Long-Term Monitoring of Cardiac Involvement under Migalastat Treatment Using Magnetic Resonance Tomography in Fabry Disease

Background: Fabry cardiomyopathy is characterized by left ventricular hypertrophy, myocardial fibrosis, arrhythmia, and premature death. Treatment with migalastat, an oral pharmacological chaperone, was associated with a stabilization of cardiac biomarkers and a reduction in left ventricular mass index, as measured by echocardiography. A recent study, using cardiac magnetic resonance (CMR) as the gold standard, found a stable course of myocardial involvement after 18 months of treatment with migalastat. Our study aimed to provide long-term CMR data for the treatment with migalastat. Methods: A total of 11 females and four males with pathogenic amenable GLA mutations were treated with migalastat and underwent 1.5T CMR imaging for routine treatment effect monitoring. The main outcome was a long-term myocardial structural change, reflected by CMR. Results: After migalastat treatment initiation, left ventricular mass index, end diastolic volume, interventricular septal thickness, posterior wall thickness, estimated glomerular filtration rate, and plasma lyso-Gb3 remained stable during the median follow-up time of 34 months (min.: 25; max.: 47). The T1 relaxation times, reflecting glycosphingolipid accumulation and subsequent processes up to fibrosis, fluctuated over the time without a clear trend. No new onset of late gadolinium enhancement (LGE) areas, reflecting local fibrosis or scar formation of the myocardium, could be detected. However, patients with initially present LGE showed an increase in LGE as a percentage of left ventricular mass. The median α-galactosidase A enzymatic activity increased from 37.3% (IQR 5.88-89.3) to 105% (IQR 37.2-177) of the lower limit of the respective reference level (p = 0.005). Conclusion: Our study confirms an overall stable course of LVMi in patients with FD, treated with migalastat. However, individual patients may experience disease progression, especially those who present with fibrosis of the myocardium already at the time of therapy initiation. Thus, a regular treatment re-evaluation including CMR is needed to provide the optimal management for each patient

QGyro : Schlussbericht zum Verbundvorhaben Quanten-Inertialsensorsystem (QGyro)

Das Verbundvorhaben QGyro (Quanten-Inertialsensorsystem) ist ein Teil der High-Tech-Strategie der Bundesregierung und erhält Finanzierung durch das Bundesministerium für Wirtschaft und Klimaschutz (BMWK) mit Unterstützung der Raumfahrtagentur am Deutschen Zentrum für Luft- und Raumfahrt DLR e.V. (Förderkennzeichen 50RK1957). Im Rahmen dieses Forschungsvorhabens wurden mithilfe der Quantentechnologie innovative Konzepte für die Navigation von Plattformen entwickelt. Das Hauptziel des Projekts ist die Untersuchung von Hybridansätzen zur Inertialsensorik, bei der Quantensensoren mit klassischen inertialen Messeinheiten miteinander kombiniert werden um Fehler in der Positionsbestimmung zu reduzieren. Ein Hauptaugenmerk lag auf der Entwicklung neuartiger Quantensensoren. Ein erster Ansatz war die Schaffung eines einachsigen, quantenbasierten Inertialsensors als Proof-of-Concept. Dies beinhaltet den Sensorkopf, aber auch die Perepherie, wie Lasersysteme und Elektronik. Darüber hinaus wurden Entwicklungen in Richtung von sechsachsigen quantenbasierten Intertialsensoren angestoßen und Realisierungskonzepte erarbeitet. Ein besonderer Fokus lag auf der Stabilisierung und aktiven Ausrichtung des entwickelten Messkopfes, was durch Simulationen und experimentelle Tests nachgewiesen werden konnte. Dies beinhaltete die Entwicklung eines Teststandes, die Erarbeitung eines Atom-StrapDown-Algorithmus zur Kombination von Quanten-Inertialsensoren und klassischer Inertialsensorik sowie die Umsetzung einer stabilisierten Plattform für den Sensorkopf. Die erfolgreiche Umsetzung wurde in enger Zusammenarbeit mit Forschungseinrichtungen an der Leibniz Universität Hannover (Institut für Erdmessung, Institut für Quantenoptik) sowie etablierten Unternehmen wie der iMAR GmbH erreicht. Das Projekt QGyro trägt dazu bei, die High-Tech-Strategie der Bundesregierung im Bereich der Quantentechnologie und Navigation voranzutreiben.The collaborative project QGyro (quantum inertial sensor system) is part of the German Federal Government’s High-Tech Strategy and receives funding from the German Federal Ministry of Economics and Climate Protection (BMWK) with support from the Space Agency at the German Aerospace Center DLR e.V. (funding code 50 RK 1957). This research project used quantum technology to develop innovative concepts for the navigation of kinematic platforms. The main goal of the project is to investigate hybrid approaches for inertial sensors, combining quantum technology with classical inertial measurement devices in order to reduce errors in positioning. A primary focus has been the development of novel quantum sensors. A first approach considered the creation of a single-axis, quantum-based inertial sensor as a proof-of-concept. This includes the sensor head, and also the peripherals, such as laser systems and electronics. Furthermore, developments towards a six-axis quantum-based inertial sensor were initiated and realization concepts were elaborated. Further focus was on the stabilization and active alignment of the developed sensing head. For this purpose, a stabilized platform was designed and built that can compensate linear accelerations during the measurement time of the quantum sensor. A so-called Atom Strapdown algorithm was designed and implemented for inertial navigation for the combination of quantum inertial sensors and classical inertial sensors. This algorithm has been tested, optimized and validated in extensive simulation studies. Moreover, a successful application of the algorithm to real data was achieved by emulating the CAI observations with a navigation-grade IMU during the generation of the hybrid scenario. Algorithms for determining the uncertainties of the atomic interferometer were further developed and validated on prototype measurement series. Successful implementation was achieved in close collaboration with research institutions at Leibniz Universität Hannover (Institute of Geodesy, Institute of Quantum Optics) as well as established companies such as iMAR GmbH. The QGyro project contributes to advancing the German government’s high-tech strategy in the field of quantum technology and navigation.Deutsche Raumfahrtagentur im Deutschen Zentrum für Luft- und Raumfahrt e.V./Systemuntersuchungen und Technologie für die Satellitennavigation/BMWK 50 RK 1957/E

Interseasonal RSV infections in Switzerland - rapid establishment of a clinician-led national reporting system (RSV EpiCH).

In anticipation of an interseasonal respiratory syncytial virus (RSV) epidemic, a clinician-led reporting system was rapidly established to capture RSV infections in Swiss hospitals, starting in January 2021. Here, we present details of the reporting system and first results to June 2021. An unusual epidemiology was observed with an interseasonal surge of RSV infections associated with COVID-19-related non-pharmacological interventions. These data allowed real-time adjustment of RSV prophylaxis guidelines and consequently underscore the need for and continuation of systematic nationwide RSV surveillance

A multi‐omics framework reveals strawberry flavor genes and their regulatory elements

Flavor is essential to consumer preference of foods and is an increasing focus of plant breeding programs. In fruit crops, identifying genes underlying volatile organic compounds has great promise to accelerate flavor improvement, but polyploidy and heterozygosity in many species have slowed progress. Here we use octoploid cultivated strawberry to demonstrate how genomic heterozygosity, transcriptomic intricacy and fruit metabolomic diversity can be treated as strengths and leveraged to uncover fruit flavor genes and their regulatory elements. Multi-omics datasets were generated including an expression quantitative trait loci map with 196 diverse breeding lines, haplotype-phased genomes of a highly-flavored breeding selection, a genome-wide structural variant map using five haplotypes, and volatile genome-wide association study (GWAS) with > 300 individuals. Overlaying regulatory elements, structural variants and GWAS-linked allele-specific expression of numerous genes to variation in volatile compounds important to flavor. In one example, the functional role of anthranilate synthase alpha subunit 1 in methyl anthranilate biosynthesis was supported via fruit transient gene expression assays. These results demonstrate a framework for flavor gene discovery in fruit crops and a pathway to molecular breeding of cultivars with complex and desirable flavor

Attenuated sensing of SHH by <i>Ptch1</i> underlies evolution of bovine limbs

The large spectrum of limb morphologies reflects the wide evolutionary diversification of the basic pentadactyl pattern in tetrapods. In even-toed ungulates (artiodactyls, including cattle), limbs are adapted for running as a consequence of progressive reduction of their distal skeleton to symmetrical and elongated middle digits with hoofed phalanges. Here we analyse bovine embryos to establish that polarized gene expression is progressively lost during limb development in comparison to the mouse. Notably, the transcriptional upregulation of the Ptch1 gene, which encodes a Sonic hedgehog (SHH) receptor, is disrupted specifically in the bovine limb bud mesenchyme. This is due to evolutionary alteration of a Ptch1 cis-regulatory module, which no longer responds to graded SHH signalling during bovine handplate development. Our study provides a molecular explanation for the loss of digit asymmetry in bovine limb buds and suggests that modifications affecting the Ptch1 cis-regulatory landscape have contributed to evolutionary diversification of artiodactyl limbs