Cerebrospinal fluid and positron-emission tomography biomarkers for noradrenergic dysfunction in neurodegenerative diseases: a systematic review and meta-analysis

The noradrenergic system shows pathological modifications in aging and neurodegenerative diseases and undergoes substantial neuronal loss in Alzheimer’s disease and Parkinson’s disease. While a coherent picture of structural decline in post-mortem and in vivo MRI measures seems to emerge, whether this translates into a consistent decline in available noradrenaline levels is unclear. We conducted a meta-analysis of noradrenergic differences in Alzheimer’s disease dementia and Parkinson’s disease using CSF and PET biomarkers. CSF noradrenaline and 3-methoxy-4-hydroxyphenylglycol levels as well as noradrenaline transporters availability, measured with PET, were summarized from 26 articles using a random-effects model meta-analysis. Compared to controls, individuals with Parkinson’s disease showed significantly decreased levels of CSF noradrenaline and 3-methoxy-4-hydroxyphenylglycol, as well as noradrenaline transporters availability in the hypothalamus. In Alzheimer’s disease dementia, 3-methoxy-4-hydroxyphenylglycol but not noradrenaline levels were increased compared to controls. Both CSF and PET biomarkers of noradrenergic dysfunction reveal significant alterations in Parkinson’s disease and Alzheimer’s disease dementia. However, further studies are required to understand how these biomarkers are associated to the clinical symptoms and pathology

Lagrangian Residence Time in the Bay of Gdańsk, Baltic Sea

The impact of synoptic scale and mesoscale variability on the Lagrangian residence time (LRT) of the surface water in the Bay of Gdańsk was investigated using the results from an eddy-resolving model. The computed LRT of 53–60 days was up to four times longer than the estimated flushing time reported by Witek et al. (2003). The highest residence times were those of Puck Bay and near the coast, shallower than 50 m water depth, especially during the winter. These sites also had the highest annual mean in LRT. During the summer, when the level of biological activity is high, the LRT distribution was very heterogeneous and patchy, possibly due to the dynamics of varying eddy field and to variable wind forcing. Long-term run tracking of the inflowing water from the Vistula River (VR) showed a broad spectrum of tracer distribution. The potential impact of a much higher LRT on the near-coastal nitrogen cycle, coastal filter function and genetic differentiation is discussed, and the consequences for coastal zone management are considered. Since residence time is the most important factor regulating nutrient cycling, the incorporation of residence time into the Marine Strategy Framework Directive descriptors would result in an improved, unbiased evaluation of good environmental status

Discovery of ultrapotent broadly neutralizing antibodies from SARS-CoV-2 elite neutralizers

A fraction of COVID-19 convalescent individuals mount a potent antibody response to SARS-CoV-2 with cross-reactivity to SARS-CoV-1. To uncover their humoral response in detail, we performed single B cell analysis from 10 SARS-CoV-2 elite neutralizers. We isolated and analyzed 126 monoclonal antibodies, many of which were sarbecovirus cross-reactive, with some displaying merbecovirus-and embecovirus-reactivity. Several isolated broadly neutralizing antibodies were effective against B.1.1.7, B.1.351, B.1.429, B.1.617, and B.1.617.2 variants and 19 prominent potential escape sites. Furthermore, assembly of 716,806 SARSCoV-2 sequences predicted emerging escape variants, which were also effectively neutralized. One of these broadly neutralizing potent antibodies, R40-1G8, is a IGHV3-53 RBD-class-1 antibody. Remarkably, cryo-EM analysis revealed that R40-1G8 has a flexible binding mode, targeting both upand downconformations of the RBD. Given the threat of emerging SARS-CoV-2 variants, we demonstrate that elite neutralizers are a valuable source for isolating ultrapotent antibody candidates to prevent and treat SARS-CoV-2 infection