Maternal Angiotensin Increases Placental Leptin in Early Gestation via an Alternative Renin-Angiotensin System Pathway: Suggesting a Link to Preeclampsia.

Various studies found an association of different renin-angiotensin system (RAS) components with gestational duration and preterm birth, as well as with preeclampsia. Approximately 25% of first-time pregnant women develop a mild to severe hypertension in pregnancy or even preeclampsia. Based on recently published single-cell RNA-sequencing, we hypothesized an alternative RAS function in placenta and furthermore, an implication in hypertensive disorders in pregnancy. Placental RAS expression and localization was analyzed via quantitative polymerase chain reaction and in situ mRNA padlock probes. Tissue was collected from first-trimester elective termination (n=198), from healthy third-trimester controls (n=54), from early-onset preeclamptic (n=54) and age-matched controls (n=29), as well as first-trimester placentae from women with a high uterine artery resistance index (high-risk for preeclampsia, n=9) and controls (n=8). Serum levels of Ang (angiotensin) I to IV from women before and after conception were measured via mass spectrometry (n=10). Placental explants were cultured in 2.5% oxygen with Ang II, candesartan, and leptin. Seahorse XF96 MitoStress assays assessed trophoblast metabolism. Here, we show that maternal angiotensin acts on placental LNPEP (leucine aminopeptidase), that is, angiotensin IV-receptor and fetal angiotensin on placental AGTR1 (angiotensin II receptor type 1). Maternal circulating RAS shifts towards Ang IV in pregnancy. Ang IV decreases trophoblastic mitochondrial respiration and increases placental leptin via placental LNPEP. Lower placental LNPEP in preeclampsia and in first-trimester patients at high-risk for preeclampsia suggests a new alternative route in maternal RAS signaling and may contribute to hypertension and disease in pregnancy. The study shows how hypertensive disorders in pregnancy may be connected metabolic alterations that finally seem to contribute to the multifactorial disease in pregnancy, preeclampsia

The Role of Thioredoxin Reductases in Brain Development

The thioredoxin-dependent system is an essential regulator of cellular redox balance. Since oxidative stress has been linked with neurodegenerative disease, we studied the roles of thioredoxin reductases in brain using mice with nervous system (NS)-specific deletion of cytosolic (Txnrd1) and mitochondrial (Txnrd2) thioredoxin reductase. While NS-specific Txnrd2 null mice develop normally, mice lacking Txnrd1 in the NS were significantly smaller and displayed ataxia and tremor. A striking patterned cerebellar hypoplasia was observed. Proliferation of the external granular layer (EGL) was strongly reduced and fissure formation and laminar organisation of the cerebellar cortex was impaired in the rostral portion of the cerebellum. Purkinje cells were ectopically located and their dendrites stunted. The Bergmann glial network was disorganized and showed a pronounced reduction in fiber strength. Cerebellar hypoplasia did not result from increased apoptosis, but from decreased proliferation of granule cell precursors within the EGL. Of note, neuron-specific inactivation of Txnrd1 did not result in cerebellar hypoplasia, suggesting a vital role for Txnrd1 in Bergmann glia or neuronal precursor cells

Digital base-band rf control system for the superconducting Darmstadt electron linear accelerator

The accelerating field in superconducting cavities has to be stabilized in amplitude and phase by a radio-frequency (rf) control system. Because of their high loaded quality factor superconducting cavities are very susceptible for microphonics. To meet the increased requirements with respect to accuracy, availability, and diagnostics, the previous analog rf control system of the superconducting Darmstadt electron linear accelerator S-DALINAC has been replaced by a digital rf control system. The new hardware consists of two components: An rf module that converts the signal from the cavity down to the base-band and a field-programmable gate array board including a soft CPU that carries out the signal processing steps of the control algorithm. Different algorithms are used for normal-conducting and superconducting cavities. To improve the availability of the control system, techniques for automatic firmware and software deployment have been implemented. Extensive diagnostic features provide the operator with additional information. The architecture of the rf control system as well as the functionality of its components will be presented along with measurements that characterize the performance of the system, yielding, e.g., an amplitude stabilization down to (Δ A/A)\rm rms =7 × 10⁻⁵ and a phase stabilization of (Δ φ )\rm rms = 0.8\circ for superconducting cavities

Digital base-band rf control system for the superconducting Darmstadt electron linear accelerator

The accelerating field in superconducting cavities has to be stabilized in amplitude and phase by a radio-frequency (rf) control system. Because of their high loaded quality factor superconducting cavities are very susceptible for microphonics. To meet the increased requirements with respect to accuracy, availability, and diagnostics, the previous analog rf control system of the superconducting Darmstadt electron linear accelerator S-DALINAC has been replaced by a digital rf control system. The new hardware consists of two components: An rf module that converts the signal from the cavity down to the base-band and a field-programmable gate array board including a soft CPU that carries out the signal processing steps of the control algorithm. Different algorithms are used for normal-conducting and superconducting cavities. To improve the availability of the control system, techniques for automatic firmware and software deployment have been implemented. Extensive diagnostic features provide the operator with additional information. The architecture of the rf control system as well as the functionality of its components will be presented along with measurements that characterize the performance of the system, yielding, e.g., an amplitude stabilization down to (ΔA/A)rms=7×10-5 and a phase stabilization of (ΔÏ•)rms=0.8° for superconducting cavities

Digital base-band rf control system for the superconducting Darmstadt electron linear accelerator

The accelerating field in superconducting cavities has to be stabilized in amplitude and phase by a radio-frequency (rf) control system. Because of their high loaded quality factor superconducting cavities are very susceptible for microphonics. To meet the increased requirements with respect to accuracy, availability, and diagnostics, the previous analog rf control system of the superconducting Darmstadt electron linear accelerator S-DALINAC has been replaced by a digital rf control system. The new hardware consists of two components: An rf module that converts the signal from the cavity down to the base-band and a field-programmable gate array board including a soft CPU that carries out the signal processing steps of the control algorithm. Different algorithms are used for normal-conducting and superconducting cavities. To improve the availability of the control system, techniques for automatic firmware and software deployment have been implemented. Extensive diagnostic features provide the operator with additional information. The architecture of the rf control system as well as the functionality of its components will be presented along with measurements that characterize the performance of the system, yielding, e.g., an amplitude stabilization down to (ΔA/A)_{rms}=7×10^{-5} and a phase stabilization of (Δϕ)_{rms}=0.8° for superconducting cavities