Spreading of Alzheimer tau seeds is enhanced by aging and template matching with limited impact of amyloid-ß.

In Alzheimer's disease (AD), deposition of pathological tau and amyloid-ß (Aß) drive synaptic loss and cognitive decline. The injection of misfolded tau aggregates extracted from human AD brains drives templated spreading of tau pathology within WT mouse brain. Here, we assessed the impact of Aß copathology, of deleting loci known to modify AD risk (Ptk2b, Grn, and Tmem106b) and of pharmacological intervention with an Fyn kinase inhibitor on tau spreading after injection of AD tau extracts. The density and spreading of tau inclusions triggered by human tau seed were unaltered in the hippocampus and cortex of APPswe/PSEN1ΔE9 transgenic and AppNL-F/NL-F knock-in mice. In mice with human tau sequence replacing mouse tau, template matching enhanced neuritic tau burden. Human AD brain tau-enriched preparations contained aggregated Aß, and the Aß coinjection caused a redistribution of Aß aggregates in mutant AD model mice. The injection-induced Aß phenotype was spatially distinct from tau accumulation and could be ameliorated by depleting Aß from tau extracts. These data suggest that Aß and tau pathologies propagate by largely independent mechanisms after their initial formation. Altering the activity of the Fyn and Pyk2 (Ptk2b) kinases involved in Aß-oligomer-induced signaling, or deleting expression of the progranulin and TMEM106B lysosomal proteins, did not alter the somatic tau inclusion burden or spreading. However, mouse aging had a prominent effect to increase the accumulation of neuritic tau after injection of human AD tau seeds into WT mice. These studies refine our knowledge of factors capable of modulating tau spreading.

Evaluation of diagnostic pigments to estimate phytoplankton size classes.

Phytoplankton accessory pigments are commonly used to estimate phytoplankton size classes, particularly during development and validation of biogeochemical models and satellite ocean color-based algorithms. The diagnostic pigment analysis (DPA) is based on bulk measurements of pigment concentrations and relies on assumptions regarding the presence of specific pigments in different phytoplankton taxonomic groups. Three size classes are defined by the DPA: picoplankton, nanoplankton, and microplankton. Until now, the DPA has not been evaluated against an independent approach that provides phytoplankton size calculated on a per-cell basis. Automated quantitative cell imagery of microplankton and some nanoplankton, used in combination with conventional flow cytometry for enumeration of picoplankton and nanoplankton, provide a novel opportunity to perform an independent evaluation of the DPA. Here, we use a data set from the North Atlantic Ocean that encompasses all seasons and a wide range of chlorophyll concentrations (0.18-5.14 mg m-3). Results show that the DPA overestimates microplankton and picoplankton when compared to cytometry data, and subsequently underestimates the contribution of nanoplankton to total biomass. In contrast to the assumption made by the DPA that the microplankton size class is largely made up of diatoms and dinoflagellates, imaging-in-flow cytometry shows significant presence of diatoms and dinoflagellates in the nanoplankton size class. Additionally, chlorophyll b is commonly attributed solely to picoplankton by the DPA, but Chl b-containing phytoplankton are observed with imaging in both nanoplankton and microplankton size classes. We suggest revisions to the DPA equations and application of uncertainties when calculating size classes from diagnostic pigments.

Information content of absorption spectra and implications for ocean color inversion.

The increasing use of hyperspectral optical data in oceanography, both in situ and via remote sensing, holds the potential to significantly advance characterization of marine ecology and biogeochemistry because, in principle, hyperspectral data can provide much more detailed inferences of ecosystem properties via inversion. Effective inferences, however, require careful consideration of the close similarity of different signals of interest, and how these interplay with measurement error and uncertainty to reduce the degrees of freedom (DoF) of hyperspectral measurements. Here we discuss complementary approaches to quantify the DoF in hyperspectral measurements in the case of in situ particulate absorption measurements, though these approaches can also be used on other such data, e.g., ocean color remote sensing. Analyses suggest intermediate (${\sim}5 $∼5) DoF for our dataset of global hyperspectral particulate absorption spectra from the Tara Oceans expedition, meaning that these data can yield coarse community structure information. Empirically, chlorophyll is an effective first-order predictor of absorption spectra, meaning that error characteristics and the mathematics of inversion need to be carefully considered for hyperspectral data to provide information beyond that which chlorophyll provides. We also discuss other useful analytical tools that can be applied to this problem and place our results in the context of hyperspectral remote sensing.

Persistent repression of tau in the brain using engineered zinc finger protein transcription factors.

Neuronal tau reduction confers resilience against ß-amyloid and tau-related neurotoxicity in vitro and in vivo. Here, we introduce a novel translational approach to lower expression of the tau gene MAPT at the transcriptional level using gene-silencing zinc finger protein transcription factors (ZFP-TFs). Following a single administration of adeno-associated virus (AAV), either locally into the hippocampus or intravenously to enable whole-brain transduction, we selectively reduced tau messenger RNA and protein by 50 to 80% out to 11 months, the longest time point studied. Sustained tau lowering was achieved without detectable off-target effects, overt histopathological changes, or molecular alterations. Tau reduction with AAV ZFP-TFs was able to rescue neuronal damage around amyloid plaques in a mouse model of Alzheimer's disease (APP/PS1 line). The highly specific, durable, and controlled knockdown of endogenous tau makes AAV-delivered ZFP-TFs a promising approach for the treatment of tau-related human brain diseases.

A global compilation of in situ aquatic high spectral resolution inherent and apparent optical property data for remote sensing applications.

Light emerging from natural water bodies and measured by radiometers contains information about the local type and concentrations of phytoplankton, non-algal particles and colored dissolved organic matter in the underlying waters. An increase in spectral resolution in forthcoming satellite and airborne remote sensing missions is expected to lead to new or improved capabilities for characterizing aquatic ecosystems. Such upcoming missions include NASA's Plankton, Aerosol, Cloud, ocean Ecosystem (PACE) mission; the NASA Surface Biology and Geology designated observable mission; and NASA Airborne Visible/Infrared Imaging Spectrometer - Next Generation (AVIRIS-NG) airborne missions. In anticipation of these missions, we present an organized dataset of geographically diverse, quality-controlled, high spectral resolution inherent and apparent optical property (IOP-AOP) aquatic data. The data are intended to be of use to increase our understanding of aquatic optical properties, to develop aquatic remote sensing data product algorithms, and to perform calibration and validation activities for forthcoming aquatic-focused imaging spectrometry missions. The dataset is comprised of contributions from several investigators and investigating teams collected over a range of geographic areas and water types, including inland waters, estuaries, and oceans. Specific in situ measurements include remote-sensing reflectance, irradiance reflectance, and coefficients describing particulate absorption, particulate attenuation, non-algal particulate absorption, colored dissolved organic matter absorption, phytoplankton absorption, total absorption, total attenuation, particulate backscattering, and total backscattering. The dataset can be downloaded from https://doi.org/10.1594/PANGAEA.902230 (Casey et al., 2019).

Small phytoplankton dominate western North Atlantic biomass.

The North Atlantic phytoplankton spring bloom is the pinnacle in an annual cycle that is driven by physical, chemical, and biological seasonality. Despite its important contributions to the global carbon cycle, transitions in plankton community composition between the winter and spring have been scarcely examined in the North Atlantic. Phytoplankton composition in early winter was compared with latitudinal transects that captured the subsequent spring bloom climax. Amplicon sequence variants (ASVs), imaging flow cytometry, and flow-cytometry provided a synoptic view of phytoplankton diversity. Phytoplankton communities were not uniform across the sites studied, but rather mapped with apparent fidelity onto subpolar- and subtropical-influenced water masses of the North Atlantic. At most stations, cells < 20-µm diameter were the main contributors to phytoplankton biomass. Winter phytoplankton communities were dominated by cyanobacteria and pico-phytoeukaryotes. These transitioned to more diverse and dynamic spring communities in which pico- and nano-phytoeukaryotes, including many prasinophyte algae, dominated. Diatoms, which are often assumed to be the dominant phytoplankton in blooms, were contributors but not the major component of biomass. We show that diverse, small phytoplankton taxa are unexpectedly common in the western North Atlantic and that regional influences play a large role in modulating community transitions during the seasonal progression of blooms.

Approach for Propagating Radiometric Data Uncertainties Through NASA Ocean Color Algorithms.

Spectroradiometric satellite observations of the ocean are commonly referred to as "ocean color" remote sensing. NASA has continuously collected, processed, and distributed ocean color datasets since the launch of the Sea-viewing Wide-field-of-view Sensor (SeaWiFS) in 1997. While numerous ocean color algorithms have been developed in the past two decades that derive geophysical data products from sensor-observed radiometry, few papers have clearly demonstrated how to estimate measurement uncertainty in derived data products. As the uptake of ocean color data products continues to grow with the launch of new and advanced sensors, it is critical that pixel-by-pixel data product uncertainties are estimated during routine data processing. Knowledge of uncertainties can be used when studying long-term climate records, or to assist in the development and performance appraisal of bio-optical algorithms. In this methods paper we provide a comprehensive overview of how to formulate first-order first-moment (FOFM) calculus for propagating radiometric uncertainties through a selection of bio-optical models. We demonstrate FOFM uncertainty formulations for the following NASA ocean color data products: chlorophyll-a pigment concentration (Chl), the diffuse attenuation coefficient at 490 nm (K d,490), particulate organic carbon (POC), normalized fluorescent line height (nflh), and inherent optical properties (IOPs). Using a quality-controlled in situ hyperspectral remote sensing reflectance (R rs,i ) dataset, we show how computationally inexpensive, yet algebraically complex, FOFM calculations may be evaluated for correctness using the more computationally expensive Monte Carlo approach. We compare bio-optical product uncertainties derived using our test R rs dataset assuming spectrally-flat, uncorrelated relative uncertainties of 1, 5, and 10%. We also consider spectrally dependent, uncorrelated relative uncertainties in R rs . The importance of considering spectral covariances in R rs , where practicable, in the FOFM methodology is highlighted with an example SeaWiFS image. We also present a brief case study of two POC algorithms to illustrate how FOFM formulations may be used to construct measurement uncertainty budgets for ecologically-relevant data products. Such knowledge, even if rudimentary, may provide useful information to end-users when selecting data products or when developing their own algorithms.

Synaptic Tau Seeding Precedes Tau Pathology in Human Alzheimer's Disease Brain.

Alzheimer's disease (AD) is defined by the presence of intraneuronal neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau aggregates as well as extracellular amyloid-beta plaques. The presence and spread of tau pathology through the brain is classified by Braak stages and thought to correlate with the progression of AD. Several in vitro and in vivo studies have examined the ability of tau pathology to move from one neuron to the next, suggesting a "prion-like" spread of tau aggregates may be an underlying cause of Braak tau staging in AD. Using the HEK293 TauRD-P301S-CFP/YFP expressing biosensor cells as a highly sensitive and specific tool to identify the presence of seed competent aggregated tau in brain lysate-i.e., tau aggregates that are capable of recruiting and misfolding monomeric tau-, we detected substantial tau seeding levels in the entorhinal cortex from human cases with only very rare NFTs, suggesting that soluble tau aggregates can exist prior to the development of overt tau pathology. We next looked at tau seeding levels in human brains of varying Braak stages along six regions of the Braak Tau Pathway. Tau seeding levels were detected not only in the brain regions impacted by pathology, but also in the subsequent non-pathology containing region along the Braak pathway. These data imply that pathogenic tau aggregates precede overt tau pathology in a manner that is consistent with transneuronal spread of tau aggregates. We then detected tau seeding in frontal white matter tracts and the optic nerve, two brain regions comprised of axons that contain little to no neuronal cell bodies, implying that tau aggregates can indeed traverse along axons. Finally, we isolated cytosolic and synaptosome fractions along the Braak Tau Pathway from brains of varying Braak stages. Phosphorylated and seed competent tau was significantly enriched in the synaptic fraction of brain regions that did not have extensive cellular tau pathology, further suggesting that aggregated tau seeds move through the human brain along synaptically connected neurons. Together, these data provide further evidence that the spread of tau aggregates through the human brain along synaptically connected networks results in the pathogenesis of human Alzheimer's disease.

Ocean plankton. Environmental characteristics of Agulhas rings affect interocean plankton transport.

Agulhas rings provide the principal route for ocean waters to circulate from the Indo-Pacific to the Atlantic basin. Their influence on global ocean circulation is well known, but their role in plankton transport is largely unexplored. We show that, although the coarse taxonomic structure of plankton communities is continuous across the Agulhas choke point, South Atlantic plankton diversity is altered compared with Indian Ocean source populations. Modeling and in situ sampling of a young Agulhas ring indicate that strong vertical mixing drives complex nitrogen cycling, shaping community metabolism and biogeochemical signatures as the ring and associated plankton transit westward. The peculiar local environment inside Agulhas rings may provide a selective mechanism contributing to the limited dispersal of Indian Ocean plankton populations into the Atlantic.