Neuron to glia signaling triggers myelin membrane exocytosis from endosomal storage sites

During vertebrate brain development, axons are enwrapped by myelin, an insulating membrane produced by oligodendrocytes. Neuron-derived signaling molecules are temporally and spatially required to coordinate oligodendrocyte differentiation. In this study, we show that neurons regulate myelin membrane trafficking in oligodendrocytes. In the absence of neurons, the major myelin membrane protein, the proteolipid protein (PLP), is internalized and stored in late endosomes/lysosomes (LEs/Ls) by a cholesterol-dependent and clathrin-independent endocytosis pathway that requires actin and the RhoA guanosine triphosphatase. Upon maturation, the rate of endocytosis is reduced, and a cAMP-dependent neuronal signal triggers the transport of PLP from LEs/Ls to the plasma membrane. These findings reveal a fundamental and novel role of LEs/Ls in oligodendrocytes: to store and release PLP in a regulated fashion. The release of myelin membrane from LEs/Ls by neuronal signals may represent a mechanism to control myelin membrane growth

Tree species traits but not diversity mitigate stem breakage in a subtropical forest following a rare and extreme ice storm

Peer reviewedPublisher PD

Provable Security Analysis of Decentralized Cryptographic Contact Tracing

Automated contact tracing leverages the ubiquity of smartphones to warn users about an increased exposure risk to COVID-19. In the course of only a few weeks, several cryptographic protocols have been proposed that aim to achieve such contract tracing in a decentralized and privacy-preserving way. Roughly, they let users\u27 phones exchange random looking pseudonyms that are derived from locally stored keys. If a user is diagnosed, her phone uploads the keys which allows other users to check for any contact matches. Ultimately this line of work led to Google and Apple including a variant of these protocols into their phones which is currently used by millions of users. Due to the obvious urgency, these schemes were pushed to deployment without a formal analysis of the achieved security and privacy features. In this work we address this gap and provide the first formal treatment of such decentralized cryptographic contact tracing. We formally define three main properties in a game-based manner: pseudonym and trace unlinkability to guarantee the privacy of users during healthy and infectious periods, and integrity ensuring that triggering false positive alarms is infeasible. A particular focus of our work is on the timed aspects of these schemes, as both keys and pseudonyms are rotated regularly, and we specify different variants of the aforementioned properties depending on the time granularity for which they hold. We analyze a selection of practical protocols (DP-3T, TCN, GAEN) and prove their security under well-defined assumptions

Gustatory Function in Acute COVID‐19 ‐ Results From Home‐Based Psychophysical Testing

Objective Gustatory function during COVID-19 is self-reported by around 50% of patients. However, only a few studies assessed gustation using psychophysical testing during acute infection. The objective of this study is to test gustatory function on threshold tests in the very first days of COVID-19. Methods Psychophysical testing consisted of validated and blinded tests for olfaction (NHANES Pocket Smell Test) and gustation (Taste Strips Test). These test kits were sent to home-quarantined patients and self-administered using a detailed instruction sheet. Results A total of 51 patients were included in this study. Testing was performed 6.5 ± 2.7 days after sampling of respiratory swabs. At this time 37% of patients stated to currently experience a gustatory impairment. The mean Taste Strips score was 10.0 ± 3.4 with 28% scoring in the range of hypogeusia. Interestingly, no significant difference in the results of gustatory testing could be observed between the group with subjectively preserved gustation and the group with self-rated taste impairment. Conclusion During the very first days of COVID-19, psychophysical gustatory testing revealed hypogeusia in 28%. This is far lower than patients' self-reports. Different from previous studies, we did not find clear evidence for an impairment of only certain taste qualities

Daphniaperformance on diets containing different combinations of high-quality algae, heterotrophic bacteria, and allochthonous particulate organic matter

Filter-feeding zooplankton in lakes feed on a mixture of phytoplankton, bacteria, and terrestrial particles and the proportions and nutritional value of these components can be highly variable. However, the extent to which food quality interacts with food quantity in affecting overall zooplankton performance is not yet fully resolved. Here we performed laboratory feeding experiments to test how the performance of the unselective filter feederDaphnia galeatawas affected if various quantities of high-quality food (the phytoplanktonRhodomonas) were diluted with low-quality food such as heterotrophic bacteria (Pseudomonas) or terrestrial detritus particles (t-POM) from the riparian zone of a boreal forest stream. We hypothesised: that increased proportions of bacteria and t-POM in the diet will lead to decreased survival, somatic growth; and reproduction ofDaphniadespite the presence of phytoplankton; that these effects are more pronounced for t-POM than for heterotrophic bacteria; and that this response is stronger when phytoplankton availability is low. Increasing the concentrations ofPseudomonasaffectedDaphniasurvival, growth, and reproduction negatively whenRhodomonaswas available at intermediate (0.37 mgC/L) and high (0.55 mgC/L) quantities. WhenRhodomonasquantity was low (0.22 mgC/L), the addition ofPseudomonasgenerally resulted in betterDaphniaperformance except at very high concentrations of the bacterium relative toRhodomonas. In contrast, the addition of t-POM was detrimental for overallDaphniaperformance at allRhodomonasconcentrations. Daphniaperformance was best described by a model including the interaction between food quality and quantity, with stronger negative effects onDaphniawhen high-quality food was supplemented with t-POM than withPseudomonas. The results indicate that the ability of zooplankton to use low-quality food is affected by the concurrent availability of high-quality food. Furthermore, food sources that can be used but do not fulfil dietary requirements of grazers (e.g. bacteria), may still provide nutritional benefits as long as other complementary food components are available in sufficient quantities to compensate for biochemical deficiencies. Therefore, we conclude that heterotrophic bacteria, but not peat layer t-POM, can be an important component of zooplankton diets in boreal lakes, especially if the concentration of phytoplankton is low

Fronto-striatal alterations correlate with apathy severity in behavioral variant frontotemporal dementia

Structural and functional changes in cortical and subcortical regions have been reported in behavioral variant frontotemporal dementia (bvFTD), however, a multimodal approach may provide deeper insights into the neural correlates of neuropsychiatric symptoms. In this multicenter study, we measured cortical thickness (CTh) and subcortical volumes to identify structural abnormalities in 37 bvFTD patients, and 37 age- and sex-matched healthy controls. For seed regions with significant structural changes, whole-brain functional connectivity (FC) was examined in a sub-cohort of N = 22 bvFTD and N = 22 matched control subjects to detect complementary alterations in brain network organization. To explore the functional significance of the observed structural and functional deviations, correlations with clinical and neuropsychological outcomes were tested where available. Significantly decreased CTh was observed in the bvFTD group in caudal middle frontal gyrus, left pars opercularis, bilateral superior frontal and bilateral middle temporal gyrus along with subcortical volume reductions in bilateral basal ganglia, thalamus, hippocampus, and amygdala. Resting-state functional magnetic resonance imaging showed decreased FC in bvFTD between: dorsal striatum and left caudal middle frontal gyrus;putamen and fronto-parietal regions;pallidum and cerebellum. Conversely, bvFTD showed increased FC between: left middle temporal gyrus and paracingulate gyrus;caudate nucleus and insula;amygdala and parahippocampal gyrus. Additionally, cortical thickness in caudal, lateral and superior frontal regions as well as caudate nucleus volume correlated negatively with apathy severity scores of the Neuropsychiatry Inventory Questionnaire. In conclusion, multimodal structural and functional imaging indicates that fronto-striatal regions have a considerable influence on the severity of apathy in bvFTD

Association of latent factors of neuroinflammation with Alzheimer's disease pathology and longitudinal cognitive decline

INTRODUCTION: We investigated the association of inflammatory mechanisms with markers of Alzheimer's disease (AD) pathology and rates of cognitive decline in the AD spectrum.METHODS: We studied 296 cases from the Deutsches Zentrum für Neurodegenerative Erkrankungen Longitudinal Cognitive Impairment and Dementia Study (DELCODE) cohort, and an extension cohort of 276 cases of the Alzheimer's Disease Neuroimaging Initiative study. Using Bayesian confirmatory factor analysis, we constructed latent factors for synaptic integrity, microglia, cerebrovascular endothelial function, cytokine/chemokine, and complement components of the inflammatory response using a set of inflammatory markers in cerebrospinal fluid.RESULTS: We found strong evidence for an association of synaptic integrity, microglia response, and cerebrovascular endothelial function with a latent factor of AD pathology and with rates of cognitive decline. We found evidence against an association of complement and cytokine/chemokine factors with AD pathology and rates of cognitive decline.DISCUSSION: Latent factors provided access to directly unobservable components of the neuroinflammatory response and their association with AD pathology and cognitive decline.</p

Amyloid pathology but not APOE ε4 status is permissive for tau-related hippocampal dysfunction

We investigated whether the impact of tau-pathology on memory performance and on hippocampal/medial temporal memory function in non-demented individuals depends on the presence of amyloid pathology, irrespective of diagnostic clinical stage. We conducted a cross-sectional analysis of the observational, multicentric DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE). Two hundred and thirty-five participants completed task functional MRI and provided CSF (92 cognitively unimpaired, 100 experiencing subjective cognitive decline and 43 with mild cognitive impairment). Presence (A+) and absence (A-) of amyloid pathology was defined by CSF amyloid-β42 (Aβ42) levels. Free recall performance in the Free and Cued Selective Reminding Test, scene recognition memory accuracy and hippocampal/medial temporal functional MRI novelty responses to scene images were related to CSF total-tau and phospho-tau levels separately for A+ and A- individuals. We found that total-tau and phospho-tau levels were negatively associated with memory performance in both tasks and with novelty responses in the hippocampus and amygdala, in interaction with Aβ42 levels. Subgroup analyses showed that these relationships were only present in A+ and remained stable when very high levels of tau (>700 pg/ml) and phospho-tau (>100 pg/ml) were excluded. These relationships were significant with diagnosis, age, education, sex, assessment site and Aβ42 levels as covariates. They also remained significant after propensity score based matching of phospho-tau levels across A+ and A- groups. After classifying this matched sample for phospho-tau pathology (T-/T+), individuals with A+/T+ were significantly more memory-impaired than A-/T+ despite the fact that both groups had the same amount of phospho-tau pathology. ApoE status (presence of the E4 allele), a known genetic risk factor for Alzheimer's disease, did not mediate the relationship between tau pathology and hippocampal function and memory performance. Thus, our data show that the presence of amyloid pathology is associated with a linear relationship between tau pathology, hippocampal dysfunction and memory impairment, although the actual severity of amyloid pathology is uncorrelated. Our data therefore indicate that the presence of amyloid pathology provides a permissive state for tau-related hippocampal dysfunction and hippocampus-dependent recognition and recall impairment. This raises the possibility that in the predementia stage of Alzheimer's disease, removing the negative impact of amyloid pathology could improve memory and hippocampal function even if the amount of tau-pathology in CSF is not changed, whereas reducing increased CSF tau-pathology in amyloid-negative individuals may not proportionally improve memory function

Fornix fractional anisotropy mediates the association between Mediterranean diet adherence and memory four years later in older adults without dementia

Here, we investigated whether fractional anisotropy (FA) of hippocampus-relevant white-matter tracts mediates the association between baseline Mediterranean diet adherence (MeDiAd) and verbal episodic memory over four years. Participants were healthy older adults with and without subjective cognitive decline and patients with amnestic mild cognitive impairment from the DELCODE cohort study (n = 376; age: 71.47 ± 6.09 years; 48.7 % female). MeDiAd and diffusion data were obtained at baseline. Verbal episodic memory was assessed at baseline and four yearly follow-ups. The associations between baseline MeDiAd and white matter, and verbal episodic memory's mean and rate of change over four years were tested with latent growth curve modeling. Baseline MeDiAd was associated with verbal episodic memory four years later (95 % confidence interval, CI [0.01, 0.32]) but not with its rate of change over this period. Baseline Fornix FA mediated - and, thus, explained - that association (95 % CI [0.002, 0.09]). Fornix FA may be an appropriate response biomarker of Mediterranean diet interventions on verbal memory in older adults.</p