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Aβ42 is one of the most extensively studied blood and Cerebrospinal fluid (CSF) biomarkers for the diagnosis of symptomatic and prodromal Alzheimer’s disease (AD). Because of the heterogeneity and transient nature of Aβ42 oligomers (Aβ42Os), the development of technologies for dynamically detecting changes in the blood or CSF levels of Aβ42 monomers (Aβ42Ms) and Aβ42Os is essential for the accurate diagnosis of AD. The currently commonly used Aβ42 ELISA test kits usually mis-detected the elevated Aβ42Os, leading to incomplete analysis and underestimation of soluble Aβ42, resulting in a comprised performance in AD diagnosis. Herein, we developed a dual-target lateral flow immunoassay (dLFI) using anti-Aβ42 monoclonal antibodies 1F12 and 2C6 for the rapid and point-of-care detection of Aβ42Ms and Aβ42Os in blood samples within 30 min for AD diagnosis. By naked eye observation, the visual detection limit of Aβ42Ms or/and Aβ42Os in dLFI was 154 pg/mL. The test results for dLFI were similar to those observed in the enzyme-linked immunosorbent assay (ELISA). Therefore, this paper-based dLFI provides a practical and rapid method for the on-site detection of two biomarkers in blood or CSF samples without the need for additional expertise or equipment. Graphical Abstract

Highlights • Standard procedures and appropriate assessment of exercise are proposed for the commonly used animal models related to chronic exercise (e.g., treadmill running, voluntary wheel running, swimming exercise, and resistance exercise) in cardiovascular research. • Optimal design of animal exercise studies in cardiovascular research should consider the choice of exercise models, control of exercise protocols, exercise at different stages of disease, and other factors, such as age, sex, and genetic background. • An optimal design for studying exercise-induced physiological cardiac growth and its related beneficial effects against cardiovascular diseases is presented., Growing evidence has demonstrated exercise as an effective way to promote cardiovascular health and protect against cardiovascular diseases However, the underlying mechanisms of the beneficial effects of exercise have yet to be elucidated. Animal exercise studies are widely used to investigate the key mechanisms of exercise-induced cardiovascular protection. However, standardized procedures and well-established evaluation indicators for animal exercise models are needed to guide researchers in carrying out effective, high-quality animal studies using exercise to prevent and treat cardiovascular diseases. In our review, we present the commonly used animal exercise models in cardiovascular research and propose a set of standard procedures for exercise training, emphasizing the appropriate measurements and analysis in these chronic exercise models. We also provide recommendations for optimal design of animal exercise studies in cardiovascular research, including the choice of exercise models, control of exercise protocols, exercise at different stages of disease, and other considerations, such as age, sex, and genetic background. We hope that this position paper will promote basic research on exercise-induced cardiovascular protection and pave the way for successful translation of exercise studies from bench to bedside in the prevention and treatment of cardiovascular diseases., Graphical abstract Image, graphical abstract

Cellulose paper has strong potential as an analytical platform owing to its unique characteristics. In the present study, we investigated a procedure for functionalizing the surface of cellulose paper by dip-coating a mixture of a functional polymer and a perfluoroalkylated surfactant (surfactant 1). The functional polymer comprised a mixture of methyl methacrylate and poly(ethylene glycol) methacrylate monomers. The monomer ratio in the functional polymer affected the hydrophilicity and water absorbance of the cellulose paper after dip-coating. Furthermore, the presence of surfactant 1 during dip-coating promoted the surface segregation of poly(ethylene glycol) (PEG) moieties in the polymer, which enhanced the hydrophilicity, prevented nonspecific protein adsorption, and maintained the water absorbance of the dip-coated cellulose paper. Dip-coating with another functional polymer containing biotin groups produced a cellulose paper with a biotin-decorated surface in a one-step procedure. The displayed biotin groups immobilized avidin on the surface, and the PEG moieties in the polymer prevented nonspecific protein adsorption. We then immobilized a thrombin-binding DNA aptamer on the avidin-immobilized cellulose paper to prepare a paper-based analytical device. It is possible to visualize thrombin in model solutions and serum using the paper-based analytical device.

Phenotypic plasticity, the ability to produce multiple phenotypes from a single genotype, represents an excellent model with which to examine the relationship between gene expression and phenotypes. Analyses of the molecular foundations of phenotypic plasticity are challenging, however, especially in the case of complex social phenotypes. Here we apply a machine learning approach to tackle this challenge by analyzing individual-level gene expression profiles of Polistes dominula paper wasps following the loss of a queen. We find that caste-associated gene expression profiles respond strongly to queen loss, and that this change is partly explained by attributes such as age but occurs even in individuals that appear phenotypically unaffected. These results demonstrate that large changes in gene expression may occur in the absence of outwardly detectable phenotypic changes, resulting here in a socially mediated de-differentiation of individuals at the transcriptomic level but not at the levels of ovarian development or behavior., Connecting genotypes to complex social behaviour is challenging. Taylor et al. use machine learning to show a strong response of caste-associated gene expression to queen loss, wherein individual wasp’s expression profiles become intermediate between queen and worker states, even in the absence of behavioural changes.

Allergy to Polistes dominula (European paper wasp) venom is of particular relevance in Southern Europe, potentially becoming a threat in other regions in the near future, and can be effectively cured by venom immunotherapy (VIT). As allergen content in extracts may vary and have an impact on diagnostic and therapeutic approaches, the aim was to compare five therapeutic preparations for VIT of P. dominula venom allergy available in Spain. Products from five different suppliers were analyzed by SDS-PAGE and LC-MS/MS and compared with a reference venom sample. Three products with P. dominula venom and one product with a venom mixture of American Polistes species showed a comparable band pattern in SDS-PAGE as the reference sample and the bands of the major allergens phospholipase A1 and antigen 5 were assignable. The other product, which consists of a mixture of American Polistes species, exhibited the typical band pattern in one, but not in another sample from a second batch. All annotated P. dominula allergens were detected at comparable levels in LC-MS/MS analysis of products containing P. dominula venom. Due to a lack of genomic information on the American Polistes species, the remaining products were not analyzed by this method. The major Polistes allergens were present in comparable amounts in the majority, but not in all investigated samples of venom preparations for VIT of P. dominula venom allergy.

Paper spray ionization (PSI) is an extractive ambient ionization technique for mass spectrometry (MS), whereby a triangular paper tip serves as the sampling base and the electrospray tip. During PSI, analytes are extracted and transported to the edge of the paper tip by the applied spraying solvent. Analytes can be purified from a sample matrix and separated from each other by this transportation process. In this study, we investigated and utilized the analyte transportation process of PSI for the in situ separation and analysis of lipid mixtures. We found that differential transport of phosphatidylcholine (PC) and triacylglycerol (TAG), the two most abundant lipid classes in animals, occurred during PSI. We also found that the order in which these lipids moved strongly depended on how the spraying solvent was applied to the paper base. The more polar PC moved faster than the less polar TAG during PSI, when a polar solvent was slowly fed into a paper tip, whereas TAG was transported faster than PC when excess solvent was applied to the tip at once. In addition, we achieved a complete separation and detection of PC and TAG by slowly supplying a nonpolar solvent to a PSI tip.

Invasive species can be particularly disruptive when they intersect with organisms of conservation concern. Stabilizing the declining eastern migratory population of monarch butterflies (Danaus plexippus) is projected to require extensive habitat restoration across multiple land use sectors including metropolitan areas. Numerous conservation programs encourage urban citizens to plant gardens with milkweeds, the obligate larval host plants of the monarch. Here, we show that predation by Polistes dominula, an invasive paper wasp that is particularly abundant in urban settings, can turn such sites into ecological traps for monarch larvae. Polistes dominula was the predominant paper wasp seen foraging in central Kentucky pollinator gardens. In 120 observed encounters with monarch larvae on milkweeds in gardens, most second to fourth instars were killed, whereas most fifth instars escaped by thrashing or dropping. The wasps bit and carried off second instars whole, whereas third and fourth instar kills were first gutted, then processed and carried away piecemeal. Predation on sentinel larvae was much higher in urban gardens than in rural settings. The wasps exploited ornamental butterfly “hibernation boxes” in pollinator gardens as nesting habitat. Polistes dominula is an under-recognized predator that may diminish the urban sector’s contributions to monarch habitat restoration.

This work reports on fully integrated “sample‐in‐signal‐out” microfluidic paper‐based analytical devices (μPADs) relying on bioluminescence resonance energy transfer (BRET) switches for analyte recognition and colorimetric signal generation. The devices use BRET‐based antibody sensing proteins integrated into vertically assembled layers of functionalized paper, and their design enables sample volume‐independent and fully reagent‐free operation, including on‐device blood plasma separation. User operation is limited to the application of a single drop (20–30 μL) of sample (serum, whole blood) and the acquisition of a photograph 20 min after sample introduction, with no requirement for precise pipetting, liquid handling, or analytical equipment except for a camera. Simultaneous detection of three different antibodies (anti‐HIV1, anti‐HA, and anti‐DEN1) in whole blood was achieved. Given its simplicity, this type of device is ideally suited for user‐friendly point‐of‐care testing in low‐resource environments.

This is a pre-copyedited, author-produced version of an article accepted for publication in Cardiovascular Research (CVR) following peer review. The version of record Perrino, Ferdinandy, Bøtker, Brundel, Collins, Davidson, Den Ruijter, Engel, Gerdts, Girao, Gyöngyösi, Hausenloy, Lecour, Madonna, Marber, Murphy, Pesce, Regitz-Zagrosek, Sluijter, Steffens, Gollmann-Tepeköylü, Van Laake, Van Linthout, Schulz, Ytrehus. Improving translational research in sex-specific effects of comorbidities and risk factors in ischaemic heart disease and cardioprotection: Position paper and recommendations of the ESC Working Group on Cellular Biology of the Heart. Cardiovascular Research (CVR). 2021;117(2):367-385, is available online at: https://doi.org/10.1093/cvr/cvaa155. Ischaemic heart disease (IHD) is a complex disorder and a leading cause of death and morbidity in both men and women. Sex, however, affects several aspects of IHD, including pathophysiology, incidence, clinical presentation, diagnosis as well as treatment and outcome. Several diseases or risk factors frequently associated with IHD can modify cellular signalling cascades, thus affecting ischaemia/reperfusion injury as well as responses to cardioprotective interventions. Importantly, the prevalence and impact of risk factors and several comorbidities differ between males and females, and their effects on IHD development and prognosis might differ according to sex. The cellular and molecular mechanisms underlying these differences are still poorly understood, and their identification might have important translational implications in the prediction or prevention of risk of IHD in men and women. Despite this, most experimental studies on IHD are still undertaken in animal models in the absence of risk factors and comorbidities, and assessment of potential sex-specific differences are largely missing. This ESC WG Position Paper will discuss: (i) the importance of sex as a biological variable in cardiovascular research, (ii) major biological mechanisms underlying sex-related differences relevant to IHD risk factors and comorbidities, (iii) prospects and pitfalls of preclinical models to investigate these associations, and finally (iv) will provide recommendations to guide future research. Although gender differences also affect IHD risk in the clinical setting, they will not be discussed in detail here.

In recent years, the use of microalgae as feedstock for many marketable products, such as animal/aqua feeds, bioplastics and fertilizers, has gained renewed interest due to their fast growth potential coupled with relatively high lipid, carbohydrate and nutrient content. An algal biorefinery at an industrial site has the potential to sustainably and profitably convert carbon dioxide emissions into microalgal biomass and concomitantly reduce nitrogen and phosphorus from wastewaters. Industrial wastewaters are a potential alternative to traditional media used for large-scale microalgal cultivation. Pulp and paper mills are major consumers of water resources and discharge a huge amount of water to nearby lakes or rivers. This study investigated whether pulp and paper mill waste water is suitable for microalgal cultivation with the aim of achieving significant biomass production. Six different process waters from one Canadian pulp and paper mill were tested with two freshwater green microalgae. All of these waters were unable to support growth of microalgae due to inadequate nutrient concentrations, colour, turbidity and possible toxicity issues. HIGHLIGHTS Two freshwater microalgae strains were screened for potential growth on pulp and paper effluents.; Pulp and paper wastewater effluents were unable to support growth of the microalgae.; Chemical residues from the pulping process, such as peroxide and tannin, may inhibit algal growth.

The microbiota can play important roles in the development of human immunity and the establishment of immune homeostasis. Lifestyle factors including diet, hygiene, and exposure to viruses or bacteria, and medical interventions with antibiotics or anti‐ulcer medications, regulate phylogenetic variability and the quality of cross talk between innate and adaptive immune cells via mucosal and skin epithelia. More recently, microbiota and their composition have been linked to protective effects for health. Imbalance, however, has been linked to immune‐related diseases such as allergy and cancer, characterized by impaired, or exaggerated immune tolerance, respectively. In this AllergoOncology position paper, we focus on the increasing evidence defining the microbiota composition as a key determinant of immunity and immune tolerance, linked to the risk for the development of allergic and malignant diseases. We discuss novel insights into the role of microbiota in disease and patient responses to treatments in cancer and in allergy. These may highlight opportunities to improve patient outcomes with medical interventions supported through a restored microbiome.

Antibiotics are classes of antimicrobial substances that are administered widely in the field of veterinary science to promote animal health and feed efficiency. Cattle-administered antibiotics hold a risk of passing active residues to milk, during the milking process. This becomes a public health concern as these residues can cause severe allergic reactions to sensitive groups and considerable economic losses to the farmer. Hence, to ensure that the produced milk is safe to consume and adheres to permissible limits, an on-farm quick and reliable test is essential. This study illustrates the design and development of a microfluidic paper biosensor as a proof-of-concept detection system for gentamicin in milk. Localized surface plasmon resonance (LSPR) properties of gold nanoparticles have been explored to provide the user a visual feedback on the test, which was also corroborated by RGB analysis performed using Image J. The assay involves the use of a short stretch of single stranded DNA, called aptamer, which is very specific to the gentamicin present in the milk sample. The camera-based LOD for the fabricated paper device for milk samples spiked with gentamicin was calculated to be 300 nM, with a reaction time of 2 min.

With the appearance of plants and animals, new challenges emerged. These multicellular eukaryotes had to solve for example the difficulties of multifaceted communication between cells and adaptation to new habitats. In this paper, we are looking for one piece of the puzzle that made the development of complex multicellular eukaryotes possible with a focus on regulation of P2B autoinhibited Ca 2+-ATPases. P2B ATPases pump Ca 2+ out of the cytosol at the expense of ATP hydrolysis, and thereby maintain a steep gradient between the extra- and intracytosolic compartments which is utilized for Ca 2+-mediated rapid cell signaling. The activity of these enzymes is regulated by a calmodulin (CaM)-responsive autoinhibitory region, which can be located in either termini of the protein, at the C-terminus in animals and at the N-terminus in plants. When the cytoplasmic Ca 2+ level reaches a threshold, the CaM/Ca 2+ complex binds to a calmodulin-binding domain (CaMBD) in the autoinhibitor, which leads to the upregulation of pump activity. In animals, protein activity is also controlled by acidic phospholipids that bind to a cytosolic portion of the pump. Here, we analyze the appearance of CaMBDs and the phospholipid-activating sequence and show that their evolution in animals and plants was independent. Furthermore, we hypothesize that different causes may have initiated the appearance of these regulatory layers: in animals, it is linked to the appearance of multicellularity, while in plants it co-occurs with their water-to-land transition.

Endothelial cells (ECs) are sentinels of cardiovascular health. Their function is reduced by the presence of cardiovascular risk factors, and is regained once pathological stimuli are removed. In this European Society for Cardiology Position Paper, we describe endothelial dysfunction as a spectrum of phenotypic states and advocate further studies to determine the role of EC subtypes in cardiovascular disease. We conclude that there is no single ideal method for measurement of endothelial function. Techniques to measure coronary epicardial and micro-vascular function are well established but they are invasive, time-consuming, and expensive. Flow-mediated dilatation (FMD) of the brachial arteries provides a non-invasive alternative but is technically challenging and requires extensive training and standardization. We, therefore, propose that a consensus methodology for FMD is universally adopted to minimize technical variation between studies, and that reference FMD values are established for different populations of healthy individuals and patient groups. Newer techniques to measure endothelial function that are relatively easy to perform, such as finger plethysmography and the retinal flicker test, have the potential for increased clinical use provided a consensus is achieved on the measurement protocol used. We recommend further clinical studies to establish reference values for these techniques and to assess their ability to improve cardiovascular risk stratification. We advocate future studies to determine whether integration of endothelial function measurements with patient-specific epigenetic data and other biomarkers can enhance the stratification of patients for differential diagnosis, disease progression, and responses to therapy.

Fibrinogen concentration is a major determinant of both clotting and bleeding risk. Clotting and bleeding disorders cause extensive morbidity and mortality, particularly in resource-poor and emergency settings. This is exacerbated by a lack of timely intervention informed by measurement of fibrinogen levels under conditions such as thrombosis or postpartum haemorrhage. There is an absence of simple, rapid, low-cost, and sustainable diagnostic devices for fibrinogen measurement that can be deployed in such environments. Paper-based analytical devices are of significant interest due to their potential for low-cost production, ease of use, and environmental sustainability. In this work, a device for measuring blood plasma fibrinogen using chromatography paper was developed. Wax printing was used to create hydrophobic structures to define the test channel and sample application zone. Test strips were modified with bovine thrombin. Plasma samples (22 μL) were applied, and the flow rate was monitored over 5 min. As the sample traversed the strip, clotting was induced by the conversion of soluble fibrinogen to insoluble fibrin. The flow rate and distance travelled by the sample were dependent on fibrinogen concentration. The device was able to measure fibrinogen concentration in the range of 0.5–7.0 ± 0.3 mg/mL (p < 0.05, n = 24) and had excellent correlation with laboratory coagulometry in artificial samples (r2 = 0.9582, n = 60). Devices were also stable at 4–6 °C for up to 3 weeks.