbation at one site in a biomolecule elicits a functional response at a distal location(s). It is integral to biological processes, such as cellular signaling, metabolism, and transcription regulation. Understanding allostery is also crucial for rational drug discovery. In this work, we focus on an allosteric S100B protein that belongs to the S100 class of EF-hand Ca2+-binding proteins. The Ca2+-binding affinity of S100B is modulated allosterically by TRTK-12 peptide binding 25 Å away from the Ca2+-binding site. We investigated S100B allostery by carrying out nuclear magnetic resonance (NMR) measurements along with microsecond-long molecular dynamics (MD) simulations on S100B/Ca2+ with/without TRTK-12 at different NaCl salt concentrations. NMR HSQC results show that TRTK-12 reorganizes how S100B/Ca2+ responds to different salt concentrations at both orthosteric and allosteric sites. The MD data suggest that TRTK-12 breaks the dynamic aromatic and hydrogen-bond interactions (not observed in X-ray crystallographic structures) between the hinge/helix and Ca2+-binding EF-hand loop of the two subunits in the homodimeric protein. This triggers rearrangement in the protein network architectures and leads to allosteric communication. Finally, computational studies of S100B at distinct ionic strengths suggest that ligand-bound species are more robust to the changing environment relative to the S100B/Ca2+ complex.

Analysis of Prey-Predator Scheme in Conjunction with Help and Gestation Delay

This paper presents a three-dimensional continuous time dynamical system of three species, two of which are competing preys and one is a predator. We also assume that during predation, the members of both teams of preys help each other and the rate of predation of both teams is different. The interaction between prey and predator is assumed to be governed by a Holling type II functional response and discrete type gestation delay of the predator for consumption of the prey. In this work, we establish the local asymptotic stability of various equilibrium points to understand the dynamics of the model system. Different conditions for the coexistence of equilibrium solutions are discussed. Persistence, permanence of the system, and global stability of the positive interior equilibrium solution are discussed by constructing suitable Lyapunov functions when the gestation delay is zero, and there is no periodic orbit within the interior of the first quadrant of state space around the interior equilibrium. As we introduced time delay due to the gestation of the predator, we also discuss the stability of the delayed model. It is observed that the existence of stability switching occurs around the interior equilibrium point as the gestation delay increases through a certain critical threshold. Here, a phenomenon of Hopf bifurcation occurs, and a stable limit cycle corresponding to the periodic solution of the system is also observed. This study reveals that the delay is taken as a bifurcation parameter and also plays a significant role for the stability of the proposed model. Computer simulations of numerical examples are given to explain our proposed model. We have also addressed critically the biological implications of our analytical findings with proper numerical examples.

Spatiotemporal and Trade-Off Dynamics in Prey–Predator Model with Domed Functional Response and Fear Effect

In the ecological scenario, predators often risk their lives pursuing dangerous prey, potentially reducing their chances of survival due to injuries. Prey, on the other hand, try to strike a balance between reproduction rates and safety. In our study, we introduce a two-dimensional prey–predator model inspired by Tostowaryk’s work, specifically focusing on the domed-shaped functional response observed in interactions between pentatomid predators and neo-diprionid sawfly larvae. To account for the varying effectiveness of larval group defense, we incorporate a new component into the response equation. Our investigation delves into predator trade-off dynamics by adjusting the predator’s mortality rate to reflect losses incurred during encounters with dangerous prey and prey’s trade-off between safety and reproduction rate incorporating this domed-shaped functional response. Our model demonstrates bistability and undergoes various bifurcations, including transcritical, saddle-node, Hopf, Bogdanov–Takens, and Homoclinic bifurcations. Critical parameters impact both predator and prey populations, potentially leading to predator extinction if losses due to dangerous prey encounters become excessive, highlighting the risks predators face for their survival. Furthermore, the efficacy of group defense mechanisms can further endanger predators. Expanding our analysis to a spatially extended model under different perturbations, we explore Turing instability to explain the relationship between diffusion and encounter parameters through both stationary and dynamic pattern formation. Sensitivity to initial conditions uncovers spatiotemporal chaos. These findings provide valuable insights into comprehending the intricate dynamics of prey–predator interactions within ecological systems.

Influence of climate, physical and chemical variables on the taxonomic and functional responses of macroinvertebrate communities in tropical island rivers

Influence of climate, physical and chemical variables on the taxonomic and functional responses of macroinvertebrate communities in tropical island rivers

Effect of a water-soluble form of dihydroquercetin on age-dependent LPS-induced gliovascular remodeling of the substantia nigra in rats

Background. The molecular and cellular mechanisms of action of the water-soluble form of dihydroquercetin (DHA-VF) on neurogliovascular units, age-related disturbances of intrasystem connections that may underlie neuroinflammatory and neurodegenerative diseases, remain unclear.The aim: to study structural changes of microcirculatory vessels and functional responses of micro- and astroglial cells in the substantia nigra of young and old rats in response to intranigral injection of lipopolysaccharide (LPS) and subsequent oral administration of DHA-VF.Methods. Young (250-320 g) and old (390-450 g) Wistar rats were injected with 2 μL LPS solution at a concentration of 0.01 μL/mL (experimental group; n=24) or 2 μL sterile physiological solution (control group; n=12) into the substantia nigra area of the brain using a stereotaxic device. Half of the animals in the experimental groups (6 animals of each age group) were given 2 ml of a solution containing DHA-VF at a concentration of 3 mg/mL daily by gavage with a probe. After 8 weeks, the animals were decapitated and cryostat sections were obtained for histochemical (FITC-labeled tomato lectin) and immunohistochemical (antibodies against GFAP and CD-11β) staining of vascular endothelium and glial cells, respectively. Results. 8 weeks after LPS administration to old rats in the CS, a significant excess of areas occupied by cell bodies and processes of microglial and astroglial cells as well as the number of vessels at standard sites was found compared to both young animals exposed to similar exposure and old control animals. Oral administration of DHA-VF to rats significantly reduced LPS-induced glial activation in young and old animals. In addition, administration of DHA-VF to old animals reduced the intensity of LPS-induced microvascular remodeling of the CS. Conclusions. LPS administration in the rat CS induces neuroinflammation and vascular angiogenesis, which are maximally expressed in old animals. Administration of DHA-VF for 8 weeks significantly reduced these LPS-induced changes.

Biological and functional responses of the benthic surf zone community to different beach types

In this study, we analyzed the biological descriptors and functional traits of the benthic community inhabiting the water/bottom layer in the surf zones of three sandy beaches: a tide-dominated flat, and two intermediate beaches, from tide-modified to wave-dominated. Samples were collected seasonally in the inner surf zone by hand-towing a benthic sledge equipped with two nets, one above the other, across transects parallel to the shore, capturing the benthic community in two levels, close to the seafloor. A total of 116 species were collected, with a total of 327,678 specimens. Arthropods were 99.63% of all individuals caught across the three beaches, mainly represented by peracarid crustaceans. An important species turnover was detected along the shore, with a significant change in community composition. The biological descriptors and some functional traits vary among beaches: the total density, the density of individuals of small (5–10 mm length) and very small sizes (<5 mm length), the density of larval forms, and the presence of colonial species were higher in the tide-dominated flat (sometimes also in the tide-modified beach). More arthropods and more mobile individuals were found in those beaches, while mollusks and sedentary individuals were found in high number in the wave-dominated beach. Stratification was present across the three studied beaches, with higher densities in the near-bottom layer. In the tide-dominated beach, there was also a higher richness in this layer, with a nested community between levels. In the wave-dominated beach, similar richness was registered between levels, with a different community composition (and some differences in functional traits), indicating that some species can maintain their position close to the bottom despite the turbulent conditions experienced on this beach. Differences in wave conditions among beach types could be an important factor driving the biological descriptors and functional traits of the benthic community in surf zone ecosystems. Therefore, acknowledging their role is crucial in deciphering global patterns in surf zone biodiversity.

Spatiotemporal Dynamics of a General Two-Species System with Taxis Term

In this paper, we investigate the spatiotemporal dynamics in a diffusive two-species system with taxis term and general functional response, which means the directional movement of one species upward or downward the other one. The stability of positive equilibrium and the existences of Turing bifurcation, Turing–Hopf bifurcation and Turing–Turing bifurcation are investigated. An algorithm for calculating the normal form of the Turing–Hopf bifurcation induced by the taxis term and another parameter is derived. Furthermore, we apply our theoretical results to a cooperative Lotka–Volterra system and a predator–prey system with prey-taxis. For the cooperative system, stable equilibrium becomes unstable by taxis-driven Turing instability, which is impossible for the cooperative system without taxis. For a predator–prey system with prey-taxis, the dynamical classification near the Turing–Hopf bifurcation point is clearly described. Near the Turing–Hopf point, there are spatially inhomogeneous steady-state solution, spatially homogeneous/nonhomogeneous periodic solution and pattern transitions from one spatiotemporal state to another one.

Differential and Functional Response Time Item Analysis: An Application to Understanding Paper versus Digital Reading Processes

AbstractDespite the growing interest in incorporating response time data into item response models, there has been a lack of research investigating how the effect of speed on the probability of a correct response varies across different groups (e.g., experimental conditions) for various items (i.e., differential response time item analysis). Furthermore, previous research has shown a complex relationship between response time and accuracy, necessitating a functional analysis to understand the patterns that manifest from this relationship. In this study, response time data are incorporated into an item response model for two purposes: (a) to examine how individuals' speed within an experimental condition affects their response accuracy on an item, and (b) to detect the differences in individuals' speed between conditions in the presence of within‐condition effects. For these two purposes, by‐variable smooth functions are employed to model differential and functional response time effects by experimental condition for each item. This model is illustrated using an empirical data set to describe the effect of individuals' speed on their reading comprehension ability in two experimental conditions of reading medium (paper vs. digital) by item. A simulation study showed that the recovery of parameters and by‐variable smooth functions of response time was satisfactory, and that the type I error rate and power of the test for the by‐variable smooth function of response time were acceptable in conditions similar to the empirical data set. In addition, the proposed method correctly identified the range of response time where between‐condition differences in the effect of response time on the probability of a correct response were accurate.

Ablation-induced left atrial mechanical dysfunction recovers in weeks after ablation.

The immediate impact of catheter ablation on left atrial mechanical function and the timeline for its recovery in patients undergoing ablation for atrial fibrillation (AF) remain uncertain. The mechanical function response to catheter ablation in patients with different AF types is poorly understood. A total of 113 AF patients were included in this retrospective study. Each patient had three magnetic resonance imaging (MRI) studies in sinus rhythm: one pre-ablation, one immediate post-ablation (within 2days after ablation), and one post-ablation follow-up MRI (≤ 3months). We used feature tracking in the MRI cine images to determine peak longitudinal atrial strain (PLAS). We evaluated the change in strain from pre-ablation, immediately after ablation to post-ablation follow-up in a short-term study (< 50days) and a 3-month study (3months after ablation). The PLAS exhibited a notable reduction immediately after ablation, compared to both pre-ablation levels and those observed in follow-up studies conducted at short-term (11.1 ± 9.0days) and 3-month (69.6 ± 39.6days) intervals. However, there was no difference between follow-up and pre-ablation PLAS. The PLAS returned to 95% pre-ablation level within 10days. Paroxysmal AF patients had significantly higher pre-ablation PLAS than persistent AF patients in pre-ablation MRIs. Both type AF patients had significantly lower immediate post-ablation PLAS compared with pre-ablation and post-ablation PLAS. The present study suggested a significant drop in PLAS immediately after ablation. Left atrial mechanical function recovered within 10days after ablation. The drop in PLAS did not show a substantial difference between paroxysmal and persistent AF patients.

Pancreatic Beta Cell Function in Infants Varies by Maternal Weight

Background: The Asian Indian Beta Cell function (ABCs) in Infants Study examined the associations of maternal weight on infant pancreatic beta cell function across 7 months postpartum. Methods: Pregnant women aged 18–35 years were recruited in Hyderabad, India. Women were classified by first trimester weight as underweight (UW), BMI &lt; 18.5 kg/m2; normal weight (NW), BMI 18.5–22.9 kg/m2; or overweight (OW), BMI 23.0 through &lt;28.5 kg/m2. At age &gt; 7 months, infants had an oral glucose tolerance test (OGTT, 1.75 g glucose/kg bodyweight) following a 3 h fast. Infant blood samples were assayed for C-peptide and glucose. Infant beta cell function (HOMA2-B; disposition index, DI) and insulin resistance (HOMA2-IR) were compared across maternal weight groups. Results: Mothers (UW n = 63; NW n = 43; OW n = 29) had similar age at delivery and second trimester 50 g glucose challenge test results. Cord HOMA2-B values were 51% greater for IUW (83.5, SD 55.2) and 44% greater for IOW (79.9, SD 60.8) vs. INW (55.4, SD 51.5), forming a U-shaped relationship between maternal weight and HOMA2-B. No qualitative differences in HOMA2-IR were found at birth. However, at 7 months postpartum, HOMA2-IR changed most within IUW (−64% median reduction) and changed the least in IOW (−7% median reduction). At seven months postpartum, DI was higher in IUW vs. the other groups (geometric mean IUW 1.9 SD 2.5; INW 1.3 SD 2.6 or vs. IOW mean 1.2 SD 3.7), reflecting a +49% difference in DI. Conclusions: Evidence from this study illustrates adaptations in the pancreatic functional response of infants associated with the maternal nutritional environment.

Existence and stability of steady-state bifurcations in a prey–predator system with a nonmonotonic functional response

A cross-diffusion prey–predator system exhibiting the prey group defense under homogeneous Neumann boundary conditions is studied. By considering the diffusive rate of the prey as a bifurcation parameter, we investigate sudden changes in the population dynamics of the prey and predator which can have a substantial effect on population size of the species. First a priori estimate for positive steady states is obtained. Next we prove the existence of a pitchfork bifurcation of positive steady states at a simple eigenvalue. The structure of the global steady-state bifurcation is discussed. We also investigate the stability of the trivial solution line and nontrivial steady-state solutions via the eigenvalue perturbation theory. To illustrate our theoretical results some numerical simulations are given. Numerical examples contain a supercritical and a subcritical pitchfork bifurcation.

Apoptotic cell identity induces distinct functional responses to IL-4 in efferocytic macrophages.

Macrophages are functionally heterogeneous cells essential for apoptotic cell clearance. Apoptotic cells are defined by homogeneous characteristics, ignoring their original cell lineage identity. We found that in an interleukin-4 (IL-4)-enriched environment, the sensing of apoptotic neutrophils by macrophages triggered their tissue remodeling signature. Engulfment of apoptotic hepatocytes promoted a tolerogenic phenotype, whereas phagocytosis of T cells had little effect on IL-4-induced gene expression. In a mouse model of parasite-induced pathology, the transfer of macrophages conditioned with IL-4 and apoptotic neutrophils promoted parasitic egg clearance. Knockout of phagocytic receptors required for the uptake of apoptotic neutrophils and partially T cells, but not hepatocytes, exacerbated helminth infection. These findings suggest that the identity of apoptotic cells may contribute to the development of distinct IL-4-driven immune programs in macrophages.

Hopf bifurcation in an age-structured predator–prey system with Beddington–DeAngelis functional response and constant harvesting

In this paper, an age-structured predator–prey system with Beddington–DeAngelis (B–D) type functional response, prey refuge and harvesting is investigated, where the predator fertility function f(a) and the maturation function β(a)\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\beta (a)$$\\end{document} are assumed to be piecewise functions related to their maturation period τ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ au $$\\end{document}. Firstly, we rewrite the original system as a non-densely defined abstract Cauchy problem and show the existence of solutions. In particular, we discuss the existence and uniqueness of a positive equilibrium of the system. Secondly, we consider the maturation period τ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ au $$\\end{document} as a bifurcation parameter and show the existence of Hopf bifurcation at the positive equilibrium by applying the integrated semigroup theory and Hopf bifurcation theorem. Moreover, the direction of Hopf bifurcation and the stability of bifurcating periodic solutions are studied by applying the center manifold theorem and normal form theory. Finally, some numerical simulations are given to illustrate of the theoretical results and a brief discussion is presented.

Endocrinopathies with impact on the canine cardiovascular system

The hormones’ synthesis and secretion are performed by endocrine glands which, when under the effect of physiological disturbance, can result in abnormal hormones’ secretion, resulting in alteration of the organism's functionality, stimulus or physiological response. The hormones’ secretion at levels below or above necessary can result in cardiovascular changes that can be presented as symptoms that can be commun associated to behavioral characteristics, racial association, sedentary lifestyle, aging or even nutritional management failures. Prolonged exposure to lower levels of hormonal secretion can lead the endocrine patient to develop chronic changes in cardiac functionality such as arrhythmia and bradycardia, as well as anatomical variation such as left ventricular hypertrophy and narrowing of the vena cava. Not enough, the dog may present laboratoial alterations and specific symptoms that can act as obstacles to the physiological functioning of the cardiovascular system, such as weight gain, muscle weakness, lethargy, hyperkalemia, hypercortisolemia and hyperglycemia. This paper lists the main impacts of endocrinopathies on the cardiovascular system, aiming to raise awareness among veterinarians about the importance of monitoring the cardiovascular, both during and after the end of treatment or stabilization of an endocrinopathy.

Functioning human lung organoids model pulmonary tissue response from carbon nanomaterial exposures

Human lung organoids (HLOs) are increasingly used to model development and infectious diseases, however their ability to recapitulate functional pulmonary tissue response to nanomaterial (NM) exposures has yet to be demonstrated. Here, we established a lung organoid exposure model that utilises microinjection to present NMs into the lumen of organoids. Our model assures efficient, reproducible and controllable exposure of the apical pulmonary epithelium, emulating real-life human exposure scenario. By comparing the impact of two well studied carbon-based NMs, graphene oxide sheets (GO) and multi-walled carbon nanotubes (MWCNT), we validated lung organoids as tools for predicting pulmonary NM-driven responses. In agreement with established in vivo data, we demonstrate that MWCNT, but not GO, elicit adverse effects on lung organoids, leading to a pro-fibrotic phenotype. Our findings reveal the capacity and suitability of HLOs for hazard assessment of NMs, aligned with the much sought-out 3Rs (animal research replacement, reduction, refinement) framework.