Overview of the MOSAiC expedition: Physical oceanography

Arctic Ocean properties and processes are highly relevant to the regional and global coupled climate system, yet still scarcely observed, especially in winter. Team OCEAN conducted a full year of physical oceanography observations as part of the Multidisciplinary drifting Observatory for the Study of the Arctic Climate (MOSAiC), a drift with the Arctic sea ice from October 2019 to September 2020. An international team designed and implemented the program to characterize the Arctic Ocean system in unprecedented detail, from the seafloor to the air-sea ice-ocean interface, from sub-mesoscales to pan-Arctic. The oceanographic measurements were coordinated with the other teams to explore the ocean physics and linkages to the climate and ecosystem. This paper introduces the major components of the physical oceanography program and complements the other team overviews of the MOSAiC observational program. Team OCEAN’s sampling strategy was designed around hydrographic ship-, ice- and autonomous platform-based measurements to improve the understanding of regional circulation and mixing processes. Measurements were carried out both routinely, with a regular schedule, and in response to storms or opening leads. Here we present along-drift time series of hydrographic properties, allowing insights into the seasonal and regional evolution of the water column from winter in the Laptev Sea to early summer in Fram Strait: freshening of the surface, deepening of the mixed layer, increase in temperature and salinity of the Atlantic Water. We also highlight the presence of Canada Basin deep water intrusions and a surface meltwater layer in leads. MOSAiC most likely was the most comprehensive program ever conducted over the ice-covered Arctic Ocean. While data analysis and interpretation are ongoing, the acquired datasets will support a wide range of physical oceanography and multi-disciplinary research. They will provide a significant foundation for assessing and advancing modeling capabilities in the Arctic Ocean

The Comprehensive Native Interactome of a Fully Functional Tagged Prion Protein

The enumeration of the interaction partners of the cellular prion protein, PrPC, may help clarifying its elusive molecular function. Here we added a carboxy proximal myc epitope tag to PrPC. When expressed in transgenic mice, PrPmyc carried a GPI anchor, was targeted to lipid rafts, and was glycosylated similarly to PrPC. PrPmyc antagonized the toxicity of truncated PrP, restored prion infectibility of PrPC-deficient mice, and was physically incorporated into PrPSc aggregates, indicating that it possessed all functional characteristics of genuine PrPC. We then immunopurified myc epitope-containing protein complexes from PrPmyc transgenic mouse brains. Gentle differential elution with epitope-mimetic decapeptides, or a scrambled version thereof, yielded 96 specifically released proteins. Quantitative mass spectrometry with isotope-coded tags identified seven proteins which co-eluted equimolarly with PrPC and may represent component of a multiprotein complex. Selected PrPC interactors were validated using independent methods. Several of these proteins appear to exert functions in axomyelinic maintenance

Reduced microvascular density in omental biopsies of children with chronic kidney disease

Endothelial dysfunction is an early manifestation of cardiovascular disease (CVD) and consistently observed in patients with chronic kidney disease (CKD). We hypothesized that CKD is associated with systemic damage to the microcirculation, preceding macrovascular pathology. To assess the degree of "uremic microangiopathy", we have measured microvascular density in biopsies of the omentum of children with CKD.Omental tissue was collected from 32 healthy children (0-18 years) undergoing elective abdominal surgery and from 23 age-matched cases with stage 5 CKD at the time of catheter insertion for initiation of peritoneal dialysis. Biopsies were analyzed by independent observers using either a manual or an automated imaging system for the assessment of microvascular density. Quantitative immunohistochemistry was performed for markers of autophagy and apoptosis, and for the abundance of the angiogenesis-regulating proteins VEGF-A, VEGF-R2, Angpt1 and Angpt2.Microvascular density was significantly reduced in uremic children compared to healthy controls, both by manual imaging with a digital microscope (median surface area 0.61% vs. 0.95%, p<0.0021 and by automated quantification (total microvascular surface area 0.89% vs. 1.17% p = 0.01). Density measured by manual imaging was significantly associated with age, height, weight and body surface area in CKD patients and healthy controls. In multivariate analysis, age and serum creatinine level were the only independent, significant predictors of microvascular density (r2 = 0.73). There was no immunohistochemical evidence for apoptosis or autophagy. Quantitative staining showed similar expression levels of the angiogenesis regulators VEGF-A, VEGF-receptor 2 and Angpt1 (p = 0.11), but Angpt2 was significantly lower in CKD children (p = 0.01).Microvascular density is profoundly reduced in omental biopsies of children with stage 5 CKD and associated with diminished Angpt2 signaling. Microvascular rarefaction could be an early systemic manifestation of CKD-induced cardiovascular disease

Overview of the MOSAiC expedition: Physical oceanography

Arctic Ocean properties and processes are highly relevant to the regional and global coupled climate system, yet still scarcely observed, especially in winter. Team OCEAN conducted a full year of physical oceanography observations as part of the Multidisciplinary drifting Observatory for the Study of the Arctic Climate (MOSAiC), a drift with the Arctic sea ice from October 2019 to September 2020. An international team designed and implemented the program to characterize the Arctic Ocean system in unprecedented detail, from the seafloor to the air-sea ice-ocean interface, from sub-mesoscales to pan-Arctic. The oceanographic measurements were coordinated with the other teams to explore the ocean physics and linkages to the climate and ecosystem. This paper introduces the major components of the physical oceanography program and complements the other team overviews of the MOSAiC observational program. Team OCEAN’s sampling strategy was designed around hydrographic ship-, ice- and autonomous platform-based measurements to improve the understanding of regional circulation and mixing processes. Measurements were carried out both routinely, with a regular schedule, and in response to storms or opening leads. Here we present alongdrift time series of hydrographic properties, allowing insights into the seasonal and regional evolution of the water column from winter in the Laptev Sea to early summer in Fram Strait: freshening of the surface, deepening of the mixed layer, increase in temperature and salinity of the Atlantic Water. We also highlight the presence of Canada Basin deep water intrusions and a surface meltwater layer in leads. MOSAiC most likely was the most comprehensive program ever conducted over the ice-covered Arctic Ocean. While data analysis and interpretation are ongoing, the acquired datasets will support a wide range of physical oceanography and multi-disciplinary research. They will provide a significant foundation for assessing and advancing modeling capabilities in the Arctic Ocean

Associations between imaging, cognitive and motor-function test procedures in the early detection of Parkinson's Disease

Jährlich wird bei ca. 13.000 Personen in der Bundesrepublik Deutschland die Diagnose „M. Parkinson“ gestellt. Nach anfänglich vergleichsweise milder Symptomatik ist diese Erkrankung jedoch im weiteren Verlauf durch einen zunehmenden Abbau nicht nur motorischer sondern auch kognitiver, emotionaler und vegetativer Funktionen gekennzeichnet, die die Lebensqualität stark beeinträchtigen und in Spätstadien ein hohes Maß an Pflegebedürftigkeit mit sich bringen. Im Jahr 1995 wurde bei Parkinson-Patienten erstmals eine typische Ultra-schallsignalveränderung der Substantia nigra (SN) beschrieben, die im Vergleich zur Norm in ihrer zweidimensionalen Ausbreitung vergrößert sowie signalreicher (hyperechogen; SN+) imponierte. Trotz der Notwendigkeit einer gewissen Erfahrung zur Erhebung und Interpretation des Ultraschallbefundes besticht diese Methode aufgrund ihrer hohen Sensitivität als nicht-invasives und kostengünstiges Verfahren in der Diagnostik des M. Parkinson. Epidemiologische Studien ergaben, dass 10-16% der Allgemeinbevölkerung ebenfalls dieses Ultraschallmerkmal aufweisen. Die Assoziation von SN+ mit vier von fünf prodromalen Markern als auch mit funktionellen Veränderungen des nigro-striatalen Transmittersystems führte zu der These, dass Personen mit SN+ ein erhöhtes Risiko tragen, an M. Parkinson zu erkranken. Dieses beläuft sich aktuellen Studien zufolge auf das 17-fache gegenüber Personen mit SN-. Da bei internationaler Arbeit an der Verfügbarkeit neuroprotektiver Substanzen die Detektion möglicher Risikopersonen unerlässlich ist, war ein Ziel dieser Studie herauszufinden, inwiefern das Leistungsprofil von Personen mit SN+ dem von Parkinson-Patienten entsprach. Diese Subgruppe SN-Hyperechogener hätte wahrscheinlich ein höheres Risiko, an M. Parkinson zu erkranken und könnte von zukünftigen prophylaktischen Maßnahmen profitieren. Für diese Fragestellung verwendeten wir klinisch leicht anwendbare Testverfahren, für die in der Literatur häufig Auffälligkeiten bei Parkinson-Patienten beschrieben wurden sowie die 1.5T-Magnetresonanztomographie als vielerorts verfügbare, nicht-radioaktive bildgebende Methode. Unsere Ergebnisse sprechen dafür, dass die Detektion einer Risikopopulation mit SN+ nicht anhand eines einzigen Testmerkmals der in dieser Studie verwendeten Methoden möglich ist, sondern dass vielmehr eine Kumulation von Einzelmerkmalen vonnöten ist, um eine valide Einschätzung geben zu können. Insbesondere das Vorhandensein von zwei oder mehr prodromalen Markern in Assoziation mit SN-Hyperechogenität mag ein erhöhtes Risiko für eine Parkinsonerkrankung im weiteren Lebensverlauf darstellen. Die in unserer SN+ Gruppe ermittelten Auffälligkeiten betrafen insbesondere eine verminderte sowie häufiger als pathologisch eingestufte Riechfunktion, ein sowohl klinisch als auch kinematisch detektierbares, marginal vermindertes Armschwungausmaß sowie vereinzelte Einschränkungen neuropsychologischer Funktionen insbesondere exekutiver und psychomotorischer Aufmerksamkeits- und Geschwindigkeitsleistungen. Interessanterweise fanden wir in unserer SN+ Gruppe über das Niveau der SN- Gruppe hinausreichende Leistungen in der Diadochokinese-Testung. Es ist möglich, dass eine passagere Leistungssteigerung durch kortikale sowie subkortikale Kompensationsmechanismen bedingt wird. Zudem fanden wir bei unseren Patienten im Frühstadium der Erkrankung bereits Hinweise auf atrophe Prozesse in Form kleinerer SN-Volumina, die mittels konventioneller 1,5T-MR-Tomographie detektierbar waren. Tendenziell geringere gesamt SN-Volumenwerte wurden auch in der SN+ Gruppe gemessen, was möglicherweise ebenfalls auf beginnende atrophierende Prozesse bei einer Subgruppe mit SN+ hinweisen könnte. Methodische Assoziationen fanden sich besonders zwischen den klinischen Testverfahren. Die Ergebnisse der bildgebenden Verfahren zeigten keinerlei Zusammenhänge, so dass mittels TCS und MRT unterschiedliche Aspekte des gleichen Prozesses dargestellt werden und diese Verfahren nicht gegeneinander austauschbar sind. Für keine der bildgebenden Untersuchungsmethoden fanden wir ausreichend stabile Korrelationen mit klinischen und neuropsychologischen Parametern, so dass die Leistungsveränderungen durch jenseits der morphologischen Veränderung der SN parallel verlaufende Prozesse bedingt werden müssen.Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide. Although symptoms may be relatively mild during the initial stages, as the disease progresses, deterioration occurs not only in motor, but also in cognitive, emotional and vegetative functions, significantly reducing quality of life. The development of neuroprotective strategies has become a key focus for current research efforts. However, it is known that classical motor symptoms allowing PD diagnosis occur after the underlying neurodegenerative process has proceeded for years to decades. To effectively use neuroprotective strategies, an earlier (premotor) diagnosis is essential. Thus markers and techniques are needed to detect people at high risk for developing PD in later life. Transcranial B-mode ultrasound imaging has been suggested as a technique for detecting individuals with an icreased risk for PD. This method offers a high level of sensitivity with the advantage of being non-invasive, easy to apply and unexpensive. Compared to the normal population, the B-mode ultrasound reflection pattern of the substantia nigra (SN) in PD patients typically involves an increase in the two-dimensional extension and signal-intensity of the SN (SN+). It has been shown that 10-16% of the normal population also present with hyperechogenicity of the SN, and – underscoring the value of this marker for identifying individuals at risk for PD – that healthy individuals older than 50 years of age have a 17-fold increased risk of developing PD within 3 years. Furthermore, SN+ is associated with several prodromal markers of PD as well as functional changes of the nigrostriatal transmitter system. However, the relation of individuals with SN+ to early PD signs is not clear, yet. Thus, the present study investigated whether people aged 50 years or above with SN+ showed similar results as PD patients at an early stage of the disease on a range of clinical tests and on 1.5T Magnetic Resonance imaging. Three groups were recruited to the study: a healthy control group who were SN- (n=20), people with SN+ (n=29) and patients with early PD (n=13). Clinical tests selected were those previously shown to be sensitive to detecting changes in PD and included standard measures of disease symptoms (UPDRS III), mood (BDI), a report of constipation, neuropsychological testing and a kinematic analysis. Associations between the different assessments were also studied. Results showed that no single measure, used in isolation, could reliably detect individuals at risk; instead, we hypothesize that a combination of two of more prodromal markers in association with SN+ might identify those with a higher chance of developing PD in later life. The greatest performance changes found in the SN+ group consisted of an abnormally decreased smelling function, as well as reductions in arm swing amplitude, which could be detected clinically as well as kinematically. Some reductions in neuropsychological functions were also observed, including poorer performances in attention, executive function and psychomotor speed. Interestingly, by contrast, increased performances on the diadochokinese testing were observed in the SN+ group, exceeding that of the SN- group. This may reflect a possible intermittent increase in motor function caused by both cortical and subcortical compensatory mechanisms. On imaging, indication for atrophic processes was found in the PD group, with smaller SN-volumes detected on 1.5T MR, even at an early stage of the disease. The total SN-volumes in the SN+ group also showed rather smaller volumes compared to the SN- group, suggesting that some atrophic processes may already be present in this subgroup. Finally, although some clinical test procedures were associated with each other, there was no significant relationship between the B-mode ultrasound and MR-imaging techniques. This suggests that each contributes different information about the risk for PD and the disease process and cannot be replaced by one another. Neither of the imaging techniques showed a persistent significant association with clinical or neuropsychological parameters. This reflects the likelihood that the measured cognitive and clinical changes resulted from processes outside the SN, including possible biochemical deviations and the contribution of other brain regions. In conclusion, we found that SN hyperechogenicity in healthy persons older than 50 years is associated with some characteristic, mainly clinical features, that can typically be observed in PD patients. Longitudinal studies will have to show which set of the here presented non-invasive, radiation-free test procedures and imaging techniques will be best suitable as screening tools to detect people with SN+ in a prodromal stage with the ultimate aim to apply neuroprotective therapies in the future