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Meiotic chromosome movement is important for the pairwise alignment of homologous chromosomes, which is required for correct chromosome segregation. Movement is driven by cytoplasmic forces, transmitted to chromosome ends by nuclear membrane-spanning proteins. In animal cells, lamins form a prominent scaffold at the nuclear periphery, yet the role lamins play in meiotic chromosome movement is unclear. We show that chromosome movement correlates with reduced lamin association with the nuclear rim, which requires lamin phosphorylation at sites analogous to those that open lamina network crosslinks in mitosis. Failure to remodel the lamina results in delayed meiotic entry, altered chromatin organization, unpaired or interlocked chromosomes, and slowed chromosome movement. The remodeling kinases are delivered to lamins via chromosome ends coupled to the nuclear envelope, potentially enabling crosstalk between the lamina and chromosomal events. Thus, opening the lamina network plays a role in modulating contacts between chromosomes and the nuclear periphery during meiosis.
Background: Diabetes mellitus type 2 (DM2) is highly associated with increased risk for chronic kidney disease (CKD), end stage renal disease (ESRD) and cardiovascular morbidity. Epidemiological and genetic studies generate hypotheses for innovative strategies in DM2 management by unravelling novel mechanisms of diabetes complications, which is essential for future intervention trials. We have thus initiated the DIAbetes COhoRtE study (DIACORE).
Methods: DIACORE is a prospective cohort study aiming to recruit 6000 patients of self-reported Caucasian ethnicity with prevalent DM2 for at least 10 years of follow-up. Study visits are performed in University-based recruiting clinics in Germany using standard operating procedures. All prevalent DM2 patients in outpatient clinics surrounding the recruiting centers are invited to participate. At baseline and at each 2-year follow-up examination, patients are subjected to a core phenotyping protocol. This includes a standardized online questionnaire and physical examination to determine incident micro-and macrovascular DM2 complications, malignancy and hospitalization, with a primary focus on renal events. Confirmatory outcome information is requested from patient records. Blood samples are obtained for a centrally analyzed standard laboratory panel and for biobanking of aliquots of serum, plasma, urine, mRNA and DNA for future scientific use. A subset of the cohort is subjected to extended phenotyping, e. g. sleep apnea screening, skin autofluorescence measurement, non-mydriatic retinal photography and non-invasive determination of arterial stiffness.
Discussion: DIACORE will enable the prospective evaluation of factors involved in DM2 complication pathogenesis using high-throughput technologies in biosamples and genetic epidemiological studies.
Miniaturized satellites on a nanosatellite scale below 10kg of total mass contribute most to the number of launched satellites into Low Earth Orbit today. This results from the potential to design, integrate and launch these space missions within months at very low costs. In the past decade, the reliability in the fields of system design, communication, and attitude control have matured to allow for competitive applications in Earth observation, communication services, and science missions. The capability of orbit control is an important next step in this development, enabling operators to adjust orbits according to current mission needs and small satellite formation flight, which promotes new measurements in various fields of space science. Moreover, this ability makes missions with altitudes above the ISS comply with planned regulations regarding collision avoidance maneuvering.
This dissertation presents the successful implementation of orbit control capabilities on the pico-satellite class for the first time. This pioneering achievement is demonstrated on the 1U CubeSat UWE–4. A focus is on the integration and operation of an electric propulsion system on miniaturized satellites. Besides limitations in size, mass, and power of a pico-satellite, the choice of a suitable electric propulsion system was driven by electromagnetic cleanliness and the use as a combined attitude and orbit control system. Moreover, the integration of the propulsion system leaves the valuable space at the outer faces of the CubeSat structure unoccupied for future use by payloads. The used NanoFEEP propulsion system consists of four thruster heads, two neutralizers and two Power Processing Units (PPUs).
The thrusters can be used continuously for 50 minutes per orbit after the liquefaction of the propellant by dedicated heaters. The power consumption of a PPU with one activated thruster, its heater and a neutralizer at emitter current levels of 30-60μA or thrust levels of 2.6-5.5μN, respectively, is in the range of 430-1050mW. Two thruster heads were activated within the scope of in-orbit experiments. The thrust direction was determined using a novel algorithm within 15.7° and 13.2° of the mounting direction. Despite limited controllability of the remaining thrusters, thrust vector pointing was achieved using the magnetic actuators of the Attitude and Orbit Control System.
In mid 2020, several orbit control maneuvers changed the altitude of UWE–4, a first for pico-satellites. During the orbit lowering scenario with a duration of ten days, a single thruster head was activated in 78 orbits for 5:40 minutes per orbit. This resulted in a reduction of the orbit altitude by about 98.3m and applied a Delta v of 5.4cm/s to UWE–4. The same thruster was activated in another experiment during 44 orbits within five days for an average duration of 7:00 minutes per orbit. The altitude of UWE–4 was increased by about 81.2m and a Delta v of 4.4cm/s was applied. Additionally, a collision avoidance maneuver was executed in July 2020, which increased the distance of closest approach to the object by more than 5000m.
Family studies suggest a genetic component to the etiology of chronic kidney disease (CKD) and end stage renal disease (ESRD). Previously, we identified 16 loci for eGFR in genome-wide association studies, but the associations of these single nucleotide polymorphisms (SNPs) for incident CKD or ESRD are unknown. We thus investigated the association of these loci with incident CKD in 26,308 individuals of European ancestry free of CKD at baseline drawn from eight population-based cohorts followed for a median of 7.2 years (including 2,122 incident CKD cases defined as eGFR < 60ml/min/1.73m(2) at follow-up) and with ESRD in four case-control studies in subjects of European ancestry (3,775 cases, 4,577 controls). SNPs at 11 of the 16 loci (UMOD, PRKAG2, ANXA9, DAB2, SHROOM3, DACH1, STC1, SLC34A1, ALMS1/NAT8, UBE2Q2, and GCKR) were associated with incident CKD; p-values ranged from p = 4.1e-9 in UMOD to p = 0.03 in GCKR. After adjusting for baseline eGFR, six of these loci remained significantly associated with incident CKD (UMOD, PRKAG2, ANXA9, DAB2, DACH1, and STC1). SNPs in UMOD (OR = 0.92, p = 0.04) and GCKR (OR = 0.93, p = 0.03) were nominally associated with ESRD. In summary, the majority of eGFR-related loci are either associated or show a strong trend towards association with incident CKD, but have modest associations with ESRD in individuals of European descent. Additional work is required to characterize the association of genetic determinants of CKD and ESRD at different stages of disease progression.
The electric propulsion system NanoFEEP was integrated and tested in orbit on the UWE-4 satellite, which marks the first successful demonstration of an electric propulsion system on board a 1U CubeSat. In-orbit characterization measurements of the heating process of the propellant and the power consumption of the propulsion system at different thrust levels are presented. Furthermore, an analysis of the thrust vector direction based on its effect on the attitude of the spacecraft is described. The employed heater liquefies the propellant for a duration of 30 min per orbit and consumes 103 ± 4 mW. During this time, the respective thruster can be activated. The propulsion system including one thruster head, its corresponding heater, the neutralizer and the digital components of the power processing unit consume 8.5 ± 0.1 mW ⋅μ A\(^{−1}\) + 184 ± 8.5 mW and scales with the emitter current. The estimated thrust directions of two thruster heads are at angles of 15.7 ± 7.6∘ and 13.2 ± 5.5∘ relative to their mounting direction in the CubeSat structure. In light of the very limited power on a 1U CubeSat, the NanoFEEP propulsion system renders a very viable option. The heater of subsequent NanoFEEP thrusters was already improved, such that the system can be activated during the whole orbit period.