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The hop cyst nematode, Heterodera humuli, is the most common plant-parasitic nematode associated with hop worldwide. This study reports the draft genome of H. humuli generated on the PacBio Sequel IIe System with the ultra-low DNA input HiFi sequencing method, and the corresponding genome annotation. This genome resource will help further studies on H. humuli and other cyst nematodes.

Tegaserod (1-{[(5-methoxy-1H-indol-3-yl)methyliden]amino}-3-pentylguanidine) is a potent agonist at human recombinant 5-HT 4 serotonin receptors. Consequently, tegaserod is utilized in the treatment of bowel diseases. The objective of this study was to test the hypothesis that tegaserod stimulates human cardiac atrial 5-HT 4 -receptors via cyclic adenosine monophosphate (cAMP)-dependent pathways. Tegaserod exerted positive inotropic effects (PIEs) and positive chronotropic effects (PCEs) in isolated left and right atrial preparations, respectively, from mice with cardiac-specific overexpression of the human 5-HT 4 serotonin receptor (5-HT 4 -TG) in a concentration- and time-dependent manner. However, no effect was observed in the hearts of littermates of wild-type mice (WT). Western blot analysis revealed that the expression of 5-HT 4 receptors was significantly higher in 5-HT 4 -TG mice compared to WT mice. The specificity of the signal for the 5-HT 4 receptor was confirmed by the absence of the signal in the hearts of 5-HT 4 receptor knockout mice. Furthermore, tegaserod increased the force of contraction (at concentrations as low as 10 nM), reduced the time of tension relaxation, and increased the rate of tension development in isolated electrically stimulated (at a rate of 60 beats per minute) human right atrial preparations (HAPs, obtained during open-heart surgery) when administered alone. The potency and efficacy of tegaserod to raise the force of contraction were enhanced in the presence of cilostamide, a phosphodiesterase III inhibitor. The positive inotropic effect of tegaserod in HAPs was found to be attenuated by the 5-HT 4 serotonin receptor antagonist GR 125487 (0.1 µM). The efficacy of tegaserod (10 µM) in raising the force of contraction in HAPs was less pronounced than that of serotonin (10 µM) or isoprenaline (1 µM). Tegaserod shifted the concentration-response curve of the force of contraction to serotonin to the right in HAPs, indicating that it is a partial agonist at 5-HT 4 serotonin receptors in this model. We propose that the mechanism of action of tegaserod in HAPs involves cAMP-dependent phosphorylation of cardiac regulatory proteins.

Athletes have been found to demonstrate a superior ability to detect subtle variations in dynamic displays (e.g., point-light displays and videos) depicting expert actions compared to non-athletes. The current study aimed to determine whether this advantage also exists when dynamic information is unavailable (i.e., using static images). Using a staircase procedure, two frames from a video depicting an athlete either walking (everyday action) or performing a sprint start (expert action) were presented, and athletes (sprinters) and non-athletes were asked to indicate whether the images were identical or different. We examined whether presenting the images sequentially (temporal task) or simultaneously (spatial task) influenced participants' discrimination performance. We predicted that the sprinters would outperform the non-sprinters in the spatial task as body postures could be compared directly but not in the temporal task due to larger representational momentum effects for athletes. Contrary to our hypotheses, the sprinters and non-sprinters performed similarly in all tasks and conditions. In line with the prediction that representational momentum may impair performance, participants' thresholds were lower for the spatial than the temporal task. However, post-hoc analysis suggested that this effect is likely to be better explained by a task order effect whereby participants who completed the temporal task first exhibited an advantage in the spatial task, while there were no performance differences for participants who completed the opposite task order. In sum, our results provide no evidence for the idea that motor expertise affects action perception (i.e., perceptual resonance) in a simple psychophysical task employing static images., Competing Interests: Declaration of competing interest The authors have no competing interests to declare that are relevant to the content of this article., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Extracorporeal circulation induces pronounced effects on haemostasis and rheology. To study these, an ex vivo simulation model is an attractive alternative but often requires large amounts of blood. We sought to create a miniaturized roller pump circuit requiring minimal amounts of blood and to test if the circuit could be used to compare coagulation, platelet function and blood rheology between a dextran-based and a crystalloid-based priming solution., Methods: A miniaturized roller pump circuit requiring only 27 ml of blood was created. Blood samples from 8 cardiac surgery patients were mixed with either a dextran-based or a crystalloid-based solution and circulated for 60 min. Coagulation was assessed by rotational thromboelastometry, and platelet function by impedance aggregometry and flow cytometry, before and at 5 and 60 min of circulation., Results: A time-dependent impairment of coagulation was observed in both groups. Maximum clot firmness was lower with dextran-based than with crystalloid-based priming at 5 min (HEPTEM 37 ± 4 vs 43 ± 4 mm, P < 0.001; EXTEM 37 ± 4 vs 43 ± 4 mm, P < 0.001; FIBTEM 3 ± 2 vs 9 ± 2 mm, P < 0.001) and at 60 min (HEPTEM 29 ± 9 vs 38 ± 5 mm, P < 0.001; EXTEM 30 ± 7 vs 39 ± 5 mm, P < 0.001; FIBTEM 3 ± 2 vs 8 ± 3 mm, P = 0.002). The EXTEM clotting time was longer with dextran-based solution at 5 (109 ± 19 vs 63 ± 7 sec, P < 0.001) and at 60 min (176 ± 72 vs 73 ± 7 sec, P = 0.004)., Conclusions: The novel miniaturized roller pump circuit can be used to mimic extracorporeal circulation for selected research questions. Dextran-based priming caused a significant impairment in haemostasis compared with a standard crystalloid solution., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Zacopride (4-amino-5-chloro-2-methoxy-N-(quinuclidin-3-yl)-benzamide) is a potent agonist in human 5-HT 4 serotonin receptors in vitro and in the gastrointestinal tract. Zacopride was studied as an antiemetic drug and was intended to treat gastric diseases. Zacopride has been speculated to be useful as an antiarrhythmic agent in the human ventricle by inhibiting cardiac potassium channels. It is unknown whether zacopride is an agonist in human cardiac 5-HT 4 serotonin receptors. We tested the hypothesis that zacopride stimulates human cardiac atrial 5-HT 4 serotonin receptors. Zacopride increased the force of contraction and beating rate in isolated atrial preparations from mice with cardiac-specific overexpression of human 5-HT 4 serotonin receptors (5-HT 4 -TG). However, it was inactive in wild-type mouse hearts (WT). Zacopride was as effective as serotonin in raising the force of contraction and beating rate in atrial preparations of 5-HT 4 -TG. Zacopride raised the force of contraction in human right atrial preparations (HAP) in the absence and presence of the phosphodiesterase III inhibitor cilostamide (1 µM). The positive inotropic effect of zacopride in HAP was attenuated by either 10 µM tropisetron or 1 µM GR125487, both of which are antagonists at 5-HT 4 serotonin receptors. These data suggest that zacopride is also an agonist at 5-HT 4 serotonin receptors in the human atrium., (© 2024. The Author(s).)

Mosapride (4-amino-5-chloro-2-ethoxy-N-[[4-[(4-fluorophenyl) methyl]-2-morpholinyl]-methyl] benzamide) is a potent agonist at gastrointestinal 5-HT 4 receptors. Mosapride is an approved drug to treat several gastric diseases. We tested the hypothesis that mosapride also stimulates 5-HT 4 receptors in the heart. Mosapride increased the force of contraction and beating rate in isolated atrial preparations from mice with cardiac overexpression of human 5-HT 4 -serotonin receptors (5-HT 4 -TG). However, it is inactive in wild-type mouse hearts (WT). Mosapride was less effective and potent than serotonin in raising the force of contraction or the beating rate in 5-HT 4 -TG. Only in the presence of cilostamide (1 μM), a phosphodiesterase III inhibitor, mosapride, and its primary metabolite time dependently raised the force of contraction under isometric conditions in isolated paced human right atrial preparations (HAP, obtained during open heart surgery). In HAP, mosapride (10 μM) reduced serotonin-induced increases in the force of contraction. Mosapride (10 µM) shifted the concentration-response curves to serotonin in HAP to the right. These data suggest that mosapride is a partial agonist at 5-HT 4 -serotonin receptors in HAP., (© 2024. The Author(s).)

Segmented filamentous bacteria (SFB) are members of the commensal intestinal microbiome. They are known to contribute to the postnatal maturation of the gut immune system, but also to augment inflammatory conditions in chronic diseases such as Crohn's disease. Living primary tissue slices are ultrathin multicellular sections of the intestine and provide a unique opportunity to analyze tissue-specific immune responses ex vivo. This study aimed to investigate whether supplementation of the gut flora with SFB promotes T helper 17 (Th17) cell responses in primary intestinal tissue slices ex vivo. Primary tissue slices were prepared from the small intestine of healthy Taconic mice with SFB-positive and SFB-negative microbiomes and stimulated with anti-CD3/CD28 or Concanavalin A. SFB-positive and -negative mice exhibited distinct microbiome compositions and Th17 cell frequencies in the intestine and complex microbiota including SFB induced up to 15-fold increase in Th17 cell-associated mediators, serum amyloid A (SAA), and immunoglobulin A (IgA) responses ex vivo. This phenotype could be transmitted by co-housing of mice. Our findings highlight that changes in the gut microbiome can be observed in primary intestinal tissue slices ex vivo. This makes the system very attractive for disease modeling and assessment of new therapies., (© 2024 The Authors. European Journal of Immunology published by Wiley‐VCH GmbH.)

The evolutionary theory of loneliness (ETL) argues that human belongingness is essential to survival and failing to meet belongingness needs constitutes a threat to viability. In two separate studies (total N  = 1,609), links between loneliness and nightmares were examined as a test of ETL postulates. As hypothesized, loneliness predicted nightmare frequency (both studies) and nightmare intensity (Study Two only). Although stress mediated the relationship between loneliness and nightmare frequency in Study One, stress was not a significant mediator of this relationship in Study Two. As predicted, in Study Two both hyperarousal and rumination mediated the relationships between loneliness and nightmare frequency and between loneliness and nightmare intensity. Theoretical implications include support for both the aversive signaling and implicit vigilance postulates of ETL.

In grasping studies, maximum grip aperture (MGA) is commonly used as an indicator of the object size representation within the visuomotor system. However, a number of additional factors, such as movement safety, comfort, and efficiency, might affect the scaling of MGA with object size and potentially mask perceptual effects on actions. While unimanual grasping has been investigated for a wide range of object sizes, so far very small objects (<5 mm) have not been included. Investigating grasping of these tiny objects is particularly interesting because it allows us to evaluate the three most prominent explanatory accounts of grasping (the perception-action model, the digits-in-space hypothesis, and the biomechanical account) by comparing the predictions that they make for these small objects. In the first experiment, participants ( N = 26 ) grasped and manually estimated the height of square cuboids with heights from 0.5 to 5 mm. In the second experiment, a different sample of participants ( N = 24 ) performed the same tasks with square cuboids with heights from 5 to 20 mm. We determined MGAs, manual estimation apertures (MEA), and the corresponding just-noticeable differences (JND). In both experiments, MEAs scaled with object height and adhered to Weber's law. MGAs for grasping scaled with object height in the second experiment but not consistently in the first experiment. JNDs for grasping never scaled with object height. We argue that the digits-in-space hypothesis provides the most plausible account of the data. Furthermore, the findings highlight that the reliability of MGA as an indicator of object size is strongly task-dependent., (© 2024. The Author(s).)

Dopamine can exert effects in the mammalian heart via five different dopamine receptors. There is controversy whether dopamine receptors increase contractility in the human heart. Therefore, we have generated mice that overexpress the human D 1 -dopamine receptor in the heart (D 1 -TG) and hypothesized that dopamine increases force of contraction and beating rate compared to wild-type mice (WT). In D 1 -TG hearts, we ascertained the presence of D 1 -dopamine receptors by autoradiography using [ 3 H]SKF 38393. The mRNA for human D 1 -dopamine receptors was present in D 1 -TG hearts and absent in WT. We detected by in-situ-hybridization mRNA for D 1 -dopamine receptors in atrial and ventricular D 1 -TG cardiomyocytes compared to WT but also in human atrial preparations. We noted that in the presence of 10 µM propranolol (to antagonize β-adrenoceptors), dopamine alone and the D 1 - and D 5 -dopamine receptor agonist SKF 38393 (0.1-10 µM cumulatively applied) exerted concentration- and time-dependent positive inotropic effects and positive chronotropic effects in left or right atrial preparations from D 1 -TG. The positive inotropic effects of SKF 38393 in left atrial preparations from D 1 -TG led to an increased rate of relaxation and accompanied by and probably caused by an augmented phosphorylation state of the inhibitory subunit of troponin. In the presence of 0.4 µM propranolol, 1 µM dopamine could increase left ventricular force of contraction in isolated perfused hearts from D 1 -TG. In this model, we have demonstrated a positive inotropic and chronotropic effect of dopamine. Thus, in principle, the human D 1 -dopamine receptor can couple to contractility in the mammalian heart., (© 2024. The Author(s).)

Covalent adaptable networks and vitrimers are novel polymers with dynamic reversible bond exchange reactions for crosslinks, enabling them to modulate their properties between those of thermoplastics and thermosets. They have been gathering interest as materials for their recycling and self-healing properties. In this review, we discuss different molecular simulation efforts that have been used over the last decade to investigate and understand the nanoscale and molecular behaviors of covalent adaptable networks and vitrimers. In particular, molecular dynamics, Monte Carlo, and a hybrid of molecular dynamics and Monte Carlo approaches have been used to model the dynamic bond exchange reaction, which is the main mechanism of interest since it controls both the mechanical and rheological behaviors. The molecular simulation techniques presented yield sufficient results to investigate the structure and dynamics as well as the mechanical and rheological responses of such dynamic networks. The benefits of each method have been highlighted. The use of other tools such as theoretical models and machine learning has been included. We noticed, amongst the most prominent results, that stress relaxes as the bond exchange reaction happens, and that at temperatures higher than the glass transition temperature, the self-healing properties are better since more bond BERs are observed. The lifetime of dynamic covalent crosslinks follows, at moderate to high temperatures, an Arrhenius-like temperature dependence. We note the modeling of certain properties like the melt viscosity with glass transition temperature and the topology freezing transition temperature according to a behavior ruled by either the Williams-Landel-Ferry equation or the Arrhenius equation. Discrepancies between the behavior in dissociative and associative covalent adaptable networks are discussed. We conclude by stating which material parameters and atomistic factors, at the nanoscale, have not yet been taken into account and are lacking in the current literature.

The respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections associated with numerous hospitalizations. Recently, intramuscular (i.m.) vaccines against RSV have been approved for elderly and pregnant women. Noninvasive mucosal vaccination, e.g., by inhalation, offers an alternative against respiratory pathogens like RSV. Effective mucosal vaccines induce local immune responses, potentially resulting in the efficient and fast elimination of respiratory viruses after natural infection. To investigate this immune response to an RSV challenge, low-energy electron inactivated RSV (LEEI-RSV) was formulated with phosphatidylcholine-liposomes (PC-LEEI-RSV) or 1,2-dioleoyl-3-trimethylammonium-propane and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DD-LEEI-RSV) for vaccination of mice intranasally. As controls, LEEI-RSV and formalin-inactivated-RSV (FI-RSV) were used via i.m. vaccination. The RSV-specific immunogenicity of the different vaccines and their protective efficacy were analyzed. RSV-specific IgA antibodies and a statistically significant reduction in viral load upon challenge were detected in mucosal DD-LEEI-RSV-vaccinated animals. Alhydrogel-adjuvanted LEEI-RSV i.m. showed a Th2-bias with enhanced IgE, eosinophils, and lung histopathology comparable to FI-RSV. These effects were absent when applying the mucosal vaccines highlighting the potential of DD-LEEI-RSV as an RSV vaccine candidate and the improved performance of this mucosal vaccine candidate., Competing Interests: SU and MT are authors of patents and patent applications covering LEEI to inactivate liquids: WO2018041953, DE102015224206B3, US10080795, DE 102017002645.9. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Eberlein, Rosencrantz, Finkensieper, Besecke, Mansuroglu, Kamp, Lange, Dressman, Schopf, Hesse, Thoma, Fertey, Ulbert and Grunwald.)

Background: This study aimed to investigate the changes in force-velocity (F/v) and power-velocity (P/v) relationships with increasing work rate up to maximal oxygen uptake and to assess the resulting alterations in optimal cadence, particularly at characteristic metabolic states. Methods: Fourteen professional track cyclists (9 sprinters, 5 endurance athletes) performed submaximal incremental tests, high-intensity cycling trials, and maximal sprints at varied cadences (60, 90, 120 rpm) on an SRM bicycle ergometer. Linear and non-linear regression analyses were used to assess the relationship between heart rate, oxygen uptake (V.O 2 ), blood lactate concentration and power output at each pedaling rate. Work rates linked to various cardiopulmonary and metabolic states, including lactate threshold (LT1), maximal fat combustion (FAT max ), maximal lactate steady-state (MLSS) and maximal oxygen uptake (V.O 2max ), were determined using cadence-specific inverse functions. These data were used to calculate state-specific force-velocity (F/v) and power-velocity (P/v) profiles, from which state-specific optimal cadences were derived. Additionally, fatigue-free profiles were generated from sprint data to illustrate the entire F/v and P/v continuum. Results: HR, V.O 2 demonstrated linear relationships, while BLC exhibited an exponential relationship with work rate, influenced by cadence ( p < 0.05, η 2 ≥ 0.655). Optimal cadence increased sigmoidally across all parameters, ranging from 66.18 ± 3.00 rpm at LT1, 76.01 ± 3.36 rpm at FAT max , 82.24 ± 2.59 rpm at MLSS, culminating at 84.49 ± 2.66 rpm at V.O 2max ( p < 0.01, η 2 = 0.936). A fatigue-free optimal cadence of 135 ± 11 rpm was identified. Sprinters and endurance athletes showed no differences in optimal cadences, except for the fatigue-free optimum ( p < 0.001, d = 2.215). Conclusion: Optimal cadence increases sigmoidally with exercise intensity up to maximal aerobic power, irrespective of the athlete's physical condition or discipline. Threshold-specific changes in optimal cadence suggest a shift in muscle fiber type recruitment toward faster types beyond these thresholds. Moreover, the results indicate the need to integrate movement velocity into Henneman's hierarchical size principle and the critical power curve. Consequently, intensity zones should be presented as a function of movement velocity rather than in absolute terms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Dunst, Hesse and Ueberschär.)