Involvement Of Vascular Aldosterone Synthase In Phosphate-Induced Osteogenic Transformation Of Vascular Smooth Muscle Cells

Vascular calcification resulting from hyperphosphatemia is a major determinant of mortality in chronic kidney disease (CKD). Vascular calcification is driven by aldosterone-sensitive osteogenic transformation of vascular smooth muscle cells (VSMCs). We show that even in absence of exogenous aldosterone, silencing and pharmacological inhibition (spironolactone, eplerenone) of the mineralocorticoid receptor (MR) ameliorated phosphate-induced osteo-/chondrogenic transformation of primary human aortic smooth muscle cells (HAoSMCs). High phosphate concentrations up-regulated aldosterone synthase (CYP11B2) expression in HAoSMCs. Silencing and deficiency of CYP11B2 in VSMCs ameliorated phosphate-induced osteogenic reprogramming and calcification. Phosphate treatment was followed by nuclear export of APEX1, a CYP11B2 transcriptional repressor. APEX1 silencing up-regulated CYP11B2 expression and stimulated osteo-/chondrogenic transformation. APEX1 overexpression blunted the phosphate-induced osteo-/chondrogenic transformation and calcification of HAoSMCs. Cyp11b2 expression was higher in aortic tissue of hyperphosphatemic klotho-hypomorphic (kl/kl) mice than in wild-type mice. In adrenalectomized kl/kl mice, spironolactone treatment still significantly ameliorated aortic osteoinductive reprogramming. Our findings suggest that VSMCs express aldosterone synthase, which is up-regulated by phosphate-induced disruption of APEX1-dependent gene suppression. Vascular CYP11B2 may contribute to stimulation of VSMCs osteo-/chondrogenic transformation during hyperphosphatemia

A low-cost wind tunnel for bird flight experiments.

A blower-type wind tunnel for physiological bird flight experiments has been developed, constructed and evaluated. Since the birds to be investigated are rather big (Northern Bald Ibis, Geronticus eremita), the cross-sectional area of the test section measures 2.5 m × 1.5 m. The maximum achievable flow speed is approximately 16 ms-1. The wind tunnel exhibits a flexible outlet nozzle to provide up- and downdraft to allow for gliding and climbing flights. The current paper describes in detail the layout, design and construction of the wind tunnel including its control. Numerical simulations of the flow and measurements of the velocity distribution in the test section are presented. Apart from a non-homogeneous flow region in the mixing layer at the boundaries of the free jet, the test section exhibits a very even velocity distribution; the local speed deviates by less than two percent from the mean velocity. The turbulence intensity inside the test section was measured to be between 1 and 2%. As a constraint, a limited budget was available for the project. Four northern bald ibises were hand-raised and trained to fly in the wind tunnel. Supplementary Information The online version contains supplementary material available at 10.1007/s10336-021-01945-2

Cardiac Imaging Using Clinical 1.5 T MRI Scanners in a Murine Ischemia/Reperfusion Model

To perform cardiac imaging in mice without having to invest in expensive dedicated equipment, we adapted a clinical 1.5 Tesla (T) magnetic resonance imaging (MRI) scanner for use in a murine ischemia/reperfusion model. Phase-sensitive inversion recovery (PSIR) sequence facilitated the determination of infarct sizes in vivo by late gadolinium enhancement. Results were compared to histological infarct areas in mice after ischemia/reperfusion procedure with a good correlation (r = 0.807, P < .001). In addition, fractional area change (FAC) was assessed with single slice cine MRI and was matched to infarct size (r = −0.837) and fractional shortening (FS) measured with echocardiography (r = 0.860); both P < .001. Here, we demonstrate the use of clinical 1.5 MRI scanners as a feasible method for basic phenotyping in mice. These widely available scanners are capable of investigating in vivo infarct dimensions as well as assessment of cardiac functional parameters in mice with reasonable throughput

The Maintenance of Traditions in Marmosets: Individual Habit, Not Social Conformity? A Field Experiment

Social conformity is a cornerstone of human culture because it accelerates and maintains the spread of behaviour within a group. Few empirical studies have investigated the role of social conformity in the maintenance of traditions despite an increasing body of literature on the formation of behavioural patterns in non-human animals. The current report presents a field experiment with free-ranging marmosets (Callithrix jacchus) which investigated whether social conformity is necessary for the maintenance of behavioural patterns within groups or whether individual effects such as habit formation would suffice.Using a two-action apparatus, we established alternative behavioural patterns in six family groups composed of 36 individuals. These groups experienced only one technique during a training phase and were thereafter tested with two techniques available. The monkeys reliably maintained the trained method over a period of three weeks, despite discovering the alternative technique. Three additional groups were given the same number of sessions, but those 21 individuals could freely choose the method to obtain a reward. In these control groups, an overall bias towards one of the two methods was observed, but animals with a different preference did not adjust towards the group norm. Thirteen of the fifteen animals that discovered both techniques remained with the action with which they were initially successful, independent of the group preference and the type of action (Binomial test: exp. proportion: 0.5, p<0.01).The results indicate that the maintenance of behavioural patterns within groups 1) could be explained by the first rewarded manipulation and subsequent habit formation and 2) do not require social conformity as a mechanism. After an initial spread of a behaviour throughout a group, this mechanism may lead to a superficial appearance of conformity without the involvement of such a socially and cognitively complex mechanism. This is the first time that such an experiment has been conducted with free-ranging primates

Evidence for Emulation in Chimpanzees in Social Settings Using the Floating Peanut Task

The authors have no support or funding to report.Background: It is still unclear which observational learning mechanisms underlie the transmission of difficult problem-solving skills in chimpanzees. In particular, two different mechanisms have been proposed: imitation and emulation. Previous studies have largely failed to control for social factors when these mechanisms were targeted. Methods: In an attempt to resolve the existing discrepancies, we adopted the 'floating peanut task', in which subjects need to spit water into a tube until it is sufficiently full for floating peanuts to be grasped. In a previous study only a few chimpanzees were able to invent the necessary solution (and they either did so in their first trials or never). Here we compared success levels in baseline tests with two experimental conditions that followed: 1) A full model condition to test whether social demonstrations would be effective, and 2) A social emulation control condition, in which a human experimenter poured water from a bottle into the tube, to test whether results information alone (present in both experimental conditions) would also induce successes. Crucially, we controlled for social factors in both experimental conditions. Both types of demonstrations significantly increased successful spitting, with no differences between demonstration types. We also found that younger subjects were more likely to succeed than older ones. Our analysis showed that mere order effects could not explain our results. Conclusion: The full demonstration condition (which potentially offers additional information to observers, in the form of actions), induced no more successes than the emulation condition. Hence, emulation learning could explain the success in both conditions. This finding has broad implications for the interpretation of chimpanzee traditions, for which emulation learning may perhaps suffice.Publisher PDFPeer reviewe

Mutual regulation of CD4+ T cells and intravascular fibrin in infections

Innate myeloid cells especially neutrophils and their extracellular traps are known to promote intravascular coagulation and thrombosis formation in infections and various other conditions. Innate myeloid cell dependent fibrin formation can support systemic immunity while its dysregulation enhances the severity of infectious diseases. Less is known about the immune mechanisms preventing dysregulation of fibrin homeostasis in infection. During experimental systemic infections local fibrin deposits in the liver microcirculation cause rapid arrest of CD4+ T cells. Arrested T helper cells mostly represent Th17 cells that partially originate from the small intestine. Intravascular fibrin deposits activate mouse and human CD4+ T cells which can be mediated by direct fibrin - CD4+ T cell interactions. Activated CD4+ T cells suppress fibrin deposition and microvascular thrombosis by directly counteracting coagulation activation by neutrophils and classical monocytes. T cell activation, which is initially triggered by IL- 12p40- and MHC-II dependent mechanisms, enhances intravascular fibrinolysis via LFA-1. Moreover, CD4+ T cells disfavor the association of the fibrinolysis inhibitor TAFI with fibrin whereby fibrin deposition is increased by TAFI in the absence but not presence of T cells. In human infections thrombosis development is inversely related to microvascular levels of CD4+ T cells. Thus, fibrin promotes LFA-1 dependent T helper cell activation in infections which drives a negative feedback cycle that rapidly restricts intravascular fibrin and thrombosis development

Breakdown of the ideal free distribution under conditions of severe and low competition

Under the ideal free distribution (IFD), the number of organisms competing for a resource at different sites is proportional to the resource distribution among sites. The ideal free distribution of competitors in a heterogeneous environment often predicts habitat matching, where the relative number of individuals using any two patches matches the relative availability of resources in those same two patches. If a resource is scarce, access might be restricted to individuals with high resource holding potential, resulting in deviation from the IFD. The distribution of animals may also deviate from the IFD in the case of resource abundance, when social attraction or preference for specific locations rather than competition may determine distribution. While it was originally developed to explain habitat choice, we apply the habitat matching rule to microscale foraging decisions. We show that chickens feeding from two nondepleting feeders distribute proportionally to feeder space under intermediate levels of competition. However, chicken distribution between the feeders deviates from the IFD when feeder space is limited and competition high. Further, despite decreasing aggression with increasing feeder space, deviation from IFD is also observed under an excess supply of feeder space, indicating different mechanisms responsible for deviations from the IFD. Besides demonstrating IFD sensitivity to competition, these findings highlight IFD's potential as a biological basis for determining minimal resource requirements in animal housing.Significance statementThe ideal free distribution (IFD) predicts how animals ought to distribute themselves within a habitat in order to maximize their payoff. Recent studies, however, have questioned the validity of the IFD concept following anomalous results. We studied the IFD in chickens by systematically varying the amount and distribution of space at two feed troughs. We show that when tested over a sufficiently large range, the distribution of birds depends on the overall resource availability. Furthermore, behavioral data suggest that distinctly different mechanisms account for deviations from the IFD at shortage and excess supply of feeder space, respectively